Development of a comprehensive cardiovascular disease genetic risk assessment test.

Background: Despite monogenic and polygenic contributions to cardiovascular disease (CVD), genetic testing is not widely adopted, and current tests are limited by the breadth of surveyed conditions and interpretation burden. Methods: We developed a comprehensive clinical genome CVD test with semi-automated interpretation. Monogenic conditions and risk alleles were selected based on the strength of disease association and evidence for increased disease risk, respectively. Non-CVD secondary findings genes, pharmacogenomic (PGx) variants and CVD polygenic risk scores (PRS) were assessed for inclusion. Test performance was modeled using 2,594 genomes from the 1000 Genomes Project, and further investigated in 20 previously tested individuals. Results: The CVD genome test is composed of a panel of 215 CVD gene-disease pairs, 35 non-CVD secondary findings genes, 4 risk alleles or genotypes, 10 PGx genes and a PRS for coronary artery disease. Modeling of test performance using samples from the 1000 Genomes Project revealed ~6% of individuals with a monogenic finding in a CVD-associated gene, 6% with a risk allele finding, ~1% with a non-CVD secondary finding, and 93% with CVD-associated PGx variants. Assessment of blinded clinical samples showed complete concordance with prior testing. An average of 4 variants were reviewed per case, with interpretation and reporting time ranging from 9-96 min. Conclusions: A genome sequencing based CVD genetic risk assessment can provide comprehensive genetic disease and genetic risk information to patients with CVD. The semi-automated and limited interpretation burden suggest that this testing approach could be scaled to support population-level initiatives.

Pregnancy-related risk factors and receipt of postpartum care among Texas Medicaid pregnant enrollees: Opportunities for pharmacist services.

BACKGROUND: The United States (US) experiences the highest rate of maternal mortality of similar countries. Postpartum care (PPC) focused on chronic disease management is potentially lifesaving, especially among pregnancies complicated by risk factors such as diabetes, hypertension, and mental health conditions (MHCs), which are conditions in which pharmacists can have an impact. OBJECTIVE: To evaluate the prevalence of maternal mortality risk factors and their relationships with receipt of PPC among Texas Medicaid enrollees. METHODS: A retrospective study included women with a delivery between 3/25/2014-11/1/2019 who were continuously enrolled in Texas Medicaid during the study period from 84 days pre-delivery to 60 days post-delivery. PPC was defined as ≥1 visit associated with postpartum follow-up services. Maternal mortality risk factors (diabetes, hypertension, and MHCs) during and after pregnancy were identified using diagnoses and medication utilization. Age, race/ethnicity, cesarean delivery, and preterm birth served as covariates. Multivariable logistic regression was used to address the study objective. RESULTS: The sample (N = 617,010) was 26.5±5.7 years, primarily (52.8%) Hispanic, and 33.0% had cesarean deliveries and 9.3% had preterm births. Risk factor prevalence included: diabetes (14.0%), hypertension (14.3%), and MHCs during (6.3%) and after (9.1%) pregnancy. A majority (77.9%) had a PPC visit within 60 days of delivery. The odds of receiving PPC were 1.2 times higher for patients with diabetes (OR = 1.183; 95% CI = 1.161-1.206; P < 0.0001), 1.1 times higher for patients with hypertension (OR = 1.109; 95% CI= 1.089-1.130; P < 0.0001), and 1.1 times higher for patients with MHCs (OR=1.138; 95% CI = 1.108-1.170; P < 0.0001) than patients without, respectively. CONCLUSION: Over three-quarters of Texas Medicaid pregnant enrollees received PPC within 60 days of delivery and risk factors were prevalent and predictive of receipt of PPC. Pharmacists can have a positive impact on maternal health by addressing hypertension, diabetes, and MHC risk factors.

Z-code documentation to identify social determinants of health among Medicaid beneficiaries.

INTRODUCTION: Social determinants of health (SDoH) are non-medical factors that impact individuals' health. SDoH can be documented in claims data using International Classification of Disease (ICD) 10th revision codes Z55 - Z65. The study objective was to describe the documentation of SDoH Z-codes among Medicaid beneficiaries in Texas. METHODS: Texas Medicaid medical and enrollment claims data were utilized. Beneficiaries with at least one claim associated with SDoH Z-codes between 2016 and 2019 were identified excluding those 65+ years of age and others dually eligible for Medicare. RESULTS: SDoH Z-code documentation was associated with approximately 1.2 million claims for 181,136 unique beneficiaries. Females (54.3%) and Hispanics (47.9%) comprised a majority of beneficiaries with Z-code documentation, and the average age was 14.2 ± 13.4 years. Nearly 40% had Z-code documentation of "problems related to upbringing" (Z62) (N = 68,478, 37.8%), followed by "problems related to primary support group including family circumstances" (Z63) (N = 42,378, 23.4%), and "problems related to education and literacy" (Z55) (N = 28,848, 15.9%). SDoH Z-code documentation increased slightly over the years from 1% of Medicaid beneficiaries in 2016 to 1.3% in 2019. CONCLUSION: A steady increase in SDoH Z-code documentation was observed among Medicaid beneficiaries but represented a relatively small proportion of the beneficiaries overall.

Procurement and use of social determinants of health data among key health care stakeholders.

BACKGROUND: A growing body of evidence supports the need for health systems to shift towards addressing social determinants of health (SDoH) as part of routine care. However, little is known about the state of the industry in terms of procurement and use of SDoH data. OBJECTIVES: To assess stakeholders' perceptions and experiences in collecting and utilizing SDoH data. METHODS: A prospective, cross-sectional study was conducted using a 24-item electronic survey. The pilot-tested survey was distributed to a diverse convenience sample of 94 health care stakeholder organizations that are members of the Pharmacy Quality Alliance organization. Survey responses were collected from November to December 2020. Descriptive statistics were used to analyze responses. RESULTS: A total of 25 respondents completed the survey (response rate = 26.6%). More than half (n = 14, 56.0%) collected and tracked SDoH data, and of those, most (n = 6, 42.85%) reported using organization-specific tools instead of standardized SDoH tools. Economic stability and health and health care indicators were the most frequently identified types of SDoH data collected. Participants reported that both identifying (mean = 3.88 ± SD = 0.88; 1 = not important to 5 = extremely important) and addressing (3.88 ± 0.93) patients' SDoH were moderately important to their organization. Lack of standard data format (72.0%), lack of time (52.0%), and lack of technological capabilities (44.0%) were the most commonly reported barriers to collecting SDoH data. However, value-based payment programs that reward addressing SDoH needs (76.0%) and a coding structure or reimbursement mechanism for identification and management of SDoH (60.0%) were most commonly reported as mechanisms to overcome SDoH data collection barriers. CONCLUSIONS: Health care stakeholders consider patient SDoH indicators important but report significant challenges in collecting these data. Solutions that address data standardization, time burden, technological barriers, and the offering of incentives could facilitate its collection and effective use. DISCLOSURES: Pharmacy Quality Alliance received an unrestricted grant from Pfizer, Inc, to support this work.

Feasibility, Acceptability, and Design of a Mobile Ecological Momentary Assessment for High-Risk Men Who Have Sex With Men in Hanoi, Vietnam: Qualitative Study.

BACKGROUND: Men who have sex with men (MSM) are at a disproportionate risk for HIV infection and common mental disorders worldwide. In the context of HIV, common mental disorders are important and are frequent drivers of suboptimal prevention and treatment outcomes. Mobile ecological momentary assessments (EMAs), or the repeated sampling of people's behaviors and psychological states in their daily lives using mobile phones, can clarify the triggers and HIV-related sequelae of depressive-anxious symptoms and contribute toward the design of ecological momentary interventions (EMIs) that cater to the contextually varying needs of individuals to optimize prevention and treatment outcomes. OBJECTIVE: This study aims to characterize the feasibility and acceptability of mobile EMA among high-risk MSM in Hanoi, Vietnam. It aims to evaluate the perceived relevance, usability, and concerns of this group with regard to the content and delivery of mobile EMA and the potential of leveraging such platforms in the future to deliver EMIs. METHODS: Between January and April 2018, a total of 46 participants were recruited. The participants completed 6 to 8 mobile EMA surveys daily for 7 days. Surveys occurred once upon waking, 4 to 6 times throughout the day, and once before sleeping. All surveys queried participants' perceived safety, social interactions, psychological state, and mental health symptoms. The morning survey further queried on sleep and medication use within the past 24 hours, whereas the night survey queried on sexual activity and substance use and allowed participants to share an audio recording of a stressful experience they had that day. At the end of the week, participants were interviewed about their experiences with using the app. RESULTS: Participants completed an average of 21.7 (SD 12.7) prompts over the 7-day period. Excluding nonresponders, the average compliance rate was 61.8% (SD 26.6%). A thematic analysis of qualitative interviews suggested an overall positive reception of the app and 5 recurring themes, which were centered on the relevance of psychological and behavioral items to daily experiences (eg, mental health symptoms and audio recording), benefits of using the app (eg, increased self-understanding), worries and concerns (eg, privacy), usability (eg, confusion about the interface), and recommendations for future design (eg, integrating more open-ended questions). CONCLUSIONS: Mobile EMA is feasible and acceptable among young MSM in Vietnam; however, more research is needed to adapt EMA protocols to this context and enhance compliance. Most participants eagerly provided information about their mental health status and daily activities. As several participants looked toward the app for further mental health and psychosocial support, EMIs have the potential to reduce HIV and mental health comorbidity among MSM.

"It's Time to Represent": shifting the paradigm to improve the quality of inputs into value assessment frameworks.

"It's Time to Represent" integrates 2 strategies that challenge the status quo to increase the diversity of populations that participate in research and address drivers of health disparities to better inform value assessment. The first, a community-engaged campaign, proposes to develop authentic, long-term partnerships with community members, their health care providers, and researchers to tailor recruitment and retention methods for underrepresented groups and hold researchers accountable for equitable selection of study participants. The second proposes to create an expectation for researchers to routinely collect patient-reported, actionable social determinants of health data to generate enhanced real-world evidence and thereby improve the quality of inputs utilized in value assessment frameworks. DISCLOSURE: No specific funding was received for this manuscript. The authors report no potential conflicts of interest.

"It's Time to Represent": shifting the paradigm to improve the quality of inputs into value assessment frameworks.

"It's Time to Represent" integrates 2 strategies that challenge the status quo to increase the diversity of populations that participate in research and address drivers of health disparities to better inform value assessment. The first, a community-engaged campaign, proposes to develop authentic, long-term partnerships with community members, their health care providers, and researchers to tailor recruitment and retention methods for underrepresented groups and hold researchers accountable for equitable selection of study participants. The second proposes to create an expectation for researchers to routinely collect patient-reported, actionable social determinants of health data to generate enhanced real-world evidence and thereby improve the quality of inputs utilized in value assessment frameworks. DISCLOSURE: No specific funding was received for this manuscript. The authors report no potential conflicts of interest.

Impact of a G-CSF Policy to Reduce Low-Value Care on Guideline Adherence and Mortality.

PURPOSE: Practice guidelines recommend the prophylactic use of granulocyte colony-stimulating factors (G-CSFs) in patients with high risk of febrile neutropenia, but evidence suggests that G-CSFs are frequently overused. The objectives of this study were (1) to determine the prevalence and prescribing patterns of G-CSF and (2) to evaluate the impact of a program initiative on G-CSF prescribing patterns, adherence to guidelines, and mortality. METHODS: In this retrospective cohort study, data were used from the electronic health records of patients with metastatic colorectal cancer who received care at a multicenter oncology practice network during two time periods: July 01, 2013, to December 31, 2014, and July 01, 2017, to December 31, 2017. Beginning 2016, a site-wide program initiative that involved educational materials, appropriate nonuse recommendations, and prior authorization was introduced in the oncology practice network with an aim of reducing G-CSF overutilization. Descriptive statistics, t tests, and chi-squared tests were employed to analyze program impact. RESULTS: There were 3,426 chemotherapy regimens corresponding to 2,968 patients. There were a total of 387 (11.3%) G-CSF-treated patients and 3,095 G-CSF administrations during the study period. G-CSF use was significantly lower in the postperiod, compared with the preperiod (P < .0001). Adherence to guidelines was significantly higher in the postperiod, compared with the preperiod (P < .0001). Mortality rates did not significantly differ between the two time periods. CONCLUSION: This study demonstrates that policy initiatives have the potential to positively affect G-CSF prescription patterns and promote guideline adherence. These findings could help prescribers adopt a cost-effective approach in patients with metastatic colorectal cancer, leading to enhanced clinical practice and value-based care.

Evaluation of access to care issues in patients with breast cancer.

AIMS: System-level efforts have been deployed to improve oncology care and access while reducing utilization and costs. Understanding the nature of access to care from the perspective of patients themselves is an unmet need. This study examined access to care in a population of women with breast cancer and its relationship to overall patient satisfaction. MATERIALS AND METHODS: Patients with breast cancer from six oncology clinics in five states completed a survey during routine office visits. Access to care (higher scores indicated increasing access barriers), overall patient satisfaction, and patient demographic/clinical characteristics were measured. The relationships between access (composite and factor scores) and satisfaction were assessed using multivariable analyses controlling for age (the only significant characteristic from bivariate analyses). RESULTS: A total of 180 patients completed the survey. Factor analysis of access to care items revealed an 8-factor measure - Insurance, Health System, Emotional, Holistic Treatment, Family Support, Knowledge/Understanding, Information Quality, and Financial Support - with high reliability (Composite: Cronbach alpha = 0.93; Factors: Cronbach alpha range = 0.85-0.91). Access composite score was moderately low (mean = 1.90), indicating an overall low level of access barriers, and overall patient satisfaction was high (mean = 4.59). The composite score (p < .001) and the Health System and Knowledge/Understanding factors (p < .01) were significant and negative predictors of overall satisfaction. LIMITATIONS: Study sites were high functioning clinics and all, but one, are Oncology Care Model practices. Thus, the scope of access to care issues for patients of under-resourced clinics might not be well addressed. CONCLUSIONS: Access to care overall and by factor was significantly predictive of patient satisfaction with care. In addition, access to care factors varied across several demographic and clinical characteristics. Future strategies that address access to care challenges should consider these modifiable, patient-centric, and system-based issues.

Understanding value in oral health: the oral health value-based care symposium.

OBJECTIVE: There are both opportunities and challenges with the implementation of oral health value-based care (OHVBC). To tackle concerns and advance conversation, a symposium was convened with subject matter experts to develop a gap analysis and capture insights into professional readiness for value-based care design. METHODS: The symposium was convened as a private event for 46 participants over the course of one and a half days in December 2019. Thematic analyses utilized the OHVBC Readiness Framework (DentaQuest Partnership, 2019) to further codify conversations as part of the gap-analysis process. Poll Everywhere, a text messaging application that allows participants to answer questions in real time, was also employed to solicit responses. RESULTS: Attendees of the symposium felt that OHVBC would have a large portion of market share within the next 10 years. A qualitative assessment of multiple table discussions determined that the participants developed more consensus around themes for the current state and the future-desired state than the action-planning needed to close the gap between the two. This may relate to individual ideology, and the siloed environment is still prevalent in the oral health realm. In a postsymposium survey, respondent attendees did not perceive that COVID-19 would delay or negatively impact the adoption of OHVBC and may result in accelerating its utilization. CONCLUSION: The oral health community is experiencing multiple drivers to adopt more OHVBC within business and care models. However, there is still a lack of uniformity on how to execute this delivery model.

Assessment of long non-coding RNA expression reveals novel mediators of the lung tumour immune response.

The tumour immune microenvironment is a crucial mediator of lung tumourigenesis, and characterizing the immune landscape of patient tumours may guide immunotherapy treatment regimens and uncover novel intervention points. We sought to identify the landscape of tumour-infiltrating immune cells in the context of long non-coding RNA (lncRNAs), known regulators of gene expression. We examined the lncRNA profiles of lung adenocarcinoma (LUAD) tumours by interrogating RNA sequencing data from microdissected and non-microdissected samples (BCCRC and TCGA). Subsequently, analysis of single-cell RNA sequencing data from lung tumours and flow-sorted healthy peripheral blood mononuclear cells identified lncRNAs in immune cells, highlighting their biological and prognostic relevance. We discovered lncRNA expression patterns indicative of regulatory relationships with immune-related protein-coding genes, including the relationship between AC008750.1 and NKG7 in NK cells. Activation of NK cells in vitro was sufficient to induce AC008750.1 expression. Finally, siRNA-mediated knockdown of AC008750.1 significantly impaired both the expression of NKG7 and the anti-tumour capacity of NK cells. We present an atlas of cancer-cell extrinsic immune cell-expressed lncRNAs, in vitro evidence for a functional role of lncRNAs in anti-tumour immune activity, which upon further exploration may reveal novel clinical utility as markers of immune infiltration.

The impact of the COVID-19 pandemic on cardiology services.

OBJECTIVE: The COVID-19 pandemic resulted in prioritisation of National Health Service (NHS) resources to cope with the surge in infected patients. However, there have been no studies in the UK looking at the effect of the COVID-19 work pattern on the provision of cardiology services. We aimed to assess the impact of the pandemic on cardiology services and clinical activity. METHODS: We analysed key performance indicators in cardiology services in a single centre in the UK in the periods prior to and during lockdown to assess reduction or changes in service provision. RESULTS: There has been a greater than 50% drop in the number of patients presenting to cardiology and those diagnosed with myocardial infarction. All areas of cardiology service provision sustained significant reductions, which included outpatient clinics, investigations, procedures and cardiology community services such as heart failure and cardiac rehabilitation. CONCLUSIONS: As ischaemic heart disease continues to be the leading cause of death nationally and globally, cardiology services need to prepare for a significant increase in workload in the recovery phase and develop new pathways to urgently help those adversely affected by the changes in service provision.

Willingness to Seek Help for Depression in Young African American Adults: Study Protocol.

BACKGROUND: In the United States, among those living with mental illness, 81% of African American (AA) young adults do not seek treatment compared with 66% of their white counterparts. Although the literature has identified unique culturally related factors that impact help seeking among AAs, limited information exists regarding the development and evaluation of interventions that incorporate these unique factors. OBJECTIVE: This study aims to describe a study protocol designed to develop a culturally relevant, theory-based, psychoeducational intervention for AA young adults; to determine if exposure to the intervention impacts AA young adults' willingness to seek help; and to determine whether cultural factors and stigma add to the prediction of willingness to seek help. METHODS: The Theory of Planned Behavior (TPB) and Barrera and Castro's framework for cultural adaptation of interventions were used as guiding frameworks. In stage 1 (information gathering), a literature review and three focus groups were conducted to identify salient cultural beliefs. Using stage 1 results, the intervention was designed in stage 2 (preliminary adaptation design), and in stage 3 (preliminary adaptation tests), the intervention was tested using pretest, posttest, and 3-month follow-up surveys. An experimental, mixed methods, prospective one-group intervention design was employed, and the primary outcomes were participants' willingness and intention to seek help for depression and actual help-seeking behavior. RESULTS: This study was funded in May 2016 and approved by the University of Texas at Austin institutional review board. Data were collected from November 2016 to March 2016. Of the 103 students who signed up to participate in the study, 70 (67.9%) completed the pre- and posttest surveys. The findings are expected to be submitted for publication in 2020. CONCLUSIONS: The findings from this research are expected to improve clinical practice by providing empirical evidence as to whether a culturally relevant psychoeducational intervention is useful for improving help seeking among young AAs. It will also inform future research and intervention development involving the TPB and willingness to seek help by identifying the important factors related to willingness to seek help. Advancing this field of research may facilitate improvements in help-seeking behavior among AA young people and reduce the associated mental health disparities that apparently manifest early on. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16267.

Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice.

Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. Forty-one percent of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.

Using Visual Metaphors in Health Messages: A Strategy to Increase Effectiveness for Mental Illness Communication.

Depression is highly prevalent among college students. Although treatment is often available on university campuses, many stigma-based barriers prevent students from seeking help. Communication strategies, such as the use of metaphors, are needed to reduce barriers. Specially, the use of visual metaphors, as a strategic message design tactic, may be an effective communication strategy to increase message appeal and engagement. Using a 2-phase approach, this study first identified common metaphors students use to conceptualize mental illness. Messages incorporating conceptual and visual metaphors were then designed and tested to determine their potential in reducing stigma. Participants (n = 256) were randomly assigned to 1 of 4 conditions in a between-subjects experiment: messages with visual and textual metaphors, messages with straightforward visuals and textual metaphors, text-based metaphor messages, or a control group. Overall, metaphorical messages are appealing, the use of visual metaphors leads to greater message engagement, and messages based on conceptual metaphors have the potential to reduce stigma. The use of conceptual and visual metaphors in campaign design is an effective strategy to communicate about a complex health topic, such as mental illness, and should be considered for use in campaigns to reduce barriers for help-seeking behavior.

Predictors of prostate cancer screening using Andersen's Behavioral Model of Health Services Use.

PURPOSE: The purposes of the study were to examine the prevalence of prostate cancer screening (PCS) in the United States and to identify predictors of PCS guided by Andersen's Behavioral Model of Health Services Use (ABM). METHODS: PCS rates were analyzed in men (aged ≥40y) using 2014 data from the Behavioral Risk Factor Surveillance System. Descriptive analysis was conducted using sampling weights to determine the prevalence of PCS (i.e., had a prostate-specific antigen test). Multiple logistic regression within the framework of ABM was used to identify predictors of PCS. The ABM variables of predisposing (e.g., age), enabling (e.g., health insurance), and need (e.g., comorbidities) comprised the independent variables. RESULTS: Among the 131,415 men, 62.4% (N = 82,014) reported that they had a prostate-specific antigen test in the last 2 years. Among predisposing factors, age, education, income, and employment status were significantly associated with undergoing PCS. Informed decision-making process, health care coverage, regular health care provider, and length of time since last routine checkup were significant enabling factors. Health care provider recommendation and previous cancer diagnosis were significant need factors. CONCLUSIONS: Most older men in the United States had previously engaged in PCS. Several ABM variables were predictive of PCS and should be considered when developing future strategies to encourage PCS in at-risk men with the recommended life expectancies. Such strategies should also ensure that the decision to undergo PCS is an informed process between patients and their health care providers.