Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.

BACKGROUND: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD). OBJECTIVE: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses. METHODS: Briefly, male C57BL/6J mice were exposed to 0.2mg/kg polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification. RESULTS: Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in >4,000 differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice. DISCUSSION: Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.

Population-average mediation analysis for zero-inflated count outcomes.

Mediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret. To overcome these limitations, we propose a new mediation methodology for zero-inflated count outcomes using the marginalized zero-inflated Poisson (MZIP) model and the counterfactual approach to mediation. This novel work gives population-average mediation effects whose variance can be estimated rapidly via delta method. This methodology is extended to cases with exposure-mediator interactions. We apply this novel methodology to explore if diabetes diagnosis can explain BMI differences in healthcare utilization and test model performance via simulations comparing the proposed MZIP method to existing zero-inflated and Poisson methods. We find that our proposed method minimizes bias and computation time compared to alternative approaches while allowing for straight-forward interpretations.

Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract.

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study (NCT04139577), third-party, single donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive one induction dose (15 capsules/day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules/dose. The primary endpoint of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary endpoint, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at Day 28 was 70%. Initial clinical response was observed within 1 week for all responders and clinical responses were durable, without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased following FMT. While recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted.

Spatial working memory in a disappearing object task is impaired in female but not male dogs with chronic osteoarthritis.

Chronic pain in humans is associated with impaired working memory but it is not known whether this is the case in long-lived companion animals, such as dogs, who are especially vulnerable to developing age-related chronic pain conditions. Pain-related impairment of cognitive function could have detrimental effects on an animal's ability to engage with its owners and environment or to respond to training or novel situations, which may in turn affect its quality of life. This study compared the performance of 20 dogs with chronic pain from osteoarthritis and 21 healthy control dogs in a disappearing object task of spatial working memory. Female neutered osteoarthritic dogs, but not male neutered osteoarthritic dogs, were found to have lower predicted probabilities of successfully performing the task compared to control dogs of the same sex. In addition, as memory retention interval in the task increased, osteoarthritic dogs showed a steeper decline in working memory performance than control dogs. This suggests that the effects of osteoarthritis, and potentially other pain-related conditions, on cognitive function are more clearly revealed in tasks that present a greater cognitive load. Our finding that chronic pain from osteoarthritis may be associated with impaired working memory in dogs parallels results from studies of human chronic pain disorders. That female dogs may be particularly prone to these effects warrants further investigation.

Attitudes toward research and scholarly activities among medical laboratory science professionals in the United States.

BACKGROUND: Medical laboratory science (MLS) professionals play a crucial role in health care teams. However, research culture in the profession has not been well developed or studied. It is necessary to characterize attitudes toward research and scholarly activities among MLS professionals and identify ways to promote research in the profession. METHODS: A cross-sectional survey was administered through American Society for Clinical Laboratory Science channels. Survey responses were summarized using descriptive statistics, and linear regression models were constructed to identify characteristics that predicted 2 research attitudes: "valuing the role of research" and "perceived research environment" in the profession. RESULTS: Of the 116 MLS professionals in this study, 53% reported currently participating in research activities. Opinions toward research were generally positive, although many respondents were not currently conducting research. Individuals with education and research practice focuses tended to place greater value on research, and education level was a significant predictor of perceived research environment. Dedicated research time and mentorship were cited as effective ways for employers to promote research in MLS. CONCLUSION: Overall, respondents had favorable attitudes toward research in MLS, but approximately half of participants noted a lack of incentives to conduct research. This study highlights several initiatives that may be effective for promoting increased research activity among MLS professionals.

A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.

BACKGROUND: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. METHODS: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 µg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 µg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). FINDINGS: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight). INTERPRETATION: Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. FUNDING: Wellcome and PredictImmune Ltd.

Computed tomography scanning is feasible in select patients with REBOA catheter deployment.

BACKGROUND: Rapidly localizing and controlling bleeding is central to treating hemorrhagic shock. While REBOA allows temporary control, identifying the source of bleeding remains challenging. CT imaging with REBOA in place may provide information to direct hemorrhage control. The purpose of this study is to provide a descriptive summary of data comparing patients who did and did not undergo CT scan following REBOA deployment. Our hypothesis was that performing CT scan after REBOA placement in select patients is safe and can guide management of hemorrhagic shock. METHODS: We queried the AAST AORTA registry for patients receiving REBOA at our level 1 trauma center from May 2017 to December 2021. Clinical data was obtained through the Trauma Registry of the American College of Surgeons (TRACS). Comparison groups were those who underwent CT scan after REBOA deployment versus those who did not undergo CT scan after REBOA deployment. The primary outcome was inhospital mortality, and secondary outcomes included hospital-, ICU-, and ventilator-free days. RESULTS: 61 patients underwent CT scan with REBOA in place; 25 patients proceeded directly to hemorrhage control. Patients with REBOA prior to CT were more likely to have blunt mechanism, higher ISS, pelvic bleeding, and zone 3 REBOA placement. Mortality was not significantly different (51 % vs. 64 %). Patients who underwent CT with REBOA were more likely to undergo hemorrhage control in interventional radiology (43 % vs. 0 %). There was no difference in hospital-, ICU-, and ventilator-free days. DISCUSSION: We demonstrate the feasibility of performing CT in select trauma patients who undergo REBOA. We describe a pathway to enable expeditious workup and management of these patients. Optimal hemorrhage control management is impacted by CT scans when it can be performed. It is important to note that this is a severely injured patient population, and mortality is high even when hemorrhage is controlled. LEVEL OF EVIDENCE: III.

Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

BACKGROUND: Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. METHODS: This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. RESULTS: There were 165 patients with a BMI of at least 40 kg/m2 and 320 patients with a BMI less than 40 kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16-2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36-3.92). CONCLUSION: There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity.

Obesogenic polystyrene microplastic exposures disrupt the gut-liver-adipose axis.

Microplastics (MP) derived from the weathering of polymers, or synthesized in this size range, have become widespread environmental contaminants and have found their way into water supplies and the food chain. Despite this awareness, little is known about the health consequences of MP ingestion. We have previously shown that the consumption of polystyrene (PS) beads was associated with intestinal dysbiosis and diabetes and obesity in mice. To further evaluate the systemic metabolic effects of PS on the gut-liver-adipose tissue axis, we supplied C57BL/6J mice with normal water or that containing 2 sizes of PS beads (0.5 and 5 µm) at a concentration of 1 µg/ml. After 13 weeks, we evaluated indices of metabolism and liver function. As observed previously, mice drinking the PS-containing water had a potentiated weight gain and adipose expansion. Here we found that this was associated with an increased abundance of adipose F4/80+ macrophages. These exposures did not cause nonalcoholic fatty liver disease but were associated with decreased liver:body weight ratios and an enrichment in hepatic farnesoid X receptor and liver X receptor signaling. PS also increased hepatic cholesterol and altered both hepatic and cecal bile acids. Mice consuming PS beads and treated with the berry anthocyanin, delphinidin, demonstrated an attenuated weight gain compared with those mice receiving a control intervention and also exhibited a downregulation of cyclic adenosine monophosphate (cAMP) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. This study highlights the obesogenic role of PS in perturbing the gut-liver-adipose axis and altering nuclear receptor signaling and intermediary metabolism. Dietary interventions may limit the adverse metabolic effects of PS consumption.

Treatment patterns and economic burden of bacterial vaginosis among commercially insured women in the USA.

Aim: Bacterial vaginosis (BV) is a common vaginal dysbiosis associated with adverse clinical sequelae, most notably, increased risk of sexually transmitted infections (STIs). The aims of this study were to estimate the frequency of BV recurrence, treatment patterns, other gynecological (GYN) conditions, and the associated healthcare resource utilization (HCRU) and costs among commercially insured patients in the USA. Patients & methods: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication (fungal treatment only excluded) were selected from the Merative™ MarketScan commercial database (2017-2020). During a minimum 12-month follow-up, additional treatment courses, treatment patterns, frequency of other GYN conditions, and HCRU and costs were assessed. Generalized linear models were used to identify baseline predictors of total all-cause healthcare costs and number of treatment courses. Results: The study population included 140,826 patients (mean age: 31.5 years) with an incident vaginitis diagnosis and ≥1 BV medication claim. During the follow-up, 64.2% had 1 treatment course, 22.0% had 2, 8.1% had 3, and 5.8% had ≥4; 35.8% had a BV recurrence (≥2 BV medication claims). The most commonly prescribed BV medication was oral metronidazole (73.6%). Approximately 12% (n = 16,619) of patients had a new diagnosis of another GYN condition in the follow-up; 8.2% had a new STI, which were more common among patients with ≥4 treatment courses (12.9%). During follow-up, total all-cause healthcare costs averaged $8987 per patient per year (PPPY) of which $470 was BV-related. BV-related healthcare costs increased from $403 PPPY among those with 1 treatment course to $806 PPPY among those with ≥4 with nearly half the costs attributed to outpatient office visits. Conclusion: BV recurrence among this population represented a substantial clinical and healthcare economic burden warranting improvements in women's healthcare.

Application of marginalized zero-inflated models when mediators have excess zeroes.

Mediation analysis has become increasingly popular over the last decade as researchers are interested in assessing mechanistic pathways for intervention. Although available methods have increased, there are still limited options for mediation analysis with zero-inflated count variables where the distribution of response has a "cluster" of data at the zero value (i.e. distribution of number of cigarettes smoked per day, where nonsmokers cluster at zero cigarettes). The currently available methods do not obtain unbiased population average effects of mediation effects. In this paper, we propose an extension of the counterfactual approach to mediation with direct and indirect effects to scenarios where the mediator is a count variable with excess zeroes by utilizing the Marginalized Zero-Inflated Poisson Model (MZIP) for the mediator model. We derive direct and indirect effects for continuous, binary, and count outcomes, as well as adapt to allow mediator-exposure interactions. Our proposed work allows straightforward calculation of direct and indirect effects for the overall population mean values of the mediator, for scenarios in which researchers are interested in generalizing direct and indirect effects to the population. We apply this novel methodology to an application observing how alcohol consumption may explain sex differences in cholesterol and assess model performance via a simulation study comparing the proposed MZIP mediator framework to existing methods for marginal mediator effects.

What is the functional reach of wastewater surveillance for respiratory viruses, pathogenic viruses of concern, and bacterial antibiotic resistance genes of interest?

BACKGROUND: Despite a clear appreciation of the impact of human pathogens on community health, efforts to understand pathogen dynamics within populations often follow a narrow-targeted approach and rely on the deployment of specific molecular probes for quantitative detection or rely on clinical detection and reporting. MAIN TEXT: Genomic analysis of wastewater samples for the broad detection of viruses, bacteria, fungi, and antibiotic resistance genes of interest/concern is inherently difficult, and while deep sequencing of wastewater provides a wealth of information, a robust and cooperative foundation is needed to support healthier communities. In addition to furthering the capacity of high-throughput sequencing wastewater-based epidemiology to detect human pathogens in an unbiased and agnostic manner, it is critical that collaborative networks among public health agencies, researchers, and community stakeholders be fostered to prepare communities for future public health emergencies or for the next pandemic. A more inclusive public health infrastructure must be built for better data reporting where there is a global human health risk burden. CONCLUSIONS: As wastewater platforms continue to be developed and refined, high-throughput sequencing of human pathogens in wastewater samples will emerge as a gold standard for understanding community health.

Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Isoform-resolved transcriptome of the human preimplantation embryo.

Human preimplantation development involves extensive remodeling of RNA expression and splicing. However, its transcriptome has been compiled using short-read sequencing data, which fails to capture most full-length mRNAs. Here, we generate an isoform-resolved transcriptome of early human development by performing long- and short-read RNA sequencing on 73 embryos spanning the zygote to blastocyst stages. We identify 110,212 unannotated isoforms transcribed from known genes, including highly conserved protein-coding loci and key developmental regulators. We further identify 17,964 isoforms from 5,239 unannotated genes, which are largely non-coding, primate-specific, and highly associated with transposable elements. These isoforms are widely supported by the integration of published multi-omics datasets, including single-cell 8CLC and blastoid studies. Alternative splicing and gene co-expression network analyses further reveal that embryonic genome activation is associated with splicing disruption and transient upregulation of gene modules. Together, these findings show that the human embryo transcriptome is far more complex than currently known, and will act as a valuable resource to empower future studies exploring development.

Opioid use and associated factors in 1676 patients with inflammatory bowel disease: a multicentre quality improvement project.

Objective: Despite its association with poorer outcomes, opioid use in inflammatory bowel disease (IBD) is not well characterised in the UK. We aimed to examine the extent of opioid use, the associated factors and the use of mitigation techniques such as pain-service review and opioid weaning plans among individuals with IBD. Methods: Data were collected from consecutive patients attending IBD outpatient appointments at 12 UK hospitals. A predefined questionnaire was used to collect data including patient demographics, IBD history, opioid use in the past year (>2 weeks) and opioid-use mitigation techniques. Additionally, consecutive IBD-related hospital stays leading up to July 2019 were reviewed with data collected regarding opioid use at admission, discharge and follow-up as well as details of the admission indication. Results: In 1352 outpatients, 12% had used opioids within the past 12 months. Over half of these individuals were taking opioids for non-IBD pain and less than half had undergone an attempted opioid wean.In 324 hospitalised patients, 27% were prescribed opioids at discharge from hospital. At 12 months postdischarge, 11% were using opioids. Factors associated with opioid use in both cohorts included female sex, Crohn's disease and previous surgery. Conclusions: 1 in 10 patients with IBD attending outpatient appointments were opioid exposed in the past year while a quarter of inpatients were discharged with opioids, and 11% continued to use opioids 12 months after discharge. IBD services should aim to identify patients exposed to opioids, reduce exposure where possible and facilitate access to alternative pain management approaches.

Consultation patterns before and after embedding pediatric palliative care into a pediatric hematology/oncology clinic.

INTRODUCTION: Palliative care is a critical component of pediatric oncology care. Embedded pediatric palliative care (PPC) is relatively new in pediatric hematology/oncology (PHO) and may improve access, utilization, and quality of PPC. In June 2020, the Mayo Clinic PPC service transitioned from an afternoon, physically independent clinic to an all-day clinic embedded within PHO. METHODS: Retrospective chart review was used to quantify consultation rates from PHO to PPC in 12-month study periods before and after establishment of an embedded clinic. Changes in descriptive statistics and consult patterns were calculated. Study periods were compared using either chi-square or Fisher's exact tests for categorical variables and Wilcox rank sum tests for continuous variables. RESULTS: There was an 89% increase in consultations from PHO to PPC after initiation of an embedded clinic (n = 20 vs. n = 38 per 12 months). The absolute number of completed outpatient consults increased from three (15% of visits) pre-embedment to fourteen (37%) post-embedment (p = .082). The median number of days from first oncology visit to PPC assessment was unchanged after embedment (36 vs. 47 days, p = .98). Consults for solid tumors increased from 22% (n = 4) pre-embedment to 60% (n = 18) post-embedment (p < .05). Consults for symptom management increased from 60% (n = 12) to 87% (n = 33) (p < .05). CONCLUSIONS: Embedment of PPC into a PHO workspace was associated with an increased number of total consults, outpatient consults, solid tumor consults, and consults for symptom management. Our "partial-PPO" model allowed for provision of PPC in the outpatient oncology setting in a clinic where there is not enough volume to support a full-time oncology-focused clinician team.

Effects of Neighborhood Disconnection on Psychological Distress and Suicide Risk Associated with Interpersonal Violence Within Racial Groups.

Negative mental health outcomes have been associated with adverse childhood experiences (ACEs) and intimate partner violence (IPV); however, few studies have identified risk and protective factors across levels of the social ecology that mitigate the onset of psychological distress and suicide risk associated with trauma. This study examines the relationship between ACEs, IPV, and mental health (i.e., psychological distress, suicidal ideation, and suicide attempts) within racial sub-populations of Black American, Latinx, and White adults. An online, cross-section survey was administered to a general population sample of adults in Baltimore and New York City. ACEs, IPV, and mental health outcomes were assessed within racial sub-populations of Black American (N = 390), Latinx (N = 178), and White (N = 339) adults, while accounting for within-group demographic differences. Moderating effects of social support and neighborhood disconnection on the relationship between ACEs, IPV, and mental health outcomes were also assessed. IPV was associated with psychological distress and suicidal ideation for Black and Latinx adults, but not for White adults. ACEs were associated with increased psychological distress for all three groups, and increased odds for suicidal ideation among Black and Latinx adults.. A significant negative interaction effect for neighborhood disconnection was found in the relationship between ACEs and psychological distress for Black adults. Findings highlight the significant mental health burdens of ACEs and IPV within racial and ethnic groups. Neighborhood disconnection may exacerbate psychological distress associated with ACEs among populations most impacted by interpersonal violence and mental health inequalities.

Bacterial Vaginosis Treatment Patterns, Associated Complications, and Health Care Economic Burden of Women With Medicaid Coverage in the United States.

BACKGROUND: Bacterial vaginosis (BV) is a highly prevalent vaginal infection. OBJECTIVES: Primary objectives of this study were to examine treatment patterns among female patients with Medicaid coverage who were diagnosed with incident BV, the frequency of BV-associated complications, and health care resource utilization (HCRU) and associated costs of incident BV and its recurrence. Secondary objectives were to identify predictors of total all-cause health care costs and number of treatment courses. METHODS: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication were selected from the Merative MarketScan Medicaid database (2017-2020). Additional treatment courses were evaluated during a ≥12-month follow-up period, in which new cases of BV-associated complications and HCRU and the associated costs were also measured. Generalized linear models were used to identify baseline predictors of total all-cause health care costs and number of treatment courses. RESULTS: An incident vaginitis diagnosis and ≥1 BV medication claim were present in 114 313 patients (mean age: 28.4 years; 48.6% black). During the follow-up, 56.6% had 1 treatment course, 24.9% had 2, 10.2% had 3, and 8.3% had ≥4; 43.4% had BV recurrence. Oral metronidazole (88.5%) was the most frequently prescribed medication. Nearly 1 in 5 had a new occurrence of a BV-associated complication; most (76.6%) were sexually transmitted infections (STIs). Total all-cause and BV-related costs averaged $5794 and $300, respectively, per patient; both increased among those with more treatment courses. Older age, pregnancy, comorbidity, any STIs, postprocedural gynecological infection (PGI), and infertility were predictive of higher total all-cause health care costs, while race/ethnicity other than white was predictive of lower costs. Older age, black race, any STIs, pelvic inflammatory disease, and PGI were predictive of >1 treatment courses. CONCLUSION AND RELEVANCE: The high recurrence of BV represents an unmet need in women's health care and better treatments are necessary.