Designing implementation strategies to improve identification, cascade testing, and management of families with familial hypercholesterolemia: An intervention mapping approach.

Introduction: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care. Methods: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific literature was searched using key words including "barriers" or "facilitators" and "familial hypercholesterolemia" from inception to December 1, 2021. The parallel mixed method study recruited individuals and families with FH to participate in either dyadic interviews (N = 11 dyads/22 individuals) or online surveys (N = 98 respondents). Data generated from the scoping review, dyadic interviews, and online surveys were used in the 6-step intervention mapping process. Steps 1-3 included a needs assessment, development of program outcomes and creation of evidence-based implementation strategies. Steps 4-6 included program development, implementation, and evaluation of implementation strategies. Results: In steps 1-3, a needs assessment found barriers to FH care included underdiagnosis of the condition which led to suboptimal management due to a myriad of determinants including knowledge gaps, negative attitudes, and risk misperceptions by individuals with FH and clinicians. Literature review highlighted barriers to FH care at the health system level, notably the relative lack of genetic testing resources and infrastructure needed to support FH diagnosis and treatment. Examples of strategies to overcome identified barriers included development of multidisciplinary care teams and educational programs. In steps 4-6, an NHLBI-funded study, the Collaborative Approach to Reach Everyone with FH (CARE-FH), deployed strategies that focused on improving identification of FH in primary care settings. The CARE-FH study is used as an example to describe program development, implementation, and evaluation techniques of implementation strategies. Conclusion: The development and deployment of evidence-based implementation strategies that address barriers to FH care are important next steps to improve identification, cascade testing, and management.

A RE-AIM Framework Analysis of DNA-Based Population Screening: Using Implementation Science to Translate Research Into Practice in a Healthcare System.

Introduction: DNA-based population screening has been proposed as a public health solution to identify individuals at risk for serious health conditions who otherwise may not present for medical care. The clinical utility and public health impact of DNA-based population screening is a subject of active investigation. Geisinger, an integrated healthcare delivery system, was one of the first healthcare systems to implement DNA screening programs (MyCode Community Health Initiative (MyCode) and clinical DNA screening pilot) that leverage exome data to identify individuals at risk for developing conditions with potential clinical actionability. Here, we demonstrate the use of an implementation science framework, RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance), to conduct a post-hoc evaluation and report outcomes from these two programs to inform the potential impact of DNA-based population screening. Methods: Reach and Effectiveness outcomes were determined from the MyCode research program, while Adoption and Implementation outcomes were measured using the clinical DNA screening pilot. Reach was defined as the number of patients who were offered and consented to participate in MyCode. Effectiveness of DNA screening was measured by reviewing MyCode program publications and synthesizing findings from themes. Adoption was measured by the total number of DNA screening tests ordered by clinicians at the clinical pilot sites. Implementation was assessed by interviewing a subset of clinical pilot clinicians about the deployment of and recommended adaptations to the pilot that could inform future program dissemination. Results: Reach: As of August 2020, 68% (215,078/316,612) of individuals approached to participate in the MyCode program consented. Effectiveness: Published evidence reported from MyCode demonstrates that DNA screening identifies at-risk individuals more comprehensively than clinical ascertainment based on phenotypes or personal/family history. Adoption: From July 2018 to June 2021, a total of 1,026 clinical DNA screening tests were ordered by 60 clinicians across the three pilot clinic sites. Implementation: Interviews with 14 clinicians practicing at the pilot clinic sites revealed motivation to provide patients with DNA screening results and yielded future implementation strategies. Conclusion: The RE-AIM framework offers a pragmatic solution to organize, analyze, and report outcomes across differently resourced and designed precision health programs that include genomic sequencing and return of clinically actionable genomic information.

Examining self-reported social functioning, sleep quality, and psychotic-like experiences in college students.

Impairments in social and role functioning have been associated with the prodromal phase of psychosis. Additionally, sleep disturbances impacting daily functioning have been detected across the schizophrenia spectrum. Relationships between social functioning, sleep quality, and psychotic-like experiences (PLEs) in undergraduate-level student populations are less understood. The current project aimed to investigate whether self-reported measures of sleep quality would moderate the relationship between social functioning and PLE endorsement in a community sample of 3042 undergraduate student participants between the ages of 18-35. Participants completed the Social Functioning Scale, the Pittsburgh Sleep Quality Index, and the Prodromal Questionnaire, which indexed PLEs. Bivariate correlations revealed significant associations between social functioning, sleep, and PLEs. As expected, poor sleep and poor social functioning were associated with increased endorsement of PLEs. Contrary to expectation, poor sleep quality was associated with better social functioning. In hierarchical multiple regression models, the interaction between social functioning and sleep was not associated with PLE endorsement. Results indicated that both poor sleep and poor social functioning were significantly associated with PLEs when included in the same model. These findings suggest that poor social functioning and disrupted sleep may act additively to influence PLEs, and that they are both important contributors to psychotic symptoms. Due to deleterious effects of poor sleep on physical and emotional health, these findings provide impetus to further investigate relationships between sleep quality, social functioning, and PLEs using such high-resolution methods as actigraphy, mobile sensing, ecological momentary assessment, and neuroimaging.

Behavioural inhibition system sensitivity is no longer associated with psychotic-like experiences after controlling for depression and anxiety symptoms.

AIM: Elevated behavioural inhibition system sensitivity has been reported among schizophrenia patients. Yet, no study has investigated the relationship between behavioural inhibition system sensitivity and the occurrence of psychotic-like experiences (subthreshold psychotic symptoms considered to be less severe or impairing), despite evidence that behavioural inhibition system sensitivity is related to other forms of psychopathology known to co-occur with psychotic-like experiences, such as depression and anxiety. Thus, the aim of this study was to assess the relationship between behavioural inhibition system levels and psychotic-like experiences while controlling for depression and anxiety symptoms. We hypothesized that behavioural inhibition system sensitivity would be positively associated with the number of reported psychotic-like experiences, and that this association would be nonsignificant after accounting for depression and anxiety symptoms. METHODS: Psychotic-like experiences, behavioural inhibition system sensitivity, depression symptoms, and anxiety symptoms were measured in 1162 young adults. Bivariate correlations were calculated and linear regressions performed to measure the relationship between variables of interest. RESULTS: Psychotic-like experiences, behavioural inhibition system sensitivity, and symptoms of depression, and anxiety were all significantly and positively correlated with one another. Behavioural inhibition system sensitivity was no longer related to the number of psychotic-like experiences reported after controlling for anxiety symptoms, with and without controlling for depression symptoms. DISCUSSION: These findings suggest that the hypersensitivity to threat observed among individuals reporting higher levels of psychotic-like experiences is likely related to co-occurring depression and anxiety symptoms. Thus, behavioural inhibition system sensitivity may be more reflective of a transdiagnostic phenotype of general psychopathology than specifically related to psychosis.

Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure.

INTRODUCTION: Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. METHODS: Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. RESULTS: Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. CONCLUSIONS: Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.