Identification of pyrimidine structure-based compounds as allosteric ligands of the dopamine transporter as therapeutic agents for NeuroHIV.

The disruption of dopamine neurotransmission by the HIV-1 Transactivator of transcription (Tat) during HIV-1 infection has been linked to the development of neurocognitive disorders, even under combined antiretroviral therapy (cART) treatment. We have demonstrated that SRI-32742, a novel allosteric modulator of dopamine (DA) transporter (DAT), attenuates cocaine- and Tat-binding to DAT, alleviates Tat-induced cognitive deficits and potentiation of cocaine reward in inducible Tat transgenic mice. The current study determined the in vitro pharmacological profile of SRI-32743 and its optimized second-generation analogs and their effects as allosteric modulators. Through structure-activity relationship studies of SRI-32743, 170 compounds were synthesized and evaluated for their ability to modulate DAT function. We identified 21 analogs as atypical competitors of DAT (Emax {less than or equal to}60%). Four compounds, SRI-46564, SRI-47056, SRI-46286 and SRI-47867, displayed IC50 values for [3H]DA uptake inhibition from 9.33 {plus minus} 0.50 to 0.96 {plus minus} 0.05 µM and from 3.96 {plus minus} 1.36 to 1.29 {plus minus} 0.19 for DAT binding, respectively. The four analogs also displayed high potency at two different concentrations (0.5 nM and 0.05 nM) to attenuate Tat-induced inhibition of [3H]DA uptake and cocaine-mediated dissociation of [3H]WIN35,428 binding in CHO cells expressing hDAT, suggesting that the effects occur through an allosteric mechanism. In further ex vivo studies using Fast-Scan Cyclic Voltammetry, we demonstrated that the analogs do not disrupt the baseline phasic-like DA release. These findings provide a new insight into the potential for development of novel therapeutic agents to attenuate DAT-Tat interactions to normalize DA neurotransmission in NeuroHIV. Significance Statement The allosteric inhibition of the dopamine (DA) transporter by the HIV-1 Transactivator of transcription (Tat) disrupts dopamine homeostasis, leading to HIV-associated neurocognitive disorders (HANDs). Analogs of SRI-32743, a novel allosteric modulator of the Tat-DAT interaction, were evaluated in the current study and characterized as atypical ligands of DA uptake. Four novel lead compounds demonstrated high potency to attenuate Tat-induced inhibition of hDAT-mediated DA uptake in an allosteric modulatory manner with no effects on the dynamics of DA uptake-release in DAT.

Trauma-focused therapy retention among military sexual trauma survivors: relationship with veterans' sexual or gender minority identification.

Military servicemembers identifying as sexual and gender minorities (SGM) are at increased risk for military sexual trauma (MST) exposure and Post-traumatic Stress Disorder (PTSD). Although evidence-based treatments can reduce symptoms of PTSD, treatment attrition is concerning. Unfortunately, evaluations of such approaches with veterans identifying as SGM are currently restricted to case studies offering limited information regarding treatment completion. Both historic and current contextual factors related to military and mental health practices may uniquely influence minority veterans' treatment engagement in veteran healthcare settings. We explored associations between SGM identification and treatment of MST-focused therapy completion patterns (finishing the full protocol [FP] or receiving minimally adequate care [MAC; defined as attending eight or more sessions]). Veterans (N = 271, 12.5% SGM) enrolled in individual Prolonged Exposure or Cognitive Processing Therapies at a Midwestern veterans hospital system. Those identifying as SGM were more likely than non-identifying peers to complete FP treatment and, even when attrition occurred, they were retained longer. For MAC, the SGM group was as likely as non-SGM peers to be retained. This research suggests SGM veterans represent a notable minority of those seeking treatment in association with MST and do not appear at greater risk for discontinuation from trauma-focused treatment.

Effects of SRI-32743, a Novel Quinazoline Structure-Based Compound, on HIV-1 Tat and Cocaine Interaction with Norepinephrine Transporter.

Prolonged exposure to HIV-1 transactivator of transcription (Tat) protein dysregulates monoamine transmission, a physiological change implicated as a key factor in promoting neurocognitive disorders among people living with HIV. We have demonstrated that in vivo expression of Tat in Tat transgenic mice decreases dopamine uptake through both dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex. Further, our novel allosteric inhibitor of monoamine transporters, SRI-32743, has been shown to attenuate Tat-inhibited dopamine transport through DAT and alleviates Tat-potentiated cognitive impairments. The current study reports the pharmacological profiles of SRI-32743 in basal and Tat-induced inhibition of human NET (hNET) function. SRI-32743 exhibited less affinity for hNET binding than desipramine, a classical NET inhibitor, but displayed similar potency for inhibiting hDAT and hNET activity. SRI-32743 concentration-dependently increased hNET affinity for [3H]DA uptake but preserved the Vmax of dopamine transport. SRI-32743 slowed the cocaine-mediated dissociation of [3H]Nisoxetine binding and reduced both [3H]DA and [3H]MPP+ efflux but did not affect d-amphetamine-mediated [3H]DA release through hNET. Finally, we determined that SRI-32743 attenuated a recombinant Tat1-86-induced decrease in [3H]DA uptake via hNET. Our findings demonstrated that SRI-32743 allosterically disrupts the recombinant Tat1-86-hNET interaction, suggesting a potential treatment for HIV-infected individuals with concurrent cocaine abuse.

Examining Ethnoracial Differences in Retention in Evidence-Based Treatments for Posttraumatic Stress Disorder Secondary to Military Sexual Trauma.

Improving and expanding mental health treatment for Veterans who have experienced military sexual trauma (MST) is currently a top priority in Veterans Healthcare Administration. Many of these Veterans develop posttraumatic stress disorder (PTSD), and there is increasing recognition that diversity is a core treatment consideration for Veterans who have experienced trauma. As such, more information is needed concerning the relationship between trauma-focused treatment attrition and ethnoracial identity in Veterans who have experienced MST. This article presents two studies exploring dropout from a Midwestern Department of Veterans Affairs (VA) PTSD clinic in samples of Veterans who experienced MST. These studies aim to reduce this knowledge gap by contrasting Black and White Veterans' retention in trauma-focused care. In Study 1 (n = 141), we examined ethnoracial differences in dropout in a cohort of treatment-seeking Veterans who experienced MST and engaged in cognitive processing therapy (CPT) in a VA specialty PTSD clinic. In Study 2 (n = 109), we explored the same questions related to treatment attrition in a separate cohort of treatment-seeking Veterans who experienced MST and engaged in prolonged exposure (PE) in a VA specialty PTSD clinic. Results from both studies did not indicate ethnoracial differences in attrition rate (for both total sessions and an 8-week minimally adequate care [MAC] window) across evidence-based PTSD treatment. However, it remains important to consider the impact of racial and cultural factors on retention. Future research should aim to recruit a larger racially and ethnically diverse sample to explore possible varying retention outcomes of CPT and PE for MST-related PTSD.

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. During an approximate 3-year period, 17 936 newborns received normal IRR and there were 27 812 visits to the portal. Most surveyed parents reported viewing their baby's results (86%, 1410/1639). Parents largely found the portal easy to use to get results, and helpful in understanding the results. However, 10% of parents said it was difficult to find enough information to understand their baby's results. In Early Check, providing normal IRR via the portal made a large-scale study practical, and was highly rated by most users. Return of normal IRR may be particularly amenable to web-based portals, as the consequences to participants from not viewing results are modest, and the interpretation of a normal result is relatively straightforward.

Change in posttraumatic stress disorder-related thoughts during treatment: Do thoughts drive change when pills are involved?

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p < .001, for the lagged effect of symptoms on negative thoughts about self in the SERT+EMM condition, indicating a bidirectional association between such thoughts and PTSD symptoms. In the PE+PLB condition, no significant association between posttraumatic thoughts and PTSD symptoms emerged in either direction. These results suggest that the previously demonstrated role of change in posttraumatic thoughts leading to PTSD symptom reduction in PE may be altered when combined with pill administration, either active or placebo.

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. This study convened expert stakeholders to assess challenges to the NBS system and propose solutions for its modernization. METHODS: NBS stakeholders (researchers, clinicians, state NBS leaders, advocates, industry professionals, and current/former advisory committee members) participated in one of five mixed-stakeholder panel discussions. Prior to panels, participants completed a survey in which they reviewed and ranked NBS challenges generated from relevant literature. During panels, participants deliberated on challenges and explored potential solutions. Pre-panel survey data were analyzed descriptively. Data from panel discussions were analyzed using a rapid qualitative analysis. RESULTS: Median scores of the ranked challenges (1 = most important) reveal the top three most important barriers to address: critical missing data for NBS decision-making (Median = 2), burden on state NBS laboratories (Median = 3), and the amount of time required for state-level implementation of screening for new conditions (Median = 4). Panel discussions were rooted in recurring themes: the infant's well-being should be the focal point; the transformative therapy pipeline, although undeniably positive for individuals with rare diseases, is a threat to NBS capacity; decisions about modernizing NBS should be evidence-based; additional financial support is required but not sufficient for modernization; and modernization will require participation of multiple NBS stakeholders. This final overarching theme is reported in depth, including expertise, coordination, and collaboration challenges facing NBS and novel approaches to oversight, partnership, and coordination that were suggested by participants. CONCLUSIONS: This study engaged representatives from multiple stakeholder groups to generate potential solutions to challenges facing NBS in the United States. These solutions provide a rich starting point for policy makers and other stakeholders who desire to maximize the impact of new transformative therapies for babies, families, and society.

Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. METHOD: We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053). RESULTS: Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. CONCLUSIONS: This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

Early Check: translational science at the intersection of public health and newborn screening.

BACKGROUND: Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. METHODS: To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. DISCUSSION: Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

Context Matters: Posttraumatic Stress Disorder Symptom Associations With Military Sexual Trauma Event Characteristics and Dual Histories of Interpersonal Trauma.

Despite the high rates of military sexual trauma (MST) experienced by service members and veterans, little is known about how contextual features of the MST event or concurrent histories of other interpersonal traumas are associated with diverse clinical presentations. This study examined contextual factors of MST events (number of perpetrators, location of MST, relationship to perpetrator, location of MST) and dual history of interpersonal traumas (including sexual abuse or assault throughout the lifespan, repeated MST, and intimate partner violence) in relation to total symptoms and symptom clusters of Posttraumatic Stress Disorder (PTSD). MST involving multiple perpetrators was related to higher avoidance and hyperarousal. MST while combat-deployed was associated with higher hyperarousal. Veterans endorsing a history of partner violence presented with higher reexperiencing and avoidance. Recognition of phenotypic differences may assist providers in treatment planning and optimizing outcomes.

How do Kenyan orphan girls experience less meaningful lives and how much does it matter for 'health'?

BACKGROUND: Currently, 2.5 million orphaned children are living in Kenya and 56 million orphaned children are living across sub-Saharan Africa. No empirical research has investigated meaningfulness of life among this population, and few studies provide perspectives on the life-course consequences of losing a parent during childhood. METHODS: In this study, we assess life meaningfulness in cross section of Kenyan women (n = 1974) in a semi-rural area of the country (Meru County) collected during June 2015. We used two sets of mediation analyses to assess (1) whether meaningfulness of life was lower among women who reported a parental death during their childhood, and how this association was mediated by social support, family functioning, school completion and HIV+ status of household, and (2) the extent to which lower subjective overall health among women who experienced orphanhood during childhood was mediated by less meaningfulness of life. RESULTS: Women who experienced a parental death during childhood reported significantly less meaningful lives as adults. Lower social support and family functioning explained approximately 40% of the disparity. Women who experienced a parental death during childhood also had significantly worse subjective overall health, 18% of which was explained by lower meaningfulness of life. CONCLUSIONS: Further study on life meaningfulness and family capital in the context of the orphan crisis in sub-Saharan Africa is warranted, and required to promote equity across the lifespan. Policy efforts to support orphans and vulnerable children should target strengthening support networks and family functioning to optimize self-reported health outcomes.

Physical Activity Moderates the Association Between Pain and PTSD in Treatment-Seeking Veterans.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and pain are frequently comorbid conditions that can result in bidirectional exacerbations. Initial research suggests physical activity may prevent PTSD symptoms or assist with recovery. Unfortunately, Veterans with PTSD are less likely to engage in physical activity, often citing pain as a primary reason. The current study examines the potential role of physical activity as a moderator of the pain and PTSD relationship. DESIGN: Data were collected from 239 Veterans who were seeking PTSD treatment at a Veterans Affairs (VA) hospital between 2006 and 2013. Veterans completed the Clinician-Administered PTSD Scale (CAPS) to measure PTSD severity and self-report inventories to measure pain and physical activity. Multiple moderated linear regressions were used to examine the influence of physical activity on the relationship between pain and PTSD symptoms. RESULTS: Pain severity and interference were associated with more severe PTSD. Physical activity did not have main effects on PTSD severity. However, it did moderate the relationship between PTSD and pain, such that those who were active, despite high levels of pain severity or pain interference, had fewer PTSD symptoms. CONCLUSIONS: For Veterans seeking treatment for PTSD, physical activity was particularly salient for those reporting high levels of pain severity and intensity. While assessment of pain is recommended with all Veterans, it may also be beneficial to evaluate physical activity in those with prominent pain complaints. Further examination of the role of exercise in integrated care for pain and PTSD is warranted.

Severe Maternal Morbidity: The Impact of Race on Tricare Beneficiaries.

Maternal morbidity and mortality rates in the United States have increased in the last two decades with a disproportionate impact on women of color. While numerous factors contribute to the inequities in pregnancy-related mortality, access to health insurance is among the most significant. Military Tricare models universal health care access; however, in studies looking at births in military treatment facilities, disparities still exist for women of color. This study analyzed maternal delivery outcomes for all women with Tricare coverage, including deliveries in the civilian sector. We analyzed data from 6.2 million births in the Centers for Disease Control (CDC) Wide-ranging Online Data for Epidemiology Research (WONDER) Linked Birth/Infant Death Records for 2017-2019. Data included all-cause morbidity (transfusions, perineal lacerations, uterine rupture, unplanned hysterectomy, and ICU admissions), severe maternal morbidity (SMM) excluding lacerations, and SMM excluding transfusion. Risk ratios were calculated by comparing overall maternal morbidity rates between Tricare, Medicaid, self-pay, and private insurance. In addition, risk ratios were calculated between insurance types stratified by race. In conclusion, there is an increased risk for women identifying as racial minorities for SMM and SMM excluding transfusion. While Tricare coverage seems to decrease the risk, the decrease is not significant and disparities in outcomes persist among women identifying as minorities. The risk of severe maternal morbidity remains elevated for women of color despite access to Tricare health insurance.

Age-Related Variation in Ecological Resources Among Veterans Seeking Treatment Related to Military Sexual Trauma.

Approximately 16% of Veterans experience military sexual trauma (MST), defined as sexual assault or harassment experienced during military service. Veterans across life stages may possess differing resources and face unique stressors that impact their ability to engage in mental health treatment or require additional liaison to services. The present study sought to characterize age-related differences in the socioecological contexts of Veterans seeking mental health treatment following MST in the domains of economic sufficiency, housing, spiritual coping, supportive relationships, and interpersonal violence. From 2009 to 2019, Veterans (N = 640) seeking mental health services following exposure to MST attended evaluation and treatment planning sessions at a Midwestern Veterans Health Administration posttraumatic stress disorder specialty clinic. Veterans completed semistructured interviews that included surveys and diagnostic screenings to assess psychosocial needs and resources. ANOVA and ordinal regressions were used to evaluate potential disparities in socioecological resources by age. No age-related differences in economic sufficiency and stable housing emerged, though most Veterans (57%) endorsed financial difficulties. Veterans who endorsed spiritual beliefs were significantly older than those who did not. Veterans who reported having a support system were significantly younger than Veterans who denied having a support system. Less than half (46%) of Veteran reported having peer relationships. Veterans who endorsed frequent interaction with their peers were significantly older than those who did not. Veterans who reported past-year exposure to interpersonal violence were significantly younger. Greater clarity about age-related differences in the socioecological contexts of Veterans can support clinicians in providing responsive mental health treatment and connecting Veterans to additional Veterans Health Administration resources following MST.

Worry differentially mediates posttraumatic cognition and posttraumatic stress symptom relationships among veterans seeking treatment associated with military sexual trauma.

Research has established negative posttraumatic cognitions (NPC) affect the development and course of posttraumatic stress symptoms (PTSS) following trauma exposure (L. A. Brown et al., 2019). Previous studies in civilian and combat veteran populations also suggest positive associations among worry, NPC (Beck et al., 2004; Bennett et al., 2009), and PTSS (Fergus & Bardeen, 2017). However, little research has investigated the prevalence of worry in veterans who have experienced military sexual trauma (MST), and no research has examined the role of worry in the relation between NPC and PTSS among veterans seeking treatment associated with MST. This project examined the prevalence of worry in a MST sample and whether worry mediated NPC-PTSS associations. Veterans (N = 91) seeking MST-related treatment presented to a Veterans Affairs Posttraumatic Stress Disorder specialty clinic for assessment and treatment recommendations. Veterans completed questionnaires assessing NPC, worry, and PTSS. Bootstrapped mediation analyses examined NPC-PTSS associations. Veterans reported similar levels of worry as nonveterans seeking treatment associated with generalized anxiety disorder. Mediation analyses showed worry significantly mediated NPC-PTSS relationships for beliefs about the world, self-blame, and coping competence but not for beliefs about the self or global NPC severity. Further, the degree of mediation differed by NPC type. Though a limitation of this study is the use of cross-sectional data, these results inform the use of clinical intervention strategies targeting worry in trauma-focused interventions and necessitate further research on whether trauma-focused interventions ameliorate co-occurring worry among veterans exposed to MST. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

PTSD and pain: exploring the impact of posttraumatic cognitions in veterans seeking treatment for PTSD.

OBJECTIVE: Previous research has demonstrated a significant relationship between posttraumatic stress disorder (PTSD) and pain. While several models attempt to explain this relationship, significant questions remain regarding factors that may play a role in this interaction. The purpose of this study was to determine whether posttraumatic cognitions mediate the relationship between PTSD and pain. DESIGN: The sample comprised 136 veterans who presented to the VA Ann Arbor Health Care System seeking evaluation and treatment in the PTSD clinic. Participants completed the Clinician-Administered PTSD Scale, the Posttraumatic Cognitions Inventory, and Brief Pain Inventory-Short Form, along with other assessments as part of their evaluation. RESULTS: This study showed that the majority of patients (86.8%) reported some problems with pain. Further, the findings indicate that there is a significant relationship between PTSD severity and pain severity. Posttraumatic cognitions were not related to the level of pain experienced, but they were related to pain interference in this population. CONCLUSIONS: In particular, negative cognitions regarding the self were associated with the level of pain-related interference, and partially mediated the relationship between PTSD and pain. The clinical implications of these findings are discussed.

Experience and Attitudes Toward Telehealth in Student-Run Free Clinics (SRFC).

INTRODUCTION/OBJECTIVES: Telehealth services expanded during the coronavirus disease 2019 (COVID-19) pandemic. Student-run free clinics (SRFC) deliver important health care services to underserved populations, who may face barriers to telehealth use. This study characterizes telehealth usage, experiences, and attitudes among individuals working in SRFCs. METHODS: In November 2021, a survey adapted from the COVID-19 Healthcare Coalition Telehealth Impact Physician Survey was sent to all registrants who identified themselves as students at the 2020 Society of Student-Run Free Clinics Annual Conference. RESULTS: Thirty-eight individuals of 576 registrants (7%) representing 21 of 88 (24%) SRFCs completed the survey. Twenty-one (58%) individuals reported using telehealth in their clinic. Those that did not cited lack of infrastructure as a barrier (eg, broadband, Internet challenges, technology investments), were more likely to serve homeless (P = .01), and less likely to serve non-English speaking populations (P = .02). There were increases in telehealth and decreases in in-person visits after March 11, 2020 though changes did not reach statistical significance. At least 15 (68%) wanted to continue chronic disease management, preventative care, and mental/behavioral health via telehealth after COVID-19. Most felt that telehealth was easy to use and improved the health, safety, and timeliness of care of patients, but not work satisfaction or access to care. Difficulty accessing physical devices, Internet, and data was the most-cited barrier to maintaining and accessing telehealth. CONCLUSIONS: Nearly all participants cited significant benefits and barriers to telehealth that impacted perceived access to care and sustainability. SRFCs' experiences may be modulated by their underserved populations and role in student education. Addressing barriers, particularly patient- and clinic-level technology challenges, could work to improve inequities in telehealth uptake.

A Mixed-Method Study Exploring Patient-Experienced and Caregiver-Reported Benefits and Side Effects of Corticosteroid Use in Duchenne Muscular Dystrophy.

BACKGROUND: Corticosteroids are recommended to all people with Duchenne as standard of care; patient experience data is important to guide corticosteroid decision making and as a comparator for new treatment options. OBJECTIVE: This study assesses patient and caregiver-reported benefits and side effects from corticosteroids to treat Duchenne muscular dystrophy, their importance, and satisfaction. METHODS: Using one-on-one interviews (n = 28) and an online survey (n = 236), parents and adults with Duchenne reported corticosteroid benefits and side effects rated as both experienced and important. RESULTS: Benefits to breathing, heart function, arm strength, slowing progression of weakness, and getting around were rated as particularly important, regardless of ambulatory status. Important side effects included increased fracture risk, unwanted weight gain, and diabetes/prediabetes. Parents rated behavior issues and adults rated delayed puberty as having high importance. Being ambulatory was independently associated with reporting more net benefit (p = 0.02). For side effects, parent scores were significantly higher than adult score (p = 0.02). Corticosteroid type was not significant. Participants were, overall, satisfied with corticosteroids (means ranging from 6.2 to 7.7 on a scale of 0-10), with no significant differences based on corticosteroid type. CONCLUSIONS: Overall, most participants were satisfied with the use of corticosteroids. While a range of side effects were rated as important and relatively common, individuals using corticosteroids and their caregivers indicate that benefits outweigh the side effects. Qualitative data indicate that high acceptability is influenced by lack of treatment alternatives. Patient experience data on use of corticosteroids in Duchenne may be relevant to drug development, regulatory assessment of new treatments, and to families making decisions about corticosteroid use.

Using the multiphase optimization strategy to adapt cognitive processing therapy (CPT MOST): study protocol for a randomized controlled factorial experiment.

BACKGROUND: Approximately ten percent of US military veterans suffer from posttraumatic stress disorder (PTSD). Cognitive processing therapy (CPT) is a highly effective, evidence-based, first-line treatment for PTSD that has been widely adopted by the Department of Veterans Affairs (VA). CPT consists of discrete therapeutic components delivered across 12 sessions, but most veterans (up to 70%) never reach completion, and those who discontinue therapy receive only four sessions on average. Unfortunately, veterans who drop out prematurely may never receive the most effective components of CPT. Thus, there is an urgent need to use empirical approaches to identify the most effective components of CPT so CPT can be adapted into a briefer format. METHODS: The multiphase optimization strategy (MOST) is an innovative, engineering-inspired framework that uses an optimization trial to assess the performance of individual intervention components within a multicomponent intervention such as CPT. Here we use a fractional factorial optimization trial to identify and retain the most effective intervention components to form a refined, abbreviated CPT intervention package. Specifically, we used a 16-condition fractional factorial experiment with 270 veterans (N = 270) at three VA Medical Centers to test the effectiveness of each of the five CPT components and each two-way interaction between components. This factorial design will identify which CPT components contribute meaningfully to a reduction in PTSD symptoms, as measured by PTSD symptom reduction on the Clinician-Administered PTSD Scale for DSM-5, across 6 months of follow-up. It will also identify mediators and moderators of component effectiveness. DISCUSSION: There is an urgent need to adapt CPT into a briefer format using empirical approaches to identify its most effective components. A brief format of CPT may reduce attrition and improve efficiency, enabling providers to treat more patients with PTSD. The refined intervention package will be evaluated in a future large-scale, fully-powered effectiveness trial. Pending demonstration of effectiveness, the refined intervention can be disseminated through the VA CPT training program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05220137. Registration date: January 21, 2022.