A systematic framework for selecting gene-condition pairs for inclusion in newborn sequencing panels: Early Check implementation.

Purpose: Research is underway worldwide to investigate the feasibility, acceptability, and utility of sequencing-based newborn screening. Different methods have been used to select gene-condition pairs for screening, leading to highly inconsistent gene lists across studies.

Methods: Early Check developed and utilized actionability-based frameworks for evaluating gene-condition pairs for inclusion in newborn panels (panel 1-high actionability, panel 2-possible actionability).

Prioritizing research needs and opportunities at the intersection of implementation science and engagement science.

Background: There has been increased attention to the need for, and the positive impact of, engaged or participatory science in recent years. Implementation scientists have an opportunity to leverage and contribute to engagement science (ES) through the systematic integration of engagement into implementation science (IS). The purpose of this study was to gather information from researchers and others to develop a prioritized list of research needs and opportunities at the intersection of IS and ES.

Age-Related Blood Levels of Creatine Kinase-MM in Newborns and Patients with Duchenne Muscular Dystrophy: Considerations for the Development of Newborn Screening Algorithms.

Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder and the most common type of muscular dystrophy in children. As newborn screening (NBS) for DMD undergoes evaluation for the Recommended Uniform Screening Panel and is already mandated in multiple states, refining NBS algorithms is of utmost importance. NBS for DMD involves measuring creatine kinase-MM (CK-MM) concentration-a biomarker of muscle damage-in dried blood spots.

Facilitators and Barriers to Adherence to Anti-Retroviral Treatment Among Pregnant or Breastfeeding Women Living with HIV and Perinatally Infected Infants: A Scoping Review.

In 2022, 54% of 1.5 million children (age 0-14) living with HIV had access to anti-retroviral medication (ART). Adherence to ART for pregnant or breastfeeding HIV + women is critical for maintaining their personal health and to prevent mother-to-child-transmission (MTCT).

Role Preferences in Medical Decision Making: Relevance and Implications for Health Preference Research.

Health preference research (HPR) is being increasingly conducted to better understand patient preferences for medical decisions. However, patients vary in their desire to play an active role in medical decisions. Until now, few studies have considered patients' preferred roles in decision making.

Two years of newborn screening for Duchenne muscular dystrophy as a part of the statewide Early Check research program in North Carolina.

Purpose: Current and emerging treatments for Duchenne muscular dystrophy (DMD) position DMD as a candidate condition for newborn screening (NBS). In anticipation of the nomination of DMD for universal NBS, we conducted a prospective study under the Early Check voluntary NBS research program in North Carolina, United States.

Methods: We performed screening for creatine kinase-MM (CK-MM), a biomarker of muscle damage, on residual routine newborn dried blood spots (DBS) from participating newborns.

Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity.

Corrigendum to "HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption" [J Virus Erad 9 (2) (June 2023) 100331].

[This corrects the article DOI: 10.1016/j.jve.

HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption.

Early-phase HIV remission ("cure") trials aim to test interventions developed to eradicate HIV or to sustainably control HIV without antiretroviral treatment (ART). Many remission trials include analytic treatment interruption (ATI) to evaluate interventions, which increases the risk to participants and their sexual partners. We conducted an online questionnaire of international HIV remission trial investigators and other study team members to assess their expectations regarding the time to achieve long-term control of HIV replication without treatment (functional cure) or complete eradication of replication-competent HIV virus (sterilizing cure); attitudes toward HIV remission research and the feasibility, acceptability, and efficacy of six HIV transmission risk mitigation strategies during trials with ATI of fixed duration.

Defining critical educational components of informed consent for genetic testing: views of US-based genetic counselors and medical geneticists.

The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts.

Misunderstood terms and concepts identified through user testing of educational materials for fragile X premutation: "Not weak or fragile?".

Complicated genetic mechanisms and unpredictable health risks associated with the FMR1 premutation can result in challenges for patient education when the diagnosis is made in a newborn. From October 15, 2018, to December 10, 2021, North Carolina parents could obtain FMR1 premutation results about their newborns through a voluntary expanded newborn screening research study. The study provided confirmatory testing, parental testing, and genetic counseling.

Reporting Individual-Level Research Results from Neurocognitive and Psychological Research in People Living with HIV: Lessons from Dementia Research.

Purpose Of Review: There are growing expectations for the return of individual-level research results (RoR), which promotes autonomy and potential clinical and personal benefits. There are ethical and practical challenges, however, that may be exacerbated in research that assesses neurocognitive and psychological outcomes, including HIV-associated neurocognitive disorder (HAND). This paper reviews central concepts for RoR and recent empirical and conceptual articles from Alzheimer's disorder (AD) as a model for HIV.

Use of a web-based portal to return normal individual research results in Early Check: Exploring user behaviors and attitudes.

Early Check is a voluntary, large-scale expanded newborn screening study in North Carolina that uses a self-directed web-based portal for return of normal individual research results (IRR). Little is known about participant perspectives in using web-based portals to receive IRR. This study explored user attitudes and behaviors within the Early Check portal using three methods: (1) a feedback survey available to the consenting parent of participating infants (typically mothers), (2) semi-structured interviews conducted with a subset of parents, and (3) Google Analytics.

Corrigendum to 'Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok,' [Contemporary Clinical Trials Communication (2023)101054].

[This corrects the article DOI: 10.1016/j.conctc.

Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok.

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens. Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy.

GM1-gangliosidosis: The caregivers' assessments of symptom impact and most important symptoms to treat.

GM1-gangliosidosis (GM1) is a rare neurodegenerative disorder leading to early mortality and causing progressive decline of physical skills and cerebral functioning. No approved treatment for GM1 exists. In this study-the first to explore priorities of parents of subjects with pediatric onset forms of GM1-we address a crucial gap by characterizing symptoms most critical to caregivers of children with GM1 to treat.

Perceptions of HIV cure and willingness to participate in HIV cure-related trials among people enrolled in the Netherlands cohort study on acute HIV infection.

Background: People who initiate antiretroviral therapy (ART) during acute HIV infection are potential candidates for HIV cure-related clinical trials, as early ART reduces the size of the HIV reservoir. These trials, which may include ART interruption (ATI), might involve potential risks. We explored knowledge and perception of HIV cure and willingness to participate in cure-related trials among participants of the Netherlands Cohort Study on Acute HIV infection (NOVA study), who started antiretroviral therapy immediately after diagnosis of acute HIV infection.

Education and Consent for Population-Based DNA Screening: A Mixed-Methods Evaluation of the Early Check Newborn Screening Pilot Study.

A challenge in implementing population-based DNA screening is providing sufficient information, that is, understandable and acceptable, and that supports informed decision making. Early Check is an expanded newborn screening study offered to mothers/guardians whose infants have standard newborn screening in North Carolina. We developed electronic education and consent to meet the objectives of feasibility, acceptability, trustworthiness, and supporting informed decisions.

Caregivers' assessment of meaningful and relevant clinical outcome assessments for Sanfilippo syndrome.

Objectives: Sanfilippo syndrome is a rare multisystem disease with no approved treatments. This study explores caregiver perspectives on the most impactful symptoms and patient-relevant clinical outcomes assessments. The pediatric onset and progressive neurodegenerative nature of Sanfilippo limits use of self-report in clinical research.

Role Attainment in Emerging Adulthood: Subjective Evaluation by Male Adolescents and Adults with Duchenne and Becker Muscular Dystrophy.

Background: Youth with Duchenne and Becker muscular dystrophy (DBMD) experience challenges in attaining adult roles, which may impact quality of life. New interventions and treatments may facilitate adult role attainment through improved function. Historical data on adult role attainment is important to assess the impact of new interventions on teens and young adults with DBMD.

Evaluation of the GSP Creatine Kinase-MM Assay and Assessment of CK-MM Stability in Newborn, Patient, and Contrived Dried Blood Spots for Newborn Screening for Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal X-linked disorder with a birth prevalence of 19.8:100,000 males worldwide. Elevated concentration of the muscle enzyme creatine kinase-MM (CK-MM) allows for presymptomatic screening of newborns using Dried Blood Spots (DBS).

Leveraging electronic health records to inform genetic counseling practice surrounding psychiatric disorders.

Since nearly one-fifth of US adults have a psychiatric disorder, genetic counselors (GCs) will see many patients with these indications. However, GCs' reports of inadequate preparation and low confidence in providing care for patients with psychiatric disorders can limit their ability to meet patient's needs. How frequently psychiatric disorders present in GC sessions is currently unclear.

Preparing newborn screening for the future: a collaborative stakeholder engagement exploring challenges and opportunities to modernizing the newborn screening system.

Background And Objectives: Projections that 60 transformative cell and gene therapies could be approved by the U.S. Food and Drug Administration (FDA) within 10 years underscore an urgent need to modernize the newborn screening (NBS) system.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

Background: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years.

Methods: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months.

Attitudes About Analytic Treatment Interruption (ATI) in HIV Remission Trials with Different Antiretroviral Therapy (ART) Resumption Criteria.

HIV remission trials often require temporary stopping of antiretroviral therapy (ART)-an approach called analytic treatment interruption (ATI). Trial designs resulting in viremia raise risks for participants and sexual partners. We conducted a survey on attitudes about remission trials, comparing ART resumption criteria (lower-risk "time to rebound" and higher-risk "sustained viremia") among participants from an acute HIV cohort in Thailand.