Citations

Introduction: Pregnancy can be a complex and risk filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods: The GRADE process was used when sufficient published data were available and the RAND process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results: The topics were divided into 10 categories with 34 GRADE recommendations and 35 Consensus statements. Discussion: Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.

Objective: Analyzing textbook outcome (TO) following rectal cancer resection and its association with long-term survival when compared to hospital case volume alone. Background: TO is a quality metric representing the ideal result following complex cancer surgery. Prior studies have suggested improved long-term survival for rectal cancer patients undergoing surgery at HV institutions. Methods: Patients undergoing surgery for rectal adenocarcinoma from 2014 to 2015 were identified using the National Cancer Database. Low (LV), medium (MV), and high-volume (HV) hospital strata were defined by quartile cutoffs (low <25th, high >75th, and 25–75th medium volume). TO was achieved with adequate lymph node count (≥12), negative margins (R0 resection), length of stay <75th percentile, absence of 30-day readmission/mortality event, and appropriate plus timely systemic therapy. Adjusted analyses for long-term survival were performed using a hierarchical multivariable Cox regression model. Results: TO was achieved in 28.5% of 48,484 patients. LV or MV hospital patients were more likely to be older, uninsured/Medicaid, and less likely to achieve a TO (HV 31.2% vs MV 29.6% vs LV 23.2%, P < 0.001). TO was associated with improved 5-year survival (84.0% vs 72.0%, P < 0.001). On multivariable analyses, TO was the strongest protective factor against mortality (HR 0.60, 95% confidence interval = 0.56–0.64), even after controlling for case volume. Conclusions: Only 28.5% of patients undergoing resection for rectal cancer achieve TO. However, they had a 40% reduction in long-term mortality independent of hospital volume. Optimizing long-term survival in patients with rectal cancer can be achieved by TO criteria rather than increasing surgical case volume.

Opioids are often prescribed to children for pain relief related to procedures, acute injuries, and chronic conditions. Around-the-clock dosing of opioids can produce physiologic opioid dependence within 5 days. According to a 2001 consensus paper from the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, dependence is defined as “a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, or administration of an antagonist.” The experience of children undergoing iatrogenic withdrawal symptoms is variable and may be mild and go unreported or can be severe and even life threatening. Guidance on opioid withdrawal is available only for adults and primarily for adults with substance use disorders. This report will summarize existing literature and provide readers with information on how to screen for symptoms of iatrogenic opioid withdrawal as well as mechanisms for opioid withdrawal prevention.

Abstract Objectives Evaluation of differences in the intestinal microbiome and resistome among high-risk patients (i.e. intensive care, oncology, transplant recipients) who are and are not colonized with carbapenem-resistant Enterobacterales (CRE). Methods One hundred and twelve rectal swabs were obtained from 85 patients with known CRE colonization status and cohorted. Long-read metagenomic next-generation sequencing (mNGS) was performed on rectal swabs. Microbiome and resistome analysis were performed by assessing α-diversity, β-diversity, relative abundance assessment and linear discriminant analysis effect size (LEfSe), comparing patients colonized (CRE positive) and not colonized (CRE negative) with CRE. Longitudinal analysis of sequential swabs collected over multiple hospital encounters on a subset of patients was performed at the patient level. Results The microbiomes of cohorts were similar when comparing α- and β-diversity measures and relative abundance. LEfSe analysis identified Gram-negative pathobionts enriched among CRE-positive samples and Gram-positive taxa enriched among CRE-negative samples. α-Diversity of the resistome differed at class, gene and allele levels. Relative abundance and LEfSe analysis demonstrated enrichment of genes conferring β-lactam resistance among CRE-positive patients; LEfSe also demonstrated enrichment of antimicrobial resistance genes to multiple antimicrobial classes. At the patient level, fluctuations in the microbiome and resistome among longitudinally collected swabs were associated with antibiotic exposure. Conclusions Differences between the microbiomes of CRE-positive- and CRE-negative-colonized patients at the cohort level were relatively muted, whereas statistically significant differences were observed among their resistomes. In patients followed longitudinally, shifts in microbiome and resistome composition were dramatic in between encounters and antibiotic exposures.

ABSTRACT Objective To evaluate the long‐term safety and clinical effect of INO‐3107 immunotherapy in adults with recurrent respiratory papillomatosis (RRP). Methods RRP‐002 was a retrospective, observational extension study that followed patients enrolled in the 52‐week RRP‐001 study. Patients with moderate to severe juvenile or adult‐onset RRP who had undergone ≥ 2 surgical interventions in the year preceding dosing were eligible for enrollment in RRP‐001. Participants underwent surgical debulking within 14 days prior to initial dosing and then received INO‐3107 on Day 0, Weeks 3, 6, and 9. Efficacy assessments during RRP‐002 follow‐up were the frequency of surgical interventions and alternative medication use. The safety evaluation included reported serious adverse events (SAEs). Results Twenty‐eight (28) of 32 participants from the 52‐week RRP‐001 study were enrolled in RRP‐002. The median follow‐up time for RRP‐002 was 1.8 years (range: 1.2–2.4 years) for a total median assessment time of 2.8 years (range: 1.0–3.5 years). There were no SAEs or long‐term safety concerns identified. The mean number of surgeries was reduced from 4.1 in the pre‐treatment period to 1.7 in the first year post‐INO‐3107 treatment (Year 1) to 0.9 in the second year (Year 2). The complete response rate (0 surgeries per year) increased from 28% (9/32) in Year 1 to 50% (14/28) in Year 2. Conclusion INO‐3107 is well tolerated and provides a continued clinical effect against HPV‐6 and 11 RRP that results in further reduction of the surgical burden observed in Year 1. These data support the role of INO‐3107 immunotherapy for adult patients with RRP. Level of Evidence: III.

Pharmacogenomics (PGx) has the potential to improve prescribing practices. In 2012, our institution developed a multidisciplinary program to implement PGx-CDS to support the clinical practice. CDS has been implemented for 45 drug-gene interactions, in 42,000 patients with PGx tests results, and in 2023, approximately 9281 CDS interventions have triggered at the time of prescribing. The program has been successful.

Background Percutaneous left atrial appendage occlusion (LAAO) is an alternative to long‐term anticoagulation for preventing ischemic stroke in patients with atrial fibrillation. There are limited long‐term outcomes data for “real‐world” patients undergoing LAAO. Methods We performed a retrospective cohort study using the National Cardiovascular Data Registry LAAO registry from January 1, 2016, through December 31, 2019. We linked LAAO data to inpatient Medicare fee‐for‐service claims data using probabilistic matching to establish a cohort of patients 65 years and older undergoing LAAO with a WATCHMAN device. The primary outcomes were any stroke and all‐cause mortality. Results A total of 34 975 patients with a mean±SD CHA 2 DS 2 ‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) score of 4.7±1.4 were included. The median follow‐up was 2.8 years (interquartile range, 2.2–3.7 years). The cumulative incidence of any stroke was 1.57 per 100 person‐years (95% CI, 1.45–1.70), with a 1‐year and 5‐year any stroke estimate of 1.70% (95% CI, 1.57–1.84%) and 5.70% (95% CI, 5.37–6.05%), respectively. The cumulative incidence of ischemic stroke was 1.36 per 100 person‐years (95% CI, 1.25–1.48), with a 1‐year and 5‐year ischemic stroke estimate of 1.42% (95% CI, 1.30–1.54%) and 5.03% (95% CI, 4.71–5.36%), respectively. The cumulative incidence of death was 10.82 per 100 person‐years (95% CI, 10.49–11.13), with a 5‐year mortality estimate of 44.34% (95% CI, 43.35–45.23%). Conclusions Long‐term stroke rates in a large nationally representative cohort of Medicare patients following LAAO were low and durably consistent during long‐term follow‐up despite a high thromboembolic risk. High mortality rates in this elderly population underscore the importance of incorporating patient values and preferences when considering LAAO.

Health problems associated with post-acute COVID-19, also known as “Long COVID,” range from mild to severe. The best defense against this potentially serious condition is to prevent COVID-19 infection and reinfection. The same preventive measures for COVID-19 may be used to help prevent the spread of Long COVID. This study used the Health Belief Model (HBM) to examine whether and how public understanding and awareness of Long COVID and its prevention shape the adoption of COVID-19 preventive behaviors. N = 605 English-speaking U.S.-based adults were recruited via Qualtrics. Predictors of intention to carry out COVID-19 preventive behaviors were investigated. Outcomes included behaviors relevant to preventing both acute and Long COVID. Across all models, except the one examining intent to get a vaccine booster, Black respondents were more likely than White respondents to express intent to carry out COVID-19 preventive behaviors. In addition, HBM constructs added significantly to the regression models. Susceptibility to Long COVID was significant for all behavioral outcomes (all p s < .05), self-efficacy for wearing a mask ( p < .001), and self-efficacy for testing for COVID-19 after exposure and before a social event ( p s < .001). In addition, perceived benefits for Long COVID prevention predicted intent of mask-wearing ( p < .001), testing before a social event ( p = .002), and getting a vaccine booster ( p = .001). Perceived severity of Long COVID did not significantly predict adherence to preventive behaviors. U.S. adults are more likely to express intent to carry out COVID-19 preventive behaviors, such as masking and receiving booster vaccines, when they report feeling greater susceptibility to Long COVID as well as greater self-efficacy for engaging in these preventive behaviors. Public health messaging about Long COVID with incorporation of HBM constructs may be an effective means of increasing continued recommended COVID-19 preventive behaviors, which also hold co-benefits for prevention of infections, such as influenza and measles, as well as emerging viruses such as avian flu.

Menstrual irregularities and abnormal uterine bleeding have been increasingly reported following severe acute respiratory syndrome coronavirus 2 infection, likely due to viral-induced endocrine disruption and immune dysregulation. A woman in her late 30s, with previously regular menses, developed persistent abnormal uterine bleeding after recovering from coronavirus disease 2019. Lab work-up over the next 2 years demonstrated high follicle-stimulating hormone, low anti-Müllerian hormone, low estrogen, and borderline antinuclear antibody titers. A pelvic ultrasound showed low antral follicle count, and she had challenges with fertility preservation. The patient was suspected of having an exaggerated immune reaction to severe acute respiratory syndrome coronavirus 2 infection with her strong family history of autoimmune disease and borderline antinuclear antibody, which may have led to an autoimmune-induced premature ovarian insufficiency. This case highlights the need to recognize post-viral menstrual irregularities and endocrine dysfunction as a potential consequence of coronavirus disease 2019. Clinicians should consider postinfectious endocrine disturbances in patients with new-onset abnormal uterine bleeding or infertility and evaluate for immune-mediated mechanisms when appropriate. Further research is needed to elucidate the long-term impact of coronavirus disease 2019 on reproductive health.