Education and Training of Non-Genetics Providers on the Return of Genome Sequencing Results in a NICU Setting.

To meet current and expected future demand for genome sequencing in the neonatal intensive care unit (NICU), adjustments to traditional service delivery models are necessary. Effective programs for the training of non-genetics providers (NGPs) may address the known barriers to providing genetic services including limited genetics knowledge and lack of confidence. The SouthSeq project aims to use genome sequencing to make genomic diagnoses in the neonatal period and evaluate a scalable approach to delivering genome sequencing results to populations with limited access to genetics professionals.

Variation in serum urate levels in the absence of gout and urate lowering therapy.

Background: Previous studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.

Development of a multi-component intervention to promote participation of Black and Latinx individuals in biomedical research.

Introduction: Barriers to research participation by racial and ethnic minority group members are multi-factorial, stem from historical social injustices and occur at participant, research team, and research process levels. The informed consent procedure is a key component of the research process and represents an opportunity to address these barriers. This manuscript describes the development of the Strengthening Translational Research in Diverse Enrollment (STRIDE) intervention, which aims to improve research participation by individuals from underrepresented groups.

Lessons learned about harmonizing survey measures for the CSER consortium.

Introduction: Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

Objective: To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect.

Methods: We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.

A REDCap-based model for electronic consent (eConsent): Moving toward a more personalized consent.

Introduction: The updated common rule, for human subjects research, requires that consents "begin with a 'concise and focused' presentation of the key information that will most likely help someone make a decision about whether to participate in a study" (Menikoff, Kaneshiro, Pritchard. . 2017; (7): 613-615.

Depressive Symptoms and the Effectiveness of a Urate-Lowering Therapy in a Clinical Trial.

Objective: This ancillary study examined the impact of depressive symptoms on the effectiveness of a urate-lowering therapy in the context of a clinical trial.

Methods: Participants included 67 adults (ages 18-40) with elevated blood pressure who were enrolled in a double-blind, randomized, crossover clinical trial evaluating the effectiveness of allopurinol (300 mg/d) versus placebo to decrease blood pressure. Depressive symptoms were measured at the beginning of each 4-week phase with the Center for Epidemiological Studies Depression scale (CESD-10).

Use of path modeling to inform a clinical decision support application to encourage osteoporosis medication use.

Background: Osteoporosis medication use is suboptimal. Simple interventions personalized to a patients' stage of readiness are needed to encourage osteoporosis medication use.

Objectives: To estimate interrelationships of sociodemographic factors, perceived fracture risk, health literacy, receipt of medication information, medication trust and readiness to use osteoporosis medication; and apply observed relationships to inform design specifications for a clinical decision support application that can be used for personalized patient counseling.

Which factors predict discordance between a patient and physician on a gout flare?

Objective: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare.

Methods: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively.

Cardiovascular safety risks associated with gout treatments.

Introduction: Uric acid is the final byproduct of purine metabolism. The loss of the enzyme that hydrolyzes uric acid to allantoin was lost, leading to a decrease in uric acid excretion and its further accumulation. The buildup of uric acid leads to damage in different organ systems, including the cardiovascular system.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

Objective: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS).

Methods: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare.

Simulation-based power and sample size calculation for designing interrupted time series analyses of count outcomes in evaluation of health policy interventions.

Objective: The purpose of this study was to present the design, model, and data analysis of an interrupted time series (ITS) model applied to evaluate the impact of health policy, systems, or environmental interventions using count outcomes. Simulation methods were used to conduct power and sample size calculations for these studies.

Methods: We proposed the models and analyses of ITS designs for count outcomes using the Strengthening Translational Research in Diverse Enrollment (STRIDE) study as an example.

Severity of Hypertension Mediates the Association of Hyperuricemia With Stroke in the REGARDS Case Cohort Study.

Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases. We assessed the relationship between hyperuricemia and ischemic stroke (≈900 cases) using a large data set from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). We employed a case-cohort design (incident stroke cases and randomly selected cohort participants) and weighted Cox-proportional hazard models to estimate the association of serum urate level ≥6.

Glucocorticoid-induced osteoporosis: from clinical trials to clinical practice.

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. To date, six large randomized controlled clinical trials on the efficacy of pharmaceutical treatment in GIOP have been conducted. All of these studies have focused predominately on bone mineral density outcomes, and none of them have been statistically powered to address fracture endpoints.

Design, analysis, power, and sample size calculation for three-phase interrupted time series analysis in evaluation of health policy interventions.

Objective: To discuss the study design and data analysis for three-phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies.

Methods: We consider the design and analysis of three-phase ITS studies using a study funded by National Institutes of Health as an exemplar.

Global Transcriptomic Profile of Dorsal Root Ganglion and Physiological Correlates of Cisplatin-Induced Peripheral Neuropathy.

Background: Multiple cell signaling pathways are implicated in the development, progression, and persistence of cisplatin-induced peripheral neuropathy. Although advances have been made in terms of understanding specific neurotoxic mechanisms, there are few predictive factors identified that can help inform the clinician approach to symptom prevention or management.

Objective: We investigate the differential sensitivity to cisplatin-induced peripheral neuropathy and examine the contribution of dorsal root ganglion (DRG) transcriptional profiles across two inbred strains of mice.

Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting Barriers to Osteoporosis Care: A Randomized Clinical Trial.

Osteoporosis treatment rates are declining, even among those with past fractures. Novel, low-cost approaches are needed to improve osteoporosis care. We conducted a parallel group, controlled, randomized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use.

Brief Report: Validation of a Definition of Flare in Patients With Established Gout.

Objective: To perform external validation of a provisional definition of disease flare in patients with gout.

Methods: Five hundred nine patients with gout were enrolled in a cross-sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition.

Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats.

Chronic stress triggers a variety of physical and mental health problems, and how individuals cope with stress influences risk for emotional disorders. To investigate molecular mechanisms underlying distinct stress coping styles, we utilized rats that were selectively-bred for differences in emotionality and stress reactivity. We show that high novelty responding (HR) rats readily bury a shock probe in the defensive burying test, a measure of proactive stress coping behavior, while low novelty responding (LR) rats exhibit enhanced immobility, a measure of reactive coping.

The effects of urate lowering therapy on inflammation, endothelial function, and blood pressure (SURPHER) study design and rationale.

Background: The association between hyperuricemia and hypertension is controversial. Animal models, epidemiological data, and small clinical trials have favored a causative role for hyperuricemia in hypertension but more studies are necessary to elucidate putative mechanisms, population susceptibility, and potential for urate-lowering therapies (ULT) to decrease blood pressure (BP).

Purpose: To describe the background and design of the Serum Urate Reduction to Prevent Hypertension (SURPHER) study.

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function.

Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus.

A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material.

Objective: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake.

Methods: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers.

Do long delay conditioned stimuli develop inhibitory properties?

In long-delay conditioning, a long conditioned stimulus (CS) is paired in its final segments with an unconditioned stimulus. With sufficient training, this procedure usually results in conditioned responding being delayed until the final segment of the CS, a pattern of responding known as inhibition of delay. However, there have been no systematic investigations of the associative structure of long delay conditioning, and whether the initial segment of a long delay CS actually becomes inhibitory is debatable.

Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery.

Background: Chemotherapeutic treatment results in chronic pain in an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics an urgent one. We compared the effects of prophylactic cannabinoids as a preventative strategy for suppressing development of paclitaxel-induced nociception.

Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior in females but not males and protection from neurological deficits during proestrus.

Background: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is one of the most prevalent neurological disorders in the industrialized world. This disease afflicts more than two million people worldwide, over two thirds of which are women. MS is typically diagnosed between the ages of 20-40 and can produce debilitating neurological impairments including muscle spasticity, muscle paralysis, and chronic pain.