Evaluating the Effect of Maternal Opioid Maintenance Dose on the NOWS-COS Outcome Criteria: A Pilot Study.

This retrospective cohort study included 77 mother-infant dyads that delivered term pregnancies at a single tertiary care institution. The primary objective was to investigate whether maternal dose of opioid maintenance therapy during pregnancy affects infant outcomes. All infants had prenatal exposure to opioid maintenance therapies. Maternal dose was converted into morphine milligram equivalents (MMEs) and stratified into high- (MME >1000 mg) and low-dose groups (MME ≤1000 mg). Associations between infant outcomes and MME dosage were examined using Wilcoxon rank-sum and Fisher's Exact tests. Days to symptom control were significantly higher in the high MME group (5 days vs 2.8 days, P = .016). Rates of developmental delay at 24 months were higher in the high MME group (21.2% vs 4.5%, P = .0335). Maternal MME did not predict need for NOWS treatment. Higher MME-exposed infants should have optimized nonpharmacologic interventions for consolation and be increasingly observed for signs of developmental delay.

Is there a future for nitrous oxide in anaesthetic practice?

Although nitrous oxide is widely used for analgesia and anxiolysis, its use is under scrutiny because of concerns about its environmental impact and potential implications for mental health. This article discusses the advantages and disadvantages of this agent.

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 adverse childhood experiences and perinatal depression symptom trajectories.

BACKGROUND: Having a history of adverse childhood experiences is associated with an increased risk for treatment-resistant depression in the general population. Whether this relationship is true in the perinatal context is unknown. OBJECTIVE: This study aimed to examine the association between adverse childhood experiences and the trajectories of antenatal and postpartum depression among people enrolled in a perinatal collaborative care program for mental healthcare. STUDY DESIGN: This retrospective cohort study included all pregnant and postpartum people who were referred to and enrolled in a perinatal collaborative care program for mental healthcare and who delivered at a single, quaternary care institution between March 2016 and March 2021. Individuals referred to the collaborative care program were linked with a care manager and had access to evidence-based mental health treatment such as a psychiatric consult, pharmacotherapy, and psychotherapy. All individuals enrolled in the collaborative care program underwent adverse childhood experience screens at intake. A score of >3 on the validated Adverse Childhood Experiences Questionnaire was defined as a high adverse childhood experience score. Depression symptom monitoring occurred via electronic Patient Health Questionaire-9 screening every 2 to 4 weeks, and escalation of care was recommended for those without evidence of improvement. Antenatal depression trajectories were determined by comparing the earliest available prenatal Patient Health Questionaire-9 score closest to the time of referral to collaborative care with the latest Patient Health Questionaire-9 score before delivery. Postpartum trajectories were determined by comparing the earliest postpartum Patient Health Questionaire-9 score after delivery with the latest score before 12 weeks' postpartum. Depression trajectories were categorized as improved, stable, or worsened based on whether the Patient Health Questionaire-9 scores changed by at least 2 standard deviations (ie, 5 points on the Patient Health Questionaire-9 scale). Bivariable and multivariable analyses were performed. RESULTS: Of the 1270 people who met the inclusion criteria, 294 (23.1%) reported a high adverse childhood experience score. Those with a high adverse childhood experience score were more likely to experience a worsened antenatal depression trajectory than those with a low adverse childhood experience score (10.3% vs 4.3%; P=.008). This association persisted after adjusting for potential confounders (adjusted odds ratio, 2.39; 95% confidence interval, 1.05-5.46). There was no significant difference in the postpartum depression trajectories between those with a high and those with a low adverse childhood experience score. CONCLUSION: Having a high adverse childhood experience score is associated with a worsened antenatal depression trajectory for those enrolled in a collaborative care program. Given its high prevalence, future research should evaluate effective modalities of perinatal depression prevention and treatment specific for pregnant people with a history of adverse childhood experiences.

Association Between Antenatal Depression Symptom Trajectories and Preterm Birth.

OBJECTIVE: To evaluate whether, among pregnant people referred for mental health care, improvement in antenatal depression symptoms before delivery was associated with a reduction in preterm birth. METHODS: This retrospective cohort study included all pregnant people referred to a perinatal collaborative care program for mental health care who delivered between March 2016 and March 2021. Those referred to the collaborative care program had access to subspecialty mental health treatment, including psychiatric consultation, psychopharmacotherapy, and psychotherapy. Depression symptoms were monitored with the self-reported PHQ-9 (Patient Health Questionnarie-9) screens in a patient registry. Antenatal depression trajectories were determined by comparing the earliest prenatal PHQ-9 score after collaborative care referral with the score closest to delivery. Trajectories were categorized as improved, stable, or worsened according to whether PHQ-9 scores changed by at least 5 points. Bivariable analyses were performed. A propensity score was generated to control for confounders that were significantly different on bivariable analyses according to trajectories. This propensity score was then included in multivariable models. RESULTS: Of the 732 pregnant people included, 523 (71.4%) had mild or more severe depressive symptoms (PHQ-9 score 5 or higher) on their initial screen. Antenatal depression symptoms improved in 256 (35.0%), remained stable in 437 (59.7%), and worsened in 39 (5.3%); the corresponding incidence of preterm birth was 12.5%, 14.0%, and 30.8%, respectively ( P =.009). Compared with those with a worsened trajectory, pregnant people who had an improved antenatal depression symptom trajectory had a significantly decreased odds of preterm birth (adjusted odds ratio 0.37, 95% CI 0.15-0.89). CONCLUSION: Compared with worsened symptoms, an improved antenatal depression symptom trajectory is associated with decreased odds of preterm birth for pregnant people referred for mental health care. These data further underscore the public health importance of incorporating mental health care into routine obstetric care.

Sense of community and anxiety during a global pandemic: The role of world assumptions in couples.

The current study was designed to examine the role of sense of community at the outset of COVID-19 pandemic-related shutdowns as a longitudinal predictor of anxiety in couples. We also sought to investigate whether self-reported changes in perceived levels of benevolent world assumptions would serve as an indirect conveyor of this association. Data were collected at three time points during the first 6-months of pandemic shutdowns in the US and the current study utilized responses from 535 heterosexual cisgender couples. Mplus was used to path model lagged associations between sense of community at wave 1, world assumptions at waves 1 and 2 and anxiety symptoms at all three waves for both partners. Findings demonstrated direct effects within men and women with a stronger sense of community at wave 1 relating to lower anxiety at waves 2, and within women this effect extended to wave 3. Further, we found that a higher sense of community at wave 1 in men associated with perceived strengthening of benevolent world assumptions at the next wave for men and women. We noted that perceived strengthened benevolent world assumptions at wave 2 associated with lower anxiety at wave 3 within men. Indirect effects showed that a stronger sense of community at wave 1 associated with lower anxiety at wave 3 within men.

Twelve-Month Longitudinal Serology in SARS-CoV-2 Naïve and Experienced Vaccine Recipients and Unvaccinated COVID-19-Infected Individuals.

Longitudinal data comparing SARS-CoV-2 serology in individuals following infection and vaccination over 12 months are limited. This study compared the magnitude, decay, and variability in serum IgG, IgA, and neutralizing activity induced by natural infection (n = 218) or mRNA vaccination in SARS-CoV-2 naïve (n = 143) or experienced (n = 122) individuals over time using enzyme-linked immunosorbent assays and an in vitro virus neutralization assay. Serological responses were found to be highly variable after natural infection compared with vaccination but durable through 12 months. Antibody levels in vaccinated, SARS-CoV-2 naïve individuals peaked by 1 month then declined through 9 months, culminating in non-detectable SARS-CoV-2-specific serum IgA. Individuals with both infection and vaccination showed SARS-CoV-2-specific IgG and IgA levels that were more robust and slower to decline than the other groups; neutralizing activity remained highest in this group at 9 months past vaccination. These data reinforce the benefit of vaccination after SARS-CoV-2 recovery.

The association between engagement in a perinatal collaborative care program and breastfeeding among people with identified mental health conditions.

BACKGROUND: Untreated antenatal mental health conditions are associated with noninitiation and early discontinuation of breastfeeding. Whether interventions designed to optimize perinatal mental health can mitigate this association is unknown. OBJECTIVE: This study aimed to examine whether engagement of pregnant people with mental health conditions in a perinatal mental health collaborative care program was associated with differences in breastfeeding initiation and continuation and whether any observed association was mediated by changes in depressive symptoms. STUDY DESIGN: This retrospective cohort study included all pregnant people who were referred antenatally by their obstetrical clinician to a perinatal collaborative care program and who delivered viable neonates between January 2017 and June 2018. Pregnant people were dichotomized by whether they engaged in collaborative care services. Breastfeeding initiation (endorsed at delivery) and continuation at the postpartum visit were compared between individuals who did and did not engage in collaborative care using bivariable and multivariable analyses. Mediation analyses were performed to determine if any observed associations were mediated by improvements or remission in depressive symptoms. RESULTS: During the study period, 350 eligible pregnant people were referred to the perinatal collaborative care program because of an identified mental health condition. Of these people, 264 (75.4%) engaged in collaborative care. Compared with those who did not engage in collaborative care, people who engaged in collaborative care were more likely to initiate breastfeeding (168 [95%] vs 47 [87%]; P=.046) and continue breastfeeding at the postpartum visit (92 [74%] vs 20 [53%]; P=.012). These associations persisted after controlling for potential confounders (adjusted odds ratio for initiation, 3.30; 95% confidence interval, 1.09-9.98; adjusted odds ratio for continuation, 3.08; 95% confidence interval, 1.29-7.36). Neither association was mediated by improvements or remission in depressive symptoms. CONCLUSION: Although antenatal mental health conditions are a risk factor for lack of initiation or early cessation of breastfeeding, engagement in a collaborative care program was associated with improvements in both breastfeeding initiation and continuation. This association was independent of improvement in depressive symptoms, suggesting that the benefits of perinatal collaborative care may extend beyond its psychological impact.

Timing of perinatal mental health needs: data to inform policy.

BACKGROUND: The policies pertaining to perinatal healthcare should be informed by medical needs. The windows of standard obstetrical care and mandated Medicaid coverage eligibility typically end approximately 8 weeks postpartum, even though women may have perinatal health concerns, including suicidal ideation, which are identified beyond this period. OBJECTIVE: To evaluate the timing of mental health needs across the perinatal period with a focus on how frequently the initial referral and suicidal ideation occur outside of standard obstetrical care windows. STUDY DESIGN: This retrospective cohort study included all women during pregnancy or up to one year postpartum referred to a perinatal mental health collaborative care program (COMPASS) between September 2017 and September 2019. The timing of initial referral to COMPASS was identified, with women referred postpartum categorized by whether the referral was made after 8 weeks postpartum. The characteristics of the women were compared according to the timing of the initial mental health referral with receiver operating characteristic curves to identify whether patient characteristics could accurately classify women whose initial mental health needs were not recognized until after 8 weeks postpartum. Similarly, the assessment of suicidal ideation, either at or after referral, was ascertained, with the evaluation of the timing at which suicidal ideation was first expressed. RESULTS: Of 1421 women referred for mental healthcare during the study period, 774 (54%) were initially referred antenatally and 647 (46%) were initially referred postpartum. The women who were referred antenatally exhibited no clustering in the timing of referral. Of the women referred postpartum, 203 (31%) were referred after 8 weeks postpartum. Sociodemographic and medical characteristics were unable to accurately classify which women were referred for mental health care after 8 weeks postpartum (area under the curve, 0.64; 95% confidence interval, 0.58-0.68). A total of 215 (16%) women reported suicidal ideation at or after the time of initial referral: 129 (17%) antenatally and 86 (14%) postpartum. The incidence of suicidal ideation was not significantly different before vs 8 weeks postpartum. CONCLUSION: Perinatal mental health needs, including suicidal ideation, are often first recognized beyond 8 weeks postpartum. These data should be taken into consideration in policymaking discussions pertaining to the approach to medical care continuity and postpartum healthcare coverage.

Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients.

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels. Influenza disease correlates with increases in IL-6/IL-8/MIP-1α/ß cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells correlates with peak antibody-secreting cells and influenza heamaglutinin-specific memory B-cell numbers, which phenotypically differs from vaccination-induced B-cell responses. Numbers of influenza-specific CD8+ or CD4+ T cells increase early in disease and retain an activated phenotype during patient recovery. We report the characterisation of immune cellular networks underlying recovery from influenza infection which are highly relevant to other infectious diseases.

Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil.

After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility between 2002 and 2019, which could explain the synchronous decline of dengue in the country, partially as a result of protective immunity from prior ZIKV and/or DENV infections. Furthermore, we performed phylogeographic analyses using 69 newly sequenced genomes of dengue virus serotype 1 and 2 from Brazil, and found that the outbreaks in 2018-2019 were caused by local DENV lineages that persisted for 5-10 years, circulating cryptically before and after the Zika epidemic. We hypothesize that DENV lineages may circulate at low transmission levels for many years, until local conditions are suitable for higher transmission, when they cause major outbreaks.

Delivery room cuddles for extremely preterm babies and parents: concept, practice, safety, parental feedback.

AIM: Following extreme preterm birth, there has traditionally been felt an imperative to rush baby to the neonatal unit for ongoing intensive care. Immediate needs of parents to bond with their babies through direct early physical contact have often been overlooked; many weeks can pass before parents get to hold their babies for the first time. Recognition of the importance of early contact is growing. We aimed to review the safety and value of routinely practising delivery room cuddles for extremely preterm babies. METHODS: We reviewed delivery room cuddles in babies born <27 weeks' gestation in our centre between 2006 and 2017 via case-control. We also conducted a questionnaire survey of mothers who experienced a delivery room cuddle to gain their feedback and perspectives. RESULTS: We found no difference in age or temperatures on neonatal unit admission. There was no case of inadvertent extubation associated with cuddles. Parental feedback was very positive. CONCLUSION: With appropriate safeguards, delivery room cuddles are feasible and achievable for extremely preterm babies irrespective of birth gestation. Facilitation of the cuddle is an early and very important family-centred care practice which seems much appreciated by parents and which may improve bonding, lactation, and maternal mental health.

Tumor-intrinsic and -extrinsic determinants of response to blinatumomab in adults with B-ALL.

Blinatumomab, a bispecific antibody that directs CD3+ T cells to CD19+ tumor cells, shows variable efficacy in B-progenitor acute lymphoblastic leukemia (B-ALL). To determine tumor-intrinsic and -extrinsic determinants of response, we studied 44 adults with relapsed or refractory B-ALL (including 2 minimal residual disease positive) treated with blinatumomab using bulk tumor and single-cell sequencing. The overall response rate in patients with hematological disease was 55%, with a high response rate in those with CRLF2-rearranged Philadelphia chromosome-like ALL (12 [75%] of 16). Pretreatment samples of responders exhibited a tumor-intrinsic transcriptomic signature of heightened immune response. Multiple mechanisms resulted in loss of CD19 expression, including CD19 mutations, CD19-mutant allele-specific expression, low CD19 RNA expression, and mutations in CD19 signaling complex member CD81. Patients with low hypodiploid ALL were prone to CD19- relapse resulting from aneuploidy-mediated loss of the nonmutated CD19 allele. Increased expression of a CD19 isoform with intraexonic splicing of exon 2, CD19 ex2part, at baseline or during therapy was associated with treatment failure. These analyses demonstrate both tumor-intrinsic and -extrinsic factors influence blinatumomab response. We show that CD19 mutations are commonly detected in CD19- relapse during blinatumomab treatment. Identification of the CD19 ex2part splice variant represents a new biomarker predictive of blinatumomab therapy failure.

Fifteen-minute consultation: The EATERS method for the diagnosis of food allergies.

The EATERS mnemonic is a novel method for taking an allergy focused clinical history. It provides a degree of certainty for diagnosing food allergy and can be used in both IgE and non IgE mediated reactions. EATERS will allow health care professionals to use their existing clinical skills to interpret the history of an allergic reaction, and by doing so will help to make sense of allergy test results.

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates.

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a-/- zebrafish mutant, pinotage (pnt tq209 ), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1-/- mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development.

Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.

Background: Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods: The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. Results: In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. Conclusions: rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

16S rRNA survey revealed complex bacterial communities and evidence of bacterial interference on human adenoids.

Adenoid microbiota plays an important role in the development of various infectious and non-infectious diseases of the upper airways, such as otitis media, adenotonsillitis, rhinosinusitis and adenoid hypertrophy. Studies have suggested that adenoids could act as a potential reservoir of opportunistic pathogens. However, previous bacterial surveys of adenoids were mainly culture based and therefore might only provide an incomplete and potentially biased assessment of the microbial diversity. To develop an in-depth and comprehensive understanding of the adenoid microbial communities and test the 'pathogen reservoir hypothesis', we carried out a 16S rRNA based, culture-independent survey of bacterial communities on 67 human adenoids removed by surgery. Our survey revealed highly diverse adenoid bacterial communities distinct from those of other body habitats. Despite large interpersonal variations, adenoid microbiota shared a core set of taxa and can be classified into at least five major types based on its bacterial species composition. Our results support the 'pathogen reservoir hypothesis' as we found common pathogens of otitis media to be both prevalent and abundant. Co-occurrence analyses revealed evidence consistent with the bacterial interference theory in that multiple common pathogens showed 'non-coexistence' relationships with non-pathogenic members of the commensal microflora.