Genetic Testing for Hypertriglyceridemia in Academic Lipid Clinics: Implications for Precision Medicine-Brief Report.

BACKGROUND: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. METHODS: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight's Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL). RESULTS: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [P=0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. CONCLUSIONS: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

Patient and Clinician Perceptions of Precision Cardiology Care: Findings From the HeartCare Study.

BACKGROUND: Routine genome-wide screening for cardiovascular disease risk may inform clinical decision-making. However, little is known about whether clinicians and patients would find such testing useful or acceptable within the context of a genomics-enabled learning health system. METHODS: We conducted surveys with patients and their clinicians who were participating in the HeartCare Study, a precision cardiology care project that returned results from a next-generation sequencing panel of 158 genes associated with cardiovascular disease risk. Six weeks after return of results, we assessed patients' and clinicians' perceived utility and disutility of HeartCare, the effect of the test on clinical recommendations, and patients' attitudes toward integration of research and clinical care. RESULTS: Among 666 HeartCare patients with a result returned during the survey study period, 42.0% completed a full or partial survey. Patient-participants who completed a full survey (n=224) generally had positive perceptions of HeartCare independent of whether they received a positive or negative result. Most patient-participants considered genetic testing for cardiovascular disease risk to have more benefit than risk (88.3%) and agreed that it provided information that they wanted to know (81.2%), while most disagreed that the test caused them to feel confused (77.7%) or overwhelmed (78.0%). For 122 of their patients with positive results, clinicians (n=13) reported making changes in clinical care for 66.4% of patients, recommending changes in health behaviors for 36.9% of patients, and recommending to 33.6% of patients that their family members have clinical testing. CONCLUSIONS: Both patients and clinicians thought the HeartCare panel screen for cardiovascular disease risk provided information that was useful in terms of personal or health benefits to the patient and that informed clinical care without causing patients to be confused or overwhelmed. Further research is needed to assess perceptions of genome-wide screening among the US cardiology clinic population.

Behavioral health service use post-jail release and reduced risk of return to jail.

This study examined whether behavioral health service use post-jail release was associated with reduced risk of jail reincarceration. The study sample included 20,615 individuals who had behavioral health diagnoses and were released from the Philadelphia County jail. Using administrative records of the county jail and state-, county-, and Medicaid-funded behavioral health service use from 2010 to 2018, we conducted Cox proportional hazard analyses to estimate the association between behavioral health service use post-jail release and the risk of return to jail within 3 years. Nearly 50% of the sample returned to jail within 3 years. Individuals who used behavioral health services were 26%-38% less likely to return to jail within 3 years than were individuals who did not. The study results suggest that connecting individuals with behavioral health services upon release from jail can reduce the risk of repeated jail incarceration.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. RESULTS: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. CONCLUSION: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

How Do We Incorporate Polygenic Risk Scores in Cardiovascular Disease Risk Assessment and Management?

PURPOSE OF REVIEW: The potential of polygenic risk scores (PRS) to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment and management has stoked significant interest in their incorporation into clinical management. The goal of this review is to apprise the readers of the latest developments and evidence of PRS readiness for clinical integration. We also discuss current limitations that must be addressed before PRS can be implemented into routine clinical practice. RECENT FINDINGS: PRS have been shown to improve risk stratification for ASCVD and to identify patients who may derive increased benefit from primary and secondary prevention. Risk captured by PRS appears largely independent of traditional risk factors and can be ascertained at birth, prior to the development of traditional clinical risk factors. Genetic risk is modifiable through lifestyle modifications and medications. PRS offers a valuable way to improve early identification of actionable CVD risk. However, further work is needed before PRS can be implemented clinically.

Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland.

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.

Genetic Risk Stratification: A Paradigm Shift in Prevention of Coronary Artery Disease.

Coronary artery disease (CAD) is a pandemic disease that is highly preventable as shown by secondary prevention. Primary prevention is preferred knowing that 50% of the population can expect a cardiac event in their lifetime. Risk stratification for primary prevention using the American Heart Association/American College of Cardiology predicted 10-year risk based on conventional risk factors for CAD is less than optimal. Conventional risk factors such as hypertension, cholesterol, and age are age-dependent and not present until the sixth or seventh decade of life. The genetic risk score (GRS), which is estimated from the recently discovered genetic variants predisposed to CAD, offers a potential solution to this dilemma. The GRS, which is derived from genotyping the population with a microarray containing these genetic risk variants, has indicated that genetic risk stratification based on the GRS is superior to that of conventional risk factors in detecting those at high risk and who would benefit most from statin therapy. Studies performed in >1 million individuals confirmed genetic risk stratification is superior and primarily independent of conventional risk factors. Prospective clinical trials based on risk stratification for CAD using the GRS have shown lifestyle changes, physical activity, and statin therapy are associated with 40% to 50% reduction in cardiac events in the high genetic risk group (20%). Genetic risk stratification has the advantage of being innate to an individual's DNA, and because DNA does not change in a lifetime, it is independent of age. Genetic risk stratification is inexpensive and can be performed worldwide, providing risk analysis at any age and thus has the potential to revolutionize primary prevention.

Artificial Intelligence in Global Health -A Framework and Strategy for Adoption and Sustainability.

Artificial Intelligence (AI) applications in medicine have grown considerably in recent years. AI in the forms of Machine Learning, Natural Language Processing, Expert Systems, Planning and Logistics methods, and Image Processing networks provide great analytical aptitude. While AI methods were first conceptualized for radiology, investigations today are established across all medical specialties. The necessity for proper infrastructure, skilled labor, and access to large, well-organized data sets has kept the majority of medical AI applications in higher-income countries. However, critical technological improvements, such as cloud computing and the near-ubiquity of smartphones, have paved the way for use of medical AI applications in resource-poor areas. Global health initiatives (GHI) have already begun to explore ways to leverage medical AI technologies to detect and mitigate public health inequities. For example, AI tools can help optimize vaccine delivery and community healthcare worker routes, thus enabling limited resources to have a maximal impact. Other promising AI tools have demonstrated an ability to: predict burn healing time from smartphone photos; track regions of socioeconomic disparity combined with environmental trends to predict communicable disease outbreaks; and accurately predict pregnancy complications such as birth asphyxia in low resource settings with limited patient clinical data. In this commentary, we discuss the current state of AI-driven GHI and explore relevant lessons from past technology-centered GHI. Additionally, we propose a conceptual framework to guide the development of sustainable strategies for AI-driven GHI, and we outline areas for future research.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

Correction to: A repeated cross-sectional study of clinicians' use of psychotherapy techniques during 5 years of a system-wide effort to implement evidence-based practices in Philadelphia.

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A repeated cross-sectional study of clinicians' use of psychotherapy techniques during 5 years of a system-wide effort to implement evidence-based practices in Philadelphia.

BACKGROUND: Little work investigates the effect of behavioral health system efforts to increase use of evidence-based practices or how organizational characteristics moderate the effect of these efforts. The objective of this study was to investigate clinician practice change in a system encouraging implementation of evidence-based practices over 5 years and how organizational characteristics moderate this effect. We hypothesized that evidence-based techniques would increase over time, whereas use of non-evidence-based techniques would remain static. METHOD: Using a repeated cross-sectional design, data were collected three times from 2013 to 2017 in Philadelphia's public behavioral health system. Clinicians from 20 behavioral health outpatient clinics serving youth were surveyed three times over 5 years (n = 340; overall response rate = 60%). All organizations and clinicians were exposed to system-level support provided by the Evidence-based Practice Innovation Center from 2013 to 2017. Additionally, approximately half of the clinicians participated in city-funded evidence-based practice training initiatives. The main outcome included clinician self-reported use of cognitive-behavioral and psychodynamic techniques measured by the Therapy Procedures Checklist-Family Revised. RESULTS: Clinicians were 80% female and averaged 37.52 years of age (SD = 11.40); there were no significant differences in clinician characteristics across waves (all ps > .05). Controlling for organizational and clinician covariates, average use of CBT techniques increased by 6% from wave 1 (M = 3.18) to wave 3 (M = 3.37, p = .021, d = .29), compared to no change in psychodynamic techniques (p = .570). Each evidence-based practice training initiative in which clinicians participated predicted a 3% increase in CBT use (p = .019) but no change in psychodynamic technique use (p = .709). In organizations with more proficient cultures at baseline, clinicians exhibited greater increases in CBT use compared to organizations with less proficient cultures (8% increase vs. 2% decrease, p = .048). CONCLUSIONS: System implementation of evidence-based practices is associated with modest changes in clinician practice; these effects are moderated by organizational characteristics. Findings identify preliminary targets to improve implementation.

Community-academic partnerships in implementation research.

Community-academic partnerships(CAPs) are a critical component of implementing and sustaining evidence-based practices (EBPs) in community settings; however, the approaches used and mechanisms of change within CAPs have not been rigorously studied. The first step to advancing the science of CAP is to operationally define and contextualize the approaches used in CAP as part of the implementation process. Our research group has gleaned valuable lessons about the best ways to develop, support, and nurture community partnerships within the context of implementation. In this article, we share these lessons learned and relate them to implementation strategies that are most relevant to community-partnered implementation endeavors. The implementation strategies most relevant to CAPs are as follows: (a) building a coalition, (b) conducting local consensus discussions, (c) identifying barriers and facilitators to implementation, (d) facilitating interactive problem solving, (e) using an advisory board or workgroup, (f) tailoring strategies, (g) promoting adaptability, and (h) auditing and providing feedback. We offer suggestions for future research to systematically evaluate these strategies, with an eye toward advancing the science of CAP and implementation science and the goal of guiding future research and improving the implementation of EBPs in community settings.

Place and community inclusion: Locational patterns of supportive housing for people with intellectual disability and people with psychiatric disorders.

PURPOSE: This study examines the locational patterns of publicly-funded supportive housing for people with intellectual disability (people with ID) and people with psychiatric disorders (people with PD). METHODS: Administrative data provided housing locations of 4599 people with ID and people with PD in one urban county and one suburban county in the United States. Census tract data captured neighborhood characteristics. Descriptive statistics and spatial analysis were used to analyze the distribution of supportive housing sites. RESULTS: People with ID were more dispersed across a larger number of census tracts with smaller number of residents per tract than people with PD. While spatial dispersion in favor of people with ID was consistent across both counties, difference in dispersion was more pronounced in the urban county. People with PD were concentrated in neighborhoods with more socio-economic disadvantage, more residential instability, and a higher level of race/ethnic diversity than people with ID. CONCLUSION: This study suggests that spatial-analytic method can serve as a useful tool for assessing the extent to which integrated housing is achieved for people with ID and people with PD. Interpretation of findings should be given due consideration of the policy context and neighborhood characteristics of the study communities.

State Adoption of Incentives to Promote Evidence-Based Practices in Behavioral Health Systems.

OBJECTIVE: Despite the critical role behavioral health care payers can play in creating an incentive to use evidence-based practices (EBPs), little research has examined which incentives are used in public mental health systems, the largest providers of mental health care in the United States. METHODS: The authors surveyed state mental health directors from 44 states about whether they used any of seven strategies to increase the use of EBPs. Participants also ranked attributes of each incentive on the basis of key characteristics of diffusion of innovation theory (perceived advantage, simplicity, compatibility, observability, and gradually implementable) and perceived effectiveness. RESULTS: Almost three-quarters of state directors endorsed using at least one financial incentive; most paid for training and technical assistance. Few used other incentives. Strategies perceived as simple and compatible were more readily adopted. Enhanced rates and paying for better outcomes were perceived as the most effective but were the least deployed, suggesting that simplicity and organizational compatibility may be the most decisive factors when choosing incentives. CONCLUSIONS: Payers are not using the incentives they perceive as most effective, and they are mostly using only one strategy for reasons of simplicity and compatibility. Future work should focus on barriers to measurement that likely hinder the adoption and implementation of paying for better outcomes and enhanced reimbursement rates, with the ultimate goal of measuring the effectiveness of incentives on EBP implementation efforts.

Are general and strategic measures of organizational context and leadership associated with knowledge and attitudes toward evidence-based practices in public behavioral health settings? A cross-sectional observational study.

BACKGROUND: Examining the role of modifiable barriers and facilitators is a necessary step toward developing effective implementation strategies. This study examines whether both general (organizational culture, organizational climate, and transformational leadership) and strategic (implementation climate and implementation leadership) organizational-level factors predict therapist-level determinants of implementation (knowledge of and attitudes toward evidence-based practices). METHODS: Within the context of a system-wide effort to increase the use of evidence-based practices (EBPs) and recovery-oriented care, we conducted an observational, cross-sectional study of 19 child-serving agencies in the City of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. Organizational variables included characteristics such as EBP initiative participation, program size, and proportion of independent contractor therapists; general factors such as organizational culture and climate (Organizational Social Context Measurement System) and transformational leadership (Multifactor Leadership Questionnaire); and strategic factors such as implementation climate (Implementation Climate Scale) and implementation leadership (Implementation Leadership Scale). Therapist-level variables included demographics, attitudes toward EBPs (Evidence-Based Practice Attitudes Scale), and knowledge of EBPs (Knowledge of Evidence-Based Services Questionnaire). We used linear mixed-effects regression models to estimate the associations between the predictor (organizational characteristics, general and strategic factors) and dependent (knowledge of and attitudes toward EBPs) variables. RESULTS: Several variables were associated with therapists' knowledge of EBPs. Clinicians in organizations with more proficient cultures or higher levels of transformational leadership (idealized influence) had greater knowledge of EBPs; conversely, clinicians in organizations with more resistant cultures, more functional organizational climates, and implementation climates characterized by higher levels of financial reward for EBPs had less knowledge of EBPs. A number of organizational factors were associated with the therapists' attitudes toward EBPs. For example, more engaged organizational cultures, implementation climates characterized by higher levels of educational support, and more proactive implementation leadership were all associated with more positive attitudes toward EBPs. CONCLUSIONS: This study provides evidence for the importance of both general and strategic organizational determinants as predictors of knowledge of and attitudes toward EBPs. The findings highlight the need for longitudinal and mixed-methods studies that examine the influence of organizational factors on implementation.

Non-participants in policy efforts to promote evidence-based practices in a large behavioral health system.

BACKGROUND: System-wide training initiatives to support and implement evidence-based practices (EBPs) in behavioral health systems have become increasingly widespread. Understanding more about organizations who do not participate in EBP training initiatives is a critical piece of the dissemination and implementation puzzle if we endeavor to increase access in community settings. METHODS: We conducted 30 1-h semi-structured interviews with leaders in non-participating agencies who did not formally participate in system-wide training initiatives to implement EBPs in the City of Philadelphia, with the goal to understand why they did not participate. RESULTS: We found that despite not participating in training initiatives, most agencies were adopting (and self-financing) some EBP implementation. Leadership from agencies that were implementing EBPs reported relying on previously trained staff to implement EBPs and acknowledged a lack of emphasis on fidelity. Most leaders at agencies not adopting EBPs did not have a clear understanding of what EBP is. Those familiar with EBPs in agencies not adopting EBPs reported philosophical objections to EBPs. When asked about quality assurance and treatment selection, leaders reported being guided by system audits. CONCLUSIONS: While it is highly encouraging that many agencies are adopting EBPs on their own, significant questions about fidelity and implementation success more broadly remain.

Ethnic Disparities in School-Based Behavioral Health Service Use for Children With Psychiatric Disorders.

BACKGROUND: We examined racial/ethnic disparities in school-based behavioral health service use for children with psychiatric disorders. METHODS: Medicaid claims data were used to compare the behavioral healthcare service use of 23,601 children aged 5-17 years by psychiatric disorder (autism, attention deficit hyperactivity disorder [ADHD], conduct/oppositional defiant disorder, and "other") and by race/ethnicity (African-American, Hispanic, white, and other). Logistic and generalized linear regression analyses were used. RESULTS: Differences in service use by racial/ethnic group were identified within and across diagnostic groups, both for in-school service use and out-of-school service use. For all disorders, Hispanic children had significantly lower use of in-school services than white children. Among children with ADHD, African-American children were less likely to receive in-school services than white children; however, there were no differences in adjusted annual mean Medicaid expenditures for in-school services by race/ethnicity or psychiatric disorders. Statistically significant differences by race/ethnicity were found for out-of-school service use for children with ADHD and other psychiatric disorders. There were significant differences by race/ethnicity in out-of-school service use for each diagnostic group. CONCLUSIONS: Differences in the use of school-based behavioral health services by racial and ethnic groups suggest the need for culturally appropriate outreach and tailoring of services to improve service utilization.

Can We Pay for Performance in Behavioral Health Care?

Pay for performance (P4P) has become a popular strategy to reward quality and cost-efficiency in behavioral health care and other health care disciplines. This column presents the results of a literature review of P4P in behavioral health care. Fifteen empirical studies evaluating the outcomes of behavioral health services provided in a P4P system were identified. The limited data suggest that P4P can achieve its desired effect. More research is needed on outcomes, performance, and unintended consequences.