Labetalol Dosing in Pregnancy: PBPK/PD and CYP2C19 Polymorphisms.

As detailed information on the pharmacokinetics (PK) of labetalol in pregnant people are lacking, the aims of this study were: (1) to build a physiologically based PK (PBPK) model of labetalol in non-pregnant individuals that incorporates different CYP2C19 genotypes (specifically, *1/*1, *1/*2 or *3, *2/*2, and *17/*17); (2) to translate this model to the second and third trimester of pregnancy; and (3) to combine the model with a previously published direct pharmacodynamic (PD) model to predict the blood pressure lowering effect of labetalol in the third trimester. Clinical data for model evaluation was obtained from the scientific literature. In non-pregnant populations, the mean ratios of simulated versus observed peak concentration (Cmax), time to reach Cmax (Tmax), and exposure (area under the plasma concentration-time curve, AUC) were 0.94, 0.82, and 1.16, respectively. The pregnancy PBPK model captured the observed PK adequately, but clearance was slightly underestimated with mean ratios of simulated versus observed Cmax, Tmax, and AUC of 1.28, 1.30, and 1.39, respectively. The results suggested that pregnant people with CYP2C19 *2/*2 alleles have similar labetalol exposure and trough levels compared to non-pregnant controls, whereas those with other alleles were found to have increased exposure and trough concentrations. Importantly, the pregnancy PBPK/PD model predicted that, despite increased exposure in some genotypes, the blood pressure lowering effect was broadly comparable across all genotypes. In view of the large inter-individual variability and the potentially increasing blood pressure during pregnancy, patients may need to be closely monitored for achieving optimal therapeutic effects and avoiding adverse events.

Acceptability of intramuscular injection of tranexamic acid in postpartum hemorrhage prevention.

BACKGROUND: Newer research comparing routes of medication administration has extended beyond efficacy as a primary endpoint to incorporate patient preference. However, little is known about the preferences of pregnant women in terms of routes of medication administration, specifically with regards to hemorrhage prevention and control. OBJECTIVE: This study aimed to understand the preferences of pregnant women in terms of medical interventions to prevent hemorrhage at the time of delivery. STUDY DESIGN: Surveys were distributed from April 2022 to September 2022 using electronic tablets at a single urban center with an annual delivery volume of 3000 women per year to women >18 years of age who were either currently pregnant or have been pregnant in the past. Subjects were asked to choose their preferred route of administration from the following options: intravenous, intramuscular, or subcutaneous. The primary outcome was patient preference on the route of medication administration during a hemorrhage event. RESULTS: The study cohort included 300 patients, mostly African American (39.8%) followed by White (32.1%), and the majority of the participants ranged from 30 to 34 years of age (31.7%). When asked which method of administration they would prefer to prevent hemorrhage before birth, the results were as follows: 31.1% would prefer intravenous, 23.0% had no preference, 21.2% were unsure, 15.9% preferred subcutaneous, and 8.8% preferred intramuscular administration. In addition, 69.4% of respondents reported that they have never declined or avoided intramuscular administration of medication if recommended by their physician. CONCLUSION: Although some survey participants preferred an intravenous route of administration, 68.9% of subjects were unsure, had no preference, or preferred nonintravenous routes. This information is helpful particularly in low-resource settings where intravenous treatments are not readily available or in urgent clinical situations in which intravenous administration routes are not easily obtainable in high-risk patients.

Emerging technology for early detection and management of postpartum hemorrhage to prevent morbidity.

Despite advances in hemorrhage detection and management, postpartum hemorrhage remains the single leading cause of maternal death worldwide. Within the United States, hemorrhage is the leading cause of maternal death on the day of delivery and within the first week after delivery. Blood transfusion after hemorrhage represents a large proportion of severe maternal morbidity during and after delivery. Blood loss during delivery has historically been assessed visually by inspecting soiled pads, linens, and laparotomy sponges. These methods underestimate the volume of blood loss by as much as 40%, becoming increasingly inaccurate as blood loss increases. Young, healthy obstetrical patients compensate for blood loss via peripheral vasoconstriction, maintaining heart rate and blood pressure in a normal range until over 1 L of blood has been lost. A significant decrease in blood pressure along with marked tachycardia (>120 bpm) may not be seen until 30% to 40% of blood volume has been lost, or 2.0 to 2.6 L in a healthy term pregnant patient, after which the patient may rapidly decompensate. In resource-poor settings especially, the narrow window between the emergence of significant vital sign abnormalities and clinical decompensation may prove catastrophic. Once hemorrhage is detected, decisions regarding blood product transfusion are routinely made on the basis of inaccurate estimates of blood loss, placing patients at risk of underresuscitation (increasing the risk of hemorrhagic shock and end-organ damage) or overresuscitation (increasing the risk of transfusion reaction, fluid overload, and alloimmunization). We will review novel technologies that have emerged to assist both in the early and accurate detection of postpartum hemorrhage and in decisions regarding blood product transfusion.

Asociación de inmunodeficiencia celular, porfiria aguda intermitente y enfermedad de still en un paciente / An association of cellular immunodeficiency, intermittent acute porphiria and Still's disease in a patient

Se discute un caso clínico en que se estableció el diagnóstico en vida del paciente de Inmunodeficiencia Celular, Porfira Aguda Intermitente y Enfermedad de Sstill. Se presentandatos anatomopatológicos que contribuuyen a confirmar los diagnósticos planteados. Se comenta la posible asociación fisiológica de las tres entidades. El diagnóstico del Síndrome de Wiscott-Aldrich se plantea como posibilidad ya que aunque el paciente cursó con la triada cracterística de infección y eczema severo, estos datos no se presentaron de acuerdo al patrón cronológico descrito para esta entidad