Obstacles to Accepting Care: Understanding Why Obstetric Patients Leave against Medical Advice.

INTRODUCTION: Discharge "against medical advice" (AMA) in the obstetric population is overall under-studied but disproportionally affects marginalized populations and is associated with worse perinatal outcomes. Reasons for discharges AMA are not well understood. The objective of this study is to identify the obstacles that prevent obstetric patients from accepting recommended care and highlight the structural reasons behind AMA discharges. METHODS: Electronic health records of patients admitted to antepartum, peripartum, or postpartum services between 2008 and 2018 who left "AMA" were reviewed. Progress notes from clinicians and social workers were extracted and analyzed. Reasons behind discharge were categorized using qualitative thematic analysis. RESULTS: Fifty-seven (0.12%) obstetric patients were discharged AMA. Reasons for discharge were organized into two overarching themes: extrinsic (50.9%) and intrinsic (40.4%) obstacles to accepting care. Eleven participants (19.3%) had no reason documented for their discharge. Extrinsic obstacles included childcare, familial responsibilities, and other obligations. Intrinsic obstacles included disagreement with provider regarding medical condition or plan, emotional distress, mistrust or discontent with care team, and substance use. DISCUSSION: The term "AMA" casts blame on individual patients and fails to represent the systemic barriers to staying in care. Obstetric patients were found to encounter both extrinsic and intrinsic obstacles that led them to leave AMA. Healthcare providers and institutions can implement strategies that ameliorate structural barriers. Partnering with patients to prevent discharges AMA would improve maternal and infant health and progress towards reproductive justice.

The association between postpartum depressive symptoms and contraception.

BACKGROUND: Postpartum depression affects 10% to 20% of birthing people and is associated with changes in healthcare use. Little is known about the association between postpartum depressive symptoms and choice to use contraception; however, both untreated or undertreated depression and short interpregnancy intervals pose substantial perinatal health risks. OBJECTIVE: This study aimed to evaluate whether postpartum depressive symptoms are associated with changes in decisions to use any method of contraception. STUDY DESIGN: This retrospective cohort study included birthing people who delivered between 2017 and 2022 and were referred to a collaborative care program for mental healthcare. Through this program, birthing people with mental health conditions have access to specialized perinatal mental healthcare and prospective symptom monitoring via a patient registry. Postpartum depressive symptoms are assessed via the Patient Health Questionnaire-9, and scores were stratified by severity according to clinical cutoffs. Contraceptive method choice was determined by documentation in the electronic health record and dichotomized as "none" if the participant declined all forms of contraception both at delivery and at the postpartum visit. Bivariable and multivariable analyses were performed. RESULTS: Of the 1871 participants that met the inclusion criteria, 160 (8.5%) had postpartum Patient Health Questionnaire-9 scores of >14, representing moderately severe or worse depressive symptoms, and 43 (2.3%) had severe (Patient Health Questionnaire-9 of >19) depressive symptoms. Birthing people with higher Patient Health Questionnaire-9 scores were more likely to have medical comorbidities; to have a higher body mass index; to self-identify as Black, Native Hawaiian or Pacific Islander, or Hispanic or Latina; and to have a preterm delivery and less likely to be married or nulliparous than those with Patient Health Questionnaire-9 scores of ≤14. There was no difference in any other sociodemographic or clinical characteristics. The choice to use any contraceptive method decreased with increasing depressive symptoms in bivariable and multivariable analyses, reaching statistical significance in birthing people with severe depressive symptoms (adjusted odds ratio, 2.92; 95% confidence interval, 1.46-5.84). CONCLUSION: Severe perinatal depressive symptoms are associated with a declination of any form of postpartum contraception. This finding becomes increasingly relevant as abortion access continues to be threatened across the United States, compounding the potential effect of opting not to use contraception.

The association between the COVID-19 pandemic and postpartum care provision.

BACKGROUND: The COVID-19 pandemic led to a rapid transformation in the healthcare system to mitigate viral exposure. In the perinatal context, one change included altering the prenatal visit cadence and increasing the utilization of telehealth methods. Whether this approach had inadvertent negative implications for postpartum care, including postpartum depression screening and contraceptive utilization, is unknown. OBJECTIVE: This study aimed to examine whether preventative health service utilization, including postpartum depression screening and contraceptive utilization, differed during the COVID-19 pandemic when compared with the prepandemic period. STUDY DESIGN: This retrospective cohort study included all pregnant patients who received prenatal care at 1 of 5 academic obstetrical practices and who delivered at Northwestern Memorial Hospital either before (delivery from September 1, 2018, to January 1, 2019) or during (delivery from February 1, 2020, to May 15, 2020) the COVID-19 pandemic. Completion of postpartum depression screening was assessed by reviewing standardized fields in the documentation associated with the screening in the electronic health record system. The method of contraception used was ascertained from the postpartum clinical documentation. Patients were classified as initiating long-acting reversible contraception use if they received NEXPLANON (etonogestrel implant) or an intrauterine device during the hospitalization for delivery or within 3 months following delivery. Bivariable and multivariable analyses were performed. RESULTS: Of the 2375 pregnant patients included in this study, 1120 (47%) delivered during the COVID-19 pandemic. Pregnant patients who delivered during the COVID-19 pandemic were significantly less likely to have undergone postpartum depression screening (45.5% vs 86.2%; P<.01); this association persisted after adjusting for potential confounders (adjusted odds ratio, 0.13; 95% confidence interval, 0.11-0.16). Pregnant patients who delivered during the COVID-19 pandemic also were significantly less likely to initiate long-acting reversible contraception use within 3 months of delivery (13.5% vs 19.6%; adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.84). CONCLUSION: The onset of the COVID-19 pandemic was associated with a decrease in the completion of postpartum depression screenings and fewer patients initiating long-acting reversible contraception use overall. These results can inform adaptations in healthcare delivery in the midst of the ongoing COVID-19 pandemic.

Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid Development.

Repair of DNA double-stranded breaks (DSBs) during lymphocyte development is essential for V(D)J recombination and forms the basis of immunoglobulin variable region diversity. Understanding of this process in lymphogenesis has historically been centered on the study of RAG1/2 recombinases and a set of classical non-homologous end-joining factors. Much less has been reported regarding the role of chromatin modifications on this process. Here, we show a role for the non-redundant histone H3 lysine methyltransferase, Setd2, and its modification of lysine-36 trimethylation (H3K36me3), in the processing and joining of DNA ends during V(D)J recombination. Loss leads to mis-repair of Rag-induced DNA DSBs, especially when combined with loss of Atm kinase activity. Furthermore, loss reduces immune repertoire and a severe block in lymphogenesis as well as causes post-mitotic neuronal apoptosis. Together, these studies are suggestive of an important role of Setd2/H3K36me3 in these two mammalian developmental processes that are influenced by double-stranded break repair.

Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common and debilitating form of cancer characterized by poor patient outcomes and low survival rates. In HNSCC, genetic aberrations in phosphatidylinositol 3-kinase (PI3K) and epidermal growth factor receptor (EGFR) pathway genes are common, and small molecules targeting these pathways have shown modest effects as monotherapies in patients. Whereas emerging preclinical data support the combined use of PI3K and EGFR inhibitors in HNSCC, in-human studies have displayed limited clinical success so far. Here, we examined the responses of a large panel of patient-derived HNSCC cell lines to various combinations of PI3K and EGFR inhibitors, including EGFR agents with varying specificity and mechanistic characteristics. We confirmed the efficacy of PI3K and EGFR combination therapies, observing synergy with α isoform-selective PI3K inhibitor HS-173 and irreversible EGFR/ERBB2 dual inhibitor afatinib in most models tested. Surprisingly, however, our results demonstrated only modest improvement in response to HS-173 with reversible EGFR inhibitor gefitinib. This difference in efficacy was not explained by differences in ERBB target selectivity between afatinib and gefitinib; despite effectively disrupting ERBB2 phosphorylation, the addition of ERBB2 inhibitor CP-724714 failed to enhance the effect of HS-173 gefitinib dual therapy. Accordingly, although irreversible ERBB inhibitors showed strong synergistic activity with HS-173 in our models, none of the reversible ERBB inhibitors were synergistic in our study. Therefore, our results suggest that the ERBB inhibitor mechanism of action may be critical for enhanced synergy with PI3K inhibitors in HNSCC patients and motivate further preclinical studies for ERBB and PI3K combination therapies.

Inhibition of MEK and ATR is effective in a B-cell acute lymphoblastic leukemia model driven by Mll-Af4 and activated Ras.

Infant B-cell acute lymphoblastic leukemias (B-ALLs) that harbor MLL-AF4 rearrangements are associated with a poor prognosis. One important obstacle to progress for this patient population is the lack of immunocompetent models that faithfully recapitulate the short latency and aggressiveness of this disease. Recent whole-genome sequencing of MLL-AF4 B-ALL samples revealed a high frequency of activating RAS mutations; however, single-agent targeting of downstream effectors of the RAS pathway in these mutated MLL-r B-ALLs has demonstrated limited and nondurable antileukemic effects. Here, we demonstrate that the expression of activating mutant N-Ras G12D cooperates with Mll-Af4 to generate a highly aggressive serially transplantable B-ALL in mice. We used our novel mouse model to test the sensitivity of Mll-Af4/N-Ras G12D leukemia to small molecule inhibitors and found potent and synergistic preclinical efficacy of dual targeting of the Mek and Atr pathways in mouse- and patient-derived xenografts with both mutations in vivo, suggesting this combination as an attractive therapeutic opportunity that might be used to treat patients with these mutations. Our studies indicate that this mouse model of Mll-Af4/N-Ras B-ALL is a powerful tool to explore the molecular and genetic pathogenesis of this disease subtype, as well as a preclinical discovery platform for novel therapeutic strategies.

Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients.

BACKGROUND: The past 2 decades have seen an increased incidence of head and neck squamous cell carcinoma (HNSCC) in a nontraditional, low-risk patient population (ie, ≤45 years of age, no substance use history), owing to a combination of human papillomavirus (HPV) infection and individual genetic variation. METHODS: Articles positing genetic variants as contributing factors in HNSCC incidence in low-risk, nontraditional patients were identified using a PubMed search, reviewed in detail, and concisely summarized herein. RESULTS: Recent data suggest that common polymorphisms in DNA repair enzymes, cell-cycle control proteins, apoptotic pathway members, and Fanconi anemia-associated genes likely modulate susceptibility to HNSCC development in low-risk, nontraditional patients. CONCLUSION: At present, there is a lack of robust, comprehensive data on genetic drivers of oncogenesis in low-risk patients and a clear need for further research on genetic alterations underlying the rising incidence of HNSCC in low-risk, nontraditional patients.

Integrative Medicine in Head and Neck Cancer.

Objective Complementary and alternative medicine, or integrative medicine, has become increasingly popular among patients with head and neck cancer. Despite its increasing prevalence, many patients feel uncomfortable discussing such therapies with their physicians, and many physicians are unaware and underequipped to evaluate or discuss their use with patients. The aim of this article is to use recent data to outline the decision making inherent to integrative medicine utilization among patients with head and neck cancer, to discuss the ethical implications inherent to balancing integrative and conventional approaches to treatment, and to highlight available resources to enhance head and neck cancer providers' understanding of integrative medicine. Data Sources Randomized controlled trials involving integrative medicine or complementary and alternative medicine treatment for cancer patients. Review Methods Trials were drawn from a systematic PubMed database search categorized into cancer prevention, treatment, and symptom management. Conclusions Integrative medicine is gaining popularity for the management of cancer and is most commonly used for symptom management. A number of randomized controlled trials provide data to support integrative therapies, yet physicians who treat head and neck cancer may be faced with ethical dilemmas and practical barriers surrounding incorporation of integrative medicine. Implications for Practice In the management of head and neck cancer, there is an increasing demand for awareness of, dialogue about, and research evaluating integrative medicine therapies. It is important for otolaryngologists to become aware of integrative therapy options, their risks and benefits, and resources for further information to effectively counsel their patients.