Engaging Sexual and Gender Minority (SGM) Communities for Health Research: Building and Sustaining PRIDEnet.

Lesbian, gay, bisexual, transgender, queer, intersex, asexual, aromantic, and other sexual and/or gender minority (LGBTQIA+) communities are underrepresented in health research and subject to documented health disparities. In addition, LGBTQIA+ communities have experienced mistreatment, discrimination, and stigma in health care and health research settings. Effectively engaging LGBTQIA+ communities and individuals in health research is critical to developing representative data sets, improving health care provision and policy, and reducing disparities. However, little is known about what engagement approaches work well with LGBTQIA+ people. This paper describes the development of PRIDEnet (pridenet.org), a national network dedicated to catalyzing LGBTQIA+ community involvement in health research and built upon well-established community-engaged research (CEnR) principles. PRIDEnet's relationship building and digital communications activities engage thousands of LGBTQIA+-identified people across the country and offer multiple low-threshold ways to participate in specific studies and shape research. These activities comprise a CEnR infrastructure that engages LGBTQIA+ people on behalf of other projects, primarily The PRIDE Study (pridestudy.org) and the National Institutes of Health's All of Us Research Program (joinallofus.org/lgbtqia). Our impact, results, and lessons learned apply to those engaging communities underserved in biomedical research and include: the importance of building adaptable infrastructure that sustains transformational relationships long-term; implementing high-touch activities to establish trust and broad-reach activities to build large data sets; nurturing a team of diverse professionals with lived experiences that reflect those of the communities to be engaged; and maintaining CEnR mechanisms that exceed advice-giving and result in substantive research contributions from beginning to end.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics.

To establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day research planning summit with 46 individuals representing key stakeholder groups, and community response to summit reports. Four high-priority research domains were identified: (a) expanding treatment access, (b) improving treatment outcomes, (c) optimizing treatment within a broader care model, and (d) evaluating outcomes beyond tic severity. Community-engaged participatory research models can efficiently delineate clear and actionable priorities for clinical research. This approach holds promise for improving the impact of clinical research in TDs and other neuropsychiatric disorders.

Do Ask, Tell, and Show: Contextual Factors Affecting Sexual Orientation and Gender Identity Disclosure for Sexual and Gender Minority People.

Purpose: Sexual and gender minority (SGM) people-including members of lesbian, gay, bisexual, transgender, and queer communities-remain underrepresented in health research due to poor collection of sexual orientation and gender identity (SOGI) data. We sought to understand the contextual factors affecting how SGM research participants interact with SOGI questions to enhance participant experience and increase the accuracy and sensitivity of research findings. Methods: We recruited SGM adults for in-person semi-structured focus groups or online cognitive interviews from 2016 to 2018. During focus groups and cognitive interviews, we asked participants to respond to SOGI question sets. We employed template analysis to describe the contextual factors that affected SGM participants' responses to SOGI questions. Results: We had a total of 74 participants, including 55 participants organized into nine focus groups and 19 participants in cognitive interviews. Most self-identified as a sexual minority person (88%), and 51% identified as a gender minority person. Two main themes were: (1) the need to know the relevance (of why SOGI questions are asked) and (2) the importance of environmental and contextual cues (communicating physical safety and freedom from discrimination that influenced SOGI disclosure). Conclusions: Contextualizing the relevance of SOGI data sought could help improve the accuracy and sensitivity of data collection efforts. Environmental cues that communicate acceptance and safety for SGM individuals in research settings may support disclosure. Researchers should consider these contextual factors when designing future studies to improve research experiences for SGM individuals and increase the likelihood of future participation.

Neurodevelopmental profiles of children with unilateral cerebral palsy associated with middle cerebral artery and periventricular venous infarctions.

AIM: To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). METHOD: In this cross-sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. RESULTS: Two hundred and forty-five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2-18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety-seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann-Whitney U=988.50, p<0.001). Bimanual hand usage (Children's Hand-use Experience Questionnaire) (Mann-Whitney U=425, p<0.001) and light touch (odds ratio=9.12, 95% confidence interval 1.28-400.76, Fisher's exact test p=0.017) were lower in the MCA compared to the PVI group. Full-scale IQ median centile score for the MCA group was 18.0 (IQR=35.5) and 50.0 (IQR=30.0) for the PVI group (Mann-Whitney U=382, p<0.001). INTERPRETATION: Children with unilateral CP and MCA injuries demonstrated lower hand function and usage, decreased light touch, and lower IQs compared to the PVI group. This study aids in defining rehabilitation needs informed by brain injury patterns.

What Sexual and Gender Minority People Want Researchers to Know About Sexual Orientation and Gender Identity Questions: A Qualitative Study.

Sexual and gender minority (SGM) people-including members of the lesbian, gay, bisexual, transgender, and queer communities-are understudied and underrepresented in research. Current sexual orientation and gender identity (SOGI) questions do not sufficiently engage SGM people, and there is a critical gap in understanding how SOGI questions reduce inclusion and accurate empirical representation. We conducted a qualitative study to answer the question, "For SGM people, what are the major limitations with current SOGI questions?" Focus groups probed reactions to SOGI questions adapted from prior national surveys and clinical best practice guidelines. Questions were refined and presented in semi-structured cognitive interviews. Template analysis using a priori themes guided analysis. There were 74 participants: 55 in nine focus groups and 19 in cognitive interviews. Participants were diverse: 51.3% identified as gender minorities, 87.8% as sexual minorities, 8.1% as Hispanic/Latinx, 13.5% as Black or African-American, and 43.2% as Non-white. Two major themes emerged: (1) SOGI questions did not allow for identity fluidity and complexity, reducing inclusion and representation, and (2) SOGI question stems and answer choices were often not clear as to which SOGI dimension was being assessed. To our knowledge, this represents the largest body of qualitative data studying SGM perspectives when responding to SOGI questions. We present recommendations for future development and use of SOGI measures. Attention to these topics may improve meaningful participation of SGM people in research and implementation of such research within and for SGM communities.

A digital health research platform for community engagement, recruitment, and retention of sexual and gender minority adults in a national longitudinal cohort study--The PRIDE Study.

OBJECTIVE: Sexual and gender minority (SGM) people are underrepresented in research. We sought to create a digital research platform to engage, recruit, and retain SGM people in a national, longitudinal, dynamic, cohort study (The PRIDE Study) of SGM health. MATERIALS AND METHODS: We partnered with design and development firms and engaged SGM community members to build a secure, cloud-based, containerized, microservices-based, feature-rich, research platform. We created PRIDEnet, a national network of individuals and organizations that actively engaged SGM communities in all stages of health research. The PRIDE Study participants were recruited via in-person outreach, communications to PRIDEnet constituents, social media advertising, and word-of-mouth. Participants completed surveys to report demographic as well as physical, mental, and social health data. RESULTS: We built a secure digital research platform with engaging functionality that engaged SGM people and recruited and retained 13 731 diverse individuals in 2 years. A sizeable sample of 3813 gender minority people (32.8% of cohort) were recruited despite representing only approximately 0.6% of the population. Participants engaged with the platform and completed comprehensive annual surveys- including questions about sensitive and stigmatizing topics- to create a data resource and join a cohort for ongoing SGM health research. DISCUSSION: With an appealing digital platform, recruitment and engagement in online-only longitudinal cohort studies are possible. Participant engagement with meaningful, bidirectional relationships creates stakeholders and enables study cocreation. Research about effective tactics to engage, recruit, and maintain active participation from all communities is needed. CONCLUSION: This digital research platform successfully recruited and engaged diverse SGM participants in The PRIDE Study. A similar approach may be successful in partnership with other underrepresented and vulnerable populations.

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

Home-based Nintendo Wii training to improve upper-limb function in children ages 7 to 12 with spastic hemiplegic cerebral palsy.

This pilot study compared a Nintendo Wii intervention to single-joint resistance training for the upper limb in children ages 7 to 12 with spastic hemiplegic cerebral palsy (CP). Children were randomized to Wii training (n= 3), or resistance training (n= 3) and trained at home for 6 weeks. Pre, post and 4-week follow-up measures were collected. Outcome measures were the Melbourne Assessment (MA2), and ABILHAND-Kids, and grip strength. Compliance, motivation and feasibility of each intervention was explored using daily logbook responses and questionnaires. Descriptive statistics were used. Three children improved in the MA2, two of which were in the Wii training group. Improvements in the ABILHAND-Kids were minimal for all participants. Grip strength improvements were observed in 3 participants, two of which were in the resistance training group. The Wii training group reported higher compliance and more consistently positive responses to motivation and feasibility questions. Therefore, Wii training may be an effective home-based rehabilitation strategy, and is worth exploring in a larger trial. Implications of Wii training in the context of motivation theory are discussed.

Making sure research is used: community-generated recommendations for disseminating research.

Academic research, no matter how innovative, will never make a difference in the lives of people unless it is disseminated in an appropriate and timely manner to providers and organizations serving the public. Yet many researchers are not trained, rewarded, or supported to disseminate research findings. The Community Advisory Board (CAB) of the University of California, San Francisco, Center for AIDS Prevention Studies (CAPS) developed a set guidelines to support researchers' intentions to disseminate their findings through nontraditional venues. These guidelines are unique because community members, many of whom have struggled with accessing research in a timely way, generated them. In addition to developing the guidelines, the CAB also conceived and implemented a dissemination strategy for the guidelines. The purpose of this article is to present specific guidelines for disseminating research developed by the CAPS CAB.

Gender Differences in service connection for PTSD.

BACKGROUND: Mentally ill female veterans obtain a smaller proportion of their care from Department of Veterans Affairs (VA) facilities than mentally ill male veterans do, possibly because women are less likely than men to be service connected for psychiatric disabilities. "Service connected" veterans have documented, compensative conditions related to or aggravated by military service, and they receive priority for enrollment into the VA healthcare system. OBJECTIVES: To see if there are gender discrepancies in rates of service connection for posttraumatic stress disorder (PTSD) and, if so, to see if these discrepancies could be attributed to appropriate subject characteristics (eg, differences in symptom severity or impairment). RESEARCH DESIGN: Mailed survey linked to administrative data. Claims audits were conducted on 11% of the sample. SUBJECTS: Randomly selected veterans seeking VA disability benefits for PTSD. Women were oversampled to achieve a gender ratio of 1:1. RESULTS: A total of 3337 veterans returned usable surveys (effective response rate, 68%). Men's unadjusted rate of service connection for PTSD was 71%; women's, 52% (P < 0.0001). Adjustment for veterans' PTSD symptom severity or functional impairment did not appreciably reduce this discrepancy, but adjustment for dissimilar rates of combat exposure did. Estimated rates of service connection were 53% for men and 56% for women after adjusting for combat exposure. This combat preference could not be explained by more severe PTSD symptoms or greater functional impairment. CONCLUSIONS: Instead of a gender bias in awards for PTSD service connection, we found evidence of a combat advantage that disproportionately favored men. The appropriateness of this apparent advantage is unclear and needs further investigation.