Moving to the Middle Ground: Redefining Genomic Utility to Expand Understanding of Familial Benefit.

Translational research has tended to ignore the question of whether receiving a genomic diagnosis provides utility in community care contexts outside of doctors' offices and hospitals. However, empirical research with parents has highlighted numerous ways that a genomic diagnosis might be of practical value in the care provided by teachers, physical or occupational therapists, speech-language pathologists, behavior analysts, and nonphysician mental health providers. In this essay, we propose a new conceptual model of genomic utility that offers the opportunity to better capture a broad range of potential implications of genomic technologies for families in various social and organizational systems. We explore crucial research directions to better understand how redefined utility might affect families and nonphysician professionals.

Parents' Perspectives on the Utility of Genomic Sequencing in the Neonatal Intensive Care Unit.

BACKGROUND: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents' experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. METHODS: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child's sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. RESULTS: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child's future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent-infant bonding, and reported variable impact on their feelings of guilt. CONCLUSION: Parents reported that GS during the neonatal period was useful because it provided a "backbone" for their child's care. Parents did not consistently endorse negative impacts like interference with parent-infant bonding.

The Therapeutic Odyssey: Positioning Genomic Sequencing in the Search for a Child's Best Possible Life.

Background: The desire of parents to obtain a genetic diagnosis for their child with intellectual disability and associated symptoms has long been framed as a diagnostic odyssey, an arduous and sometimes perilous journey focused on the goal of identifying a cause for the child's condition.Methods: Semi-structured interviews (N = 60) were conducted with parents of children (N = 59, aged 2-24 years) with intellectual disability and/or developmental delay (IDD) who underwent genome sequencing at a single pediatric multispecialty clinic. Interviews were conducted after parents received their child's sequencing result (positive findings, negative findings, or variants of unknown significance). Thematic analysis was performed on all interviews.Results: Parents reported that obtaining a genetic diagnosis was one important step in their overall goal of helping their child live their best life possible life. They intended to use the result as a tool to help their child by seeking the correct school placement and obtaining benefits and therapeutic services.Conclusions: For the parents of children with IDD, the search for a genetic diagnosis is best conceptualized as a part of parents' ongoing efforts to leverage various diagnoses to obtain educational and therapeutic services for their children. Cleaving parents' search for a genetic diagnosis from these broader efforts obscures the value that some parents place on a sequencing result in finding and tailoring therapies and services beyond the clinic. Interviews with parents reveal, therefore, that genomic sequencing is best understood as one important stage of an ongoing therapeutic odyssey that largely takes place outside the clinic. Findings suggest the need to expand translational research efforts to contextualize a genetic diagnosis within parents' broader efforts to obtain educational and therapeutic services outside clinical contexts.

Intersections between Young Women's Racial/Ethnic Identities and Sexual Orientation on Rates of Sexual Violence and Substance Use.

BACKGROUND: Little is known about whether there are differences in rates of sexual violence and its association with substance use based on women's identities, specifically the intersection of their race/ethnicity and sexual orientation. METHOD: Women (N = 546; 18 to 29 years of age) recruited from a reproductive healthcare clinic reported their race, ethnicity, sexual orientation, sexual violence history and substance use. Five logistic regressions examined (a) rates of sexual violence, and (b) the strength of the associations between sexual violence and four substance use outcomes (heavy alcohol use, marijuana use, cigarette use, number of cigarettes used) based on sexual orientation. Subsequent logistic regressions examined race/ethnicity as a moderator of the associations between sexual orientation and (a) rates of sexual violence and (b) substance use. RESULTS: Most women surveyed were heterosexual (64%), and 35% of all women reported unwanted sex. Sexual minority women (SMW) reported higher rates of sexual violence and substance use than heterosexual women. Sexual violence was more strongly associated with heavy alcohol use, but not with marijuana or cigarette use, for SMW than heterosexual women. Rates of sexual violence varied based on the intersection of sexual orientation and race/ethnicity. Although SMW were more likely to report sexual violence than heterosexual women, this association was weaker for Black/Latinx women than for non-Hispanic White women (aOR = 0.39, 95%CI [0.18, 0.82]). Race/ethnicity did not moderate the strength of associations between sexual violence and substance use. CONCLUSIONS: SMW exhibit increased risk for sexual violence and substance use, and victimization was associated with heavy alcohol use. Few racial/ethnic differences emerged as a function of sexual orientation, so SMW are a group with unique needs around sexual violence experiences and substance use, regardless of race/ethnicity. Healthcare providers should be aware of the link between substance use and prior victimization when treating SMW.

Telephone-delivered behavioral health interventions for people living with HIV: patients' perspectives from a qualitative study.

People living with HIV (PLWH) often experience mental health concerns as well as difficulties with medication adherence; they also report barriers to receipt of health services. Telephone-delivered interventions can overcome some of these barriers. To obtain patients' perspectives on telephone-delivered behavioral health services, we conducted a qualitative study with patients who participated in one of two telephone-delivered interventions (mindfulness training, health coaching) in a research trial. Patients (N = 42; M age = 46 years, 50% female, 26% Black) participated in semi-structured qualitative interviews after completing the study. They identified several advantages (e.g., being able to schedule sessions more flexibly compared to in-person appointments, ease of developing rapport with interventionists) as well as occasional challenges of phone delivery (e.g., network connectivity). Overall, PLWH view telephone-delivery as a convenient and flexible method to engage in behavioral health interventions.

Partner Type and Young Women's Sexual Behavior: A Qualitative Inquiry.

The incidence of sexually transmitted infections (STIs) has increased over recent years, particularly among young women. Partner type is believed to influence women's STI risk. However, researchers often restrict partner type to "casual" versus "committed," labels that can mask risk variability. Therefore, in this study, we identified and explored a range of sexual partner types in order to understand how young women's perceived risk and condom use intentions vary by partner type. Data were obtained during six focus groups of young women (N =25) who were recruited from a community reproductive healthcare clinic. Women described a range of monogamous and non-monogamous partner types that were distinguished based on partner regularity (i.e., whether the sexual partnership was ongoing) and personal relationship (i.e., degree of involvement outside of the sexual relationship). Women's perceived STI risk was higher and condom use intentions stronger with new partners, particularly unfamiliar partners (i.e., "one-night stand," "fuck boy"). Women identified potential harm from condom negotiation with all but the "friends with benefits" partners. However, the nature of this harm differed by partner type. Clinicians and researchers should consider how to support women in advocating for safer sexual behaviors across these partner types by understanding how partner regularity, degree of personal relationship, and emotional attachment differentially impact couples' condom use decisions.

A Brief Clinic-Based Intervention to Reduce Alcohol Misuse and Sexual Risk Behavior in Young Women: Results from an Exploratory Clinical Trial.

This exploratory trial determined the feasibility, acceptability, and preliminary efficacy of a brief intervention (BI), supplemented with text messaging and a curated Web site, on alcohol use and sexual risk behavior among young women. Young women seeking care at a reproductive health clinic were screened for alcohol misuse and sexual risk behavior. Those who screened positive and who agreed to participate (N = 48; M = 22.67 years) were randomized to either (a) a brief in-person session during which personalized feedback regarding alcohol use and sexual risk taking was provided and discussed, or (b) a control condition. Feasibility was assessed by recruitment and retention rates. Acceptability was assessed with participant ratings of their intervention. Efficacy was measured using self-reported alcohol use and sexual behavior at baseline and during a 3-month follow-up. We supplemented the quantitative data with qualitative data from semi-structured interviews. Feasibility data indicated that 64% of eligible women agreed to participate, 74% of eligible women were enrolled, and 86% of enrolled women were retained through follow-up. Acceptability data showed that women who received the BI reported strong satisfaction with their intervention (M = 4.65 vs. 3.98 on a five-point scale) and also reported that text messaging was helpful (M = 4.73 on a seven-point scale) and acceptable (M = 5.27 on a seven-point scale). Qualitative data provided additional support for BI feasibility and acceptability. Efficacy data showed that women in both conditions reduced alcohol use and sexual risk behavior over time; women who received the BI reduced their maximum daily alcohol intake more than controls (BI from 7.68 to 4.82 standard drinks vs. control from 6.48 to 5.65; Wald χ2 = 4.93, p < .05). Women in the BI reported fewer occasions of condomless sex (median = 2.50) than controls (median = 5.00) at the follow-up, but this difference was not statistically significant (OR = 0.61, 95% CI [0.32, 1.15]). A brief intervention, supplemented with text messaging and a Web site, that targeted alcohol use and sexual behavior was feasible and acceptable to young women and led to lower levels of alcohol misuse and sexual risk behavior.

Telephone-Delivered Mindfulness Training to Promote Medication Adherence and Reduce Sexual Risk Behavior Among Persons Living with HIV: An Exploratory Clinical Trial.

This study explored whether telephone-delivered mindfulness training (MT) to promote medication adherence and reduce sexual risk behavior was feasible for and acceptable to people living with HIV. Participants (N = 42; 50% female; M age = 47.5 years) were randomized to MT or health coaching (HC). Pre- and post-intervention, and at 3-month follow-up, we assessed adherence to ART, sexual risk behavior, and hypothesized mediators; we also conducted individual interviews to obtain qualitative data. Results showed that 55% of patients assigned to MT completed ≥ 50% of the training calls compared with 86% of HC patients (p < .05). Most patients reported satisfaction with their intervention (MT = 88%, HC = 87%). Patients in MT and HC reported improvements in medication adherence, mindfulness, and sexual risk reduction as well as reductions in anxiety, depressive symptoms, perceived stress, and impulsivity over time; however, no between-groups differences were observed.

Sexual risk behavior and substance use among young, diverse women seeking care at a reproductive health clinic.

BACKGROUND: To describe sexual risk behavior, alcohol (and other substance) use, and perceived health promotion needs among young adult women seeking care from an urban reproductive health care clinic in the Northeastern United States, and to examine if these needs differ by race and ethnicity. METHODS: Women 18-29 years old presenting for a routine medical visit were invited to participate. Of 486 eligible women, 466 (96%) agreed to participate and completed a brief survey on a tablet computer. Most of the sample (53%) identified as non-Hispanic White. One-quarter (25%) identified as Hispanic/Latina. A smaller proportion of women identified as African American (19%). RESULTS: One-third (31%) of women reported a history of sexually transmitted infection (STI), and women reported infrequent condom use with recent sexual partners. Regarding behavioral health needs, nearly three-quarters of women (72%) reported regular alcohol use, approximately one-third had used marijuana (37%) or tobacco (33%) in the last month, and 19% reported clinically significant depressive symptoms in the last two weeks. Women reported moderate-to-strong interest in receiving information about relationships and sexual health; however, the majority were not interested in information about their substance use. Hispanic and African-American women were more likely to report STI history despite reporting fewer sexual partners than non-Hispanic White women. Minority women also reported significantly less alcohol and cigarette use, but more water pipe tobacco use, and reported significantly greater interest in interventions to promote sexual health. Hispanic women also evidenced significantly elevated rates of depressive symptoms, with 26% of Hispanic women reporting a clinically significant level of depressive symptoms. CONCLUSIONS: Reproductive health centers are opportune settings to address a broad range of healthcare needs, including sexual health, substance use, and mental health. These centers engage a diverse group of women, which is important given observed disparities in health outcomes based on race/ethnicity. Young women, particularly racial and ethnic minority women, report the most interest in services addressing sexual and relationship health.

Alcohol Use and Sexual Risk Behavior in Young Women: A Qualitative Study.

Alcohol use and sexual behavior co-occur frequently in young women, increasing risk for HIV and other sexually transmitted infections. To inform preventive interventions, we used qualitative methods to better understand how women think about the contribution of alcohol use to sexual risk-taking. Young women (N = 25; M = 22.8 years; 64% White) were recruited from a community-based reproductive health clinic to attend focus groups; a semi-structured agenda was used to investigate both a priori explanatory mechanisms as well as participant-driven explanations for the alcohol-sex association. Women reported that alcohol reduced their social anxiety, helped them to feel outgoing and confident, and lowered inhibitions and other barriers to sexual encounters (consistent with alcohol expectancies). During drinking events, women described being less concerned with risks, less discriminating regarding sexual partners, and less likely to insist on safer sex practices (consistent with alcohol myopia). These empirical findings support previous theory-based guidance for tailoring preventive programs for alcohol use and sexual risk reduction for young women.

Genomic sequencing identifies secondary findings in a cohort of parent study participants.

PURPOSE: Clinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability. METHODS: Exome/genome sequencing and analysis of 789 "unaffected" parents was performed. RESULTS: Pathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the American College of Medical Genetics and Genomics. These 25 individuals self-reported either relevant clinical diagnoses (5); relevant family history or symptoms (13); or no relevant family history, symptoms, or clinical diagnoses (7). A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate pairs (n = 365) to identify cases in which both parents were carriers for the same recessive disease, yielding three such cases (0.8%), two of which had children with the relevant recessive disease. Four participants had two findings (one carrier and one noncarrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings. CONCLUSION: We provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design and implementation of research and clinical sequencing efforts to identify such findings.

Providers' Behaviors and Beliefs on Prescribing Antipsychotic Medication to Children: A Qualitative Study.

Fragmentation in behavioral and mental health care to children has resulted in suboptimal care and high rates of psychotropic medication use, especially antipsychotic medications (APM). A qualitative study, based on the Theory of Planned Behavior (TPB), aimed to better understand prescribing practices, barriers to optimal treatment, and potential interventions to safeguard the use of APM for children in Kentucky. The most common barrier to optimal care was access to mental health specialists. Social norms and pressure from families contribute to increased medication use. We identify promising interventions to safeguard the use of APM through the lens of the TPB.

Telephone-Delivered Mindfulness Training for People Living with HIV: A Qualitative 360° Inquiry.

For people living with HIV and AIDS (PLWHA), life stress often undermines quality of life and interferes with medical care. Mindfulness training (MT) may help PLWHA to manage stress. Because standard MT protocols can be burdensome, we explored telephone delivery as a potentially more feasible approach. We used an innovative 360° qualitative inquiry to seek input regarding telephone-delivery of MT for PLWHA in advance of a planned intervention trial. We also sought input on a time- and attention-matched control. Twenty five HIV patients, providers and advocates, were recruited to five focus groups. Participants understood the construct of mindfulness and recognized its potential benefits for stress management and improving medication adherence. Patients preferred the term "mindfulness" to meditation. Telephone-delivery appealed to all patients but several challenges were raised. Topics for the control intervention included nutrition, sleep, and aging. The 360° approach allowed three groups (patients, providers, advocates) to influence intervention development.

Genomic diagnosis for children with intellectual disability and/or developmental delay.

BACKGROUND: Developmental disabilities have diverse genetic causes that must be identified to facilitate precise diagnoses. We describe genomic data from 371 affected individuals, 309 of which were sequenced as proband-parent trios. METHODS: Whole-exome sequences (WES) were generated for 365 individuals (127 affected) and whole-genome sequences (WGS) were generated for 612 individuals (244 affected). RESULTS: Pathogenic or likely pathogenic variants were found in 100 individuals (27%), with variants of uncertain significance in an additional 42 (11.3%). We found that a family history of neurological disease, especially the presence of an affected first-degree relative, reduces the pathogenic/likely pathogenic variant identification rate, reflecting both the disease relevance and ease of interpretation of de novo variants. We also found that improvements to genetic knowledge facilitated interpretation changes in many cases. Through systematic reanalyses, we have thus far reclassified 15 variants, with 11.3% of families who initially were found to harbor a VUS and 4.7% of families with a negative result eventually found to harbor a pathogenic or likely pathogenic variant. To further such progress, the data described here are being shared through ClinVar, GeneMatcher, and dbGaP. CONCLUSIONS: Our data strongly support the value of large-scale sequencing, especially WGS within proband-parent trios, as both an effective first-choice diagnostic tool and means to advance clinical and research progress related to pediatric neurological disease.

Phone-delivered mindfulness training to promote medication adherence and reduce sexual risk behavior among persons living with HIV: Design and methods.

INTRODUCTION: Two-thirds of people living with HIV (PLWH) show sub-optimal adherence to antiretroviral therapy (ART) and one-third engages in risky sex. Both non-adherence and risky sex have been associated with emotional distress and impulsivity. To allay distress and lessen impulsivity, mindfulness training (MT) can be helpful. In this trial, we will investigate the utility of phone-delivered MT for PWLH. The primary outcomes comprise feasibility and acceptability of phone-delivery; secondary outcomes are estimates of efficacy of MT on adherence to ART and safer sexual practices as well as on their hypothesized antecedents. METHODS/DESIGN: Fifty participants will be enrolled in this parallel-group randomized clinical trial (RCT). Outpatients recruited from an HIV treatment clinic will be randomized (1:1 ratio) to either MT or to an attention-control intervention; both interventions will be administered during 8 weekly phone calls. ART adherence (self-reported measure and unannounced phone pill counts), sexual behavior (self-reports and biomarkers), mindfulness, depression, stress, and impulsivity will be measured at baseline, post-intervention, and 3months post-intervention. CONCLUSIONS: MT has great potential to help PLWH to manage stress, depressive symptoms, and impulsivity. Positive changes in these antecedents are expected to improve safer sex practices and ART adherence. If results from this exploratory trial support our hypotheses, we will conduct a large RCT to test (a) the efficacy of MT on ART adherence and safer sex practices and (b) the hypothesis that improved ART adherence and safer sex will reduce viral load, and decrease the incidence of sexually transmitted infections, respectively.

Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.

PURPOSE: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences. METHODS: We conducted focus groups with 110 adults to understand patient perspectives on secondary genomic findings and the role that preferences should play. We then developed and refined a draft instrument and used it to elicit preferences from parents participating in a genomic sequencing study in children with intellectual disabilities. RESULTS: Patients preferred filtering of secondary genomic results to avoid information overload and to avoid learning what the future holds, among other reasons. Patients preferred to make autonomous choices about which categories of results to receive and to have their choices applied automatically before results are returned to them and their clinicians. The Preferences Instrument for Genomic Secondary Results (PIGSR) is designed to be completed by patients or research participants without assistance and to guide bioinformatic analysis of genomic raw data. Most participants wanted to receive all secondary results, but a significant minority indicated other preferences. CONCLUSIONS: Our novel instrument-PIGSR-should be useful in a wide variety of clinical and research settings.Genet Med 19 3, 337-344.