Adverse Perinatal Outcomes Associated with Stage 1 Hypertension in Pregnancy: A Retrospective Cohort Study.

OBJECTIVE: To determine if women who newly met criteria for stage 1 hypertension in early pregnancy were at increased risk for adverse perinatal outcomes compared with normotensive women. STUDY DESIGN: We conducted a retrospective cohort study of women who had prenatal care at a single institution and subsequently delivered a live infant between December 2017 and August 2019. Women with a singleton gestation who had at least two prenatal visits prior to 20 weeks of gestation were included. We excluded women with known chronic hypertension or other major maternal illness. Two groups were identified: (1) women newly diagnosed with stage 1 hypertension before 20 weeks of gestation (blood pressure [BP]: 130-139/80-89 on at least two occasions) and (2) women with no known history of hypertension and normal BP (<130/80 mm Hg) before 20 weeks of gestation. The primary outcome was any hypertensive disorder of pregnancy; secondary outcomes were indicated preterm birth and small for gestational age. Generalized linear models were used to compare risk of adverse outcomes between the groups. RESULTS: Of the 1,630 women included in the analysis, 1,443 women were normotensive prior to 20 weeks of gestation and 187 women (11.5%) identified with stage 1 hypertension. Women with stage 1 hypertension were at significantly increased risk for any hypertensive disorder of pregnancy (adjusted risk ratio [aRR]: 1.86, 95% confidence interval [CI]: 1.12-3.04) and indicated preterm birth (aRR: 1.83, 95% CI: 1.12-3.02). Black women and obese women with stage 1 hypertension were at increased for hypertensive disorder of pregnancy compared with white women and nonobese women, respectively (aRR: 1.32, 95% CI: 1.11-1.57; aRR: 1.69, 95% CI: 1.39-2.06). CONCLUSION: These results provide insight about the prevalence of stage 1 hypertension and inform future guidelines for diagnosis and management of hypertension in pregnancy. Future research is needed to assess potential interventions to mitigate risk. KEY POINTS: · Stage 1 hypertension increased risk for hypertensive disorders of pregnancy and indicated preterm birth.. · Among women with stage 1 hypertension, risk of severe preeclampsia was 2.6 times higher than normotensive women.. · Black and obese women with stage 1 hypertension were at additional risk for adverse outcomes..

Drug antagonism and single-agent dominance result from differences in death kinetics.

Cancer treatment generally involves drugs used in combinations. Most previous work has focused on identifying and understanding synergistic drug-drug interactions; however, understanding antagonistic interactions remains an important and understudied issue. To enrich for antagonism and reveal common features of these combinations, we screened all pairwise combinations of drugs characterized as activators of regulated cell death. This network is strongly enriched for antagonism, particularly a form of antagonism that we call 'single-agent dominance'. Single-agent dominance refers to antagonisms in which a two-drug combination phenocopies one of the two agents. Dominance results from differences in cell death onset time, with dominant drugs acting earlier than their suppressed counterparts. We explored mechanisms by which parthanatotic agents dominate apoptotic agents, finding that dominance in this scenario is caused by mutually exclusive and conflicting use of Poly(ADP-ribose) polymerase 1 (PARP1). Taken together, our study reveals death kinetics as a predictive feature of antagonism, due to inhibitory crosstalk between cell death pathways.

Perinatal Mental Healthcare Needs Among Women at a Community Hospital.

OBJECTIVE: Mental health problems affect up to 20% of women during pregnancy and the postpartum period. This study aimed to describe the mental health services and resources accessed by women with perinatal mental health problems (PMH) and to identify their unmet mental health care needs and preferences for support, as well as the barriers to accessing this support. METHODS: Participants were 18 years of age or older and spoke English or French. Consent was obtained 24 hours after delivery (T0) to screen for symptoms of depression and anxiety at 2 weeks postpartum (T1) using the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder Scale (GAD-7). Women with a positive screen (EPDS ≥10 or GAD-7 ≥10) were sent informational resources and were followed-up by telephone at 4 months postpartum (T2) to determine their use of these and other resources, their unmet needs, and their preferences for other resources or services. RESULTS: Seventy-three out of 344 participants (21.2%) screened positive, of whom 57 (78%) completed the T2 interview. Of those interviewed, 28% had used the informational resources provided by the study. Although 25% had consulted a health professional for mental health care, 37% had unmet mental health care needs. Preferences for additional support included web-based resources (30%), telephone support (28%), and booklets (25%). Lack of time (38%) and lack of childcare (23%) were the main barriers to seeking help. CONCLUSIONS: Web- and telephone-based approaches have the potential to address the most common barriers to access support for women experiencing perinatal mental health problems.

Tumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells.

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor-stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses.

Postdiagnosis neurological care for patients with psychogenic nonepileptic spells (PNES).

OBJECTIVE: This study investigated continuity of neurological care for patients discharged from the epilepsy monitoring unit (EMU) with a diagnosis of psychogenic nonepileptic spells (PNES). Because PNES are seizure-like episodes that cannot be explained by abnormal electrical brain activity, they are challenging for patients to understand and accept. Consequently, after diagnosis, patients commonly fail to start recommended psychotherapy and instead pursue redundant medical care. As consistent relationships with healthcare providers may help, we instituted standard follow-up for patients diagnosed with PNES. METHODS: We performed a retrospective observational cohort study of adults diagnosed with PNES in our EMU. In November 2013, we began routine scheduling of postdischarge follow-up neurology appointments. We compared preintervention (November 2010-October 2013) and postintervention (November 2013-May 2016) cohorts with regard to clinic attendance, understanding the diagnosis, compliance with recommendations, and event frequency. RESULTS: We identified 55 patients in the preintervention cohort and 123 patients in the postintervention cohort. We successfully implemented the intended practice changes; more patients had follow-up scheduled by discharge (preintervention 2% vs. postintervention 36%, p<0.001), time to follow-up decreased (46days vs. 29, p=0.001), and providers more consistently queried understanding of diagnosis (38% vs. 67%, p=0.03). Explicit planning for continued care did not produce the anticipated patient-provider relationships, as follow-up in clinic was low (38% vs. 37%). For patients who attended clinic, the intervention did not improve establishment of psychiatric care, compliance with medication recommendations, understanding of diagnosis, or event frequency. The odds of reduced event frequency were nonsignificantly increased with understanding the diagnosis (OR 3.75, p=0.14). Recommending antiepileptic drug (AED) discontinuation was associated with increased odds of event freedom (OR 6.91, p<0.01). SIGNIFICANCE: Scheduling follow-up for patients diagnosed with PNES did not facilitate ongoing patient-provider relationships due to poor clinic attendance. As follow-up is unreliable, the inpatient visit is a critical window of opportunity for intervention.

Potential Therapeutic Targets in Obesity, Sleep Apnea, Diabetes, and Fatty Liver Disease.

Obesity and metabolic syndrome affect the majority of the US population. Patients with obesity are at increased risk of developing type 2 diabetes (T2DM), obstructive sleep apnea (OSA), and metabolic dysfunction-associated steatotic liver disease (MASLD), each of which carry the risk of further complications if left untreated and lead to adverse outcomes. The rising prevalence of obesity and its comorbidities has led to increased mortality, decreased quality of life, and rising healthcare expenditures. This phenomenon has resulted in the intensive investigation of exciting therapies for obesity over the past decade, including more treatments that are still in the pipeline. In our present report, we aim to solidify the relationships among obesity, T2DM, OSA, and MASLD through a comprehensive review of current research. We also provide an overview of the surgical and pharmacologic treatment classes that target these relationships, namely bariatric surgery, the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonists.

A pilot randomized controlled trial of a lay telephone coaching and web-based intervention for postpartum depression and anxiety: The MPOWER study.

Background: Mental health problems are frequent in the postpartum period, but accessible treatment options are lacking. The MPOWER study investigated whether the use of trained lay coaches could increase the uptake and effectiveness of a web-based intervention (WBI) for women with postpartum depression and/or anxiety. Objectives: First, to compare the feasibility and acceptability of a WBI for women with postpartum depression and anxiety, with and without the addition of telephone coaching calls. Second, to estimate the effectiveness of the WBI at decreasing symptoms of depression and anxiety at 6 months, with and without coaching calls. Methods: We conducted a pilot randomized controlled trial (RCT) that enrolled women who had recently given birth and had mild to moderate postpartum depression and/or anxiety. Study participants were provided access to the WBI. Women randomized to the intervention group also received up to 7 telephone coaching calls during the 6 months of follow up. We evaluated the feasibility of the intervention through participants' usage of the WBI, as well as the completion and fidelity of planned coach calls. We measured acceptability via two questionnaires on the usability of the WBI and participant satisfaction with the intervention. To determine the potential effectiveness of the intervention, the primary outcomes were defined as symptoms of depression and anxiety at 6 months and adjusted mean differences between groups for these outcomes were estimated using linear regression models. Results: We recruited 52 participants (25 intervention; 27 control). At 6 months, 88 % (22/25) of participants randomized to the intervention arm and 59 % (16/27) of participants randomized to the control arm remained in the study. The intervention group had an average of 11 (95 % CI: [5, 18]) more website logins than the control group. Intervention group participants completed a mean of 6.2 coaching calls with high fidelity. The estimates of the effect of the intervention on mental health outcomes at 6-months were imprecise but point estimates and confidence intervals were consistent with a moderate beneficial effect of the intervention on both symptoms of depression and anxiety (fully adjusted effects sizes: 0.51 (95 % CI: [-0.14, 1.17]) and 0.56 (95 % CI: [-0.09, 1.22]), respectively). Conclusions: WBIs with coaching are feasible, acceptable, and potentially effective treatment options for women with mild to moderate postpartum depression and/or anxiety. The addition of coaching calls markedly increased engagement with the WBI, but a larger RCT is needed to determine the effectiveness of such an intervention.

Adaptation and outcomes of a lay-guided mental health self-care model: Results of six trials.

OBJECTIVE: To synthesize results of six controlled trials of self-care interventions for depression and/or anxiety, focusing on five trials in which lay guidance was compared to self-directed use of the same self-care tools. METHODS: The trials were conducted in Canada in different target populations. Self-care tools were adapted to each population. Guidance was provided in 3-15 calls over a period of 6-26 weeks. Depression and/or anxiety were assessed at follow-up (6-26 weeks). Pooled analyses used a meta-analytic approach. Engagement with the self-care tools was compared using the standardized difference or Cohen's d effect size. RESULTS: In studies with homogeneous outcomes (three for depression, four for anxiety), the pooled effect sizes of guidance vs. self-directed use of the self-care tools were 0.36 (95% CI 0.10, 0.62, N = 235) for depression and 0.21 (95% CI -0.03, 0.44, N = 285) for anxiety. Guidance consistently led to greater engagement with the tools. CONCLUSIONS: The intervention model is a potentially sustainable and accessible alternative to professionally guided self-care for people with mild-moderate depression. Factors which may have limited implementation success include: co-interventions, reduced number of guide calls (3 vs 6 or more), and delivery to dyads (patient-caregiver).

Dread and solace: Talking about perinatal mental health.

Perinatal mental health issues are a global public health challenge. Worldwide, it is estimated that 10% of pregnant women, and 13% of women who have just given birth, experience a mental disorder. Yet, for many reasons - including stigma, limited access to services, patients' lack of awareness about symptoms, and inadequate professional intervention - actual rates of clinical and subclinical perinatal mental health issues are likely higher. Studies have explored experiences such as postpartum depression, but few involve a wider-ranging exploration of a variety of self-reported perinatal mental health issues through personal narrative. We conducted 21 narrative interviews with women, in two Canadian provinces, about their experiences of perinatal mental health issues. Our aim was to deepen understanding of how individual and cultural narratives of motherhood and perinatal mental health can be sources of shame, guilt, and suffering, but also spaces for healing and recovery. We identified four predominant themes in women's narrative: feeling like a failed mother; societal silencing of negative experiences of motherhood; coming to terms with a new sense of self; and finding solace in shared experiences. These findings are consistent with other studies that highlight the personal challenges associated with perinatal mental health issues, particularly the dread of facing societal norms of the 'good mother'. We also highlight the positive potential for healing and self-care through sharing experiences, and the power of narratives to help shape feelings of self-worth and a new identity. This study adheres to the expectations for conducting and reporting qualitative research.

Drug GRADE: An Integrated Analysis of Population Growth and Cell Death Reveals Drug-Specific and Cancer Subtype-Specific Response Profiles.

When evaluating anti-cancer drugs, two different measurements are used: relative viability, which scores an amalgam of proliferative arrest and cell death, and fractional viability, which specifically scores the degree of cell killing. We quantify relationships between drug-induced growth inhibition and cell death by counting live and dead cells using quantitative microscopy. We find that most drugs affect both proliferation and death, but in different proportions and with different relative timing. This causes a non-uniform relationship between relative and fractional response measurements. To unify these measurements, we created a data visualization and analysis platform called drug GRADE, which characterizes the degree to which death contributes to an observed drug response. GRADE captures drug- and genotype-specific responses, which are not captured using traditional pharmacometrics. This study highlights the idiosyncratic nature of drug-induced proliferative arrest and cell death. Furthermore, we provide a metric for quantitatively evaluating the relationship between these behaviors.

Creating a Multisite Perinatal Psychiatry Databank: Purpose and Development.

Mental health issues during the perinatal period are common; up to 29% of pregnant and 15% of postpartum women meet psychiatric diagnostic criteria. Despite its ubiquity, little is known about the longitudinal trajectories of perinatal psychiatric illness. This paper describes a collaboration among six perinatal mental health services in Quebec, Canada, to create an electronic databank that captures longitudinal patient data over the course of the perinatal period. The collaborating sites met to identify research interests and to select a standardized set of variables to be collected during clinical appointments. Procedures were implemented for creating a databank that serves both research and clinical purposes. The resulting databank allows pregnant and postpartum patients to complete self-report questionnaires on medical and psychosocial variables during their intake appointment in conjunction with their clinicians who fill in relevant medical information. All participants are followed until 6 months postpartum. The databank represents an opportunity to examine illness trajectories and to study rare mental disorders and the relationship between biological and psychosocial variables.