Proposed comprehensive ototoxicity monitoring program for VA healthcare (COMP-VA).
ABSTRACT: Prevention and rehabilitation of hearing loss and tinnitus, the two most commonly awarded service-connected disabilities, are high priority initiatives in the Department of Veterans Affairs (VA). At least 4,000 Veterans, most with significant hearing loss, will receive cisplatin this year, with more than half sustaining permanent hearing shift and nearly 40% developing new tinnitus. With improved survivability following cancer treatment, Veterans treated with cisplatin are approached with the dual goals of effective treatment and preserved quality of life. This article describes COMP-VA, a comprehensive ototoxicity monitoring program developed for VA patients receiving cisplatin. The program includes an individualized pretreatment prediction model that identifies the likelihood of hearing shift given cisplatin dose and patient factors. It supports both manual and automated hearing testing with a newly developed portable audiometer capable of performing the recommended procedures on the chemotherapy unit during treatment. It also includes objective methods for identifying outer hair cell changes and predicting audiogram changes using distortion-product otoacoustic emissions. We describe this program of evidence-based ototoxicity monitoring protocols using a case example to give the reader an understanding of how this program would be applied, along with a plan for future work to accomplish the final stages of program development.
Project description:Cisplatin is effective in the treatment of several cancers but is a known ototoxin resulting in shifts to hearing sensitivity in up to 50-60% of patients. Cisplatin-induced hearing shifts tend to occur first within an octave of a patient's high frequency hearing limit, termed the sensitive range for ototoxicity (SRO), and progress to lower frequencies. While it is currently not possible to know which patients will experience ototoxicity without testing their hearing directly, monitoring the SRO provides an early indication of damage. A tool to help forecast susceptibility to ototoxic-induced changes in the SRO in advance of each chemotherapy treatment visit may prove useful for ototoxicity monitoring efforts, patient counseling, and therapeutic planning.This project was designed to (1) establish pretreatment risk curves that quantify the probability that a new patient will suffer hearing loss within the SRO during treatment with cisplatin and (2) evaluate the accuracy of these predictions in an independent sample of Veterans receiving cisplatin for the treatment of cancer.Two study samples were used. The Developmental sample contained 23 subjects while the Validation sample consisted of 12 subjects.Risk curve predictions for SRO threshold shifts following cisplatin exposure were developed using a Developmental sample comprised of data from a total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone thresholds were obtained within each subject's SRO at each treatment visit and compared with baseline measures. The risk of incurring an SRO shift was statistically modeled as a function of factors related to chemotherapy treatment (cisplatin dose, radiation treatment, doublet medication) and patient status (age, pre-exposure hearing, cancer location and stage). The model was reduced so that only statistically significant variables were included. Receiver-operating characteristic (ROC) curve analyses were then used to determine the accuracy of the risk curve predictions in an independent Validation sample of observations from over 62 treatment visits obtained in 24 ears of 12 Veterans.Only cumulative cisplatin dose and pre-exposure hearing were found to be significantly related to the risk for hearing shift. The dose-ototoxicity risk curve predictions developed from the Developmental sample yielded area under the ROC curve accuracy estimates of 0.85 when applied to an independent Validation sample.Cumulative cisplatin dose in combination with pre-exposure hearing provides an indication of whether hearing will shift in the SRO in advance of cisplatin administration. The validated dose-ototoxicity risk curves described herein can be used before and during treatment to anticipate hearing loss. While having such a tool would not replace serial hearing testing, it would be of great benefit to an ototoxicity monitoring program. It would promote relevant pretreatment counseling. Furthermore, for those found to be at risk of SRO shifts within the speech frequencies, the oncology treatment plan could incorporate anticipated dosing adjustments that could stave off the impact that ototoxicity might bring.
Project description:In response to widespread concerns regarding Veterans' access to VA care, Congress enacted the Veterans Access, Choice and Accountability Act of 2014, which required VA to establish the Veterans Choice Program (VCP). Since the inception of VCP, more than two million Veterans have received care from community providers, representing approximately 25% of Veterans enrolled in VA care. However, expanded access to non-VA care has created challenges in care coordination between VA and community health systems. In March 2018, the VA Health Services Research & Development Service hosted a VA State of the Art conference (SOTA) focused on care coordination. The SOTA convened VA researchers, program directors, clinicians, and policy makers to identify knowledge gaps regarding care coordination within the VA and between VA and community systems of care. This article provides a summary and synthesis of relevant literature and provides recommendations generated from the SOTA about how to evaluate cross-system care coordination. Care coordination is typically evaluated using health outcomes including hospital readmissions and death; however, in cross-system evaluations of care coordination, measures such as access, cost, Veteran/patient and provider satisfaction (including with cross-system communication), comparable quality metrics, context (urban vs. rural), and patient complexity (medical and mental health conditions) need to be included to fully evaluate care coordination effectiveness. Future research should examine the role of multiple individuals coordinating VA and non-VA care, and how these coordinators work together to optimize coordination.
Project description:A cisplatin ototoxicity monitoring protocol was recently proposed using distortion-product otoacoustic emissions (DPOAEs) measured in 1/48th octave steps over the highest obtainable quarter octave ( Dille et al, 2010 ). This protocol can take up to 40 minutes to complete in both ears among seriously ill patients in a potentially noisy test environment. The goal of the current study was to contrast the diagnostic accuracy of ototoxicity monitoring protocols based on changes in DPOAE levels at wider, more rapidly tested, primary frequency step sizes.Measure DPOAE levels in 1/48th octave steps over the highest half-octave of obtainable DPOAEs prior to treatment and at each ototoxicity monitoring session during the course of treatment with cisplatin.Nineteen cancer patients being treated with cisplatin at the Portland Veterans Affairs Medical Center were observed over 56 monitoring appointments. Hearing thresholds in the sensitive region for ototoxicity (SRO) were measured concurrently with DPOAE levels.DPOAE levels measured in 1/24th octave steps provided comparable accuracy, and half the testing time, to the 1/48th octave step protocol previously described.DPOAE level shifts measured in 1/24th octave steps may provide a basis for rapid ototoxicity monitoring among adult cancer patients treated with cisplatin.
Project description:Nonbehavioral methods for identifying cisplatin ototoxicity are important for testing patients with cancer who become too tired or sick to provide a reliable response. The auditory brainstem response (ABR) is a nonbehavioral test that is sensitive to ototoxicity but can be time consuming to implement over a range of frequencies and/or levels. To address this issue, trains of stimuli were developed that offer reliable ABR testing over a range of tone-burst frequencies and levels at a time savings of 77% relative to tone-burst stimuli presented individually. The clinical accuracy of this new method has yet to be determined on a clinical population.This project was designed to determine the test performance of a time-effective ABR methodology aimed at identifying hearing shifts from cisplatin among veterans. A secondary goal was to determine whether improved test performance could be achieved by including our previously developed ototoxicity risk assessment model in the ABR prediction algorithm.A set of discriminant functions were derived using logistic regression to model the risk for cisplatin-induced hearing change. Independent variables were one of several ABR metrics alone and combined with an ototoxicity risk assessment model that includes pre-exposure hearing and cisplatin dose. Receiver operating characteristic curve analysis was used to evaluate the test performance of these discriminant functions.Twenty-two male veterans treated with cisplatin for various cancers provided data from a total of 71 monitoring appointments.Data were collected prospectively from one ear of each participant as designated below. Hearing shift was determined for frequencies within an octave of each patient's high-frequency hearing limit, tested in 1/6th-octave steps. ABRs were monitored using a set of two intensity trains from the highest two multiple frequency tone-burst center frequencies (up to 11.3 kHz) that yielded a robust response at baseline. Each intensity train was presented at 65-105 dB peSPL in 10 dB steps. Scorable ABRs were generally limited to the highest two intensities; therefore, analyses concern those levels.The ABR measurement failure was high, up to 52% for some frequencies and levels. Furthermore, the ABR was not frequently obtained at levels below 85 dB peSPL, consistent with previous studies that suggest a stimulus level of greater than 80 dB peSPL is required to obtain a reliable response to trained stimuli. Using multivariate metrics that included the dose-ototoxicity model, the most accurate scoring function was change in amplitude at lowest half-octave frequency obtained at 105 dB (change in wave V amplitude at frequency 2/105). However, absence of wave V at a monitor patient visit of the ABR response at levels 105 or 95 dB peSPL was deemed the preferred scoring function, because it had lower measurement failure and was within one standard error of the most accurate function.Because of the large number of responses that could not be measured at baseline, this technique as implemented holds limited value as an ototoxicity-monitoring method.
Project description:BACKGROUND:Not much is known about nonelderly veterans and their reliance on care from the Veterans Affairs (VA) health care system when they have access to non-VA care. OBJECTIVES:To estimate VA reliance for nonelderly veterans enrolled in VA and Medicaid. RESEARCH DESIGN:Retrospective, longitudinal analysis of Medicaid claims data and VA administrative data to compare patients' utilization of VA and Medicaid services 12 months before and for up to 12 months after Medicaid enrollment began. SUBJECTS:Nonelderly veterans (below 65?y) receiving VA care and newly enrolled in Medicaid, calendar years 2006-2010 (N=19,890). MEASURES:VA reliance (proportion of care received in VA) for major categories of outpatient and inpatient care. RESULTS:Patients used VA outpatient care at similar levels after enrolling in Medicaid with the exceptions of emergency department (ED) and obstetrics/gynecology care, which decreased. VA inpatient utilization was similar after Medicaid enrollment for most types of care. VA-adjusted outpatient reliance was highest for mental health care (0.99) and lowest for ED care (0.02). VA-adjusted inpatient reliance was highest for respiratory (0.80) and cancer stays (0.80) and lowest for musculoskeletal stays (0.20). Associations between VA reliance and distance to VA providers varied by type of care. CONCLUSIONS:Veterans dually enrolled in Medicaid received most of their outpatient care from the VA except ED, obstetrics/gynecology, and dental care. Patients received most of their inpatient care from Medicaid except mental health, respiratory, and cancer care. Sensitivity to travel distance to VA providers explained some of these differences.
Project description:The program "Implementing Goals of Care Conversations with Veterans in VA LTC Settings" is proposed in partnership with the US Veterans Health Administration (VA) National Center for Ethics in Health Care and the Geriatrics and Extended Care Program Offices, together with the VA Office of Nursing Services. The three projects in this program are designed to support a new system-wide mandate requiring providers to conduct and systematically record conversations with veterans about their preferences for care, particularly life-sustaining treatments. These treatments include cardiac resuscitation, mechanical ventilation, and other forms of life support. However, veteran preferences for care go beyond whether or not they receive life-sustaining treatments to include issues such as whether or not they want to be hospitalized if they are acutely ill, and what kinds of comfort care they would like to receive.Three projects, all focused on improving the provision of veteran-centered care, are proposed. The projects will be conducted in Community Living Centers (VA-owned nursing homes) and VA Home-Based Primary Care programs in five regional networks in the Veterans Health Administration. In all the projects, we will use data from context and barrier and facilitator assessments to design feedback reports for staff to help them understand how well they are meeting the requirement to have conversations with veterans about their preferences and to document them appropriately. We will also use learning collaboratives-meetings in which staff teams come together and problem-solve issues they encounter in how to get veterans' preferences expressed and documented, and acted on-to support action planning to improve performance.We will use data over time to track implementation success, measured as the proportions of veterans in Community Living Centers (CLCs) and Home-Based Primary Care (HBPC) who have a documented goals of care conversation soon after admission. We will work with our operational partners to spread approaches that work throughout the Veterans Health Administration.
Project description:Cisplatin is an effective chemotherapy agent against several pediatric malignancies. One of its side effects is irreversible sensorineural hearing damage that is highly variable with a reported incidence of 22-70%. The aim of this study was to evaluate the incidence and identify clinical predictors of cisplatin-related ototoxicity.We performed a retrospective chart review of 102 pediatric patients who had completed cisplatin therapy for osteosarcoma, neuroblastoma, hepatoblastoma, or germ cell tumor. Patients were diagnosed at Riley Hospital for Children between January 1995 and June 2008, were less than 18 years old at diagnosis, and had normal hearing prior to therapy. Audiograms were scored using the Brock scale (0-4), a validated grading system for cisplatin-related hearing loss.Forty-two percent of the patients experienced hearing loss and 28% had moderate to severe ototoxicity (Brock score ?2). Males were at significantly greater risk for developing hearing loss than were females (P = 0.005, OR 4.812). Age at cancer diagnosis was inversely related to severity of ototoxicity. Patients who suffered Brock grade 3 ototoxicity had a mean age of 4.5 years versus 11.5 years and 7.2 years for grades 1 and 2, respectively (P = 0.02). Cumulative cisplatin dose was also identified as a risk factor for development of ototoxicity (P = 0.03).Gender and cumulative dose are important clinical biomarkers of cisplatin ototoxicity. Severity of ototoxicity may be inversely related to age at time of exposure, with very young patients exhibiting higher grades of hearing loss following cisplatin therapy.
Project description:Background:In a wide range of industries, noise-induced hearing loss remains one of the most prevalent occupational problems. This study aimed to assess the noise exposure level and associated factors of hearing loss among textile workers in Yangon Region, Myanmar. Methods:A cross-sectional study was conducted at a Textile mill (Thamine), Yangon Region, from April to December 2018. In total, 226 workers who were randomly selected from 3 weaving sections participated in face-to-face interviews using a structured questionnaire. A digital sound level meter and pure-tone audiometer were used for the assessment of noise exposure level and hearing loss, respectively. Logistic regression analysis was performed to assess the associated factors of hearing loss. Results:In total workers, 66.4% were exposed to ?85 dB(A) of noise exposure, and the prevalence of hearing loss was 25.7%. Age ?35 years, below high school education, hearing difficulty, tinnitus, hypertension, > 9 years of service duration in a textile mill were positively associated with hearing loss. After adjusting confounding factors, age ?35 years (adjusted odds ratio = 6.90, 95% confidence interval = 3.45-13.82) and tinnitus (adjusted odds ratio = 2.88, 95% confidence interval = 1.13-7.37) were persistently associated with hearing loss. Conclusion:Providing occupational hazard education and enforcement of occupational safety regulations should be taken to decrease the noise exposure level. The regular audiometry test should be conducted for assessment of hearing threshold shift. The employer needs to implement a hearing conservation program in workplace when noise exposure reaches or exceeds 85 dB(A) for 8 hours.
Project description:LESSONS LEARNED:Using a randomized crossover design and continuous variables such as change in hearing threshold and biomarkers of acute renal injury as short-term endpoints, it was determined that pantoprazole, an organic cation transporter 2 inhibitor, did not ameliorate cisplatin-associated nephrotoxicity or ototoxicity.Cystatin C is a robust method to estimate glomerular filtration rate in patients with cancer. Using a patient-reported outcome survey, all patients identified tinnitus and subjective hearing loss occurring "at least rarely" after cycle 1, prior to objective high-frequency hearing loss measured by audiograms.New therapies that improve outcome with less acute and long-term toxicity are needed. BACKGROUND:Organic cation transporter 2 (OCT2), which is a cisplatin uptake transporter expressed on renal tubules and cochlear hair cells but not on osteosarcoma cells, mediates cisplatin uptake. Pantoprazole inhibits OCT2 and could ameliorate cisplatin ototoxicity and nephrotoxicity. Using a randomized crossover design, we evaluated audiograms, urinary acute kidney injury (AKI) biomarkers, and glomerular filtration rate (GFR) estimated from cystatin C (GFRcysC) in patients receiving cisplatin with and without pantoprazole. MATERIALS AND METHODS:Cisplatin (60 mg/m2 × 2 days per cycle) was administered concurrently with pantoprazole (intravenous [IV], 1.6 mg/kg over 4 hours) on cycles 1 and 2 or cycles 3 and 4 in 12 patients with osteosarcoma (OS) with a median (range) age of 12.8 (5.6-19) years. Audiograms, urinary AKI biomarkers, and serum cystatin C were monitored during each cycle. RESULTS:Pantoprazole had no impact on decrements in hearing threshold at 4-8 kHz, post-treatment elevation of urinary AKI biomarkers, or GFRcysC (Fig. 1, Table 1). Histological response (percent necrosis) after two cycles was similar with or without pantoprazole. All eight patients with localized OS at diagnosis are alive and in remission; three of four patients with metastases at diagnosis have died. CONCLUSION:Pantoprazole did not ameliorate cisplatin ototoxicity or nephrotoxicity. The decrease in GFRcysC and increase in N-acetyl-ß-glucosaminidase (NAG) and creatinine demonstrate that these biomarkers can quantify cisplatin glomerular and proximal tubular toxicity. OCT2 inhibition by pantoprazole did not appear to alter antitumor response or survival.
Project description:Cisplatin ototoxicity affects different individuals in a widely variable manner. These variations are likely to be explained by genetic differences among those affected. It would be highly advantageous to identify genetic variants that predispose to cisplatin ototoxicity in order to minimize the risk to susceptible subgroups. Although this area of research is very important, only a few studies have rigorously examined the genetic basis for cisplatin-induced susceptibility to hearing loss. This article addresses recent progress in clarifying the incidence of cisplatin ototoxicity and the risk factors and controversies regarding the identification of genetic variants associated with cisplatin-induced hearing loss.