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BackgroundAdolescents are disproportionately affected by sexually transmitted infections (STIs), including HIV. Many youths with asymptomatic STI or related symptoms do not seek treatment and may not be screened if accessing the health care system for other reasons.ObjectiveWe examined intervention completion and changes in the number of new patients, the number of STI or HIV tests, and the sexual risk profile of patients over time to determine the feasibility and acceptability of a peer-driven text messaging strategy to connect youth to STI and HIV services.MethodsThe intervention enlisted consecutive patients at an adolescent medicine clinic to send a text message to 5 peers they believed were sexually active and lived in the clinic's service area. The intervention was evaluated using an interrupted time-series design in which baseline clinic service levels were documented during a 35-week lead-in period, followed by a 20-week intervention implementation period, and a 16-week period of continued clinic observation. Clinic and patient data were obtained through chart abstraction from intake forms that occurred during the entire study period. Analyses conducted in 2015 used a generalized linear mixed model.ResultsOf the 153 patients approached to participate, 100 agreed to send SMS text messages. Most (n=55, 55%) reported no concerns with sending the text message. No adverse events or negative outcomes were reported. Adolescent STI testing, positive test results, and reported risk behavior increased post intervention, although this was not statistically significant, likely because of the small sample size.ConclusionsGiven low youth uptake of health care services, and STI/HIV screening, in particular, new strategies are needed to address access barriers. Common approaches for reaching youth are resource-intensive and often miss those not connected to school or community programs. The peer-based text messaging strategy showed promise for both increasing the number of youths accessing health services and finding youths engaging in sexual risk behaviors and most in need of sexual health screening and services.

BackgroundBlack and Latinx sexual minority youth are disproportionately affected by HIV. The House Ball and gay family communities encompass sexual and ethnic minority youth who form chosen families that promote protective HIV-related health behaviors. We conducted a small-scale trial of the We Are Family intervention, leveraging these existing social dynamics to address HIV.MethodsFrom September 2018 to September 2019, we enrolled N = 118 for baseline and 6-month follow-up assessments. Eligible participants were 18 years or older, San Francisco Bay Area residents, members of a house or gay family or ball attendees in the past year, smartphone users, and sexually active. The intervention included one 2-hour in-person group session, community-level events, a mobile health app, and a dedicated service provider.ResultsNinety-seven percent of our participants were people of color, 94% were retained through follow-up. 73% attended at least 1 group session, 100% used the mobile health app, and 56% attended a community-level event. Modest changes were observed baseline to follow-up: among all participants, any condomless anal intercourse past 3 months (74.6%-66.7%, P = 0.064); among HIV-negative participants (N = 82) HIV testing past 6 months (80.7%-87.2%, P = 0.166); among HIV-positive participants (N = 34) receiving HIV primary care past 6 months (64.5%-78.8%, P = 0.139), and adherent to ART past 30 days (22.6%-28.1%, P = 0.712). 86% would be willing to refer a friend to the app, and 65% found the app to be personally relevant.ConclusionsWe Are Family reaches and retains its target population, is feasible, acceptable, and shows promise for improving HIV-related health behavior.

BACKGROUND: Children with abusive injuries have worse mortality, length-of-stay, complications, and healthcare costs compared to those sustaining an accidental injury. Long-term functional impairment is common in children with abusive head trauma but has not been examined in a cohort with heterogeneous body region injuries. OBJECTIVE: To assess for an independent association between child physical abuse and functional impairment at discharge and six-month follow-up. PARTICIPANTS AND SETTING: Seriously injured children (

IntroductionThe COVID-19 pandemic has exacerbated longstanding housing precarity. This study measures the public support for policies designed to increase housing stability and gauges whether support levels are associated with views about the role of evictions in COVID-19 transmission and the existence of racial inequities in the housing market.MethodsA cross-sectional survey with a representative sample of U.S. adults in November 2020 assessed support for 4 housing policies. Logistic regression models estimated the adjusted levels of support for each policy, with separate models testing the association with whether or not a respondent recognized the role of evictions in increased COVID-19 transmission or acknowledged racial inequities in the housing market.ResultsMost U.S. adults supported policies aimed to increase housing stability during the COVID-19 pandemic, including extending moratoriums on evictions (63%) and foreclosures (67%) and increasing emergency rental assistance (63%). In total, 54% supported increased government spending on housing vouchers. Adults who agreed that averting eviction would slow COVID-19 transmission had higher support for housing stability policies, as did those who agreed that it was easier for White families to find affordable, high-quality housing than Black families.ConclusionsSupport for housing stability policies was strong among U.S. adults, particularly among those who agreed that preventing evictions slowed COVID-19 transmission and among those who acknowledged racial inequities in the housing market. Raising public awareness of the connections among unstable housing, infectious disease transmission, and racial inequity could broaden the support for policies to keep people in their homes through the pandemic.

The coronavirus disease 2019 (COVID-19) pandemic and associated economic crisis have placed millions of US households at risk of eviction. Evictions may accelerate COVID-19 transmission by decreasing individuals' ability to socially distance. We leveraged variation in the expiration of eviction moratoriums in US states to test for associations between evictions and COVID-19 incidence and mortality. The study included 44 US states that instituted eviction moratoriums, followed from March 13 to September 3, 2020. We modeled associations using a difference-in-difference approach with an event-study specification. Negative binomial regression models of cases and deaths included fixed effects for state and week and controlled for time-varying indicators of testing, stay-at-home orders, school closures, and mask mandates. COVID-19 incidence and mortality increased steadily in states after eviction moratoriums expired, and expiration was associated with a doubling of COVID-19 incidence (incidence rate ratio = 2.1; 95% confidence interval (CI): 1.1, 3.9) and a 5-fold increase in COVID-19 mortality (mortality rate ratio = 5.4; CI: 3.1, 9.3) 16 weeks after moratoriums lapsed. These results imply an estimated 433,700 excess cases (CI: 365,200, 502,200) and 10,700 excess deaths (CI: 8,900, 12,500) nationally by September 3, 2020. The expiration of eviction moratoriums was associated with increased COVID-19 incidence and mortality, supporting the public-health rationale for eviction prevention to limit COVID-19 cases and deaths.

To cope with the COVID-19 pandemic, people not only relied on state measures and scientific knowledge, but also drew on the resources of religion. They may also have embraced conspiracy theories that sometimes led them to engage in protest behavior. Against this background, we address the following research question: 'How are people's religiosity and spirituality related to their belief in COVID-19 conspiracy theories in Germany?' We answer this question by conducting a theory-led empirical analysis. We apply quantitative methods based on primary data from a (non-representative) online survey that we carried out with 2,373 respondents in Germany between July 2020 and January 2021. The results show that belief in COVID-19 conspiracy theories is positively correlated with the image of a punitive God, with exclusivist beliefs, and with private prayer--and negatively correlated with attendance at religious services. Moreover, Catholics, Protestants, Muslims, and Jews have a lower affinity for conspiracy theories than not religiously affiliated people, while the opposite is true for Evangelicals. Keywords: conspiracy theories, COVID-19, Germany, pandemic, online survey, religiosity, spirituality, The COVID-19 pandemic shook the whole world, leaving individuals with feelings of uncertainty, anxiety, and loss of control, and forcing them to find strategies to cope with this situation. An [...]

The effectiveness of a behavior intervention package depends heavily on the ability of authentic educators to implement procedures with fidelity. However, much of the training literature focuses on teaching educators to implement procedures with relatively few components (Kirkpatrick Journal of Behavioral Education 28(3): 344-361, 2019). We used a multiple probe across participants design to evaluate the effects of intensive coaching on educator fidelity of a comprehensive, function-based intervention package (skill-based treatment; Hanley Journal of Applied Behavior Analysis 47(1): 16-36, 2014) for three public school staff members with no previous training in applied behavior analysis. Relative to a workshop-style behavioral skills training session, intensive coaching increased educators' fidelity to criterion levels. Criterion fidelity in one or both major intervention intervals generalized from implementation with an actor to implementation with a target student, and subsequently to implementation with the student in his regularly assigned classroom. Staff reported the training package to be feasible and the intervention to be effective for improving their student's behavior., Author(s): Marney S. Pollack [sup.1] , Johanna L. Staubitz [sup.1] , Blair P. Lloyd [sup.1] Author Affiliations: (1) grid.152326.1, 0000 0001 2264 7217, Department of Special Education, Vanderbilt University, , [...]

Strange C, Tkacz J, Schinkel J, et al. Int J Chron Obstruct Pulmon Dis. 2023;18:2245–2256. The authors have advised that there are errors in the 95% CI interval values on page 2248. Results, Baseline and Follow-Up Exacerbation Rates, sentence 3, the text “Relative rates of total exacerbations for prompt were 0.76, 95% CI: (0.72 – 0.79) and 0.66, 95% CI: (0.63 – 0.69) versus delayed and very delayed” should read “Relative rates of total exacerbations for prompt were 0.76, 95% CI: (0.69 – 0.83) and 0.66, 95% CI: (0.60 – 0.72) versus delayed and very delayed”. Results, Baseline and Follow-Up Exacerbation Rates, sentence 5, the text “Relative rates of severe exacerbations for prompt were 0.75 (95% CI: 0.67-0.90) and 0.38 (95% CI: 0.29-0.47) versus delayed and very delayed” should read “Relative rates of severe exacerbations for prompt were 0.75 (95% CI: 0.45-1.15) and 0.38 (95% CI: 0.22-0.55) versus delayed and very delayed”. The authors apologize for these errors and confirm that the overarching interpretation of the results and conclusions of the study remain consistent with the originally published article and no other text or figures are affected.

Charlie Strange,1 Joseph Tkacz,2 Jill Schinkel,2 Benjamin Lewing,2 Barnabie Agatep,2 Sean Swisher,3 Sushma Patel,3 Devechio Edwards,3 Daniel R Touchette,4 Edward Portillo,5 Norbert Feigler,3 Michael Pollack3 1College of Medicine, The Medical University of South Carolina, Charleston, SC, USA; 2Data Solutions, Inovalon, Bowie, MD, USA; 3BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 4College of Pharmacy - Pharmacy Systems Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA; 5Pharmacy Practice & Translational Research Division, University of Wisconsin-Madison, Madison, WI, USACorrespondence: Michael Pollack, BioPharmaceuticals Medical, AstraZeneca, 1800 Concord Pike, Bldg A1C, Wilmington, DE, 19850, USA, Tel +1 302-886-1253, Email michael.pollack1@astrazeneca.comPurpose: Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation.Patients and methods: EROS was a retrospective analysis of people with COPD using the MORE2 Registry®. Inclusion required ≥ 1 severe, ≥ 2 moderate, or ≥ 1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥ 1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31– 180 days) and very delayed (181– 365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model.Results: 2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39– 1.66); delayed 2.00 (1.92– 2.09); and very delayed 2.30 (2.20– 2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01– 1.08; p< 0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs (&dollar;5002 for prompt vs &dollar;7639 and &dollar;8724 for the delayed and very delayed groups, respectively).Conclusion: Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.Keywords: COPD, triple therapy, exacerbations, delayed therapy, budesonide/glycopyrrolate/formoterol fumarate

In previous studies, we demonstrated that panobinostat, a histone deacetylase inhibitor, and bortezomib, a proteasomal inhibitor, displayed synergistic therapeutic activity against pediatric and adult high‐grade gliomas. Despite the remarkable initial response to this combination, resistance emerged. Here, in this study, we aimed to investigate the molecular mechanisms underlying the anticancer effects of panobinostat and marizomib, a brain‐penetrant proteasomal inhibitor, and the potential for exploitable vulnerabilities associated with acquired resistance. RNA sequencing followed by gene set enrichment analysis (GSEA) was employed to compare the molecular signatures enriched in resistant compared with drug‐naïve cells. The levels of adenosine 5′‐triphosphate (ATP), nicotinamide adenine dinucleotide (NAD)+ content, hexokinase activity, and tricarboxylic acid (TCA) cycle metabolites required for oxidative phosphorylation to meet their bioenergetic needs were analyzed. Here, we report that panobinostat and marizomib significantly depleted ATP and NAD+ content, increased mitochondrial permeability and reactive oxygen species generation, and promoted apoptosis in pediatric and adult glioma cell lines at initial treatment. However, resistant cells exhibited increased levels of TCA cycle metabolites, which required for oxidative phosphorylation to meet their bioenergetic needs. Therefore, we targeted glycolysis and the electron transport chain (ETC) with small molecule inhibitors, which displayed substantial efficacy, suggesting that resistant cell survival is dependent on glycolytic and ETC complexes. To verify these observations in vivo, lonidamine, an inhibitor of glycolysis and mitochondrial function, was chosen. We produced two diffuse intrinsic pontine glioma (DIPG) models, and lonidamine treatment significantly increased median survival in both models, with particularly dramatic effects in panobinostat‐ and marizomib‐resistant cells. These data provide new insights into mechanisms of treatment resistance in gliomas.

Abstract Background One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network’s objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis. Methods We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed. Results Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55–9.60]; z = 4.728; P-value

Objective: Clinical prediction models for surgical aortic valve replacement mortality, are valuable decision tools but are often limited in their ability to account for changes in medical practice, patient selection, and the risk of outcomes over time. Recent research has identified methods to update models as new data accrue, but their effect on model performance has not been rigorously tested. Methods: The study population included 44,546 adults who underwent an isolated surgical aortic valve replacement from January 1, 1999, to December 31, 2018, statewide in Pennsylvania. After chronologically splitting the data into training and validation sets, we compared calibration, discrimination, and accuracy measures amongst a nonupdating model to 2 methods of model updating: calibration regression and the novel dynamic logistic state space model. Results: The risk of mortality decreased significantly during the validation period (P

Abstract Background While health care payers are increasingly considering approaches that help support stable and affordable housing for their beneficiaries, experience with these initiatives is limited. Through its §1115 HealthChoice waiver, Maryland Medicaid has begun experimenting with programs designed to pay for housing and tenancy support/case management services. This study investigates barriers and facilitators to the success of Maryland’s pilot program initiative — Assistance in Community Integration Services (ACIS). Methods The study focused on key stakeholders employed by the four Lead Entities that currently participate in the ACIS program. The stakeholders included members of each Lead Entity’s administration, direct service providers, state and local government officials, and case managers from local hospitals. The convenience sample was selected through an initial list of stakeholders and was supplemented using snowball sampling methods. Interviews were audio recorded and turned into transcripts via Otter.ai and then analyzed using NVivo by two independent reviewers. Results A total of 23 interviews were conducted between February 2022 and May 2022, representing a broad range of stakeholders across different Maryland geographies. A total of 4 themes were identified through the course of the interviews. Stakeholders identified difficulty finding housing for the target population in a tight housing market, challenges with communication within the program and with its clients, and problems with non-healthcare providers documenting services for reimbursement. At the same time, ACIS was seen as creating opportunities for organizations to work together across siloes in meeting client needs. Conclusions The findings of this study helps to highlight Medicaid §1115 waivers as a novel approach to using Medicaid funds to support tenancy-based services, such as ACIS and to improve the lives of individuals while reducing healthcare costs. Implementation of the ACIS program in Maryland has been a resounding success in helping individuals obtain and sustain stable housing. However, continued efforts to align capacity with demand, streamline billing and reimbursement and improve communication with clients and across partners will need to be prioritized. The program also highlights the growing need to address root causes of housing insecurity including the limited supply of affordable housing.

Abstract For decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals. Here, we report in atomic detail (between 2.2 and 2.7 Å resolution) by room-temperature, time-resolved crystallography with millisecond time-resolution (with timepoints between 3 ms and 700 ms) how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. This was made possible in part by the application of singular value decomposition to the MISC data using a program that remains functional even if unit cell parameters change up to 3 Å during the reaction.

Habitat restoration efforts are often limited by cost, making it important that available funds are used efficiently and effectively to achieve desired restoration goals. In this study, we evaluate habitat provision for oysters and motile epifauna on restored oyster reefs in a northwestern Gulf of Mexico estuary constructed with discrete high vertical relief (~0.6 m “reef mounds”) or continuous low vertical relief (

Personal care products can contain phthalates, parabens and other endocrine-disrupting chemicals. However, information on perception of risks from personal care product use and how use varies by race and ethnicity is limited. We evaluated differences in personal care product use and risk perception in a diverse sample of participants recruited from a US college campus and online. A self-administered questionnaire captured information on sociodemographic factors, personal care product use trends and perception of risk associated with them. Pearson’s chi-square and Fisher’s exact tests were used to determine differences in personal care product use and risk perception by race and ethnicity. Ordered logistic regressions were performed to measure associations between personal care product use frequency across racial/ethnic categories. Participant (n = 770) mean age was 22.8 years [standard deviation ± 6.0]. Daily use of make-up (eye = 29.3%; other = 38.0%; all = 33.7%) and skincare products (55%) was most frequently reported among Middle Eastern and North African participants. Non-Hispanic Black participants reported the highest daily use of hairstyling products (52%) and lotion (78%). Daily make-up use was more frequently reported among females (41%) than males (24.6%). Levels of agreement were similar across racial and ethnic groups, that personal care product manufacturers should be required to list all ingredients (≥87%). There were significant associations between the frequency of use of some personal care products and racial/ethnic categories when the use frequencies of participants from other racial/ethnic categories were compared to the use frequency of non-Hispanic White participants. There were significant differences in daily use frequency, levels of trust, perception of safety and health risks associated with personal care products by race and ethnicity, underscoring that there may be different sources of exposure to chemicals in personal care products by race and ethnicity.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit).Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure.Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment.Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.