Leveraging Real-World Data in Safety Signal Assessment.

PURPOSE: TransCelerate BioPharma surveyed its member biopharmaceutical companies to understand current practices and identify opportunities to complement safety signal assessment with rapid real-world data (RWD) analysis. METHODS: A voluntary 30-question questionnaire regarding the use of RWD in safety signal assessment was disseminated to subject matter experts at all TransCelerate member companies in July 2022. Responses were blinded, aggregated, summarized, and presented. RESULTS: Eighteen of 20 member companies provided responses to the questionnaire. Sixteen (89%) companies reported actively leveraging RWD in their signal assessment processes. Of 18 respondent companies, 8 (44%) routinely use rapid approaches to RWD analysis, 7 (39%) utilize rapid RWD analysis non-routinely or in a pilot setting, 2 (11%) are considering using rapid RWD analysis, and 1 (6%) has no plans to use rapid RWD analysis for their signal assessment. Most companies reported that RWD adds context to and improves quality of signal assessments. To conduct RWD analysis for signal assessment, 16 of 17 (94%) respondent companies utilize or plan to utilize internally available data, 8 (47%) utilize both internal and external data, and 3 (18%) utilize data networks. Respondents identified key challenges to rapidly performing RWD analyses, including data access/availability, time for analysis execution, and uncertainties regarding acceptance of minimal or non-protocolized approaches by health authorities. CONCLUSION: Biopharmaceutical companies reported that they see value in the use of rapid RWD analyses for complementing signal assessments. Future work is recommended to offer a framework and process for use of rapid use of RWD analyses in signal assessment.

Prion diseases motor and neuropsychiatric symptom cluster pharmacotherapy: structured scoping review.

BACKGROUND: Prion diseases are a group of rare, neurodegenerative conditions that are invariably fatal and cause a variety of symptoms, which can prove challenging to control. Through this paper, we aim to review the current evidence regarding pharmacological management of neuropsychiatric and motor symptoms of prion disease as well as draw on experts' and relatives' experience, to evaluate the current evidence and provide recommendations moving forwards. METHODS: A scoping review of the literature for pharmacological management of symptoms was conducted using the systematic review tool, COVIDENCE, with searches conducted through four databases. 120 papers were selected for inclusion, and data extraction was carried out by two independent reviewers. Given the lack of high-quality data and small numbers, no further attempt at statistical analysis was made, and results are presented in a thematic synthesis. RESULTS: Although a broad range of approaches and pharmacotherapies are trialled to manage these challenging symptoms, there are patterns emerging of some efficacy seen with the use of benzodiazepines, antipsychotic and anticonvulsant medications in both motor and neuropsychiatric symptoms in prion disease. These approaches and associated challenges were reflected in international expert opinion that was gathered via online survey. CONCLUSION: There continues to be a paucity of good-quality evidence and we suggest a need for longitudinal, population-based and standardised research to allow a robust evidence base, which in turn will guide excellent symptom control and end of life care for this group of complex patients.

Leveraging Electronic Health Records to Assess Residential Mobility Among Veterans in the Veterans Health Administration.

BACKGROUND: Residential mobility, or a change in residence, can influence health care utilization and outcomes. Health systems can leverage their patients' residential addresses stored in their electronic health records (EHRs) to better understand the relationships among patients' residences, mobility, and health. The Veteran Health Administration (VHA), with a unique nationwide network of health care systems and integrated EHR, holds greater potential for examining these relationships. METHODS: We conducted a cross-sectional analysis to examine the association of sociodemographics, clinical conditions, and residential mobility. We defined residential mobility by the number of VHA EHR residential addresses identified for each patient in a 1-year period (1/1-12/31/2018), with 2 different addresses indicating one move. We used generalized logistic regression to model the relationship between a priori selected correlates and residential mobility as a multinomial outcome (0, 1, ≥2 moves). RESULTS: In our sample, 84.4% (n=3,803,475) veterans had no move, 13.0% (n=587,765) had 1 move, and 2.6% (n=117,680) had ≥2 moves. In the multivariable analyses, women had greater odds of moving [aOR=1.11 (95% CI: 1.10,1.12) 1 move; 1.27 (1.25,1.30) ≥2 moves] than men. Veterans with substance use disorders also had greater odds of moving [aOR=1.26 (1.24,1.28) 1 move; 1.77 (1.72,1.81) ≥2 moves]. DISCUSSION: Our study suggests about 16% of veterans seen at VHA had at least 1 residential move in 2018. VHA data can be a resource to examine relationships between place, residential mobility, and health.

Change in Nutrition Behavior After Participating in an Obesity-Related Cancer Education Program in El Paso, Texas.

BACKGROUND: Roughly 25% of the U.S- Border city, El Paso, Texas is obese. Obesity is a major risk factor for 13 cancers. Cancer is the leading cause of death in El Paso. Therefore, there is a growing urgency to implement evidence-based programs that support behavioral change that helps curb the impact of obesity in El Paso and the U.S.-Mexico border region. PURPOSE: This study aimed to assess the effectiveness of an obesity-related cancer prevention program (Pasos Para Prevenir Cancer (PPPC) on changes in participant nutrition behaviors. METHODS: Culturally tailored, theory-based education was provided to adults through the PPPC program. A total of 256 PPPC participants agreed to take part in our program evaluation. Participants were asked to complete a survey at baseline and 6 months after they completed the program. Session included topics on obesity-related cancers, assessing your obesity risk, measuring body fat, SMART goal setting, and how to find the right type of physical activity. For this report we used the Food Frequency Questionnaire (FFQ) data to assess changes between baseline and six months. We also used perceived dietary barriers as moderators on the relationship between program participation and nutrition behaviors. RESULTS: Most participants (92.2%) identified as being of Mexican American descent, were between the ages of 41-75 years of age (n = 165) and identified as females (n = 225). 48.1% of the participants were born in Mexico while 50.4% were born in the U.S. Approximately 35-51% of participants improved and sustained their intake of healthier foods at 6 month follow up. Specifically, there was a statistically significant shift from higher fat and sugar content foods to light and low-fat foods, and fruits and vegetables. Participants also increased their consumption of ground chicken, lean red meat, and seafood. A key modifier in this relationship is perceived health risk. CONCLUSION: Latinos on the U.S.-Mexico border ascribe to a healthy living mindset. In general, they frequently eat fruits and vegetables. Participation in PPPC increased perceived barriers to healthy living around cost and convenience and enhanced decision-making around healthier options. Participants responded to our adapted evidence-based program resulting in sustained changes in nutrition behaviors. Using adapted evidence-based strategies developed outside of the U.S.-Mexico border region is a feasible approach to address persist health disparities.

CURE on yeast genes of unknown function increases students' bioinformatics proficiency and research confidence.

Course-based undergraduate research experiences (CUREs) can reduce barriers to research opportunities while increasing student knowledge and confidence. However, the number of widely adopted, easily transferable CUREs is relatively small. Here, we describe a CURE aimed at determining the function of poorly characterized Saccharomyces cerevisiae genes. More than 20 years after sequencing of the yeast genome, nearly 10% of open reading frames (ORFs) still have at least one uncharacterized Gene Ontology (GO) term. We refer to these genes as "ORFans" and formed a consortium aimed at assigning functions to them. Specifically, over 70 faculty members attended summer workshops to learn the bioinformatics workflow and basic laboratory techniques described herein. Ultimately, this CURE was adapted for implementation at 34 institutions, resulting in over 1,300 students conducting course-based research on ORFans. Pre-/post-tests confirmed that students gained both (i) an understanding of gene ontology and (ii) knowledge regarding the use of bioinformatics to assign gene function. After using these data to craft their own hypotheses, then testing their predictions by constructing and phenotyping deletion strains, students self-reported significant gains in several areas, including computer modeling and exposure to a project where no one knows the outcome. Interestingly, most net gains self-reported by ORFan Gene Project participants were greater than published findings for CUREs assessed with the same survey instrument. The surprisingly strong impact of this CURE may be due to the incoming lack of experience of ORFan Project participants and/or the independent thought required to develop testable hypotheses from complex data sets.

Mid-to-Late-Life Anxiety and Sleep during Initial Phase of COVID-19: Age- and Sex-Specific Insights to Inform Future Pandemic Healthcare.

This study examined associations between COVID-19-related anxiety and sleep in middle-aged and older adults and tested whether these varied by age or sex. In June/July 2020, middle-aged/older adults aged 50+ (n = 277, 45% women, Mage = 64.68 ± 7.83) in the United States completed measures of sleep and COVID-19-related anxiety. Multiple regressions examined whether anxiety was independently associated with or interacted with age or sex in its associations with sleep health, controlling for age, education, medical conditions, sleep/pain medication use, and COVID-19 status. Greater COVID-19 anxiety was associated with worse sleep quality and daytime dysfunction. COVID-19-related anxiety interacted with age (not sex) in associations with total sleep time and sleep efficiency. Greater anxiety was associated with shorter total sleep time and lower sleep efficiency in oldest-older adults (~73 years old) and youngest-older adults (~65 years old) but not middle-aged adults (~57 years old). In mid to late life, older adults may be most vulnerable to the impact of COVID-19-related anxiety on sleep health. Social and behavioral (e.g., knowledge on age-related vulnerability to COVID-19 risk/morbidity/mortality, uncertainty, and changes to daily routines) and physiological factors (sleep disruption and age-related autonomic dysfunction) may underlie these associations. Interventions that mitigate negative pandemic-related psychological and sleep outcomes may be particularly relevant for older adults.

Primary data on symptom burden and quality of life among elderly patients at risk of dying during unplanned admissions to an NHS hospital: a cohort study using EuroQoL and the integrated palliative care outcome scale.

BACKGROUND: Older people account heavily for palliative care needs at the population level and are growing in number as the population ages. There is relatively little high-quality data on symptom burden and quality of life, since these data are not routinely collected, and this group are under-recruited in primary research. It is unclear which measurement tools are best suited to capture burdens and experience. METHODS: We recruited a cohort of 221 patients aged 75 + years with poor prognosis who had an unplanned admission via the emergency department in a large urban hospital in England between 2019 and 2020. Risk of dying was assessed using the CriSTAL tool. We collected primary data and combined these with routine health records. Baseline clinical data and patient reported quality of life outcomes were collected on admission and reassessed within the first 72 h of presentation using two established tools: EQ-5D-5 L, EQ-VAS and the Integrated Palliative Outcomes Scale (IPOS). RESULTS: Completion rate was 68% (n = 151) and 33.1% were known to have died during admission or within 6 months post-discharge. The vast majority (84.8%) reported severe difficulties with at least one dimension of EQ-5D-5 L at baseline and improvements in EQ-VAS observed at reassessment in 51.7%. The baseline IPOS revealed 78.2% of patients rating seven or more items as moderate, severe or overwhelming, but a significant reduction (-3.6, p < 0.001) in overall physical symptom severity and prevalence was also apparent. No significant differences were noted in emotional symptoms or changes in communication/practical issues. IPOS total score at follow up was positively associated with age, having comorbidities (Charlson index score > = 1) and negatively associated with baseline IPOS and CriSTAL scores. CONCLUSION: Older people with poor prognosis admitted to hospital have very high symptom burden compared to population norms, though some improvement following assessment was observed on all measures. These data provide valuable descriptive information on quality of life among a priority population in practice and policy and can be used in future research to identify suitable interventions and model their effects.

Dryland rock detention structures increase herbaceous vegetation cover and stabilize shrub cover over 10 years but do not directly affect soil fertility.

Rock detention structures (RDS) such as check dams, gabions, and one rock dams are commonly used to mitigate erosion impacts in dryland ephemeral stream channels. RDS increase local water infiltration and floodplain connectivity, reduce sediment transport, and enhance vegetation growth and establishment. In addition to increasing overall vegetation cover, RDS may also buffer against a cycle of vegetation growth and collapse during years of extremely variable precipitation, helping to maintain stable cover. Although widely employed by land managers, success as reported in scientific literature varies, especially with regard to RDS effects on vegetation and soil fertility. We present the results of a 10-year field experiment in southeastern Arizona, USA, designed in collaboration with local land practitioners to measure local in-channel effects of RDS. Over 10 years, cover of herbaceous vegetation (forbs and grasses) doubled from 11 % to 22 % in channels treated with RDS, but did not significantly increase in untreated control channels. Shrub cover in treated channels was significantly less variable than in control channels over time. We analyzed the complex relationships between RDS, vegetation cover, and soil fertility using structural equation modeling (SEM), which represented conditions of the tenth year alone. SEM revealed that RDS did not directly affect soil fertility, as measured by total soil nitrogen, total soil carbon, soil organic matter, microbial richness, and potential nutrient cycling capacity. Notably, SEM did not yield the same trends as temporal monitoring, possibly because our structural equation models could not capture change over time. This discrepancy highlights the need for long-term, frequent monitoring of aboveground and belowground conditions to evaluate treatment success on a management scale. Overall, installing rock detention structures in ephemeral channels in arid and semiarid regions is a low-cost, feasible way to increase channel sediment aggradation, forb, and grass cover; stabilize shrub cover; and combat dryland degradation.