Inpatient Management of Hyperemesis Gravidarum.

Hyperemesis gravidarum has a reported incidence of approximately 0.3-3% of pregnancies. Without treatment, refractory hyperemesis gravidarum can result in dehydration, electrolyte deficiencies, and severe nutritional deficiencies, resulting in significant maternal morbidity. The overall goals of inpatient management of refractory hyperemesis gravidarum are the resumption of oral intake to an adequate level to maintain hydration and nutrition, including the ability to tolerate oral pharmacotherapy. Patients initially are stabilized with rehydration and electrolyte repletion. There are numerous pharmacotherapeutics available that can be administered intravenously to control symptoms when oral intake is not an option. However, despite maximizing typical antiemetics, there will be cases refractory to these medications, and alternative pharmacotherapeutics and nutrition-support modalities must be considered. Mirtazapine, olanzapine, corticosteroids, and gabapentin are examples of alternative pharmacotherapeutics, and enteral and parenteral nutrition are alternative therapies that can be used when oral intake is not tolerated for prolonged time periods with ongoing weight loss. In refractory cases of hyperemesis gravidarum, the risks and benefits of these alternative forms of management must be considered, along with the risks of undertreated hyperemesis gravidarum and the overall effect of hyperemesis gravidarum on patients' quality of life.

Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery.

BACKGROUND: The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated. OBJECTIVE: This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose. STUDY DESIGN: This study recruited 2 cohorts with previous spontaneous preterm birth; 1 cohort (n=143) was randomly assigned to either 250-mg or 500-mg 17-hydroxyprogesterone caproate, and the other cohort (n=16) was receiving the 250-mg dose for routine care. Steady-state trough plasma concentrations of 17-hydroxyprogesterone caproate obtained at 26 to 30 weeks of gestation were correlated to dose, spontaneous preterm birth rates, and measures of gestational length. Furthermore, maternal and neonatal safety outcomes were evaluated according to dose. RESULTS: There was a dose proportional increase in trough plasma concentrations with the 250-mg (median, 8.6 ng/m; n=66) and 500-mg (median, 16.2 ng/mL; n=55) doses. In 116 compliant participants with blood samples, drug concentration was not related to the spontaneous preterm birth rate (odds ratio, 1.00; 95% confidence interval, 0.93-1.08). However, there was a significant relationship between drug concentration and both the interval from the first administration to delivery (interval A: coefficient, 1.11; 95% confidence interval, 0.00-2.23; P=.05) and the interval from the 26- to 30-week blood draw to delivery (interval B: coefficient, 1.56; 95% confidence interval, 0.25-2.87; P=.02). The spontaneous preterm birth rate or measures of gestational length were not related to dose. Postenrollment cerclage adversely affected all pharmacodynamic assessments because it was a powerful predictor of spontaneous preterm birth (odds ratio, 4.03; 95% confidence interval, 1.24-13.19; P=.021) and both measures of gestational length (interval A [coefficient, -14.9; 95% confidence interval, -26.3 to -3.4; P=.011] and interval B [coefficient, -15.9; 95% confidence interval, -25.8 to -5.9; P=.002]). Initial cervical length was significantly related to the risk of postenrollment cerclage (odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P=.001). Maternal and neonatal safety outcomes were similar in both dosing groups. CONCLUSION: In this pharmacodynamic study, trough plasma 17-hydroxyprogesterone caproate concentrations were significantly associated with gestational age at preterm birth but not with the preterm birth rate. Postenrollment cerclage was a powerful predictor of spontaneous preterm birth rate and gestational length. Initial cervical length predicted the risk of postenrollment cerclage. Adverse events were similar with the 500-mg and 250-mg doses of 17-hydroxyprogesterone caproate.

Developing a triage predictive model for access to a spinal surgeon using clinical variables and natural language processing of radiology reports.

PURPOSE: To utilize natural language processing (NLP) of MRI reports and various clinical variables to develop a preliminary model predictive of the need for surgery in patients with low back and neck pain. Such a model would be beneficial for informing clinical practice decisions and help reduce the number of unnecessary surgical referrals, streamlining the surgical process. METHODS: A historical cohort study was conducted using de-identified data from patients referred to a spine assessment clinic. Various demographic, clinical, and radiological variables were included as potential predictors. Full-text radiology reports of patients' MRI findings were vectorized using NLP before applying machine learning algorithms to develop models predicting who underwent surgery. Outputs from these models were then entered into a logistic regression model with clinical variables to develop a preliminary model predictive of surgical recommendations. RESULTS: Of the 398 patients assessed, 71 underwent spine surgery. NLP variables were significant predictors in univariate analysis but did not remain in the final logistic regression model. An outcome of receiving surgery was predicted by a primary symptom of low back and leg pain (adjusted odds ratio 2.81), distal pain indicated by a pain diagram (adjusted odds ratio 2.49) and self-reported difficulties walking (adjusted odds ratio 2.73). CONCLUSION: A logistic regression model was created to predict which patients may require spine surgery. Simple clinical variables appeared more predictive than variables created using NLP. However, additional research with more data samples is needed to validate this model and fully evaluate the usefulness of NLP for this task.

Prospective screening for sexually transmitted infections among US service members with Chlamydia trachomatis or Neisseria gonorrhoeae infection.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial causes of sexually transmitted infection (STI) in the United States (US). The purpose of this study was to determine the frequency of reinfection during a six-month study period and to evaluate the retesting interval for those infected with CT or NG. METHODS: We conducted a prospective, six-month follow-up study among US military personnel with new onset, laboratory-confirmed CT or NG, recruited from an STI clinic at a large military base from January 2018 to January 2020. Each participant was randomly assigned to one of four groups, which differed only by the timing of the first study-associated follow-up visit after CT or NG diagnosis. RESULTS: Of the 347 initially recruited into the study, 267 participants completed a follow-up visit prior to their scheduled, final visit 6 months after initial infection. The median age at enrollment was 22 years and 41.0% were female. There were 32 (12.0%) reinfections (30 CT and 2 NG) after treatment of an index diagnosis of CT or NG within the six-month study period. Six of the CT reinfections were only detected at the final visit. A review of medical records revealed additional CT and NG reinfections. The probability of detecting a reinfection did not vary significantly by timing of follow-up. CONCLUSIONS: The likelihood of detecting CT or NG reinfection did not differ according to time of follow up visit among study participants, thus supporting CDC guidance to retest three months post treatment. Efforts should continue to focus on STI prevention and risk reduction.

Management of Diabetic Ketoacidosis in Pregnancy.

Diabetic ketoacidosis (DKA) is a rare, but potentially life-threatening complication of diabetes. Certain physiological changes during pregnancy predispose pregnant individuals to developing DKA. Early recognition and aggressive treatment are essential to avoid maternal and fetal morbidity and mortality. Although laboratory values can help to support, pregnant patients with DKA may not meet the usual criteria and the diagnosis can be made clinically. The key components to treatment include volume replacement, insulin infusion, correction of serum potassium, and fetal monitoring. With appropriate treatment, maternal mortality is low. After recovery, steps should be taken to avoid recurrence.

Rapid Development and Testing of a COVID-19 Vaccine Curriculum for Pediatricians.

BACKGROUND AND OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccines become available to children, pediatricians must navigate vaccination discussions in the setting of rapidly changing vaccine recommendations and approvals. We developed and evaluated an educational curriculum for pediatricians to improve their knowledge about COVID-19 vaccines and confidence in communicating with patients and families about COVID-19 vaccines. METHODS: Five institutions collaborated to develop an online educational curriculum. Utilizing the collaboration's multidisciplinary expertise, we developed a 3-module curriculum focused on the SARS-CoV-2 virus and vaccine basics, logistics and administration of COVID-19 vaccine, and COVID-19 vaccine communication principles. Surveys administered to clinician participants before and after completion of the curriculum assessed knowledge and confidence; a follow-up survey 1 month after the post-survey assessed persistence of initial findings. RESULTS: A total of 152 pediatric providers participated; 72 completed both pre- and post-surveys. The median knowledge score improved from the pre-survey to the post-survey (79%-93%, P < .001). There was an increase in providers' confidence after completing the curriculum, which persisted in the follow-up survey. In the post-survey, 98% of participants had had the opportunity to discuss the COVID-19 vaccine with patients, and most clinicians reported that the modules decreased apprehension some or significantly. CONCLUSIONS: This project demonstrates rapid and feasible deployment of a curriculum providing up-to-date information to front-line clinicians responsible for having complex conversations about COVID-19 vaccine decision-making. Clinicians who completed this curriculum had sustained increased confidence and decreased levels of apprehension when discussing the COVID-19 vaccine.

Modeling the Simultaneous Transport of Multiple Cryoprotectants into Articular Cartilage Using a Triphasic Model.

Cryopreserving articular cartilage by vitrification can increase the availability of tissue for osteochondral allograft transplantation to treat cartilage defects. Developing well-optimized vitrification protocols can be supported by mathematical modeling to reduce the amount of trial-and-error experimentation needed. Fick's law has been used to model cryoprotectant diffusion, but it assumes ideal, dilute solution behavior, neglects water movement, and assumes diffusion of each cryoprotectant is independent of the presence of other cryoprotectants. The modified triphasic model addresses some of these shortcomings by accounting for water movement and the nonideal, nondilute nature of cryoprotectant vitrification solutions. However, it currently only exists for solutions containing a single cryoprotectant. As such, we extend the modified triphasic model to include two permeating cryoprotectants so that simultaneous diffusion occurring in vitrification protocols can be more accurately modeled. Using previously published experimental data, we determine suitable values for the fitting parameters of the new model. We then model a successful vitrification protocol for particulated cartilage cubes by calculating concentration, freezing point, vitrifiability, and strain profiles at the end of each loading step. We observe that Fick's law consistently underestimates cryoprotectant concentration throughout the cartilage compared to the modified triphasic model, leading to an underestimation of tissue vitrifiability. We additionally observe that simultaneous diffusion of cryoprotectants increases the permeation rate of each individual cryoprotectant, which Fick's law fails to consider. This suggests that using the two-cryoprotectant modified triphasic model to develop vitrification protocols could reduce excess exposure to cryoprotectants and improve preserved tissue outcomes.

Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women.

Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum. Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow-up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7-item, and the Patient-Reported Outcomes Measurement Information System Global Health measure. A semi-parametric, group-based mixture model (trajectory analysis) was applied. Results: Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms. Conclusions: Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women.

Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum.

Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy.

Evaluation of the permeation kinetics of formamide in porcine articular cartilage.

Cryopreservation of articular cartilage will increase tissue availability for osteochondral allografting and improve clinical outcomes. However, successful cryopreservation of articular cartilage requires the precise determination of cryoprotectant permeation kinetics to develop effective vitrification protocols. To date, permeation kinetics of the cryoprotectant formamide in articular cartilage have not been sufficiently explored. The objective of this study was to determine the permeation kinetics of formamide into porcine articular cartilage for application in vitrification. The permeation of dimethyl sulfoxide was first measured to validate existing methods from our previously published literature. Osteochondral dowels from dissected porcine femoral condyles were incubated in 6.5 M dimethyl sulfoxide for a designated treatment time (1 s, 1 min, 2 min, 5 min, 10 min, 15 min, 30 min, 60 min, 120 min, 180 min, 24 h) at 22 °C (N = 3). Methods were then repeated with 6.5 M formamide at one of three temperatures: 4 °C, 22 °C, 37 °C (N = 3). Following incubation, cryoprotectant efflux into a wash solution occurred, and osmolality was measured from each equilibrated wash solution. Concentrations of effluxed cryoprotectant were calculated and diffusion coefficients were determined using an analytical solution to Fick's law for axial and radial diffusion in combination with a least squares approach. The activation energy of formamide was determined from the Arrhenius equation. The diffusion coefficient (2.7-3.3 × 10-10 m2/s depending on temperature) and activation energy (0.9±0.6 kcal/mol) for formamide permeation in porcine articular cartilage were established. The determined permeation kinetics of formamide will facilitate its precise use in future articular cartilage vitrification protocols.

The role of social media in promoting vaccine hesitancy.

PURPOSE OF REVIEW: To offer: (1) Insight into the antivaccine movement's use of social media negatively impacting vaccine hesitancy and disease outbreaks, (2) Examples via case observations, and (3) Selected resources to combat vaccine hesitancy. RECENT FINDINGS: For the past 25 years, daily social media usage has risen continually, allowing information to spread widely to a reading/listening/viewing audience via mostly unvetted social media sites. During a pandemic/epidemic (e.g., coronavirus disease 2019 pandemic), an overabundance of information from many sources, including social media, has led to what is now termed as an 'infodemic'. Infodemics arise from overwhelming amounts of both correct and incorrect information from experts and nonexperts alike. Differentiating correct from incorrect information is difficult for social media users who can be swayed by nonscientific 'influencers' or fear-mongering more than by vetted expert scientific information. Consequently, vaccine misinformation is steadily increasing via social media, the use of which is often believed to be associated with vaccine hesitancy. Stopping the spread of misinformation has been a difficult task. SUMMARY: Vaccine misinformation on social media has been detrimental to public health. Vaccine advocates must increase the use of social media to the advantage of public health in the persistent struggle against vaccine hesitancy/refusal.

Pregnancy After 40: Recommendations for Counseling, Evaluation, and Management From Preconception to Delivery.

IMPORTANCE: Pregnant patients over age 40 often have unique risk factors and potential complications before and during pregnancy that play a role in their counseling and management. OBJECTIVE: To provide practitioners an overview on how to approach preconception evaluation and counseling, prenatal care, and management of associated comorbidities, as well as potential complications, in pregnant patients over age 40. EVIDENCE ACQUISITION: Literature review was performed using OVID and PubMed, with further relevant information queried from guidelines of professional organizations. RESULTS: Pregnant patients over age 40 should receive preconception evaluations by their obstetrician-gynecologist and other appropriate specialty care providers as they pertain to preexisting medical comorbidities. In the preconception period, attention should be given to managing and optimizing preexisting medical conditions and associated pharmacotherapeutics. Referral to specialists in assisted reproductive technologies or maternal-fetal medicine should be considered if indicated for appropriate evaluation and counseling. During pregnancy, accurate dating and counseling on aneuploidy screening, with consideration for early diabetes screening, should be performed in the first trimester. A detailed anatomy scan and fetal echocardiogram should be completed by 22 weeks' gestation, along with routine and high-risk (if indicated) prenatal care. Close attention should be given to the development of pregnancy-related complications associated with advancing age. Third-trimester fetal surveillance can be considered. Given that no contraindications exist, these patients should be encouraged to pursue a vaginal delivery with consideration for induction at 39 to 40 weeks' gestation. CONCLUSIONS AND RELEVANCE: Pregnancy rates are increasing in persons over age 40. As a result, preconception evaluation and counseling tailored to that demographic are essential. In addition to standard prenatal care, they should have early screening and diligent monitoring for pregnancy-related comorbidities associated with advancing age. RELEVANCE STATEMENT: With the increased pregnancy-associated comorbidities in patients over age 40, providers should be familiar with how to evaluate, counsel, and manage them during the preconception and pregnancy periods.

Prediction of maternal and fetal pharmacokinetics of indomethacin in pregnancy.

AIMS: Indomethacin is used for the treatment of preterm labour, short cervices and idiopathic polyhydramnios during pregnancy. Few studies have described the pharmacokinetics (PK) of indomethacin during pregnancy. This study aimed to determine maternal and fetal PK of indomethacin during different trimesters of pregnancy using physiologically based PK (PBPK) modelling and simulations. METHODS: Full PBPK simulations were performed in nonpregnant subjects and pregnant subjects from each trimester of pregnancy at steady state using Simcyp's healthy volunteers and pregnancy PBPK model, respectively. The fetal exposures were predicted using a fetoplacental pregnancy PBPK model. The models were verified by comparing PBPK-based predictions with observed PK profiles. RESULTS: Predicted exposure (AUC0-6h ) and clearance of indomethacin in nonpregnant women and pregnant women are similar to the clinical observations. AUC0-6h of indomethacin is approximately 14, 24 and 32% lower, consistent with 18, 34 and 52% higher clearance in the first, second and third trimesters of pregnancy, respectively, compared to nonpregnant women. Predicted fetal plasma exposures increased by approximately 30% from the second trimester to the third trimester of pregnancy. CONCLUSION: A mechanistic PBPK model adequately described the maternal and the fetal PK of indomethacin during pregnancy. As the pregnancy progresses, a modest decrease (≤32%) in systemic exposures in pregnant women and a 33% increase in fetal exposures to indomethacin were predicted. Higher fetal exposures in the third trimester of pregnancy may pose safety risks to the fetus. Additional studies are warranted to understand the exposure-response relationship and provide appropriate dosing recommendations during pregnancy that consider both safety and efficacy.

A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia.

BACKGROUND: Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia. OBJECTIVE: We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks' gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin. STUDY DESIGN: This was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight. RESULTS: Of note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects. CONCLUSION: This study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.

Clinical Stratification of Pregnant COVID-19 Patients based on Severity: A Single Academic Center Experience.

OBJECTIVE: This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes. STUDY DESIGN: This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p-value <0.05 was considered statistically significant. RESULTS: Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19. CONCLUSION: Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy. KEY POINTS: · The majority of pregnant patients with COVID-19 are asymptomatic and <1 in 20 require oxygen support.. · Women in the later stages of pregnancy may be at increased risk for severe infection.. · Anemia, leukopenia, CRP, ferritin, and procalcitonin are associated with increasing severity..

A randomized controlled trial of an online immunization curriculum.

INTRODUCTION: Immunization education for physicians-in-training is crucial to address vaccine concerns in clinical practice. Vaccine education is not standardized across residency programs. The Collaboration for Vaccination Education and Research (CoVER) team developed an online curriculum for pediatric (Peds) and family medicine (FM) residents. METHODS: A cluster randomized controlled trial (RCT) was performed during the 2017-2018 academic year to evaluate the CoVER curriculum. A convenience sample of residency institutions were randomly allocated to the intervention or control group, with stratification by residency type. The intervention, the CoVER curriculum, consisted of four online modules and an in-person training guide. Control sites continued with their standard vaccine education. Pre-intervention and post-intervention surveys were emailed to residents in both groups. The primary outcomes compared between groups were changes in "vaccine knowledge," "vaccine attitudes/hesitancy," and "self-confidence" in immunization communication. The team assessing outcomes was unblinded to assignments. Hierarchical general linear model was used to adjust for residency type and residency year; residency site was modeled as a random effect. RESULTS: Overall, 1444 residents from 31 residency programs were eligible to participate (734 intervention, 710 control). The pre-intervention response rate was 730 (51%) and post-intervention was 526 (36%). Average knowledge scores increased from pre-intervention (control 53%; CoVER 53%) to post-intervention (control 58%; CoVER 60%). Increases in vaccine knowledge among FM residents were greater for CoVER compared to controls (p = 0.041). Vaccine hesitancy was more common among FM (23%) than Peds (10%) residents. In all three residency years, residents in the CoVER group showed greater increases in self-confidence in ability to discuss vaccines with parents/patients (p < 0.03) compared to control group. CONCLUSION: The CoVER curriculum is an effective model to standardize immunization education of physicians-in-training. This RCT demonstrated the effectiveness of the CoVER curriculum to improve resident confidence in their ability to discuss vaccines with parents and patients.

Intrauterine Vacuum-Induced Hemorrhage-Control Device for Rapid Treatment of Postpartum Hemorrhage.

OBJECTIVE: To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment. METHODS: A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device. RESULTS: Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88-98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0-5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1-3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%). CONCLUSION: Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality. FUNDING SOURCE: Alydia Health, Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02883673.

Clinicians' accounts of communication with patients in end-of-life care contexts: A systematic review.

OBJECTIVE: Communication between patients and end-of-life care providers requires sensitivity given the context and complexity involved. This systematic review uses a narrative approach to synthesise clinicians' understandings of communication in end-of-life care. METHODS: A systematic, narrative synthesis approach was adopted given the heterogeneity across the 83 included studies. The review was registered prospectively on PROSPERO (ID: CRD42019125155). Medline was searched for all articles catalogued with the MeSH terms "palliative care," "terminal care" or "end-of-life care," and "communication". Articles were assessed for quality using a modified JQI-QARI tool. RESULTS: The findings highlight the centrality and complexity of communication in end-of-life care. The challenges identified by clinicians in relation to such communication include the development of skills necessary, complexity of interpersonal interactions, and ways in which organisational factors impact upon communication. Clinicians are also aware of the need to develop strategies for interdisciplinary teams to improve communication. CONCLUSION: Training needs for effective communication in end-of-life contexts are not currently being met. PRACTICE IMPLICATIONS: Clinicians need more training to address the lack of skills to overcome interactional difficulties. Attention is also needed to address issues in the organisational contexts in which such communication occurs.

Effects of Pregnancy on the Pharmacokinetics of Metformin.

This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy (n = 24) or a combination with glyburide (n = 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 24) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women. With both 500- and 1000-mg doses, metformin bioavailability, volume of distribution beta (V ß ), clearance, and renal clearance were significantly increased during pregnancy. In addition, in the women receiving metformin 500 mg, significantly higher metformin apparent oral clearance (CL/F) (27%), weight-adjusted renal secretion clearance (64%), and apparent oral volume of distribution beta (V ß /F) (33%) were seen during pregnancy. Creatinine clearance was significantly higher during pregnancy. Increasing metformin dose from 500 to 1000 mg orally twice daily significantly increased V ß /F by 28%, weight-adjusted V ß /F by 32% and CL/F by 25%, and weight-adjusted CL/F by 28% during pregnancy. Mean metformin umbilical cord arterial-to-venous plasma concentration ratio was 1.0 ± 0.1, venous umbilical cord-to-maternal concentration ratio was 1.4 ± 0.5, and arterial umbilical cord-to-maternal concentration ratio was 1.5 ± 0.5. Systemic exposure after a 500-mg dose of metformin was lower during pregnancy compared with the nonpregnant women with T2DM. However, in patients receiving metformin 1000 mg, changes in estimated bioavailability during pregnancy offset the changes in clearance leading to no significant change in CL/F with the higher dose. SIGNIFICANCE STATEMENT: Gestational diabetes mellitus complicates 5%-13% of pregnancies and is often treated with metformin. Pregnant women undergo physiological changes that alter drug disposition. Preliminary data suggest that pregnancy lowers metformin concentrations, potentially affecting efficacy and safety. This study definitively describes pregnancy's effects on metformin pharmacokinetics and expands the mechanistic understanding of pharmacokinetic changes across the dosage range. Here we report the nonlinearity of metformin pharmacokinetics and the increase in bioavailability, clearance, renal clearance, and volume of distribution during pregnancy.