Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

The core phageome and its interrelationship with preterm human milk lipids.

Phages and lipids in human milk (HM) may benefit preterm infant health by preventing gastrointestinal pathobiont overgrowth and microbiome modulation. Lipid association may promote vertical transmission of phages to the infant. Despite this, interrelationships between lipids and phages are poorly characterized in preterm HM. Shotgun metagenomics and untargeted lipidomics of phage and lipid profiles from 99 preterm HM samples reveals that phages are abundant and prevalent from the first week and throughout the first 100 days of lactation. Phage-host richness of preterm HM increases longitudinally. Core phage communities characterized by Staphylococcus- and Propionibacterium-infecting phages are significantly correlated with long-chain fatty acid abundances over lactational age. We report here a phage-lipid interaction in preterm HM, highlighting the potential importance of phage carriage in preterm HM. These results reveal possible strategies for phage carriage in HM and their importance in early-life microbiota development.

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey.

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.

Built environment microbiomes transition from outdoor to human-associated communities after construction and commissioning.

The microbiota of the built environment is linked to usage, materials and, perhaps most importantly, human health. Many studies have attempted to identify ways of modulating microbial communities within built environments to promote health. None have explored how these complex communities assemble initially, following construction of new built environments. This study used high-throughput targeted sequencing approaches to explore bacterial community acquisition and development throughout the construction of a new build. Microbial sampling spanned from site identification, through the construction process to commissioning and use. Following commissioning of the building, bacterial richness and diversity were significantly reduced (P < 0.001) and community structure was altered (R2 = 0.14; P = 0.001). Greater longitudinal community stability was observed in outdoor environments than indoor environments. Community flux in indoor environments was associated with human interventions driving environmental selection, which increased 10.4% in indoor environments following commissioning. Increased environmental selection coincided with a 12% reduction in outdoor community influence on indoor microbiomes (P = 2.00 × 10-15). Indoor communities became significantly enriched with human associated genera including Escherichia, Pseudomonas, and Klebsiella spp. These data represent the first to characterize the initial assembly of bacterial communities in built environments and will inform future studies aiming to modulate built environment microbiota.

Bacteriophage communities are a reservoir of unexplored microbial diversity in neonatal health and disease.

Acquisition and development of the gut microbiome are vital for immune education in neonates, especially those born preterm. As such, microbial communities have been extensively studied in the context of postnatal health and disease. Bacterial communities have been the focus of research in this area due to the relative ease of targeted bacterial sequencing and the availability of databases to align and validate sequencing data. Recent increases in high-throughput metagenomic sequencing accessibility have facilitated research to investigate bacteriophages within the context of neonatal gut microbial communities. Focusing on unexplored viral diversity, has identified novel bacteriophage species and previously uncharacterised viral diversity. In doing so, studies have highlighted links between bacteriophages and bacterial community structure in the context of health and disease. However, much remains unknown about the complex relationships between bacteriophages, the bacteria they infect and their human host. With a particular focus on preterm infants, this review highlights opportunities to explore the influence of bacteriophages on developing microbial communities and the tripartite relationships between bacteriophages, bacteria and the neonatal human host. We suggest a focus on expanding collections of isolated bacteriophages that will further our understanding of the growing numbers of bacteriophages identified in metagenomes.

The association between internet use to obtain health information and receiving three doses of the Hepatitis B vaccine in a multi-ethnic population in Ohio.

While most cancer incidence and mortality rates are decreasing, liver cancer rates are increasing. The Hepatitis B Virus (HBV) vaccine prevents liver cancer, although not everyone receives all three doses of the vaccine. This study examined the association between using the internet as the primary source of health information and receiving three HBV vaccine doses among a multi-ethnic population in Ohio. From May 2017 through February 2018, participants in the Community Initiative Towards Improving Equity and Health Status (CITIES) study reported their primary health information source and if they received three HBV vaccine doses. A multivariable logistic regression model was fit using backwards selection. Overall, 26.6% received three HBV vaccine doses. After adjusting for race/ethnicity and education, the association between internet use and receiving three HBV vaccine doses was not significant (p-value = 0.73). In the process of model-building, race/ethnicity and educational attainment were identified as factors associated with completing the HBV vaccine; Hispanics (OR = 0.35; 95% CI = 0.17, 0.69) and African Americans (OR = 0.53; 95% CI = 0.35, 0.81) had lower odds of receiving three doses compared to whites; compared to college graduates, those with a high school diploma or less also had lower odds (OR = 0.33; 95% CI = 0.21, 0.52). This study suggests no association between internet use and complete HBV vaccination; however, associations between both race/ethnicity and educational attainment and HBV vaccine completion were identified. Future research should consider factors that stem from racial/ethnic and educational disparities that may influence adherence to HBV vaccination (i.e., healthcare system mistrust, access to accurate health information).

Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) in Appalachia: protocol for a group randomized, delayed intervention trial.

Appalachian regions of Kentucky and Ohio are hotspots for colorectal cancer (CRC) mortality in the USA. Screening reduces CRC incidence and mortality; however, screening uptake is needed, especially in these underserved geographic areas. Implementation science offers strategies to address this challenge. The aim of the current study was to conduct multi-site, transdisciplinary research to evaluate and improve CRC screening processes using implementation science strategies. The study consists of two phases (Planning and Implementation). In the Planning Phase, a multilevel assessment of 12 health centers (HC) (one HC from each of the 12 Appalachian counties) was conducted by interviewing key informants, creating community profiles, identifying HC and community champions, and performing HC data inventories. Two designated pilot HCs chose CRC evidence-based interventions to adapt and implement at each level (i.e., patient, provider, HC, and community) with evaluation relative to two matched control HCs. During the Implementation Phase, study staff will repeat the rollout process in HC and community settings in a randomized, staggered fashion in the remaining eight counties/HCs. Evaluation will include analyses of electronic health record data and provider and county surveys. Rural HCs have been reluctant to participate in research because of concerns about capacity; however, this project should demonstrate that research does not need to be burdensome and can adapt to local needs and HC abilities. If effective, this approach could be disseminated to HC and community partners throughout Appalachia to encourage the uptake of effective interventions to reduce the burden of CRC.

We conducted a multi-site study to evaluate and improve CRC screening processes using implementation science strategies at multiple levels including the patient, provider, health center, and community. Our goals were to increase rates of guideline-recommended CRC screening, follow-up, and referral-to-care in an Appalachian, medically underserved population.

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.

Factors related to retention in a longitudinal study of infants at familial risk for autism.

Background: Reporting retention data is critical to determining the soundness of a study's conclusions (internal validity) and broader generalizability (external validity). Although selective attrition can lead to overestimates of effects, biased conclusions, or overly expansive generalizations, retention rates are not reported in many longitudinal studies. Methods: We examined multiple child- and family-level factors potentially associated with retention in a longitudinal study of younger siblings of children with autism spectrum disorder (ASD; n = 304) or typical development (n = 163). The sample was followed from the first year of life to 36 months of age, for up to 7 visits. Results: Of the 467 infant siblings who were consented and participated in at least one research visit, 397 (85.0%) were retained to study completion at 36 months. Retention rates did not differ by familial risk group (ASD-risk vs. Low-risk), sex, race, ethnicity, age at enrollment, number of children in the family, maternal employment, marital status, or parent concerns about the child at enrollment. A stepwise regression model identified 4 variables that, together, provided the most parsimonious predictive model of study retention: maternal education, maternal age at child's birth, travel distance to the study site, and diagnostic outcome classification at the final study visit. Conclusions: The retained and not-retained groups did not differ on most demographic and clinical variables, suggesting few threats to internal and external validity. The significantly higher rate of retention of children diagnosed with ASD (95%) than typically developing children (83%) may, however, present biases when studying recurrence risk. We conclude by describing engagement and tracking methods that can be used to maximize retention in longitudinal studies of children at risk of ASD.

Effect of an Exclusive Human Milk Diet on the Gut Microbiome in Preterm Infants: A Randomized Clinical Trial.

Importance: The effect of using an exclusive human milk diet compared with one that uses bovine products in preterm infants is uncertain, but some studies demonstrate lower rates of key neonatal morbidities. A potential mediating pathway is the gut microbiome. Objective: To determine the effect of an exclusive human milk diet on gut bacterial richness, diversity, and proportions of specific taxa in preterm infants from enrollment to 34 weeks' postmenstrual age. Design, Setting, and Participants: In this randomized clinical trial conducted at 4 neonatal intensive care units in the United Kingdom from 2017 to 2020, microbiome analyses were blind to group. Infants less than 30 weeks' gestation who had only received own mother's milk were recruited before 72 hours of age. Statistical analysis was performed from July 2019 to September 2021. Interventions: Exclusive human milk diet using pasteurized human milk for any shortfall in mother's own milk supply and human milk-derived fortifiers (intervention) compared with bovine formula and bovine-derived fortifier (control) until 34 weeks' postmenstrual age. Fortifier commenced less than 48 hours of tolerating 150 mL/kg per day. Main Outcomes and Measures: Gut microbiome profile including alpha and beta diversity, and presence of specific bacterial taxa. Results: Of 126 preterm infants enrolled in the study, 63 were randomized to control (median [IQR] gestation: 27.0 weeks [26.0-28.1 weeks]; median [IQR] birthweight: 910 g [704-1054 g]; 32 [51%] male) and 63 were randomized to intervention (median [IQR] gestation: 27.1 weeks [25.7-28.1 weeks]; median [IQR] birthweight: 930 g [733-1095 g]; 38 [60%] male); 472 stool samples from 116 infants were analyzed. There were no differences in bacterial richness or Shannon diversity over time, or at 34 weeks between trial groups. The exclusive human milk diet group had reduced relative abundance of Lactobacillus after adjustment for confounders (coefficient estimate, 0.056; P = .03), but not after false discovery rate adjustment. There were no differences in time to full feeds, necrotizing enterocolitis, or other key neonatal morbidities. Conclusions and Relevance: In this randomized clinical trial in preterm infants using human milk-derived formula and/or fortifier to enable an exclusive human milk diet, there were no effects on overall measures of gut bacterial diversity but there were effects on specific bacterial taxa previously associated with human milk receipt. These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms. Trial Registration: ISRCTN trial registry identifier: ISRCTN16799022.

Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell- and CXCR3-dependent manner.

This study aimed to enhance antitumor immune responses to pancreatic cancer via Ab-based blockade of IL-6 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Mice bearing s.c. or orthotopic pancreatic tumors were treated with blocking Abs to IL­6 and/or CTLA-4. In both tumor models, dual IL-6 and CTLA-4 blockade significantly inhibited tumor growth. Additional investigations revealed that dual therapy induced an overwhelming infiltration of T cells into the tumor as well as changes in CD4+ T cell subsets. Dual blockade therapy elicited CD4+ T cells to secrete increased IFN-γ in vitro. Likewise, in vitro stimulation of pancreatic tumor cells with IFN-γ profoundly increased tumor cell production of CXCR3-specific chemokines, even in the presence of IL-6. In vivo blockade of CXCR3 prevented orthotopic tumor regression in the presence of the combination treatment, demonstrating a dependence on the CXCR3 axis for antitumor efficacy. Both CD4+ and CD8+ T cells were required for the antitumor activity of this combination therapy, as their in vivo depletion via Abs impaired outcomes. These data represent the first report to our knowledge of IL-6 and CTLA­4 blockade as a means to regress pancreatic tumors with defined operative mechanisms of efficacy.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

AIM: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. METHODS AND RESULTS: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. CONCLUSION: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.

Factors associated with the accurate self-report of cancer screening behaviors among women living in the rural Midwest region of the United States.

This study examines the accuracy of the self-report of up-to-date cancer screening behaviors (Mammography, Papanicolaou (Pap)/Human Papillomavirus (HPV) tests, Fecal Occult Blood Test (FOBT)/Fecal Immunochemical Test (FIT), Colonoscopy) compared to medical record documentation prior to eligibility determination and enrollment in a randomized controlled trial of an intervention to increase cancer screening among women living in rural counties of Indiana and Ohio. Women (n = 1,641) completed surveys and returned a medical record release form from November 2016-June 2019. We compared self-report to medical records for up-to-date cancer screening behaviors to determine the validity of self-report. Logistic regression models identified variables associated with accurate reporting. Women were up-to-date for mammography (75 %), Pap/HPV test (54 %), colonoscopy (53 %), and FOBT/FIT (6 %) by medical record. Although 39.6 % of women reported being up-to-date for all three anatomic sites (breast, cervix, and colon), only 31.8 % were up to date by medical records. Correlates of accurate reporting of up-to-date cancer screening varied by screening test. Approximately-one-third of women in rural counties in the Midwest are up-to-date for all three anatomic sites and correlates of the accurate reporting of screening varied by test. Although most investigators use medical records to verify completion of cancer screening behaviors as the primary outcome of intervention trials, they do not usually use medical records for the routine verification of study eligibility. Study results suggest that future research should use medical record documentation of cancer screening behaviors to determine eligibility for trials evaluating interventions to increase cancer screening.

Increasing breast, cervical, and colorectal cancer screening among rural women: Baseline characteristics of a randomized control trial.

BACKGROUND: Rural women suffer disproportionately from breast, cervical, and colorectal cancer mortality compared to those in urban areas. Screening behaviors for these three cancers share many similar beliefs and barriers. Unfortunately, published interventions have not attempted to simultaneously bring women up to date with screening for three cancers (breast, cervical, and colorectal) even though multiple behavior change interventions are effective. The aim of this randomized controlled study was to compare the effectiveness of a mailed interactive and tailored DVD vs. DVD plus telephonic patient navigation (DVD + PN) vs. Usual Care (UC) to increase the percentage of rural women (aged 50-74) up to date for breast, cervical, and colorectal cancer screening. METHODS: Nine hundred eighty-three participants needing one, two, or three cancer screening tests were consented and randomized to one of three groups. Prior to randomization, women were assessed for baseline characteristics including sociodemographics, health status, and cancer screening test beliefs. Screening status was assessed by medical record review. RESULTS: At baseline, the average age of participants was 58.6 years. Nineteen percent of the sample was not up to date with screenings for all three cancers. Colorectal cancer had the highest percentage of women (69%) who were not up to date with screening followed by cervical (57%) and then breast cancer (41%). Sixty percent of women reported receiving a reminder for mammography; 30%, for cervical cancer screening; 15% for colonoscopy; and 6% for FOBT/FIT. DISCUSSION: Increasing adherence to colorectal cancer screening may be the most urgent need among all screening tests. This clinical trial is registered at clinicaltrials.gov with identifier NCT02795104.

Application of the Updated WCRF/AICR Cancer Prevention Score as an Outcome for Cancer Survivors Participating in a Tailored and Intensive Dietary and Physical Activity Intervention.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has defined evidence-based guidelines for cancer prevention. These recommendations have been operationalized into a quantitative index for individual assessment. Survivors of cancer are increasingly desiring guidance for diet and lifestyle, and in the absence of research in survivors, are often instructed to follow cancer prevention and public health guidelines. In this study, we examine the utility of the quantitative updated WCRF/AICR scoring criteria to assess change among cancer survivors with overweight/obesity (OW/OB) following an intensive behavioral intervention. We applied the WCRF/AICR scoring criteria (range 0−7) to examine changes over the duration of the study by paired t-tests. Two cancer survivor cohorts with OW/OB (n = 91) completed a six-month phase II clinical trial designed to improve dietary and physical activity patterns. At enrollment and post-intervention, participants completed assessments including anthropometrics, food frequency questionnaires, and objective evaluation of physical activity. Participants improved adherence to all scored recommendations, with a significant increase in mean score from enrollment (3.22 ± 1.06) to post-intervention (4.28 ± 1.04) (p < 0.001). Mean BMI and waist circumference improved (both p < 0.001). The greatest improvements were noted for fruit and non-starchy vegetable intakes (+39%, p < 0.001); the greatest decreases were observed for processed meat consumption (−70%, p < 0.001). The updated WCRF/AICR Score can be applied to cancer survivor intervention studies and provides a tool to compare trials in regard to the baseline status of populations enrolled and the success of the intervention. Future interventions incorporating standardized assessments will help guide effective strategies to improve the health and quality of life for cancer survivors.

Caregiver Engagement During Pediatric Post-Acute Care Hospitalization.

OBJECTIVES: Caregiver engagement during acute inpatient hospitalizations has been demonstrated to provide developmental and behavioral benefits for children, decrease readmissions and length of stay, and improve caregiver confidence. Caregiver engagement has been examined in acute care settings; however, there is a gap in information regarding caregiver engagement in a pediatric post-acute care hospital (pPACH). The objective of this study was to explore caregiver engagement in a pPACH. PATIENTS AND METHODS: All patients, birth to 23 years of age, in the medical service of an independent pPACH in the Northeastern United States, January 1, 2013, through December 31, 2017, were identified. Retrospective review of electronic health records for patient demographics and caregiver engagement, identified as visit(s) and telephone call(s), was conducted. Descriptive statistics and logistic regression were used to distinguish differences and measure associations of caregiver visits and calls between demographic groups. RESULTS: The primary mode of caregiver engagement for pPACH patients (n = 614) was by visits, whereas caregiver calls were less frequent. Multivariable logistic regression analysis identified significantly greater odds of caregiver visits among patients ages 1 to 17 years, with private payer, and having a single admission, whereas lower odds of visits were identified among those <1 year or ≥18 years, with ≥2 pPACH admissions, public insurance, Child Protective Services (CPS) involvement, and African American/Black, other, and unknown race/ethnicities. CONCLUSIONS: Patients who were infants, had ≥2 admissions, had CPS involvement, and were covered under public payer experienced lower caregiver visit rates. Strategies are needed to further identify and address barriers to caregiver engagement.

Health Benefits In 2022: Premiums Remain Steady, Many Employers Report Limited Provider Networks For Behavioral Health.

In 2022 the average annual premium for family health insurance coverage was $22,463, which is similar to the $22,221 reported in 2021. On average, covered workers contributed $1,327 for single coverage and $6,106 for family coverage. Among covered workers enrolled in a plan with a general annual deductible, the average deductible for single coverage was $1,763. Almost half of large employers reported an increase from 2021 in the share of employees using mental health services. The 2022 survey asked employers about the breadth of their provider networks, especially for those using services for mental health and substance use disorders. Employers were less likely to report that their plan with the largest enrollment was very broad for mental health services than for providers overall. Fewer employers thought that their plan had a sufficient number of behavioral health providers versus primary care providers to provide timely access to enrollees.

Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants.

The development of the gut microbiome from birth plays important roles in short- and long-term health, but factors influencing preterm gut microbiome development are poorly understood. In the present study, we use metagenomic sequencing to analyse 1,431 longitudinal stool samples from 123 very preterm infants (<32 weeks' gestation) who did not develop intestinal disease or sepsis over a study period of 10 years. During the study period, one cohort had no probiotic exposure whereas two cohorts were given different probiotic products: Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) or Labinic (B. bifidum, B. longum subsp. infantis and L. acidophilus). Mothers' own milk, breast milk fortifier, antibiotics and probiotics were significantly associated with the gut microbiome, with probiotics being the most significant factor. Probiotics drove microbiome transition into different preterm gut community types (PGCTs), each enriched in a different Bifidobacterium sp. and significantly associated with increased postnatal age. Functional analyses identified stool metabolites associated with PGCTs and, in preterm-derived organoids, sterile faecal supernatants impacted intestinal, organoid monolayer, gene expression in a PGCT-specific manner. The present study identifies specific influencers of gut microbiome development in very preterm infants, some of which overlap with those impacting term infants. The results highlight the importance of strain-specific differences in probiotic products and their impact on host interactions in the preterm gut.

Short report: Experiences of Caregivers Participating in a Telehealth Evaluation of Development for Infants (TEDI).

A growing literature supports the feasibility and validity of telehealth-based assessments for autism spectrum disorder (ASD). Better understanding families' experiences is crucial for sustained use beyond the COVID-19 pandemic. This study qualitatively examines caregiver experiences with the Telehealth Evaluation of Development for Infants (TEDI) protocol to better understand benefits and challenges of telehealth-based evaluations. Caregivers (N = 32) completed an online survey following a telehealth-based evaluation with their 6-12 month-old infants. Open-ended text responses to queries about perceived benefits, challenges, and suggestions for future adaptations were coded. Most caregivers reported positive experiences with minor feedback relating to tailoring of individual needs. Responses suggest the TEDI is a feasible approach and provide guidance for components of successful telehealth evaluations more broadly.