Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Readability of patient education materials is of utmost importance to ensure understandability and dissemination of health care information in uro-oncology. We aimed to investigate the readability of the official patient education materials of the European Association of Urology (EAU) and American Urology Association (AUA). METHODS:Patient education materials for prostate, bladder, kidney, testicular, penile, and urethral cancers were retrieved from the respective organizations. Readability was assessed via the WebFX online tool for Flesch Kincaid Reading Ease Score (FRES) and for reading grade levels by Flesch Kincaid Grade Level (FKGL), Gunning Fog Score (GFS), Smog Index (SI), Coleman Liau Index (CLI), and Automated Readability Index (ARI). Layperson readability was defined as a FRES of ≥70 and with the other readability indexes <7 according to European Union recommendations. This study assessed only objective readability and no other metrics such as understandability. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Most patient education materials failed to meet the recommended threshold for laypersons. The mean readability for EAU patient education material was as follows: FRES 50.9 (standard error [SE]: 3.0), and FKGL, GFS, SI, CLI, and ARI all with scores ≥7. The mean readability for AUA patient material was as follows: FRES 64.0 (SE: 1.4), with all of FKGL, GFS, SI, and ARI scoring ≥7 readability. Only 13 out of 70 (18.6%) patient education materials' paragraphs met the readability requirements. The mean readability for bladder cancer patient education materials was the lowest, with a FRES of 36.7 (SE: 4.1). CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Patient education materials from leading urological associations reveal readability levels beyond the recommended thresholds for laypersons and may not be understood easily by patients. There is a future need for more patient-friendly reading materials. PATIENT SUMMARY/RESULTS:This study checked whether health information about different cancers was easy to read. Most of it was too hard for patients to understand.

CONTEXT/BACKGROUND:Outpatient Palliative Care (OPC) benefits persons living with serious illness, yet barriers exist in utilization. OBJECTIVES/OBJECTIVE:To identify factors associated with OPC clinic utilization. METHODS:Emergency Medicine Palliative Care Access is a multicenter, randomized control trial comparing two models of palliative care for patients recruited from the Emergency Department (ED): nurse-led telephonic case management and OPC (one visit a month for 6 months). Patients were aged 50+ with advanced cancer or end-stage organ failure and recruited from 19 EDs. Using a mixed effects hurdle model, we analyzed patient, provider, clinic and healthcare system factors associated with OPC utilization. RESULTS:Among the 603 patients randomized to OPC, about half (53.6%) of patients attended at least one clinic visit. Those with less than high school education were less likely to attend an initial visit than those with a college degree or higher (aOR 0.44; CI 0.23, 0.85), as were patients who required considerable assistance (aOR 0.45; CI 0.25, 0.82) or had congestive heart failure only (aOR 0.46; CI 0.26, 0.81). Those with higher symptom burden had a higher attendance at the initial visit (aOR 1.05; CI 1.00, 1.10). Reduced follow up visit rates were demonstrated for those of older age (aRR 0.90; CI 0.82, 0.98), female sex (aRR 0.84; CI 0.71, 0.99), and those that were never married (aRR 0.62; CI 0.52, 0.87). CONCLUSION/CONCLUSIONS:Efforts to improve OPC utilization should focus on those with lower education, more functional limitations, older age, female sex, and those with less social support. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER/UNASSIGNED:NCT03325985.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The longitudinal collection of biological samples from over 7000 birthing parents and their children within the HBCD study enables research on pre- and postnatal exposures (e.g., substance use, toxicants, nutrition), and biological processes (e.g., genetics, epigenetic signatures, proteins, metabolites) on neurobehavioral developmental outcomes. The following biosamples are collected from the birthing parent: 1) blood (i.e., whole blood, serum, plasma, buffy coat, and dried blood spots) during pregnancy, 2) nail clippings during pregnancy and one month postpartum, 3) urine during pregnancy, and 4) saliva during pregnancy and at in-person postnatal assessments. The following samples are collected from the child at in-person study assessments: 1) saliva, 2) stool, and 3) urine. Additionally, placenta tissue, cord blood, and cord tissue are collected by a subset of HBCD sites. Here, we describe the rationale for the collection of these biospecimens, their current and potential future uses, the collection protocol, and collection success rates during piloting. This information will assist research teams in the planning of future studies utilizing this collection of biological samples.

Fetal inflammation, typically measured indirectly through prenatal maternal cytokine markers, has been shown to impact early childhood executive functions (EFs), which are central to later cognitive and life outcomes. Here, we assessed the impact of prenatal inflammation on EF developmental trajectories using direct placenta histopathology measures in 131 mothers who predominantly self-identified as Black (90.8% Black; 0.8% Asian American, 1.5% biracial, 0.8% Latinx, 3.1% White, 3.1% Missing). We found that placental measures of inflammation were associated with limited gain in EF development from 3 to 5 years old. In follow up analyses, we addressed whether screening questionnaires in infancy might aid in classification of infants as higher risk for subsequent EF problems. We found that parent responses to the Ages & Stages Questionnaire and the Infant/Toddler Sensory Profile at 12 months predict the development of EF abilities in children exposed to chronic inflammation. These findings open promising opportunities for early screening of children at risk for poor executive functioning in children exposed to prenatal inflammation.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with cerebrospinal fluid/positron emission tomography biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/amyloid-β₄₂ ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

BACKGROUND:Individuals with opioid use disorder have high rates of hospital admissions, which represent a critical opportunity to engage patients and initiate medications for opioid use disorder (MOUD). However, few patients receive MOUD and, even if MOUD is initiated in the hospital, patients may encounter barriers to continuing MOUD in the community. OBJECTIVE:Describe hospital providers' experiences and perspectives to inform initiatives and policies that support hospital-based MOUD initiation and continuation in community treatment programs. DESIGN/METHODS:As part of a broader implementation study focused on inpatient MOUD (NCT#04921787), we conducted semi-structured interviews with hospital providers. PARTICIPANTS/METHODS:Fifty-seven hospital providers from 12 community hospitals. APPROACH/METHODS:Thematic analysis examined an emergent topic on challenges transitioning patients to outpatient MOUD treatment and related impacts on MOUD initiation by inpatient providers. KEY RESULTS/RESULTS:Participants described structural barriers to transitioning hospitalized patients to continuing outpatient MOUD including (a) limited outpatient buprenorphine prescriber availability, (b) the siloed nature of addiction treatment, and (c) long wait times. As a result of observing these structural barriers, participants experienced a sense of futility that deterred them from initiating MOUD. Participants proposed strategies that could better support these patient transitions, including developing partnerships between hospitals and outpatient addiction treatment and supporting in-reach services from community providers. CONCLUSIONS:We identified concerns about inadequate and inaccessible community-based care and transition pathways that discouraged hospital providers from prescribing MOUD. As hospital-based opioid treatment models continue to expand, programmatic and policy strategies to support inpatient transitions to outpatient addiction treatment are needed. NCT TRIAL NUMBER/UNASSIGNED:04921787.

BACKGROUND:The randomized, phase 2 RENEW trial (NCT01721161) evaluated efficacy/safety of opicinumab (anti-LINGO-1) versus placebo in patients with first-episode unilateral acute optic neuritis (AON). Although no significant differences in the latency recovery of visual evoked potential (VEP) were observed between opicinumab and placebo groups in the intention to treat (ITT) population, the prespecified per-protocol (PP) population showed better recovery with opicinumab than with placebo. RENEWED (NCT02657915) was a one-visit, follow-up study 2 years after the last RENEW study visit (Week 32) designed to assess the long-term electrophysiological and clinical outcomes for participants previously enrolled and having received study treatment in RENEW. METHODS:In the original study (RENEW), participants (aged 18-55 years) with a first unilateral AON episode were enrolled ≤28 days from first symptom onset and after treatment with methylprednisolone 1 g/day intravenously for 3-5 days; these participants were randomized to receive opicinumab 100 mg/kg or placebo intravenously once every 4 weeks from baseline to Week 20, assessed up to Week 32. Participants who received ≥1 dose of opicinumab 100 mg/kg or placebo in RENEW were eligible for the RENEWED follow-up study. Participants enrolled in RENEWED at 2 years (with an additional up to 12-month window) after the last RENEW study visit (Week 32) in both ITT and PP populations. The primary endpoint was change in full-field VEP (FF-VEP) latency of the affected eye at RENEWED study visit versus baseline of the fellow eye in RENEW, comparing between participants who received opicinumab and placebo in RENEW. Clinical progression and severity of multiple sclerosis (MS) were assessed. A substudy evaluated latency recovery using multifocal VEP (mfVEP) as an exploratory endpoint. RESULTS:Of 82 RENEW participants, 52 (63.4 %; opicinumab n = 28, placebo n = 24) enrolled in and completed RENEWED. The adjusted mean (95 % CI) difference in FF-VEP latency delay between opicinumab and placebo groups was -6.0 (-14.6, 2.6) msec (p = 0.165) for the PP population and -4.5 (-12.6, 3.7) msec (p = 0.274) for the ITT population at the RENEWED study visit. Nominally significant improvement on mfVEP latency in the opicinumab group versus placebo was observed in participants of the mfVEP substudy (p = 0.009). In participants from the PP population without clinically definite MS (CDMS) at RENEW baseline,12 (55 %) in the opicinumab group and 12 (67 %) in the placebo group developed CDMS from enrollment in the RENEW study up to RENEWED Day 1; the estimated proportion of participants with CDMS at 2 years after the last study visit assessment in RENEW was lower when treated with opicinumab (0.50) than when treated with placebo (0.61) (hazard ratio p-value = 0.23). No benefit on visual acuity or other neurological functions was observed in the opicinumab group vs placebo in RENEWED. CONCLUSION/CONCLUSIONS:The numerically increased VEP latency recovery with opicinumab treatment in RENEWED was consistent with those observed in the parent study RENEW. However, the VEP latency and clinical data in RENEWED should be interpreted with caution, given the nature of the follow-up study, the small sample size and the limitation in study design.

In 1992, Wacholder and colleagues developed a theoretical framework for case-control studies to minimize bias in control selection. They described three comparability principles (study base, deconfounding, and comparable accuracy) to reduce the potential for selection bias, confounding, and information bias in case-control studies. Wacholder et al. explained how these principles apply to traditional sources of controls for case-control studies, including population controls, hospital controls, controls from a medical practice, friend or relative controls, and deceased controls. The goal of the current manuscript is to extend this seminal work on case-control studies by providing a modern perspective on sources of controls. Today, there are many more potential sources of controls for case-control studies than there were in the 1990s. This is due to technological advances in computing power, internet access, and availability of 'big data' resources. These advances have vastly expanded the quantity and diversity of data available for case-control studies. In this manuscript, we discuss control selection from electronic health records, health insurance claims databases, publicly available online data sources, and social media-based data. We focus on practical considerations for unbiased control selection, emphasizing the strengths and weaknesses of each modern source of controls for case-control studies.