Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts: A Randomized Clinical Trial.

Importance: Animal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; however, precise treatment using bisensory (auditory and somatosensory) stimuli can reverse altered neural patterns and lessen tinnitus. Objective: To confirm and extend the findings of a pilot study, which suggested an increased efficacy of bisensory stimulation, to a clinical trial with a greater duration and greater number of participants. Design, Setting, and Participants: This double-blind, crossover, single-center randomized clinical trial was conducted from March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System in Ann Arbor, Michigan. Eligibility criteria included bothersome tinnitus (Tinnitus Functional Index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatments in the 6 months prior to the trial. Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment. Results were analyzed using intent-to-treat (ITT) and per protocol (PP) populations. Intervention: Precisely timed bisensory (combined auditory and somatosensory) treatment was delivered through a portable, custom, take-home device that was provided to each participant for daily, at-home treatments. Group 1 participants received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Group 2 participants received the auditory-only treatment first, followed by a washout phase, and then the bisensory treatment followed by a second washout phase. Main Outcomes and Measures: Primary end points were changes in TFI score and tinnitus loudness level from baseline through week 6 and week 12. Results: Of 337 screened individuals, 99 (mean [SD] age, 47 [12.7] years; 59 males [60%]; 85 with non-Hispanic White [86%] race and ethnicity) were enrolled into the study and randomized to treatment group 1 (n = 49) or group 2 (n = 50). The active but not the control treatment resulted in clinically significant decreases in TFI scores at week 6 of phase 1 (ITT population: -12.0 [95% CI, -16.9 to -7.9] points; P < .001; PP population: -13.2 [95% CI, -16.0 to -10.5] points; P < .001). Decreases in tinnitus loudness level were greater than 6 dB sensation level (SL; >half as loud) at week 6 for the bisensory treatment group, with little effect for the auditory-only treatment control group at week 6 of phase 1 (ITT population: -5.8 [95% CI, -9.5 to -2.2] dB; P = .08; PP population: -7.2 [95% CI, -11.4 to -3.1] dB; P = .03), and up to 11 dB SL at week 12 of phase 2 (ITT population: -10.9 [95% CI, -15.2 to -6.5] dB; P = .001; PP population: -14.1 [95% CI, -18.4 to -9.8] dB; P < .001). Decreased tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect. Conclusions and Relevance: This trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms can result from using an extended treatment duration. Trial Registration: ClinicalTrials.gov Identifier: NCT03621735.

Implementing pharmacist-prescriber collaboration to improve evidence-based anticoagulant use: a randomized trial.

BACKGROUND: Direct oral anticoagulant medications are commonly used to treat or prevent thrombotic conditions, such as pulmonary embolism, deep vein thrombosis, and atrial fibrillation. However, up to 10-15% of patients receiving these medications get unsafe doses based on a patient's kidney or liver function, potential interactions with other medications, and indication for taking the medication. Alert systems may be beneficial for improving evidence-based prescribing, but can be burdensome and are not currently able to provide monitoring after the initial prescription is written. METHODS/DESIGN: This study will improve upon existing alert systems by testing novel medication alerts that encourage collaboration between prescribers (e.g., physicians, nurse practitioners, physician assistants) and expert pharmacists working in anticoagulation clinics. The study will also improve upon the existing alert system by incorporating dynamic long-term monitoring of patient needs and encouraging collaboration between prescribers and expert pharmacists working in anticoagulation clinics. Incorporating state-of-the-art user-centered design principles, prescribing healthcare providers will be randomized to different types of electronic health record medication alerts when a patient has an unsafe anticoagulant prescription. We will identify which alerts are most effective at encouraging evidence-based prescribing and will test moderators to tailor alert delivery to when it is most beneficial. The aims of the project are to (1) determine the effect of notifications targeting existing inappropriate DOAC prescriptions; (2) examine the effect of alerts on newly prescribed inappropriate DOACs; and (3) examine changes in the magnitude of effects over time for both the new prescription alerts and existing prescription notifications for inappropriate DOACs over the 18-month study period. DISCUSSION: Findings from this project will establish a framework for implementing prescriber-pharmacist collaboration for high-risk medications, including anticoagulants. If effectively implemented at the more than 3000 anticoagulation clinics that exist nationally, hundreds of thousands of patients taking direct oral anticoagulants stand to benefit from safer, evidence-based healthcare. TRIALS REGISTRATION: NCT05351749.

Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation.

Importance: For some patients receiving warfarin, adding aspirin (acetylsalicylic acid) increases bleeding risk with unclear treatment benefit. Reducing excess aspirin use could be associated with improved clinical outcomes. Objective: To assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin. Design, Setting, and Participants: This pre-post observational quality improvement study was conducted from January 1, 2010, to December 31, 2019, at a 6-center quality improvement collaborative in Michigan among 6738 adults taking warfarin for atrial fibrillation and/or venous thromboembolism without an apparent indication for concomitant aspirin. Statistical analysis was conducted from November 26, 2020, to June 14, 2021. Intervention: Primary care professionals for patients taking aspirin were asked whether an ongoing combination aspirin and warfarin treatment was indicated. If not, then aspirin was discontinued with the approval of the managing clinician. Main Outcomes and Measures: Outcomes were assessed before and after intervention for the primary analysis and before and after 24 months before the intervention (when rates of aspirin use first began to decrease) for the secondary analysis. Outcomes included the rate of aspirin use, bleeding, and thrombotic outcomes. An interrupted time series analysis assessed cumulative monthly event rates over time. Results: A total of 6738 patients treated with warfarin (3160 men [46.9%]; mean [SD] age, 62.8 [16.2] years) were followed up for a median of 6.7 months (IQR, 3.2-19.3 months). Aspirin use decreased slightly from a baseline mean use of 29.4% (95% CI, 28.9%-29.9%) to 27.1% (95% CI, 26.1%-28.0%) during the 24 months before the intervention (P < .001 for slope before and after 24 months before the intervention) with an accelerated decrease after the intervention (mean aspirin use, 15.7%; 95% CI, 14.8%-16.8%; P = .001 for slope before and after intervention). In the primary analysis, the intervention was associated with a significant decrease in major bleeding events per month (preintervention, 0.31%; 95% CI, 0.27%-0.34%; postintervention, 0.21%; 95% CI, 0.14%-0.28%; P = .03 for difference in slope before and after intervention). No change was observed in mean percentage of patients having a thrombotic event from before to after the intervention (0.21% vs 0.24%; P = .34 for difference in slope). In the secondary analysis, reducing aspirin use (starting 24 months before the intervention) was associated with decreases in mean percentage of patients having any bleeding event (2.3% vs 1.5%; P = .02 for change in slope before and after 24 months before the intervention), mean percentage of patients having a major bleeding event (0.31% vs 0.25%; P = .001 for change in slope before and after 24 months before the intervention), and mean percentage of patients with an emergency department visit for bleeding (0.99% vs 0.67%; P = .04 for change in slope before and after 24 months before the intervention), with no change in mean percentage of patients with a thrombotic event (0.20% vs 0.23%; P = .36 for change in slope before and after 24 months before the intervention). Conclusions and Relevance: This quality improvement intervention was associated with an acceleration of a preexisting decrease in aspirin use among patients taking warfarin for atrial fibrillation and/or venous thromboembolism without a clear indication for aspirin therapy. Reductions in aspirin use were associated with reduced bleeding. This study suggests that an anticoagulation clinic-based aspirin deimplementation intervention can improve guideline-concordant aspirin use.

Depressive Symptoms and Caregiving Intensity Before and After Onset of Dementia in Partners: A Retrospective, Observational Study.

BACKGROUND: Caring for a partner with dementia poses significant emotional burden and high care demands, but changes in impacts before and after dementia onset is unclear. OBJECTIVE: Examine changes in depressive symptoms and hours of care provided by caregivers through the course of their partners' cognitive decline. METHODS: Retrospective, observational study using household survey data from 2000-2016 Health and Retirement Study and count models to evaluate older individuals' (ages ≥51 y) depressive symptoms (measured using the shortened Center for Epidemiologic Studies Depression Scale) and weekly caregiving in the 10 years before and after their partners' dementia onset (identified using Telephone Interview Cognitive Status screening). Relationships were examined overall and by sex and race. RESULTS: We identified 8298 observations for 1836 older caregivers whose partners developed dementia. From before to after partners' dementia onset, caregivers' mean (SD) depressive symptoms increased from 1.4 (1.9) to 1.9 (2.1) ( P <0.001) and weekly caregiving increased from 4.4 (19.7) to 20.8 (44.1) ( P <0.001) hours. Depressive symptoms and caregiving hours were higher for women compared with men. Depressive symptoms were higher for Blacks compared with Whites, while caregiving hours were higher for Whites. The expected count of caregivers' depressive symptoms and caregiving hours increased by 3% ( P <0.001) and 9% ( P =0.001) before partners' dementia onset and decreased by 2% ( P <0.001) and 1% ( P =0.63) following partners' dementia onset. No differences observed by sex or race. DISCUSSION: Depressive symptoms and instrumental burdens for caregivers increase substantially before the onset of dementia in partners. Early referral to specialty services is critical.

Assessing Eye Health and Eye Care Needs Among North American Native Individuals.

IMPORTANCE: There are few population-level studies on ophthalmic conditions and services among North American Native individuals. OBJECTIVE: To evaluate whether disparities in ophthalmic conditions and services exist between North American Native individuals and non-Hispanic White individuals in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used 100% Medicare fee-for-service (MFFS) enrollment data from the Vision and Eye Health Surveillance System (VEHSS) to examine ophthalmic conditions and service use in North American Native individuals and non-Hispanic White individuals in the US. In this study North American Native individuals included those who identified as American Indian, Native Alaskan, Native Hawaiian, and Pacific Islander. Data were analyzed from August 2020 to April 2021. INTERVENTIONS: Claims and sociodemographic characteristics were extracted and means computed for categories of ophthalmic conditions and select ophthalmic services. Ophthalmic conditions and services were defined in the VEHSS using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Logistic regression was used to model differences between age-adjusted mean ophthalmic condition and service claim rates among North American Native individuals and non-Hispanic White individuals for each age cohort. Matching ophthalmic condition claim rates and ophthalmic service claim rates was performed to examine disparities by racial group. MAIN OUTCOMES AND MEASURES: Mean age-adjusted claim rates for ophthalmic conditions and services among North American Native individuals vs non-Hispanic White individuals per 100 persons. RESULTS: Claims were identified for 177 100 Native American Native individuals and 24 438 000 non-Hispanic White individuals. In 16 of 17 ophthalmic condition categories and 6 of 9 service categories, North American Native individuals had significantly different claim rates from non-Hispanic White individuals. There were higher ophthalmic condition claim rates but lower service claim rates for North American Native individuals (vs non-Hispanic White individuals) for refractive errors (ophthalmic condition, 17.2 vs 11.1; service, 48.3 vs 49.6, respectively; P < .001); blindness and low vision (ophthalmic condition, 1.48 vs 0.75: service, 19.2 vs 20.1, respectively; P < .001); injury, burns, and surgical complications (ophthalmic condition, 1.8 vs 1.7; service, 19.2 vs 20.1, respectively; P < .001); and orbital and external disease (ophthalmic condition, 15.7 vs 13.3; service, 48.3 vs 49.6, respectively; P < .001). For diabetic eye diseases, North American Native individuals had higher ophthalmic condition claim rates (5.22 vs 2.20) but no difference in service claim rates (14.4 vs 14.8; P = .26) compared with non-Hispanic White individuals. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, North American Native individuals had higher prevalence of ophthalmic conditions but no corresponding increase in services (treatment for most ophthalmic conditions) compared with non-Hispanic White individuals. These results suggest worse eye health and higher unmet eyecare needs for North American Native individuals with MFFS coverage compared with non-Hispanic White individuals with MFFS coverage.

Changes in Hospital-acquired Conditions and Mortality Associated With the Hospital-acquired Condition Reduction Program.

IMPORTANCE: To improve patient safety, the Centers for Medicare and Medicaid Services announced the Hospital-Acquired Condition Reduction Program (HACRP) in August 2013. The program reduces Medicare payments by 1% for hospitals in the lowest performance quartile related to hospital-acquired conditions. Performance measures are focused on perioperative care. OBJECTIVE: To evaluate changes in HACs and 30-day mortality after the announcement of the HACRP. DESIGN: Interrupted time-series design using Medicare Provider and Analysis Review (MEDPAR) claims data. We estimated models with linear splines to test for changes in HACs and 30-day mortality before the Affordable Care Act (ACA), after the ACA, and after the HACRP. SETTING: Fee-for-service Medicare 2009-2015. PARTICIPANTS: Medicare beneficiaries undergoing surgery and discharged from an acute care hospital between January 2009 and August 2015 (N = 8,857,877). MAIN OUTCOME AND MEASURE: Changes in HACs and 30-day mortality after the announcement of the HACRP. RESULTS: Patients experienced HACs at a rate of 13.39 per 1000 discharges [95% confidence interval (CI), 13.10 to 13.68] in the pre-ACA period. This declined after the ACA was passed and declined further after the HACRP announcement [adjusted difference in annual slope, -1.34 (95% CI, -1.64 to -1.04)]. Adjusted 30-day mortality was 3.69 (95% CI, 3.64 to 3.74) in the pre-ACA period among patients receiving surgery. Thirty-day mortality continued to decline after the ACA [adjusted annual slope -0.04 (95% CI, -0.05 to -0.02)] but was flat after the HACRP [adjusted annual slope -0.01 (95% CI, -0.04 to 0.02)]. CONCLUSIONS AND RELEVANCE: Although hospital-acquired conditions targeted under the HACRP declined at a greater rate after the program was announced, 30-day mortality was unchanged.

Early (0-7 day) and late (8-30 day) readmission predictors in acute coronary syndrome, atrial fibrillation, and congestive heart failure patients.

OBJECTIVES: Thirty-day readmission following hospitalization for acute coronary syndrome (ACS), atrial fibrillation (AF), or congestive heart failure (CHF) is common, and many occur within one week of discharge. Using a cohort of patients hospitalized for ACS, AF, or CHF, we sought to identify predictors of 30-day, early (0-7 day), and late (8-30 day) all-cause readmission. METHODS: We identified 3531 hospitalizations for ACS, AF, or CHF at a large academic medical center between 2008 and 2018. Multivariable logistic regression models were created to identify predictors of 30-day, early, and late unplanned, all-cause readmission, adjusting for discharge diagnosis and other demographics and comorbidities. RESULTS: Of 3531 patients hospitalized for ACS, AF, or CHF, 700 (19.8%) were readmitted within 30 days, and 205 (29.3%) readmissions were early. Of all 30-day readmissions, 34.8% of ACS, 16.8% of AF, and 26.0% of the CHF cohorts' readmissions occurred early. Higher hemoglobin was associated with lower 30-day readmission [adjusted (adj) OR 0.92, 95% CI 0.88-0.97] while patients requiring intensive care unit (ICU) admission were more likely readmitted within 30 days (adj OR 1.31, 95% CI 1.03-1.67). Among patients with a 30-day readmission, females (adj OR 1.73, 95% CI 1.22, 2.47) and patients requiring ICU admission (adj OR 2.03, 95% CI 1.27, 3.26) were more likely readmitted early than late. Readmission predictors did not vary substantively by discharge diagnosis. CONCLUSION: Patients admitted to the ICU were more likely readmitted in the early and 30-day periods. Other predictors varied between readmission groups. Since outpatient follow-up often occurs beyond 1 week of discharge, early readmission predictors can help healthcare providers identify patients who may benefit from particular post-discharge services.

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Medication Burden for Patients With Bacterial Keratitis.

PURPOSE: To understand medication use and patient burden for treatment of bacterial keratitis (BK). METHODS: A retrospective study was conducted examining medical records of adult patients with BK in an academic cornea practice. Data collected included medications used in the treatment of BK, dosing of medications, and the number and total duration of clinical encounters. Costs of medications were estimated using the average wholesale pharmacy price. Linear regression analysis was used to investigate associations of medication use with patient demographics and corneal culture results and reported with beta estimates (ß) and 95% confidence intervals (95% CIs). RESULTS: Forty-eight patients with BK (56% female) were studied. Patients were treated for a median of 54 days with 10 visits, 5 unique medications, 587 drops, and 7 prescriptions. The estimated median medication cost was $933 (interquartile range: $457-$1422) US dollars. Positive bacterial growth was significantly associated with more visits (ß: 6.16, 95% CI: 1.75-10.6, P = 0.007), more days of treatment (ß: 86.8, 95% CI: 10.8-163, P = 0.026), more prescribed medications (ß: 2.86, 95% CI: 1.04-4.67, P = 0.003), and more doses of medications (ß: 796, 95% CI: 818-1412, P = 0.012) compared with patients who did not undergo corneal scraping. Patients were prescribed 132 more drops of medication for every 10 years of older age (ß: 132, 95% CI: 18.2-246, P = 0.024). Sex and income were not associated with medication burden or treatment length. CONCLUSIONS: Older patients and those with positive cultures incur the most medication burden in treatment of BK. Providers should be aware of medication usage and cost burden as it may affect compliance with treatment.

Retrospective Analysis of Nontuberculous Mycobacterial Infection and Monochloramine Disinfection of Municipal Drinking Water in Michigan.

Infections by nontuberculous mycobacteria (NTM) are primarily acquired from environmental sources, including exposure to municipally treated drinking water. Higher levels of NTM have been reported in drinking water disinfected with monochloramine than in that disinfected with chlorine. However, the relationships between water treatment practices and NTM infection are unclear. The objective of this study was to examine a possible relationship between residual disinfectant used for municipal drinking water treatment (monochloramine or chlorine) and NTM infection. We retrospectively reviewed NTM diagnostic tests performed at a single health care center during a 15-year period. Information on municipal water treatment practices, including disinfectant and primary source water type, was obtained for 140 cities. Based on a logistic regression model, municipal drinking water disinfection with monochloramine compared to chlorine was not associated with NTM infection (P = 0.24). An additional model variable examining water source showed that the likelihood of having an NTM infection was 1.46 times higher for patients residing in cities with drinking water derived from surface water than for those residing in cities with drinking water derived from groundwater (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.03 to 2.08; P = 0.04). In an inverse propensity score weighted regression, monochloramine disinfection was also not associated with NTM infection. A moderate effect on NTM infection rates was observed in the weighted regression for municipal drinking water derived from surface water, though the results were not statistically significant (OR, 1.24; 95% CI, 0.92 to 1.69; P = 0.17).IMPORTANCE Infections by nontuberculous mycobacteria (NTM) result in significant morbidity, mortality, and health care costs. NTM are primarily acquired from environmental sources, including exposure to municipally treated drinking water. Higher levels of NTM have been reported in drinking water disinfected with monochloramine than in drinking water disinfected with chlorine. Our results suggest that municipal drinking water disinfection with monochloramine compared to chlorine is not associated with higher risk of NTM infection. This is important given that regulations that limit drinking water concentrations of disinfection by-products, which are formed primarily when chlorine disinfection is used, incentivize drinking water utilities to change from chlorine disinfection to monochloramine disinfection.

Medication Accuracy in Electronic Health Records for Microbial Keratitis.

IMPORTANCE: Electronic health records (EHRs) contain an abundance of health information. However, researchers need to understand data accuracy to ask appropriate research questions. OBJECTIVE: To investigate the concordance of the names of medications for microbial keratitis in the structured, formal EHR medication list and the text of clinicians' progress notes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study, conducted in the cornea section of an ophthalmology department in a tertiary care, referral academic medical center, examined the medications of 53 patients with microbial keratitis treated until disease resolution from July 1, 2015, to August 1, 2018. Documentation of medications was compared between the structured medication list extracted from the EHR server and medications written into the clinical progress note and transcribed by the study team. EXPOSURE: Medication treatment for microbial keratitis. MAIN OUTCOMES AND MEASURES: Medication mismatch frequency. RESULTS: The study sample included 24 men and 29 women, with a mean (SD) age of 51.8 (19.6) years. Of the 247 medications identified, 57 (23.1%) of prescribed medications differed between the progress notes and the formal EHR-based medication list. Reasons included medications not prescribed via the EHR ordering system (25 [43.9%]), outside medications not reconciled in the internal EHR medication list (23 [40.4%]), and medications prescribed via the EHR ordering system and in the formal list, but not described in the clinical note (9 [15.8%]). Fortified antimicrobials represented the largest category for medication mismatch between modalities (17 of 70 [24.3%]). Nearly one-third of patients (17 [32.1%]) had at least 1 medication mismatch in their record. CONCLUSIONS AND RELEVANCE: Almost 1 in 4 medications were mismatched between the progress note and formal medication list in the EHR. These findings suggest that EHR data should be checked for internal consistency before use in research.

Impact of a health information technology tool addressing information needs of caregivers of adult and pediatric hematopoietic stem cell transplantation patients.

PURPOSE: We developed BMT Roadmap, a health information technology (HIT) application on a tablet, to address caregivers' unmet needs with patient-specific information from the electronic health record. We conducted a preliminary feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT patients. The study was registered on ClinicalTrials.gov (NCT03161665; NCT02409121). METHODS: BMT Roadmap was delivered to 39 caregivers of adult and pediatric patients undergoing first-time HSCT at a single study site. We assessed person-reported outcome measures (PROMs) at baseline (hospital admission), discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness); activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health ([POMS-2®]: depression, distress, vigor, and fatigue); anxiety (State-Trait Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer [CQOLC]). To identify determinants of caregiver activation and quality of life, we used linear mixed models. RESULTS: BMT Roadmap was perceived useful and activation increased from baseline to discharge (p = 0.001). Further, burden decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor and decreasing depression, distress, fatigue, and anxiety was apparent from baseline to discharge. However, overall quality of life lowered at discharge after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p = 0.04). CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in HSCT caregivers. BMT Roadmap was associated with increased activation and decreased burden, but quality of life lowered across hospitalization. Findings support the need to further develop caregiver-specific self-directed resources and provide them both inpatient and outpatient across the HSCT trajectory.

Cognitive Function and Quality of Life in Vorinostat-Treated Patients after Matched Unrelated Donor Myeloablative Conditioning Hematopoietic Cell Transplantation.

Myeloablative conditioning allogeneic hematopoietic cell transplantation (HCT) puts patients at greater risk for significant cognitive and quality of life decline compared with recipients of reduced-intensity conditioning or autologous HCT. Vorinostat, a histone deacetylase inhibitor, has been shown to have neuroprotective and neurorestorative effects in preclinical models of neurologic diseases. Thus, within the context of a myeloablative conditioning phase II clinical trial of vorinostat combined with tacrolimus and methotrexate for graft-versus-host disease prophylaxis, we conducted an ancillary study to evaluate feasibility of assessing associations between vorinostat and neurocognitive function and quality of life (ClinicalTrials.gov NCT02409134). Nine patients (mean age, 53 years; range, 36 to 66) underwent computerized neuropsychological testing (Cogstate) and completed surveys of mood (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and quality of life (Functional Assessment of Cancer Therapy-General). Control cohorts from a separate concurrent longitudinal study (19 autologous and 18 allogeneic HCT patients, who matched the vorinostat patients on relevant medical and demographic variables) completed the same test battery. All allogeneic patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched unrelated donors. The total neurocognitive performance score of vorinostat patients did not change significantly across the study duration (ie, baseline, day 30, day 100, and day 160). Depression, anxiety, and quality of life also did not differ significantly across time. In univariate analyses (analysis of variance), vorinostat-treated patients showed no difference in neurocognitive function or quality of life compared with autologous and allogeneic control subjects. However, when medical variables were accounted for in a linear mixed effects regression model, the total neurocognitive performance of vorinostat-treated patients was comparable with autologous control subjects. Notably, autologous control subjects performed significantly better than allogeneic control subjects (estimate, .64; standard error, .23; P ≤ .01). Moreover, a smaller percentage of vorinostat-treated patients were classified as mildly, moderately, or severely impaired across neurocognitive domains as well as time points compared with both control cohorts. Thus, vorinostat may have neurorestorative or neuroprotective effects in the HCT setting. Accordingly, we recognize the need for a future, full-scale randomized controlled trial to further examine this hypothesis.