The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis.

The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial) is a multicenter randomized trial addressing chronic pain among patients receiving maintenance hemodialysis for end-stage kidney disease. The trial uses a sequential, multiple assignment design with a randomized component for all participants (Phase 1) and a non-randomized component for a subset of participants (Phase 2). During Phase 1, participants are randomized to Pain Coping Skills Training (PCST), an intervention designed to increase self-efficacy for managing pain, or Usual Care. PCST consists of weekly, live, coach-led cognitive behavioral therapy sessions delivered by video- or tele-conferencing for 12 weeks followed by daily interactive voice response sessions delivered by telephone for an additional 12 weeks. At 24 weeks (Phase 2), participants in both the PCST and Usual Care groups taking prescription opioid medications at an average dose of ≥20 morphine milligram equivalents per day are offered buprenorphine, a partial opioid agonist with a more favorable safety profile than full-agonist opioids. All participants are followed for 36 weeks. The primary outcome is pain interference ascertained, for the primary analysis, at 12 weeks. Secondary outcomes include additional patient-reported measures and clinical outcomes including falls, hospitalizations, and death. Exploratory outcomes include acceptability, tolerability, and efficacy of buprenorphine. The enrollment target of 640 participants was met 27 months after trial initiation. The findings of the trial will inform the management of chronic pain, a common and challenging issue for patients treated with maintenance hemodialysis. NCT04571619.

Development of a Patient Preference Survey for Wearable Kidney Replacement Therapy Devices.

Background: Recent innovations have the potential to disrupt the current paradigm for kidney failure treatment. The US Food and Drug Administration is committed to incorporating valid scientific evidence about how patients weigh the benefits and risks of new devices into their decision making, but to date, premarket submission of patient preference information (PPI) has been limited for kidney devices. With input from stakeholders, we developed a survey intended to yield valid PPI, capturing how patients trade off the potential benefits and risks of wearable dialysis devices and in-center hemodialysis. Methods: We conducted concept elicitation interviews with individuals receiving dialysis to inform instrument content. After instrument drafting, we conducted two rounds of pretest interviews to evaluate survey face validity, comprehensibility, and perceived relevance. We pilot tested the survey with in-center hemodialysis patients to assess comprehensibility and usability further. Throughout, we used participant input to guide survey refinements. Results: Thirty-six individuals receiving in-center or home dialysis participated in concept elicitation (N=20) and pretest (N=16) interviews. Participants identified reduced fatigue, lower treatment burden, and enhanced freedom as important benefits of a wearable device, and many expressed concerns about risks related to device disconnection-specifically bleeding and infection. We drafted a survey that included descriptions of the risks of serious bleeding and serious infection and an assessment of respondent willingness to wait for a safer device. Input from pretest interviewees led to various instrument modifications, including treatment descriptions, item wording, and risk-level explanations. Pilot testing of the updated survey among 24 in-center hemodialysis patients demonstrated acceptable survey comprehensibility and usability, although 50% of patients required some assistance. Conclusions: The final survey is a 54-item web-based instrument that will yield estimates of the maximal acceptable risk for the described wearable device and willingness to wait for wearable devices with lower risk.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. CONCLUSIONS: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Adolescent driving behavior before and during restrictions related to COVID-19.

INTRODUCTION: Understanding who heeds the driving-related COVID-19 restrictions is critical for assisting public health professionals improve response to this and future pandemic events. The purpose of the current study was to characterize driving behavior changes among adolescents as a function of COVID-19 restrictions. It was hypothesized that adolescent driving would be reduced by COVID-19 restrictions, especially for younger teens, non-minorities, females, non-working teens, and those with higher prosocial tendencies. METHODS: Participants were licensed drivers in "REACT," a longitudinal study of adolescent driving attention. Upon enrollment in REACT, drivers were required to be age 16 or 18, have been issued a driver's license within the last two weeks, and be fluent in written/spoken English. The current observational cohort study was of drivers reporting driving exposure between February 8 and April 22, 2020. Linear mixed-effects models estimated differences in driving changes between COVID-19 periods. RESULTS: Results indicated a decrease across pre-COVID-19 period (February 8 - March 13, 2020) in days driven per week and vehicle miles driven (VMD) was explained by the change of slope post-COVID-19 restrictions (March 14 - April 22, 2020). Post-COVID-19, driving days per week decreased by 37 % and VMD decreased by 35 %. This decrease was lower in ethnic minorities, older adolescents, and employed adolescents. Those with greater dire prosocial tendencies showed greater post-COVID-19 driving decline. DISCUSSION: Findings provide early evidence of COVID-19 restriction-related adolescent driving changes suggesting older, employed, minority teens and teens with lower prosocial tendencies are less likely to reduce driving behavior. These observations provide a foundation for more extensive studies of adolescent drivers during various driving and contact restrictions and inform future public health campaigns for social distancing.

Patient and Caregiver Perspectives on Terms Used to Describe Kidney Health.

BACKGROUND AND OBJECTIVES: The language used to communicate important aspects of kidney health is inconsistent and may be conceptualized differently by patients and health professionals. These problems may impair the quality of communication, care, and patient outcomes. We aimed to describe the perspectives of patients on terms used to describe kidney health. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with CKD (n=54) and caregivers (n=13) from the United States, United Kingdom, and Australia participated in ten focus groups to discuss terms for kidney health (including kidney, renal, CKD, ESKD, kidney failure, and descriptors for kidney function). We analyzed the data using thematic analysis. RESULTS: We identified four themes: provoking and exacerbating undue trauma (fear of the unknown, denoting impending death, despair in having incurable or untreatable disease, premature labeling and assumptions, judgment, stigma, and failure of self); frustrated by ambiguity (confused by medicalized language, lacking personal relevance, baffled by imprecision in meaning, and/or opposed to obsolete terms); making sense of the prognostic enigma (conceptualizing level of kidney function, correlating with symptoms and effect on life, predicting progression, and need for intervention); and mobilizing self-management (confronting reality, enabling planning and preparation, taking ownership for change, learning medical terms for self-advocacy, and educating others). CONCLUSIONS: The obscurity and imprecision of terms in CKD can be unduly distressing and traumatizing for patients, which can impair decision making and self-management. Consistent and meaningful patient-centered terminology may improve patient autonomy, satisfaction, and outcomes.

A Prospective Longitudinal Investigation of Cortical Thickness and Gyrification in Schizophrenia.

BACKGROUND: Cortical thickness (CT) and gyrification are complementary indices that assess different aspects of gray matter structural integrity. Both neurodevelopment insults and acute tissue response to antipsychotic medication could underlie the known heterogeneity of treatment response and are well-suited for interrogation into the relationship between gray matter morphometry and clinical outcomes in schizophrenia (SZ). METHODS: Using a prospective design, we enrolled 34 unmedicated patients with SZ and 23 healthy controls. Patients were scanned at baseline and after a 6-week trial with risperidone. CT and local gyrification index (LGI) values were quantified from structural MRI scans using FreeSurfer 5.3. RESULTS: We found reduced CT and LGI in patients compared to controls. Vertex-wise analyses demonstrated that hypogyrification was most prominent in the inferior frontal cortex, temporal cortex, insula, pre/postcentral gyri, temporoparietal junction, and the supramarginal gyrus. Baseline CT was predictive of subsequent response to antipsychotic treatment, and increase in CT after 6 weeks was correlated with greater symptom reductions. CONCLUSIONS: In summary, we report evidence of reduced CT and LGI in unmedicated patients compared to controls, suggesting involvement of different aspects of gray matter morphometry in the pathophysiology of SZ. Importantly, we found that lower CT at baseline and greater increase of CT following 6 weeks of treatment with risperidone were associated with better clinical response. Our results suggest that cortical thinning may normalize as a result of a good response to antipsychotic medication, possibly by alleviating potential neurotoxic processes underlying gray matter deterioration.

Baseline Functional Connectivity Predicts Connectivity Changes Due to a Small Dose of Midazolam in Older Adults.

BACKGROUND: In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55-73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function. METHODS: We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults. RESULTS: Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration. CONCLUSIONS: Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults.

A longitudinal magnetic resonance spectroscopy study investigating effects of risperidone in the anterior cingulate cortex and hippocampus in schizophrenia.

Magnetic Resonance Spectroscopy is a popular approach to probe brain chemistry in schizophrenia (SZ), but no consensus exists as to the extent of alterations. This may be attributable to differential effects of populations studied, brain regions examined, or antipsychotic medication effects. Here, we measured neurometabolites in the anterior cingulate cortex (ACC) and hippocampus, two structurally dissimilar brain regions implicated in the SZ pathophysiology. We enrolled 61 SZ with the goal to scan them before and after six weeks of treatment with risperidone. We also scanned 31 matched healthy controls twice, six weeks apart. Using mixed effect repeated measures linear models to examine the effect of group and time on metabolite levels in each voxel, we report an increase in hippocampal glutamate + glutamine (Glx) in SZ compared to controls (p = 0.043), but no effect of antipsychotic medication (p = 0.330). In the ACC, we did not find metabolite alterations or antipsychotic medication related changes after six weeks of treatment with risperidone. The coefficients for the discriminant function (differentiating SZ from HC) in the ACC were greatest for NAA (-0.83), and in the hippocampus for Glx (0.76), the same metabolites were associated with greater treatment response in patients at trend level. Taken together, our data extends the existing literature by demonstrating regionally distinct metabolite alterations in the same patient group and suggests that antipsychotic medications may have limited effects on metabolite levels in these regions.