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The goal of this study is to examine in detail the relationship between pubertal timing and substance use onset using a sample of females from The National Longitudinal Study of Adolescent Health. The sample includes 966 females who were in 7th grade at Wave 1 and 8th grade at Wave 2. Participants in the sample are approximately 69% White, 20% African American, 4% Asian or Pacific Islander, 2% American Indian, 4% other, of Hispanic origin, and 1% other, not of Hispanic origin. Twenty percent of the females were identified as early maturers based on self-reports of body changes (increased breast size and body curviness) measured in 7th grade. These participants are hypothesized to be at increased risk for substance use onset. Important differences in substance use onset were found between early maturers and their on-time and late-maturing counterparts. During 7th grade, females in the early-maturing group are three times more likely to be in the most advanced stage of substance use (involving alcohol use, drunkenness, cigarette use, and marijuana use) than are those in the on-time/late group. Prevalence rates indicate that early maturers are more likely to have tried alcohol, tried cigarettes, been drunk, and tried marijuana. Prospective findings show that early developers are significantly more likely to transition out of the “No Substance Use” stage between 7th and 8th grade (47% for early developers vs. 22% for on-time and late developers). In addition, early developers are more likely to advance in substance use in general, regardless of their level of use at Grade 7. [ABSTRACT FROM AUTHOR]

BackgroundEcological momentary assessments (EMA) are ideal for capturing the dynamic nature of young adult substance use behavior in daily life and identifying contextual risk factors that signal higher-risk episodes. These methods could provide a signal to trigger real-time intervention delivery. Study compliance and engagement are common barriers to participation but may be improved by personalizing messages. This study compares compliance outcomes between one group of young adults receiving standard (generic) prompts at each assessment and another group that received additional personalization and an updated data dashboard (DD) showing study progress to date at 1 randomly selected prompt per day. ObjectiveThe primary objectives are to (1) develop a real-time DD for giving participants personalized updates on their progress in the study and (2) examine its preliminary overall effects on study compliance and experiences. Secondary objectives are to identify person-, day-, and moment-level characteristics associated with study compliance and person-level characteristics associated with perceived usefulness of the DD. MethodsThis is a protocol for Project ENGAGE, a 2-arm randomized controlled trial. Arm 1 (EMA group) is engaged in a standard EMA protocol, and arm 2 (EMA+DD group) is engaged in the same study but with additional personalization and feedback. Inclusion criteria are (1) previous participation in a recent college student survey about health behavior and mental health who indicated willingness to participate in future research studies and (2) indicated past-month alcohol use; lifetime marijuana, hashish, or Delta-8-tetrahydrocannabinol (THC) use; or some combination of these on that survey. All participants in this study completed a baseline survey; EMA at 11 AM, 2 PM, 5 PM, and 8 PM each day for 21 days; and an exit survey. Participants in arm 2 engaged in a microrandomized trial, receiving a personalized DD at 1 randomly selected prompt per day. Primary outcomes include whether a survey was completed, time to complete a survey, and subjective experiences in the study. Primary analyses will compare groups on overall study compliance and, for arm 2, use marginal models to assess the momentary effect of receiving 1 updated DD per day. ResultsApproval was granted by the university’s institutional review board on February 8, 2023. Recruitment via direct email occurred on March 30 and April 6, 2023; data collection was completed by April 29, 2023. A total of 91 individuals participated in the study. Results have been accepted for publication in JMIR Formative Research. ConclusionsResults from the evaluation of this study will indicate whether providing (at randomly selected prompts) real-time, personalized feedback on a participant’s progress in an EMA study improves study compliance. Overall, this study will inform whether a simple, automated DD presenting study compliance and incentives earned to date may improve young adults’ compliance and engagement in intensive longitudinal studies. International Registered Report Identifier (IRRID)DERR1-10.2196/57664

Inflammation likely mediates associations between nicotine use and negative health outcomes. Sex differences have been observed in nicotine use–inflammation links, and physiological processes during puberty might allow for these differences to arise. In this cross-sectional study of 498 youth (ages 8–13, 52% girls, 77% with history of child maltreatment (CM) investigation), sex-differentiated associations between self-reported nicotine use and high-sensitivity C-reactive protein (hs-CRP) were explored. Additionally, self-reported pubertal stage was investigated as a moderator of such nicotine use–hs-CRP links. Hierarchical generalized estimating equation models were adjusted for a wide range of adversity effects: CM investigation history derived from state records, self- and caregiver-report of traumatic life events, adversity-related demographic risk factors (i.e., identification with historically marginalized racial and ethnic groups, household income), and other characteristics that may influence the variables of interest (e.g., medication use, age, body mass index). Nicotine use had a negative main effect on hs-CRP among boys (β = −0.50, p = 0.02), and pubertal stage did not moderate this association (β = 0.06, p = 0.71). In contrast, pubertal stage moderated the association between nicotine use and hs-CRP among girls (β = 0.48, p = 0.02) such that a positive association between nicotine use and hs-CRP levels was stronger at more advanced pubertal stages (β = 0.45, SE = 0.21, 95% CI [0.03, 0.87]). Findings suggest that puberty may influence the effect of nicotine on inflammation in sex-differentiated ways and have implications for timing of prevention and treatment efforts geared toward reducing nicotine use and subsequent inflammation-related health risk among youth.

BackgroundThere is evidence that anxiety and stress increased among college students during the COVID-19 pandemic. However, less is known about daily experiences of affect, worry, substance use behaviors, experiences of pleasure, concern over food security, experiences of bias or discrimination, feelings of belongingness, and other indicators of well-being and how they vary across days in this population. ObjectiveThis study surveyed a wide range of indicators of health and well-being in daily life over 21 days with a sample of college students in a large university system in the United States during the pandemic. The overall variance in each daily measure was partitioned to reflect the proportion due to (1) between-person differences versus (2) within-person, day-to-day variability. This is important because measures that vary primarily due to between-person differences may be more amenable to interventions that target particular students, whereas measures that vary more due to day-to-day variability may be more amenable to interventions that target day-level contextual factors. MethodsA sample of 2068 young adult college students (aged 18-24, mean 19.8, SD 1.3 years; 66.6% women) completed a baseline survey; 97.3% (n=2012) then completed up to 21 consecutive daily surveys that assessed a comprehensive set of daily markers of health, behavior, and well-being. The daily diary study produced a total of 33,722 person-days. ResultsAmong all person-days, a minority were substance use days (eg, 14.5% of days involved alcohol use, 5.6% vaping, and 5.5% cannabis). Experiences of pleasure were reported on most (73.5%) days. Between-person differences explained more than 50% of the variance in numerous indicators of health and well-being, including daily vaping, cannabis use, other illicit substance use, experiences of bias or discrimination, positive affect, negative affect, worry, food insecurity, and feelings of belonging at the university. In contrast, within-person differences explained more than 50% of the variance in daily alcohol use, cigarette use, stress, experiences of pleasure, where the student slept last night, and physical activity. ConclusionsCollege student health and well-being are multifaceted, with some aspects likely driven by person-level characteristics and experiences and other aspects by more dynamic, contextual risk factors that occur in daily life. These findings implicate services and interventions that should target individual students versus those that should target days on which students are at high risk for poor experiences or behaviors.

Objective Chronic pain is a critical public health issue affecting approximately 20% of the adult population in the United States. Given the opioid crisis, there has been an urgent focus on non-addictive pain management methods including mindfulness-based stress reduction (MBSR). Prior work has successfully used MBSR for pain management. However, ensuring longitudinal engagement in MBSR practices remains a serious challenge. In this work, we explore the utility of a voice interface to support MBSR home practice. Methods We interviewed 10 mindfulness program facilitators to understand how such a technology might fit in the context of the MBSR class and identify potential usability issues with our prototype. We then used directed content analysis to identify key themes and sub-themes within the interview data. Results Our findings show that facilitators supported the use of the voice interface for MBSR, particularly for individuals with limited motor function. Facilitators also highlighted the unique affordances of voice interfaces, including perceived social presence, to support sustained engagement. Conclusion We demonstrate the acceptability of a voice interface to support home practice for MBSR participants among trained mindfulness facilitators. Based on our findings, we outline design recommendations for technologies aiming to provide longitudinal support for mindfulness-based interventions. Future work should further these efforts toward making non-addictive pain management interventions accessible and efficacious for a wide audience of users.

BackgroundSubstance use and use disorders in the United States have had significant and devastating impacts on individuals and communities. This escalating substance use crisis calls for urgent and innovative solutions to effectively detect and provide interventions for individuals in times of need. Recent mobile health (mHealth)–based approaches offer promising new opportunities to address these issues through ubiquitous devices. However, the design rationales, theoretical frameworks, and mechanisms through which users’ perspectives and experiences guide the design and deployment of such systems have not been analyzed in any prior systematic reviews. ObjectiveIn this paper, we systematically review these approaches and apps for their feasibility, efficacy, and usability. Further, we evaluate whether human-centered research principles and techniques guide the design and development of these systems and examine how the current state-of-the-art systems apply to real-world contexts. In an effort to gauge the applicability of these systems, we also investigate whether these approaches consider the effects of stigma and privacy concerns related to collecting data on substance use. Lastly, we examine persistent challenges in the design and large-scale adoption of substance use intervention apps and draw inspiration from other domains of mHealth to suggest actionable reforms for the design and deployment of these apps. MethodsFour databases (PubMed, IEEE Xplore, JMIR, and ACM Digital Library) were searched over a 5-year period (2016-2021) for articles evaluating mHealth approaches for substance use (alcohol use, marijuana use, opioid use, tobacco use, and substance co-use). Articles that will be included describe an mHealth detection or intervention targeting substance use, provide outcomes data, and include a discussion of design techniques and user perspectives. Independent evaluation will be conducted by one author, followed by secondary reviewer(s) who will check and validate themes and data. ResultsThis is a protocol for a systematic review; therefore, results are not yet available. We are currently in the process of selecting the studies for inclusion in the final analysis. ConclusionsTo the best of our knowledge, this is the first systematic review to assess real-world applicability, scalability, and use of human-centered design and evaluation techniques in mHealth approaches targeting substance use. This study is expected to identify gaps and opportunities in current approaches used to develop and assess mHealth technologies for substance use detection and intervention. Further, this review also aims to highlight various design processes and components that result in engaging, usable, and effective systems for substance use, informing and motivating the future development of such systems. International Registered Report Identifier (IRRID)DERR1-10.2196/35749

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account. Reprinted from Int J Womens Health 2022; 14:1783-1801, with permission from Dove Medical Press Ltd. Copyright © 2022., (Copyright © 2024 by the American Psychiatric Association.)

Background: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective., Methods: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families., Results: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens., Conclusions: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm., (© 2023. The Author(s).)

The Functional Assessment Short Test (FAST) is a clinician-administered assessment scale of psychosocial dysfunction across various domains typically impacted in individuals with bipolar disorder. The FAST is formally validated as a clinician-administered measure, but support for self-administration would allow its wider use. Therefore, this study aimed to determine whether the FAST could reliably serve as a self-report measure in individuals seeking mental health treatment. Participants completed both the self-report and clinician-administered versions of the FAST as part of their routine outpatient clinical care at the Bipolar Disorders Clinic at The University of Texas Health Austin (UTHA). We investigated correlations between self-report and clinician-administered FAST scores. There were significant positive correlations between self-report and clinician-administered scores in a diverse group of 84 individuals undergoing outpatient mental health treatment (Total FAST scores r S  = 0.75; p < .001). These findings support using the FAST as a self-report scale, further increasing its utility to measure functional disability in mental health conditions such as bipolar disorder. Self-report application will increase the utility of the FAST in busy clinical workflows and, therefore, contribute to a more comprehensive clinical assessment of recovery and spur interventions that improve psychosocial functioning and quality of life., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Child sexual abuse (CSA) is a complex and often traumatic experience that can impact youth's emotional and psychological well-being. Many clinicians do not feel adequately prepared to work with youth around topics of sexuality. In this qualitative study, we examine how licensed therapists treat youth between ages 5 and 16 who have experienced CSA. We asked participants how they incorporate sexuality into trauma work with this population. Although all participants discussed themes commonly reported in clinical work with survivors (i.e., working on trust, self-image challenges, the brain-body connection, confusion around touch and boundaries) additional themes arose that could impede the provision of sexually-competent treatment for the survivor including: considerations for gender identity and sexual orientation, youth being sexually invisible until puberty, and an inaccurate/narrow use of the term "sexuality." We discuss the need for further training on youth sexual development and the ways youth experience the many topics within the concept of sexuality in their therapeutic treatment.

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account., Competing Interests: Dr. Deligiannidis receives research funding from the National Institutes of Health (R01MH118269, R01MH120313) which supported her time for this research and manuscript. Dr. Deligiannidis has also received research funding from Sage Therapeutics, Inc. and Vorso Corporation (contracted research) and serves as a consultant to Sage Therapeutics, Inc., Brii Biosciences, GH Research, Ireland LLC and Brainify.AI. Dr. Carlini, Dr. Lanza di Scalea, Dr. McNally, and Ms. Lester have no disclosures to report for this work., (© 2022 Carlini et al.)

Background: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16)., Methods: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9., Results: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5., Limitations: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting., Conclusions: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively., (Copyright © 2021. Published by Elsevier B.V.)

The differential diagnosis of marrow failure (MF) is crucial in the diagnostic work-up, since genetic forms require specific care. We retrospectively studied all patients with single/multi-lineage MF evaluated in a single-center to identify the type and incidence of underlying molecular defects. The diepoxybutane test was used to screen Fanconi Anemia. Other congenital MFs have been searched using Sanger and/or Next Generation Sequencing analysis, depending on the available tools over the years. Between 2009-2019, 97 patients (aged 0-32 years-median 5) with single-lineage (29%) or multilineage (68%) MF were evaluated. Fifty-three (54%) and 28 (29%) were diagnosed with acquired and congenital MF, respectively. The remaining 16 (17%), with trilinear (n=9) and monolinear (n=7) MF, were found to have an underlying primary immunodeficiency (PID) and showed clinical and biochemical signs of immune-dysregulation in 10/16 (62%) and in 14/16 (87%) of cases, respectively. Clinical signs were also found in 22/53 (41%) and 8/28 (28%) patients with idiopathic and classical cMF, respectively. Eight out of 16 PIDs patients were successfully transplanted, four received immunosuppression, two did not require treatment, and the remaining two died. We show that patients with single/multi-lineage MF may have underlying PIDs in a considerable number of cases and that MF may represent a relevant clinical sign in patients with PIDs, thus widening their clinical phenotype. An accurate immunological work-up should be performed in all patients with MF, and PID-related genes should be considered when screening MF in order to identify disorders that may receive targeted treatments and/or appropriate conditioning regimens before transplant., (© 2021 Wiley Periodicals LLC.)

Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P < .001), lower severity of neutropenia (P = .03), leukopenia (P < .001), lymphopenia (P < .001) with low B+ (P = .001), increased need of granulocyte colony-stimulating factor (P = .04), and increased frequency of autoimmunity over the disease course (P < .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P < .001) and lower white blood cell (P < .001) and lymphocyte (P < .001) values, higher occurrence of apthae (P = .008), and a stronger association with autoimmune diseases/markers (P = .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease., (© 2020 by The American Society of Hematology.)

Background: Gaucher disease (GD) is a rare disorder characterized by defective function of β-glucocerebrosidase, which leads to progressive accumulation of its substrate in various organs, particularly the mononuclear phagocyte system. Hepatosplenomegaly and cytopenia represent the disease's most common features, but patients with GD also show hyperinflammation, hypergammaglobulinemia, and immune dysregulation involving B, T, and natural killer cells. As clinical phenotype can be underhand, symptoms can overlap with autoimmune lymphoproliferative syndrome (ALPS) or other ALPS-like disorders., Objective: To evaluate the ALPS-like immunological pattern and apoptosis function in patients with GD., Methods: We evaluated lymphocyte subsets and immunophenotypic and serological features of ALPS (double-negative T cells [DNTs], B220+DNTs, CD27+, T-reg/HLA-DR ratio, IL-10, IL-18, vitamin B12) in a population of patients with GD. Moreover, we tested FAS/TRAIL-induced apoptosis and CASP8/CASP10/PARP function in patients showing an immune-dysregulation pattern., Results: A total of 41 patients (33 treated, 8 treatment-naïve) were studied. Nine (21%) and 7 (17%) of 41 patients had high DNT and B220+DNT counts, respectively. Overall, 10 of 41(24%) patients showed immunological features suggestive of ALPS that were more frequent in treatment-naïve subjects (P = .040 vs P = .031) and in those with early onset of the disease (P = .046 vs P = .011), respectively. FAS-induced apoptosis and caspase activation were further evaluated in these 10 patients and were found to be defective in 7 of them., Conclusions: We show that patients with GD may have ALPS-like features and FAS-mediated apoptosis defects that are more pronounced in treatment-naïve subjects and in patients with early onset of the disease. Therefore, diagnostic workup of patients with an ALPS-like phenotype should include screening for GD., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)