Total mercury concentrations in Steller sea lion bone: Variability among locations and elements.

Mercury is a global contaminant that bioaccumulates in a tissue-specific manner in long-lived predators such as Steller sea lions (SSL). Bone is a well-preserved material amenable for studying millennial scale trends; however, little is known about the distribution and variability of total mercury concentrations ([THg]) within individual bones and among bone elements in SSL. We assessed SSL bone [THg] variability with respect to physiologic age, bone type, longitudinally within a bone, and among bone elements. Pup bones (mean ± SD; 31.4 ± 13.58 ppb) had greater [THg] than adults (7.9 ± 1.91 ppb). There were greater and more variable [THg] within individual long bones near epiphyses compared to mid-diaphysis. Pup spongy bone in ribs (62.7 ± 44.79 ppb) had greater [THg] than long bones (23.5 ± 8.83 ppb) and phalanges (19.6 ± 10.78 ppb). These differences are likely due to variability in bone composition, growth, and turnover rate. This study informs standardized sampling procedures for [THg] in bone to improve interpretations of mercury variability over time and space.

Preliminary comparisons between a point-of-care ketometer and reference method using Steller sea lion pup whole blood and plasma.

We evaluated the Precision Xtra™ ketometer as part of a larger study categorizing fasting status of free-ranging Steller sea lion (Eumetopias jubatus; SSL) pups which necessitated the identification of plasma ß-hydroxybutyrate concentrations ([ß-HBA]) around a threshold of <0.3 and ≥0.3 mmol/l. Whole blood samples mixed with sodium heparin (NaHep) or ethylenediaminetetraacetic acid liquid anticoagulants were tested <10 minutes after collection (n = 14; triplicate technical replicates). Plasma (stored at -80°C, NaHep, Thaw1) measured via our laboratory's Reference Assay (Sigma Aldrich, St. Louis, MO, Kit #MAK041) served as the standard [ß-HBA] for ketometer comparisons. Our observed ß-HBA range (0.0-1.6 mmol/l), consistent with published [ß-HBA] of free-ranging Otariid pups, represented the lower 20% of the ketometer's range (0.0-8.0 mmol/l). The maximal coefficient of variation (%CV) of ketometer technical replicates was 9.1% (NaHep, whole blood). The majority of ketometer technical replicate sets (84%, including all matrices, anticoagulants and thawings) were identical (CV = 0%). We found linear relationships and agreement of ketometer [ß-HBA] between whole blood preserved with different anticoagulants and between whole blood and plasma (Thaw1) measurements. The ketometer produced results with linearity to the Reference Assay for both whole blood and plasma (Thaw1). We identified a non-linear relationship between plasma at Thaw1 and Thaw2 (tested four months apart, NaHep), as only samples with higher SSL [ß-HBA] decreased in concentration, and all others remained the same. With respect to categorizing SSL pup fasting in our larger study, the ketometer's %Accuracy, %Sensitivity and %Specificity for samples with Reference Assay ß-HBA <0.2 and >0.4 mmol/l were 100%. We adopted a modified procedure: plasma samples with mean ketometer concentrations ±0.1 mmol/l of 0.3 mmol/l ß-HBA were re-evaluated using the Reference Assay, improving measurement precision from tenths (ketometer) to thousandths (assay) mmol/l. The Precision Xtra™ ketometer was valuable to our application over the range of [ß-HBA] observed in SSL pup plasma and whole blood samples.

Adherence and persistence of HIV pre-exposure prophylaxis use in the United States.

PURPOSE: To describe medication adherence and persistence of HIV PrEP overall and compare between sex and age groups of commercially insured individuals in the United States. METHODS: We conducted a national retrospective cohort study of the Merative MarketScan Claims Database from 2011 to 2019 to describe adherence and persistence of PrEP overall and compared between sex and age groups. High adherence was defined as ≥80% of proportion of days covered and persistence was measured in days from initiation to the first day of a 60-day treatment gap. RESULTS: A total of 29 689 new PrEP users identified. Overall adherence was high (81.9%; 95% confidence interval [CI]: 81.5%-82.3%). Females were more adherent than males (adjusted odds ratio [aOR] 1.87; 95% CI: 1.50-2.34), while those ≥45-years were less adherent than individuals <45-years (aOR 0.87: 95% CI: 0.81-0.93). More than half of individuals discontinued therapy within the first year (median 238.0 days; interquartile range 99.0-507.0 days). Females were less persistent than males (hazard ratio [HR] 1.49; 95% CI: 1.34-1.65), and people ≥45-years old were more persistent (i.e., lower risk of discontinuation) than those <45-years (HR 0.43; 95% CI: 0.33-0.55). CONCLUSIONS: These findings show adherence to daily PrEP is high among commercially insured individuals but the majority still discontinue in the first year. Future research should investigate what factors influence PrEP discontinuation among this population and ways to reduce barriers to therapy maintenance to ensure the population-level benefits of PrEP treatment.

Integrated antibody and cellular immunity monitoring are required for assessment of the long term protection that will be essential for effective next generation vaccine development.

The COVID pandemic exposed the critical role T cells play in initial immunity, the establishment and maintenance of long term protection, and of durable responsiveness against novel viral variants. A growing body of evidence indicates that adding measures of cellular immunity will fill an important knowledge gap in vaccine clinical trials, likely leading to improvements in the effectiveness of the next generation vaccines against current and emerging variants. In depth cellular immune monitoring in Phase II trials, particularly for high risk populations such as the elderly or immune compromised, should result in better understanding of the dynamics and requirements for establishing effective long term protection. Such analyses can result in cellular immunity correlates that can then be deployed in Phase III studies using appropriate, scalable technologies. Measures of cellular immunity are less established than antibodies as correlates of clinical immunity, and some misconceptions persist about cellular immune monitoring usefulness, cost, complexity, feasibility, and scalability. We outline the currently available cellular immunity assays, review their readiness for use in clinical trials, their logistical requirements, and the type of information each assay generates. The objective is to provide a reliable source of information that could be leveraged to develop a rational approach for comprehensive immune monitoring during vaccine development.

Fasting durations of Steller sea lion pups vary among subpopulations-evidence from two plasma metabolites.

Geographic differences in population growth trends are well-documented in Steller sea lions (Eumetopias jubatus), a species of North Pacific pinniped listed under the U.S. Endangered Species Act in 1990 following a marked decline in population abundance that began during the 1970s. As population growth is intrinsically linked to pup production and survival, examining factors related to pup physiological condition provides useful information to management authorities regarding potential drivers of regional differences. During dam foraging trips, pups predictably transition among three fasting phases, distinguished by the changes in the predominant metabolic byproduct. We used standardized ranges of two plasma metabolites (blood urea nitrogen and ß-hydroxybutyrate) to assign pups to fasting categories (n = 1528, 1990-2016, 12 subpopulations): Recently Fed-Phase I (digestion/assimilation-expected hepatic/muscle glycogen usage), Phase II (expected lipid utilization), transitioning between Phases II-III (expected lipid utilization with increased protein reliance), or Phase III (expected protein catabolism). As anticipated, the majority of pups were classified as Recently Fed-Phase I (overall mean proportion = 0.72) and few pups as Phase III (overall mean proportion = 0.04). By further comparing pups in Short (Recently Fed-Phase II) and Long (all other pups) duration fasts, we identified three subpopulations with significantly (P < 0.03) greater proportions of pups dependent upon endogenous sources of energy for extended periods, during a life stage of somatic growth and development: the 1) central (0.27 ± 0.09) and 2) western (0.36 ± 0.13) Aleutian Island (declining population trend) and 3) southern Southeast Alaska (0.32 ± 0.06; increasing population trend) subpopulations had greater Long fast proportions than the eastern Aleutian Islands (0.10 ± 0.05; stabilized population). Due to contrasting population growth trends among these highlighted subpopulations over the past 50+ years, both density-independent and density-dependent factors likely influence the dam foraging trip duration, contributing to longer fasting durations for pups at some rookeries.

Trends of nonoccupational postexposure prophylaxis in the United States.

OBJECTIVE: To describe national annual rates of nonoccupational postexposure prophylaxis (nPEP) in the United States. DESIGN: Retrospective cohort study of commercially insured individuals in the Merative MarketScan Database from January 1, 2010 to December 31, 2019. METHODS: Patients at least 13 years old prescribed nPEP per recommended Centers for Disease Control and Prevention guidelines were identified using pharmacy claims. Rates of use were described overall and stratified by sex, age group, and region. These rates were qualitatively compared to the diagnosis rates of human immunodeficiency virus (HIV) observed in the data. Joinpoint analysis identified inflection points of nPEP use. RESULTS: Eleven thousand, three hundred and ninety-seven nPEP users were identified, with a mean age of 33.7 years. Most were males (64.6%) and lived in the south (33.2%) and northeast (32.4%). The rate of nPEP use increased 515%, from 1.42 nPEP users per 100 000 enrollees in 2010 to 8.71 nPEP users per 10 000 enrollees in 2019. The comparative nPEP use rates among subgroups largely mirrored their HIV diagnosis rates, that is, subgroups with a higher HIV rate had higher nPEP use. In the Joinpoint analysis significant growth was observed from 2012 to 2015 [estimated annual percentage change (EAPC): 45.8%; 95% confidence interval (CI): 29.4 - 64.3] followed by a more moderate increase from 2015 to 2019 (EAPC 16.0%; 95% CI: 12.6-19.6). CONCLUSIONS: nPEP use increased from 2010 to 2019, but not equally across all risk groups. Further policy interventions should be developed to reduce barriers and ensure adequate access to this important HIV prevention tool.

Adherence to HIV Pre-Exposure Prophylaxis Testing Guidelines in the United States.

Testing guidelines for initiation of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) have been developed to ensure appropriate use of PrEP, such as among those with renal dysfunction or at high risk of seroconversion. While many studies have looked at the trends of use of PrEP in the United States, little is known about compliance with these guidelines, the quality of care of PrEP at a national level, or what provider-level factors are associated with high-quality care. We conducted a retrospective claims analysis of providers of commercially insured new users of PrEP between January 1, 2011, and December 31, 2019. Of the 4200 providers, quality of care was low, with only 6.4% having claims for ≥60% of guideline-recommended testing for their patients in the testing window for all visits. More than half of the providers did not have claims for HIV testing at initiation of PrEP and ≥40% did not for sexually transmitted infections at both initiation and follow-up visits. Even when extending the testing window, quality of care remained low. Logistic regression models found no association between provider type and high quality of care, but did find that providers with one PrEP patient were more likely to have higher quality of care than those with multiple patients for all tests [adjusted odds ratio 0.47 (95% confidence interval: 0.33-0.67)]. The study findings suggest further training and interventions, such as integrated test ordering through electronic health records, are needed to increase quality of care for PrEP and ensure appropriate monitoring of patients.

Cellular Immunity Is Critical for Assessing COVID-19 Vaccine Effectiveness in Immunocompromised Individuals.

COVID-19 vaccine clinical development was conducted with unprecedented speed. Immunity measurements were concentrated on the antibody response which left significant gaps in our understanding how robust and long-lasting immune protection develops. Better understanding the cellular immune response will fill those gaps, especially in the elderly and immunocompromised populations which not only have the highest risk for severe infection, but also frequently have inadequate antibody responses. Although cellular immunity measurements are more logistically complex to conduct for clinical trials compared to antibody measurements, the feasibility and benefit of doing them in clinical trials has been demonstrated and so should be more widely adopted. Adding significant cellular response metrics will provide a deeper understanding of the overall immune response to COVID-19 vaccination, which will significantly inform vaccination strategies for the most vulnerable populations. Better monitoring of overall immunity will also substantially benefit other vaccine development efforts, and indeed any therapies that involve the immune system as part of the therapeutic strategy.

A safe in-home disposal system with every opioid prescription? Food and Drug Administration is considering a potential new Risk Evaluation and Mitigation Strategy that could impact pharmacists.

Misuse of prescription opioids contributes to the ongoing crisis of opioid-related overdose and deaths in the United States. The failure of patients and caregivers to safely dispose of unused opioids contributes to the problems. In 2018, Public Law 115-271 provided U.S. Food and Drug Administration (FDA) authority to mandate a Risk Evaluation and Mitigation Strategy (REMS) for safe disposal packaging or safe disposal solutions for opioid analgesic medications. FDA has been collaborating with stakeholders to determine whether a new REMS is needed. A new or revised opioid REMS could substantially affect opioid packaging, pharmacist roles and services, and dispensing activities such as education, counseling, and product distribution. The pharmacy profession has provided limited input to FDA regarding a potential new or revised opioid REMS. In this commentary, we aim to (1) provide awareness and raise questions on pertinent issues regarding opioid use and safe home disposal, (2) offer considerations for regulators on needed research in the development and assessment of a new REMS, and (3) highlight actions for pharmacist engagement in patient care services to promote safe use and safe home disposal of opioids. Consideration of a potential mandate regarding enhanced safety packaging or safe disposal solutions for opioids presents opportunities to revisit professional roles and engage proactively with FDA and other stakeholders. We hope this commentary stimulates timely feedback by pharmacy leaders, researchers, and practitioners on whether and how options for safe home disposal of opioids should be included in a REMS in contemplation of potential benefits, unintended consequences, expanded professional roles, timeline, assessment of program effectiveness, and adequate compensation. We support a shared opioid REMS that funds the counseling of patients and caregivers on safe opioid use and safe home opioid disposal options and provides appropriate education and products to facilitate that disposal.

Narrative arcs and shaping influences in long-term medication adherence.

Long-term adherence to medications is not well understood and poses a significant challenge for many chronically ill persons. Past research provides insights on adherence in short durations such as a day or several weeks, even though chronically ill patients are required to take medications for periods as long as a lifetime. To fill this important knowledge gap, we study the temporal unfolding of prolonged medication-taking experiences among thirty adults, mostly African American, with chronic hypertension in the U.S. Specifically, we take an extended, experience-centered, narrative approach to examine retrospective patient accounts of adherence efforts over spans of one year to more than four decades. Applying Gergen and Gergen's concept of narrative forms (1983), we find four distinct narrative arcs, or patterned sequences of medication consumption, that we term Out of the Gate, Existential Turn, Fits and Starts, and Slow Climb, along with individual and social elements that shape and shift practices in the context of time.

A faculty and staff workshop on microaggression and implicit bias: Knowledge and awareness of student, faculty, and staff experiences.

BACKGROUND AND PURPOSE: This paper describes the context and experiences of a workshop to raise knowledge and awareness of a college of pharmacy's faculty and staff about microaggressive behaviors and implicit biases. The workshop was intended to provide a non-threatening, interactive, and informative professional development program to demonstrate the cumulative marginalizing effects on students, faculty, and staff who may perceive themselves as targets. EDUCATIONAL ACTIVITY AND SETTING: A half-day workshop was conducted during July 2018. Participants were initially provided with definitions and categories of microaggression and implicit bias. To bring the subject matter "alive" and foster receptivity, interactive videos were shown with scenarios depicting situations reflective of microaggressions and implicit biases. College faculty, staff, and students made these relatable. To foster objectivity, an outside consultant was hired to facilitate the ensuing roundtable and plenary discussions. FINDINGS: Sixty-eight participants responded to a pre-survey designed by the workshop team, and 78% indicated never having attended a training/seminar on microaggression and/or implicit bias. Sixty-two individuals responded to the post-survey with 92% indicating increased knowledge gained from workshop. Anecdotal reports suggested that the workshop had an ongoing impact, as faculty and staff continued the discussions in subsequent months and requested additional training sessions. SUMMARY: The workshop heightened awareness and increased faculty and staff knowledge on microaggressive behaviors, implicit biases, and the potential consequences thereof. It also demonstrated the importance of addressing conversations that are perceived as difficult, in order to create a diverse and inclusive workplace and learning environment for all.

Secondary effects of an opioid-focused academic detailing program on non-opioid controlled substance prescribing in primary care.

Background: Educational outreach programs that focus on safe opioid prescribing and awareness of state prescription monitoring programs may modify clinicians' prescribing behavior. The objective of this study was to evaluate the secondary effects of an opioid-focused academic detailing (AD) program on non-opioid controlled substance prescribing in primary care. Methods: A quasi-experimental pre-post study of primary care clinicians exposed and unexposed to the AD program was conducted using data from the Illinois Prescription Monitoring Program from December 2017 to February 2019. Outcomes were mean monthly prescriptions for benzodiazepines (BZD), non-BZD sedative-hypnotics, and carisoprodol, per clinician. A difference-in-differences (DID) approach utilizing repeated-measures mixed-effects linear regression models was used to compare changes in outcomes six-months before and after the program. Results: Mean monthly BZD prescriptions declined in both groups of clinicians (AD-exposed n = 151; controls n = 399) after implementation of the AD program. Although the mean monthly number of BZD prescriptions decreased in both groups after the AD program, BZD prescribing in the AD-exposed group declined at a slower rate following the AD program (DID = 0.73; 95% CI: 0.14, 1.31). The AD-exposed group had a 0.06 (95% CI: -0.11, -0.01) lower rate of mean monthly carisoprodol prescriptions compared to the control group following the AD program. There was no change in the rate of mean monthly non-BZD sedative-hypnotic prescriptions between the two groups. Conclusions: The higher relative rate of BZD prescribing in the AD-exposed group compared to the control group following the AD program may be reflective of an unintended consequence of opioid-focused AD programs as clinicians learn to be cautious about opioid prescribing. Our findings may suggest the need for incorporation of targeted education on appropriate BZD prescribing into opioid-focused AD programs as a featured component. These findings warrant further consideration and investigation before large-scale implementation of opioid-focused educational outreach programs.

MindMate: A single case experimental design study of a reminder system for people with dementia.

Prospective memory difficulties are commonly reported in people with dementia. The evidence supporting the use of prospective memory devices among the dementia population remains limited. MindMate is a recently developed smart device application that aims to support individuals with a diagnosis of dementia, improving self-management skills and quality of life. This study investigated the effectiveness and usability of the reminder tool on the MindMate application as a memory aid. Three participants with a diagnosis of Alzheimer's disease were recruited to this multiple baseline single-case experimental design study. Partners of the participants recorded their performance on everyday tasks on weekly monitoring forms during a baseline phase (between five and seven weeks) and during the intervention phase (five weeks) whilst using MindMate. Two participants successfully used the app throughout the intervention weeks and gave positive usability ratings. Tau-U analysis showed a significant increase in memory performance between baseline and intervention phase (Tau-U = 1, 0.94, p < .01). A third participant withdrew from the intervention phase following difficulties turning off the reminders and frustrations with the reminder alert sound. For two of the three participants, use of MindMate was feasible and effective in supporting remembering of everyday tasks compared to practice as usual.

Exploring Completeness of Adverse Event Reports as a Tool for Signal Detection in Pharmacovigilance.

BACKGROUND: Completeness of adverse event (AE) reports is an important component of quality for good pharmacovigilance practices. We aimed to evaluate the impact of incorporating a measure of completeness of AE reports on quantitative signal detection. METHODS: An internal safety database from a global pharmaceutical company was used in the analysis. vigiGrade, an index score of completeness, was derived for each AE report. Data from various patient support programs (PSPs) were categorized based on average vigiGrade score per PSP. Performance of signal detection was compared between: (1) weighting and not weighting by vigiGrade score; and, (2) well documented and poorly documented PSPs using sensitivity, specificity, area under the receiver operating characteristics curve (AUC) and time-to-signal detection. RESULTS: The ability to detect signals did not differ significantly when weighting by vigiGrade score [sensitivity (50% vs. 45%, p = 1), specificity (82.8% vs. 82.8%, p = 1), AUC (0.66 vs. 0.63, p = 0.051) or time-to-signal detection (HR 0.81, p = 0.63)] compared to not weighting. Well documented PSPs were better at detecting signals than poorly documented PSPs (AUC 0.66 vs. 0.52; p = 0.041) but time-to-signal detection did not differ significantly (HR 1.54, p = 0.42). CONCLUSION: Completeness of AE reports did not significantly impact the ability to detect signals when weighting by vigiGrade score or restricting the database based on the level of completeness. While the vigiGrade helps provide quality assessments of AE reports and prioritize cases for review, our findings indicate the tool might not be useful for quantitative signal detection when used by itself.

Practice change intentions after academic detailing align with subsequent opioid prescribing.

OBJECTIVE: Self-reported behavior change is used to evaluate the effectiveness of educational outreach interventions delivered to clinicians, such as academic detailing (AD). However, self-reported changes in behavior are often not corroborated with data on actual behavior change. To assess alignment between self-reported practice change intentions and actual opioid prescribing behavior among primary care clinicians after an AD intervention. METHODS: We used a difference-in-differences approach to compare pre-post changes in opioid prescribing using data from the Illinois Prescription Monitoring Program. An opioid-focused AD intervention was delivered to primary care clinicians from a large health system in the Chicago metropolitan area from June 2018 to August 2018. Immediately after the AD intervention, clinicians were administered a single-item self-reported practice change measure. Clinicians were categorized into 2 groups on the basis of their responses: (1) intention to change and (2) no-to-moderate intention to change. Outcomes were mean total opioid prescriptions and high-dose opioid prescriptions (≥ 90 morphine milligram equivalents) per clinician per month. Repeated measures linear regression models were used to compare changes in opioid prescribing outcomes between the 2 groups in the 6 months before and after the AD intervention. RESULTS: A total of 149 clinicians were included for analysis. An intention to change was reported by 72 clinicians and no-to-moderate intention to change was reported by 77 clinicians. In the 6 months after the AD intervention, there were 1.48 (95% CI -2.48 to -0.47) fewer total opioid prescriptions and 0.50 (-0.69 to -0.31) fewer high-dose opioid prescriptions per clinician per month in the intention to change group than in the no-to-moderate intention to change group. CONCLUSION: This study showed considerable alignment between self-reported practice change intentions and actual changes in opioid prescribing behavior. Future opioid-focused educational outreach interventions should consider using standardized single-item practice change measures as an immediate indicator of future behavior change.

Impact of adverse event reports from marketing authorization holder-sponsored patient support programs on the performance of signal detection in pharmacovigilance.

OBJECTIVES: Marketing authorization holder (MAH)-sponsored patient support programs (PSPs) are a major source of adverse event (AE) reports. The impact of reports from PSPs on the ability to detect AE signals is unclear. We compared signal detection performance using data from PSPs vs. non-PSP sources, and between PSPs providing clinical services vs. PSPs not providing clinical services. METHODS: Data were obtained from an internal safety database for a global pharmaceutical company 2015-2017. We assessed whether signals were detected for the reference drug-AE pairs using data from PSPs vs. non-PSP sources, and among different PSP services. The performance was evaluated by four measures including area under the receiver operating characteristic curve (AUC) and time-to-signal detection. RESULTS: While the majority of reports were from PSPs, non-PSP sources were better and faster at detecting signals (AUC 0.63 vs. 0.41, p = 0.035; HR 3.52, p = 0.014) compared to PSPs. Within PSPs, PSPs providing clinical services were marginally better at detecting signals (AUC 0.60 vs. 0.41, p = 0.053) but not faster compared to PSPs not providing clinical services. CONCLUSION: Reports of AEs from PSPs had worse signal detection performance compared to non-PSP sources. Pharmacovigilance experts should be mindful when using databases that contain reports from PSPs for signal detection.

Identification of barriers to safe opioid prescribing in primary care: a qualitative analysis of field notes collected through academic detailing.

BACKGROUND: Understanding barriers to safe opioid prescribing in primary care is critical amid the epidemic of prescription opioid abuse, misuse, and overdose in the US. Educational outreach strategies, such as academic detailing (AD), provide a forum for identification of barriers to, and strategies to facilitate, safe opioid prescribing in primary care. AIM: To identify barriers to safe opioid prescribing among primary care providers (PCPs) through AD. DESIGN AND SETTING: Qualitative analysis of data was collected through an existing AD intervention to improve safe opioid prescribing in primary care. The AD intervention was delivered from June 2018 to August 2018 to licensed PCPs with prescriptive authority within a large independent health system in the metropolitan Chicagoland area. METHOD: The AD intervention involved visits by trained detailers to PCPs who contemporaneously documented details from each visit via field notes. Using qualitative analysis, field notes were analysed to identify recurring themes related to opioid prescribing barriers. RESULTS: Detailer-entered field notes from 186 AD visits with PCPs were analysed. Barriers to safe opioid prescribing were organised into six themes: 1) gaps in knowledge; 2) lack of prescription monitoring programme (PMP) utilisation; 3) patient pressures to prescribe opioids; 4) insurance coverage policies; 5) provider beliefs; and 6) health system pain management practices. CONCLUSION: Barriers to safe opioid prescribing in primary care, identified through AD visits among this large group of PCPs, support the need for continued efforts to enhance pain-management education, maximise PMP utilisation, and increase access to, and affordability of, non-opioid treatments.

An Acoustic Characterization of Prosodic Differences in Autism Spectrum Disorder and First-Degree Relatives.

This study examined prosody through characterization of acoustic properties of the speech of individuals with ASD and their parents, during narration. A subset of utterances were low-pass filtered and rated for differences in intonation, speech rate, and rhythm. Listener ratings were minimally related to acoustic measures, underscoring the complexity of atypical prosody in ASD. Acoustic analyses revealed greater utterance-final fundamental frequency excursion size and slower speech rate in the ASD group. Slower speech rate was also evident in the ASD parent group, particularly parents with the broad autism phenotype. Overlapping prosodic differences in ASD and ASD Parent groups suggest that prosodic differences may constitute an important phenotype contributing to ASD features and index genetic liability to ASD among first-degree relatives.

Route of Infection Influences Zika Virus Shedding in a Guinea Pig Model.

Due to the recent epidemic of Zika virus (ZIKV) infection and resulting sequelae, as well as concerns about both the sexual and vertical transmission of the virus, renewed attention has been paid to the pathogenesis of this unique arbovirus. Numerous small animal models have been used in various ZIKV pathogenicity studies, however, they are often performed using immunodeficient or immunosuppressed animals, which may impact disease progression in a manner not relevant to immunocompetent humans. The use of immunocompetent animal models, such as macaques, is constrained by small sample sizes and the need for specialized equipment/staff. Here we report the establishment of ZIKV infection in an immunocompetent small animal model, the guinea pig, using both subcutaneous and vaginal routes of infection to mimic mosquito-borne and sexual transmission. Guinea pigs developed clinical signs consistent with mostly asymptomatic and mild disease observed in humans. We demonstrate that the route of infection does not significantly alter viral tissue tropism but does impact mucosal shedding mechanics. We also demonstrate persistent infection in sensory and autonomic ganglia, identifying a previously unrecognized niche of viral persistence that could contribute to viral shedding in secretions. We conclude that the guinea pig represents a useful and relevant model for ZIKV pathogenesis.

Patient-centered design in developing a mobile application for oral anticancer medications.

OBJECTIVES: To develop and test the usability and feasibility of a customizable mobile application (app) designed to help educate patients about their oral anticancer medications (OAMs) and regimens. SETTING: Outpatient cancer center and oncology pharmacy for urban, Midwestern academic health system. PRACTICE DESCRIPTION: Clinically-supervised educational intervention to support patients learning about OAMs. PRACTICE INNOVATION: With input from patient partners, our interdisciplinary team designed the first known tablet-based educational app that can interface with a patient's electronic medical record. The app is based on learning style and adherence theories and is customizable for individually prescribed OAMs. The app can accommodate multiple learning styles through text at 6th-grade reading level, pictures, animations, and audio voiceovers. Functionalities include interactive educational modules on 11 OAMs and case-based patient stories on common barriers to OAM adherence. EVALUATION: Early phase testing provided the opportunity to observe the user interface with the app and app functionality. Data were summarized descriptively from observations and comments of patient subjects. RESULTS: Thirty patient subjects provided input-19 in phase 1 usability testing and 11 in phase 2 feasibility testing. Comments provided by patient subjects during usability testing were largely positive. Responses included self-identification with patient stories, usefulness of drug information, preferences for text messages, and app limitations (e.g., perceived generational digital divide in technology use and potential patient inability to receive text messages). Using their feedback, modifications were made to the prototype app. Responses in feasibility testing demonstrated the app's usefulness across a wide range of ages. Highest opinion ratings on app usefulness were stated by patients who were newer to OAM therapy. CONCLUSION: User feedback suggests the potential benefit of the app as a tool to help patients with cancer, particularly after the first months for those starting new OAM regimens. Processes and lessons learned are transferable to other settings.