Gestational Weight Gain and Neonatal Biometry during the COVID-19 Pandemic: A Multicenter Observational Cohort.

OBJECTIVE: This study aimed to test the hypothesis that being pregnant and delivering during the coronavirus disease 2019 (COVID-19) pandemic was associated with changes in gestational weight gain (GWG) or frequency of small- (SGA) or large-for-gestational-age (LGA) neonates. STUDY DESIGN: Secondary analysis of a multicenter observational cohort comparing pregnant people who delivered during the COVID-19 pandemic (June-December 2020) to people who delivered prior to the pandemic (March-December 2019). Those with multiple gestations, fetuses with major congenital anomalies, implausible GWG values, unavailable body mass index (BMI), or who were severe acute respiratory syndrome coronavirus-2-positive were excluded. The primary outcome was frequency of optimal recommended GWG based on prepregnancy BMI. Neonatal outcomes included birth weight, ponderal index, and frequency of SGA, LGA, and small head circumference for live births. Multivariable regression analysis was used to assess associations between exposure to the pandemic and outcomes. RESULTS: A total of 10,717 pregnant people were included in our analysis. A total of 4,225 pregnant people were exposed to the pandemic and 6,492 pregnant people delivered prior to the COVID-19 pandemic. Pregnant people exposed to the pandemic were older and more likely to have gestational diabetes. The frequency of appropriate GWG was 28.0% during the pandemic and 27.6% before the pandemic (adjusted odds ratio [aOR]: 1.02, 95% confidence interval [CI]: 0.93-1.11). Excessive GWG was more likely (54.9 vs. 53.1%; aOR: 1.08, 95% CI: 1.001-1.17), and inadequate GWG was less likely during the pandemic (17.0 vs. 19.3%; aOR: 0.86, 95% CI: 0.77-0.95). The frequency of SGA was 5.4% during the pandemic and 6.1% before the pandemic (aOR: 0.90, 95% CI: 0.76-1.06), and the frequency of LGA was 16.0% during the pandemic versus 15.0% before the pandemic (aOR: 1.06, 95% CI: 0.95-1.18). Other neonatal outcomes including birth weight percentile (62.1 [35.8-83.2] vs. 60.2 [34.4-82.2]; adjusted mean difference (aMD) = 1.50, 95% CI: -0.28 to 3.29), ponderal index (2.6 g/cm3 [2.4-2.8] in both groups; aMD = 0.01, 95% CI: 0.00-0.02), and small head circumference for livebirths (<10th percentile [8.2 vs. 8.1%; aOR: 1.03, 95% CI: 0.89-1.19], <3rd percentile [3.5 vs. 3.1%; aOR: 1.16, 95% CI: 0.93-1.44]) were similar between groups as well. CONCLUSION: Being pregnant and delivering during the COVID-19 pandemic was associated with a higher likelihood of excessive GWG and a lower likelihood of inadequate GWG. KEY POINTS: · Delivering during the COVID-19 pandemic was associated with higher likelihood of excessive GWG.. · Delivering during the COVID-19 pandemic was associated with lower likelihood of inadequate GWG.. · COVID-19 pandemic was not associated with changes in frequency of SGA or LGA..

Implications of labour market disruptions on subjective wellbeing during the COVID-19 pandemic in MENA countries.

COVID-19 has caused a global health crisis and severe economic and social consequences. Unprecedented economic disruption and high unemployment are the pronounced impacts of the pandemic. The current study is primarily concerned with the effects of COVID-19-induced labour market outcomes on workers' subjective wellbeing in four MENA countries using the Combined COVID-19 MENA Monitor Household Survey. The study documented that COVID-19-induced labour market changes negatively affected workers' subjective wellbeing after controlling for work characteristics, risks, social distancing, and socio-demographic variables. Job loss, income reduction, and wage delay were the most significant labour changes that deteriorated workers' subjective wellbeing. Our findings underscore the need for policy responses that reduce workers' vulnerability and sustain their livelihoods. Mental health services and income support policies are important tools to enhance subjective wellbeing of economically affected workers.

Linezolid Population Pharmacokinetic Model in Plasma and Cerebrospinal Fluid Among Patients With Tuberculosis Meningitis.

BACKGROUND: Linezolid is evaluated in novel treatment regimens for tuberculous meningitis (TBM). Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF), as well as, following its co-administration with high-dose rifampicin. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM. METHODS: In the LASER-TBM pharmacokinetic substudy, the intervention groups received high-dose rifampicin (35 mg/kg) plus 1200 mg/day of linezolid for 28 days, which was then reduced to 600 mg/day. Plasma sampling was done on day 3 (intensive) and day 28 (sparse). A lumbar CSF sample was obtained on both visits. RESULTS: Thirty participants contributed 247 plasma and 28 CSF observations. Their median age and weight were 40 years (range, 27-56) and 58 kg (range, 30-96). Plasma pharmacokinetics was described by a 1-compartment model with first-order absorption and saturable elimination. Maximal clearance was 7.25 L/h, and the Michaelis-Menten constant was 27.2 mg/L. Rifampicin cotreatment duration did not affect linezolid pharmacokinetics. CSF-plasma partitioning correlated with CSF total protein up to 1.2 g/L, where the partition coefficient reached a maximal value of 37%. The plasma-CSF equilibration half-life was ∼3.5 hours. CONCLUSIONS: Linezolid was readily detected in CSF despite high-dose rifampicin coadministration. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults. Clinical Trials Registration. ClinicalTrials.gov (NCT03927313).

Deep Learning-Based Prediction of Alzheimer's Disease Using Microarray Gene Expression Data.

Alzheimer's disease is a genetically complex disorder, and microarray technology provides valuable insights into it. However, the high dimensionality of microarray datasets and small sample sizes pose challenges. Gene selection techniques have emerged as a promising solution to this challenge, potentially revolutionizing AD diagnosis. The study aims to investigate deep learning techniques, specifically neural networks, in predicting Alzheimer's disease using microarray gene expression data. The goal is to develop a reliable predictive model for early detection and diagnosis, potentially improving patient care and intervention strategies. This study employed gene selection techniques, including Singular Value Decomposition (SVD) and Principal Component Analysis (PCA), to pinpoint pertinent genes within microarray datasets. Leveraging deep learning principles, we harnessed a Convolutional Neural Network (CNN) as our classifier for Alzheimer's disease (AD) prediction. Our approach involved the utilization of a seven-layer CNN with diverse configurations to process the dataset. Empirical outcomes on the AD dataset underscored the effectiveness of the PCA-CNN model, yielding an accuracy of 96.60% and a loss of 0.3503. Likewise, the SVD-CNN model showcased remarkable accuracy, attaining 97.08% and a loss of 0.2466. These results accentuate the potential of our method for gene dimension reduction and classification accuracy enhancement by selecting a subset of pertinent genes. Integrating gene selection methodologies with deep learning architectures presents a promising framework for elevating AD prediction and promoting precision medicine in neurodegenerative disorders. Ongoing research endeavors aim to generalize this approach for diverse applications, explore alternative gene selection techniques, and investigate a variety of deep learning architectures.

Optimizing dosing of the cycloserine pro-drug terizidone in children with rifampicin-resistant tuberculosis.

There are no pharmacokinetic data in children on terizidone, a pro-drug of cycloserine and a World Health Organization (WHO)-recommended group B drug for rifampicin-resistant tuberculosis (RR-TB) treatment. We collected pharmacokinetic data in children <15 years routinely receiving 15-20 mg/kg of daily terizidone for RR-TB treatment. We developed a population pharmacokinetic model of cycloserine assuming a 2-to-1 molecular ratio between terizidone and cycloserine. We included 107 children with median (interquartile range) age and weight of 3.33 (1.55, 5.07) years and 13.0 (10.1, 17.0) kg, respectively. The pharmacokinetics of cycloserine was described with a one-compartment model with first-order elimination and parallel transit compartment absorption. Allometric scaling using fat-free mass best accounted for the effect of body size, and clearance displayed maturation with age. The clearance in a typical 13 kg child was estimated at 0.474 L/h. The mean absorption transit time when capsules were opened and administered as powder was significantly faster compared to when capsules were swallowed whole (10.1 vs 72.6 min) but with no effect on bioavailability. Lower bioavailability (-16%) was observed in children with weight-for-age z-score below -2. Compared to adults given 500 mg daily terizidone, 2022 WHO-recommended pediatric doses result in lower exposures in weight bands 3-10 kg and 36-46 kg. We developed a population pharmacokinetic model in children for cycloserine dosed as terizidone and characterized the effects of body size, age, formulation manipulation, and underweight-for-age. With current terizidone dosing, pediatric cycloserine exposures are lower than adult values for several weight groups. New optimized dosing is suggested for prospective evaluation.

Association between Individual versus Community-level Social Vulnerability and Neonatal Opioid Withdrawal Syndrome among Pregnant Individuals Receiving Buprenorphine for Opioid Use Disorder.

OBJECTIVE: Individual patient-level measures of adverse social determinants of health are associated with neonatal opioid withdrawal syndrome (NOWS), but the relative impact of community-level adverse social determinants of health remains to be defined. We examined the association between community-level social vulnerability and NOWS among pregnant individuals receiving buprenorphine for opioid use disorder. STUDY DESIGN: We conducted a secondary analysis of an established cohort of pregnant individuals and their infants participating in a multidisciplinary prenatal/addiction care program from 2013 to 2021. Addresses were geocoded using ArcGIS and linked at the census tract to the Centers for Disease Control and Prevention 2018 Social Vulnerability Index (SVI), incorporating 15 census variables. The primary exposure was the SVI as a composite measure of community-level social vulnerability, and secondarily, individual scores for four thematic domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation). The primary outcome was a clinical diagnosis of NOWS defined as withdrawal requiring pharmacological treatment following buprenorphine exposure. RESULTS: Among 703 pregnant individuals receiving buprenorphine, 39.8% (280/703) of infants were diagnosed with NOWS. Among our patinets, those who were nulliparous, had post-traumatic stress disorder, a term birth (≥ 37 weeks) and had a male infant were more likely to have an infant diagnosed with NOWS. Individuals with and without an infant diagnosed with NOWS had similarly high community-level social vulnerability per composite SVI scores (mean [standard deviation]: 0.6 [0.4-0.7] vs. 0.6 [0.4-0.7], p = 0.2]. In adjusted analyses, SVI, as a composite measure as well as the four domains, was not associated with NOWS diagnosis. CONCLUSION: Among pregnant persons receiving buprenorphine enrolled in a multidisciplinary prenatal and addition care program, while individual risk factors that measure adverse social determinants of health were associated with an NOWS diagnosis in the infant, community-level social vulnerability as measured by the SVI was not associated with the outcome. KEY POINTS: · Community-level SVI was not associated with neonatal opioid use disorder.. · Certain individual risk factors were identified as being associated with NOWS.. · Homogeneity of composite SVI scores may have led to lack of significant findings..

The Utilization of Animals as Models for Human Autopsies in Medical Education, Supported by Peer-Assisted Tutoring.

Background: Human autopsy is widely used to investigate and confirm the causes of death. Commonly reported cases involve the cardiovascular and cerebral systems. However, human autopsy practices have been restricted due to ethical and religious implications in many countries. Aim: The study aims to know if using human autopsy techniques on animal models might be an effective way for teaching post-mortem autopsy to medical students and exposing them to clinical pathology involving vital organs in medical education and find out the role of peer-assisted learning in improving the process. Methods: Two pre-lab sessions were conducted to emphasize the embryological and structural similarities and explain the differences between the human brain and heart and animal models: cow brain and sheep heart. Other two sessions of organ dissection were provided to perform human autopsy techniques on animal models practically for educational purposes. Peer-assisted tutoring was implemented. Questionnaires, interviews, and the Delphi technique were used to triangulate the assessment. A year later, participating foreign exchange students were interviewed to evaluate the long-term impacts based on Kirkpatrick models. Results: The questionnaire showed students' satisfaction with the autopsy workshops and peer-assisted tutoring. The last session was attended by foreign exchange students whose feedback proves the implementation can be done in different medical education systems around the globe. Conclusion: This study shows that animal model autopsy provides a valuable alternative in medical education and improves the students' comprehension and clinical skills, and peer-assisted learning has a secondary role in enhancing it. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01735-w.

Placenta Accreta Spectrum and Postpartum Hemorrhage.

Placenta accreta spectrum is a group of disorders involving abnormal trophoblastic invasion to the deep layers of endometrium and myometrium. Placenta accrete spectrum is one of the major causes of severe maternal morbidity, with increasing incidence in the past decade mainly secondary to an increase in cesarean deliveries. Severity varies depending on the depth of invasion, with the most severe form, known as percreta, invading uterine serosa or surrounding pelvic organs. Diagnosis is usually achieved by ultrasound, and MRI is sometimes used to assess invasion. Management usually involves a hysterectomy at the time of delivery. Other strategies include delayed hysterectomy or expectant management.

Linezolid population pharmacokinetic model in plasma and cerebrospinal fluid among patients with tuberculosis meningitis.

Background: Linezolid is being evaluated in novel treatment regimens for tuberculous meningitis (TBM). The pharmacokinetics of linezolid have not been characterized in this population, particularly in cerebrospinal fluid (CSF) where exposures may be affected by changes in protein concentration and rifampicin co-administration. Methods: This was a sub-study of a phase 2 clinical trial of intensified antibiotic therapy for adults with HIV-associated TBM. Participants in the intervention groups received high-dose rifampicin (35 mg/kg) plus linezolid 1200 mg daily for 28 days followed by 600 mg daily until day 56. Plasma was intensively sampled, and lumbar CSF was collected at a single timepoint in a randomly allocated sampling window, within 3 days after enrolment. Sparse plasma and CSF samples were also obtained on day 28. Linezolid concentrations were analyzed using non-linear mixed effects modelling. Results: 30 participants contributed 247 plasma and 28 CSF linezolid observations. Plasma PK was best described by a one-compartment model with first-order absorption and saturable elimination. The typical value of maximal clearance was 7.25 L/h. Duration of rifampicin co-treatment (compared on day 3 versus day 28) did not affect linezolid pharmacokinetics. Partitioning between plasma and CSF correlated with CSF total protein concentration up to 1.2 g/L where the partition coefficient reached a maximal value of 37%. The equilibration half-life between plasma and CSF was estimated at ∻3.5 hours. Conclusion: Linezolid was readily detected in CSF despite co-administration of the potent inducer rifampicin at high doses. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults.

Association between Diabetes in Pregnancy and Shoulder Dystocia by Infant Birth Weight in an Era of Cesarean Delivery for Suspected Macrosomia.

OBJECTIVE: We estimated the association between diabetes and shoulder dystocia by infant birth weight subgroups (<4,000, 4,000-4,500, and >4,500 g) in an era of prophylactic cesarean delivery for suspected macrosomia. STUDY DESIGN: A secondary analysis from the National Institute of Child Health and Human Development U.S. Consortium for Safe Labor of deliveries at ≥24 weeks with a nonanomalous, singleton fetus with vertex presentation undergoing a trial of labor. The exposure was either pregestational or gestational diabetes compared with no diabetes. The primary outcome was shoulder dystocia and secondarily, birth trauma with a shoulder dystocia. We calculated adjusted risk ratios (aRRs) with modified Poison's regression between diabetes and shoulder dystocia and the number needed to treat (NNT) to prevent a shoulder dystocia with cesarean delivery. RESULTS: Among 167,589 assessed deliveries (6% with diabetes), pregnant individuals with diabetes had a higher risk of shoulder dystocia at birth weight <4,000 g (aRR: 1.95; 95% confidence interval [CI]: 1.66-2.31) and 4,000 to 4,500 g (aRR: 1.57; 95% CI: 1.24-1.99), albeit not significantly at birth weight >4,500 g (aRR: 1.26; 95% CI: 0.87-1.82) versus those without diabetes. The risk of birth trauma with shoulder dystocia was higher with diabetes (aRR: 2.29; 95% CI: 1.54-3.45). The NNT to prevent a shoulder dystocia with diabetes was 11 and 6 at ≥4,000 and >4,500 g, versus without diabetes, 17 and 8 at ≥4,000 and >4,500 g, respectively. CONCLUSION: Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered. Guidelines providing the option of cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights. KEY POINTS: · >Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered.. · Cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights.. · These findings can inform delivery planning for providers and pregnant individuals with diabetes..

Population Pharmacokinetic Analysis of Rifampicin in Plasma, Cerebrospinal Fluid, and Brain Extracellular Fluid in South African Children with Tuberculous Meningitis.

Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). Children with TBM were included in this pharmacokinetic analysis. Sparse plasma, LCSF, and VCSF samples were collected opportunistically, as clinically indicated. Brain ECF was sampled using microdialysis (MD). Rifampicin was quantified with liquid chromatography with tandem mass spectrometry in all samples, and 25-desacetyl rifampicin in the plasma samples. The data were interpreted with nonlinear mixed-effects modeling, with the CSF and brain ECF modeled as "effect compartments." Data were available from 61 children, with median (min-max) age of 2 (0.3 to 10) years and weight of 11.0 (4.8 to 49.0) kg. A one-compartment model for parent and metabolite with first-order absorption and elimination via saturable hepatic clearance described the data well. Allometric scaling, maturation, and auto-induction of clearance were included. The pseudopartition coefficient between plasma and LCSF/VCSF was ~5%, while the value for ECF was only ~0.5%, possibly reflecting low recovery of rifampicin using MD. The equilibration half-life between plasma and LCSF/VCSF was ~4 h and between plasma and ECF ~2 h. Our study confirms previous reports showing that rifampicin concentrations in the LCSF are lower than in plasma and provides novel knowledge about rifampicin in the VCSF and the brain tissue. Despite MD being semiquantitative because the relative recovery cannot be quantified, our study presents a proof-of-concept that rifampicin reaches the brain tissue and that MD is an attractive technique to study site-of-disease pharmacokinetics in TBM.

Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone.

INTRODUCTION: The number of pregnant women with opioid use disorder (OUD) has quadrupled from 1999 to 2014. Current first line treatment for OUD in pregnancy is methadone with increasing support for buprenorphine. Limited data exist on use of buprenorphine/naloxone for OUD in pregnancy despite it being standard therapy in the non-pregnant individuals. The aim of this study was to compare neonatal opioid withdrawal syndrome (NOWS) prevalence and characteristics among neonates born to women prescribed methadone and buprenorphine/naloxone. METHODS: This is a retrospective cohort analysis of mother-neonate dyads treated with either methadone or buprenorphine/naloxone for OUD in pregnancy who received prenatal care in the substance abuse, treatment, education, and prevention program (STEPP) clinic and delivered at OSU. Primary neonatal outcomes included: neonates diagnosed and treated for NOWS, peak scores on Modified Finnegan Neonatal Abstinence Score (FNAS), number of scores ≥9 on FNAS, and duration of treatment for NOWS. Secondary outcomes included: fetal growth restriction, preterm birth (<37 weeks), neonatal head circumference, birth weight, NICU admission, five-minute Apgar score, and length of hospitalization. RESULTS: From 2013 to 2017, we identified 588 mother-neonate dyads: 149 treated with methadone and 439 treated with buprenorphine/naloxone. Ninety-eight neonates (65.8%) in the methadone group were diagnosed with NOWS requiring pharmacological interventions compared with 170 (38.7%) in the buprenorphine/naloxone group (aOR 3.46, 95% confidence interval (CI) 2.31-5.20, p < .01). Methadone-exposed neonates were six times more likely to be treated with >1 medication for NOWS (aOR 6.32, 95% CI 2.20-18.13, p < .01). Fetal growth restriction was diagnosed more often in the methadone group compared to the buprenorphine/naloxone group (aOR 1.73, 95% CI 1.02-2.93, p < .01). Significant maternal findings were that women using methadone for OUD started PNC earlier (15w vs. 17w, p = .04) and were less likely to be taking selective serotonin-reuptake inhibitors (SSRIs) (15% vs. 25%, p = .02) compared to the buprenorphine/naloxone group. CONCLUSIONS: Buprenorphine/naloxone treatment for OUD in pregnancy appears safe and has decreased NOWS and pharmacologic intervention for the neonate.

Periacetabular osteotomy: A novel application of modified Stoppa approach.

BACKGROUND: The Bernese periacetabular osteotomy (PAO) is a well-established procedure for symptomatic hip dysplasia in adolescents and young adults. However, it remains a technically demanding procedure, and several major complications have been described, many of which are related to the approach and surgical exposure. The current study evaluates the efficacy and safety of PAO performed through a modified Stoppa approach. METHODS: A prospective series of nine consecutive patients with hip dysplasia were treated PAO through the modified Stoppa approach. The mean age was 22.4 years (15-30 years) and the mean follow-up was 3.2 years (2-5 years). Harris hip score (HHS) was used as a functional score, and the radiographic indices included the lateral center-edge angle (LCEA) and Tönnis roof angle. RESULTS: The approach allowed the osteotomy lines to be performed under direct visualization from the intra-pelvic surface of the acetabulum, aided by fluoroscopy. A lateral window was added to perform the final iliac cut and for subsequent mobilization and fixation of the acetabular fragment. The mean HHS improved significantly from 70.8 ± 4.9 points to 90.1 ± 3.3 points (p < 0.001). The mean LCEA improved from 8.2° ± 4.9 (range: 0-14) to 32.7° ± 5.3 (range: 26-40), with a mean improvement of 24.5°. The mean Tönnis angle improved from 28.4° ± 4.4 (range: 22-35) to 3.8° ± 3.3 (range: 0-10). Two patients had irritation from prominent screw heads that necessitated removal 1 year after the index procedure. One patient had radiographic progression of osteoarthritis. No cases of infection, non-union, heterotopic ossification, or nerve palsy were identified till the latest follow-up. CONCLUSION: Ganz PAO can be safely conducted through the modified Stoppa approach, providing direct exposure to the osteotomized surfaces, and protecting susceptible neuro-vascular structures. LEVEL OF EVIDENCE: IV.

Association between Prenatal Marijuana and Tobacco Smoke Exposures and Small for Gestational Age at Birth.

OBJECTIVE: The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth. STUDY DESIGN: We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data. RESULTS: Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02-2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15-4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24-3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09-3.78). CONCLUSION: Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure. KEY POINTS: · Marijuana and tobacco are commonly used together in pregnancy.. · Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant.. · Further research is warranted to understand how in utero marijuana exposure impacts fetal growth..

Outcomes in Subsequent Pregnancies of Individuals With Opioid Use Disorder Treated in Multidisciplinary Clinic in Prior Pregnancy.

BACKGROUND: Untreated opioid misuse in pregnancy is associated with adverse outcomes. Limited information is available on maternal and perinatal outcomes in subsequent pregnancies for individuals initiated on medication for opioid use disorder (MOUD) in a prior pregnancy. OBJECTIVE: Evaluate maternal and neonatal outcomes in subsequent pregnancies for individuals initiated on MOUD in prior pregnancy. METHODS: Historical cohort study including individuals with opioid use disorder with ≥2 pregnancies between 2013 and 2020, received care in our colocated multidisciplinary clinic for >1 pregnancy, and delivered at our institution. Primary outcome was rate of preconception MOUD. Secondary outcomes included rate of neonatal opioid withdrawal syndrome requiring pharmacologic treatment and length of hospital stay. RESULTS: Forty-two individuals with opioid use disorder in their index pregnancies (n = 42) and 46 subsequent pregnancies were identified. Individuals were more likely to receive long-acting reversible contraception in subsequent pregnancies (35% vs 14%, P = 0.04). No differences in tobacco use, gestational age at initiation of prenatal care or delivery was noted. Individuals in their subsequent pregnancies were 6 times more likely to be on MOUD preconception (78% vs 36%; OR, 6.48; [95% CI, 2.52-16.64]) and 67% less likely to have positive illicit urine drug screen upon initiation of care (36% vs 64%; OR, 0.33; 95% [CI, 0.14-0.78]). Neonates had similar rates of neonatal abstinence withdrawal syndrome requiring pharmacological treatment, positive illicit toxicology results, and neonatal length of stay. CONCLUSIONS: Participation in multidisciplinary obstetric and opioid use disorder program increases rate of MOUD in subsequent pregnancy with decrease in illicit drug use.

Decreased severity of COVID-19 in vaccinated pregnant individuals during predominance of different SARS-CoV-2 variants.

PROBLEM: Since the start of the pandemic, Pregnant individuals have been disproportionately affected by the severe acute respiratory syndrome coronavirus 2. Vaccination has been shown to be protective against severe disease. However, data on effectiveness of vaccine in reducing disease severity are limited in pregnant individuals who later developed COVID-19. METHOD OF STUDY: This is a single academic center retrospective cohort study of pregnant individuals who tested positive for COVID-19 from December 2020 through January 2022. The cohort was divided into two groups based on vaccination status. The primary outcome of our study was progression to severe or critical disease. A secondary analysis was performed based on the timeframes of predominance of different variants of SARS-CoV-2, to determine whether the effect of vaccination was different during these epochs. RESULTS: Our cohort included 472 patients among which 125 (26.5%) were vaccinated and 347 were unvaccinated. None of the patients in the vaccinated group who later developed COVID-19 progressed to severe or critical disease compared to 7.2% in the unvaccinated one (p < .01). Similarly, after adjusting for medical comorbidities, obesity, receipt of monoclonal antibodies, and trimester at diagnosis, vaccinated individuals who later developed COVID-19 were less likely to be admitted to the hospital (1.6% vs. 14.7%, aOR .14, 95% CI .22-.47) compared with unvaccinated ones. CONCLUSION: Vaccination against SARS-CoV-2 in pregnant individuals who later develop a breakthrough infection, is associated with decreased progression to severe or critical COVID-19, and need for hospital and ICU admissions. Vaccination is specifically effective during the predominance of the more severe Delta variant.

Outpatient Use of Monoclonal Antibodies in Pregnant Individuals With Mild or Moderate Coronavirus Disease 2019 (COVID-19).

Treatment with monoclonal antibodies has been shown to significantly reduce the risk of hospitalization and disease progression among high-risk patients with coronavirus disease 2019 (COVID-19). Pregnant individuals were excluded from the original trials. In this single-center retrospective cohort study, we evaluated whether monoclonal antibody treatment in pregnant individuals is associated with decreased risk of hospitalization. Outcomes of patients who received the treatment were compared with those who were eligible but did not receive the treatment. Analyses were stratified by vaccination status. Unvaccinated pregnant patients with mild or moderate COVID-19 who received outpatient monoclonal antibodies were less likely to be admitted to the hospital (4.2% vs 15.7%, odds ratio 0.24, 95% CI 0.07-0.74), whereas among vaccinated patients, the treatment was not associated with a lower rate of hospitalization (2.3% vs 0%, P=.99).

Population pharmacokinetics of ethambutol in African children: a pooled analysis.

OBJECTIVES: Ethambutol protects against the development of resistance to co-administered drugs in the intensive phase of first-line anti-TB treatment in children. It is especially relevant in settings with a high prevalence of HIV or isoniazid resistance. We describe the population pharmacokinetics of ethambutol in children with TB to guide dosing in this population. METHODS: We pooled data from 188 intensively sampled children from the DATiC, DNDi and SHINE studies, who received 15-25 mg/kg ethambutol daily according to WHO guidelines. The median (range) age and weight of the cohort were 1.9 (0.3-12.6) years and 9.6 (3.9-34.5) kg, respectively. Children with HIV (HIV+; n = 103) received ART (lopinavir/ritonavir in 92%). RESULTS: Ethambutol pharmacokinetics were best described by a two-compartment model with first-order elimination and absorption transit compartments. Clearance was estimated to reach 50% of its mature value by 2 months after birth and 99% by 3 years. Typical steady-state apparent clearance in a 10 kg child was 15.9 L/h. In HIV+ children on lopinavir/ritonavir, bioavailability was reduced by 32% [median (IQR) steady-state Cmax = 0.882 (0.669-1.28) versus 1.66 (1.21-2.15) mg/L). In young children, bioavailability correlated with age. At birth, bioavailability was 73.1% of that in children 3.16 years or older. CONCLUSIONS: To obtain exposure within the 2-6 mg/L recommended range for Cmax, the current doses must be doubled (or tripled with HIV+ children on lopinavir/ritonavir) for paediatric patients. This raises concerns regarding the potential for ocular toxicity, which would require evaluation.

Transtibial versus independent femoral tunnel drilling techniques for anterior cruciate ligament reconstruction: evaluation of femoral aperture positioning.

BACKGROUND: Femoral tunnel can be drilled through tibial tunnel (TT), or independent of it (TI) by out-in (OI) technique or by anteromedial (AM) technique. No consensus has been reached on which technique achieves more proper femoral aperture position because there have been evolving concepts in the ideal place for femoral aperture placement. This meta-analysis was performed to analyze the current literature comparing femoral aperture placement by TI versus TT techniques in ACL reconstruction. METHODS: We performed a comprehensive systematic review and meta-analysis of English-language literature in PubMed, Cochrane, and Web of Science databases for articles comparing femoral aperture placement by TI versus TT techniques with aperture position assessed by direct measurement or by postoperative imaging, PXR and/or CT and/or MRI. RESULTS: We included 55 articles with study population of 2401 knees of whom 1252 underwent TI and 1149 underwent TT techniques. The relevant baseline characteristics, whenever compared, were comparable between both groups. There was nonsignificant difference between TI and TT techniques in the distance from aperture center to footprint center and both techniques were unable to accurately recreate the anatomic footprint position. TI technique significantly placed aperture at more posterior position than TT technique. TI technique significantly lowered position of placed aperture perpendicular to Blumensaat's line (BL) than TT technique, and modifications to TT technique had significant effect on this intervention effect. Regarding sagittal plane aperture placement along both AP anatomical axis and BL, there was nonsignificant difference between both techniques. CONCLUSION: Modifications to TT technique could overcome limitations in aperture placement perpendicular to BL. The more anterior placement of femoral aperture by TT technique might be considered, to some extent, a proper position according to recent concept of functional anatomical ACL reconstruction.