Neonatal outcomes and rationale for timing of birth in perinatal diabetes: a retrospective cohort study.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends delivery in the 39th week of pregnancy for patients with pregestational and medication-controlled gestational diabetes with consideration for earlier delivery among those with poor glucose control. OBJECTIVE: We sought to evaluate the impact of birth before 39 weeks' gestation exclusively for diabetes-related indications on neonatal outcomes and clinician rationale for these recommendations. STUDY DESIGN: This was a retrospective cohort study of all singleton, nonanomalous pregnancies complicated by diabetes. Patients were identified through an obstetrical database containing information of 90,185 births from 2011 to 2021. Patients who delivered in a given week of gestation exclusively for diabetes-related indications were compared with ongoing pregnancies. Recommended births for other obstetrical indications were excluded from the diabetes-related indications cohorts. The primary outcome was neonatal intensive care unit admission. Secondary outcomes included neonatal intensive care unit length of stay, stillbirth, neonatal death, hypoglycemia, respiratory distress syndrome, and shoulder dystocia. For all births before 39 weeks' gestation, the electronic medical records were reviewed to confirm the rationale for the intervention for a diabetes-indicated condition. RESULTS: From the 90,185 recorded births that occurred in 2011 to 2021, 4750 patients with diabetes were identified. Of those, 30.5% (n=1449) had a recommended birth for a diabetes-related indications with 2.2% of those (n=32) occurring at 36 weeks' gestation, 7.9% (n=114) at 37 weeks' gestation, 9.7% (n=141) at 38 weeks' gestation, and 63.0% (n=913) at 39 weeks' gestation. Births that occurred at 36 and 37 weeks' gestation exclusively for diabetes-related indications had higher rates of neonatal intensive care unit admission than the respective ongoing pregnancies (62.5% vs 8.7%; P<.001 and 25.4% vs 7.2%; P<.001). There was no difference in neonatal intensive care unit admission for births at 38 or 39 weeks' gestation when compared with ongoing pregnancy. For neonates born at 36 and 37 weeks' gestation in comparison with ongoing pregnancies, the median neonatal intensive care unit length of stay was 11.0 vs 2.8 days, (P<.001) and 4.4 vs 2.6 days (P=.026), respectively. There were significantly increased rates of neonatal hypoglycemia and respiratory distress syndrome among births that occurred at 36, 37, and 38 weeks' gestation when compared with ongoing pregnancies. There were no differences in the rate of stillbirth in this cohort. Primary factors cited for early birth were poor glycemic control (71.4%), recommendation by a maternal-fetal medicine specialist (38.7%), and suspected fetal macrosomia (27.9%). Overall, 46.7%, 32.8%, and 20.6% of patients had 1, 2, or ≥3 indications, respectively, listed as rationale for early birth. Overall, few objective measures were used to recommend birth before 39 weeks' gestation owing to diabetes. CONCLUSION: In pregnancies complicated by diabetes, early birth exclusively for diabetes-related indications was associated with increased neonatal intensive care unit admission and length of stay and with neonatal morbidity. Little objective data are documented by clinicians to support their recommendations for early birth associated with diabetes. Additional clinical guidelines are needed to define suboptimal glucose control necessitating birth before 39 weeks' gestation.

Model-Informed Clinical Practice - Determining an Appropriate Ampicillin-Sulbactam Redosing Regimen in Surgical Patients by Utilizing Population Pharmacokinetics and Target Attainment Analysis.

In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam. Comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 24 different redosing scenarios. Simulation results indicated that the ampicillin-sulbactam 2-h redosing scheme recommended by ASHP guidelines is likely too conservative given that 3-g dose (2-g ampicillin/1-g sulbactam) with 4-h redosing interval can reach the breakpoint of 2 mg/L for ampicillin in all populations even with the aggressive pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT > MIC. With the target 50% fT > MIC, all redosing schemes evaluated, including the 8-h redosing scenario, are predicted to be able to reach the breakpoint of 64 mg/L in all patients. According to our findings, redosing of ampicillin-sulbactam should be every 4 h instead of the currently recommended 2-h redosing schedule. Our PTA results should inform future updates to existing general antibiotic redosing guidelines; and, when used in combination with the availability of institution- and/or unit-specific ampicillin susceptibility patterns, our PTA results may be used to customize SSI prophylaxis redosing recommendations for ampicillin-sulbactam at individual hospitals.

Melatonin and risk of mortality in subjects with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a cause of morbidity associated with aneurysmal subarachnoid hemorrhage (aSAH). Neuroinflammation contributes to the development of DCI. Melatonin is a sleep-promoting hormone known to have cerebral anti-inflammatory properties. We hypothesized that synthetic melatonin (or the selective melatonin receptor agonist ramelteon) incidentally prescribed to improve sleep may lower the incidence of DCI among hospitalized aSAH patients. METHODS: Subjects with a Hunt and Hess Grade I-III were identified from a data registry involving all aSAH patients admitted to our hospital between January 2015 and September 1, 2018. A cohort of patients who received either melatonin or ramelteon during their hospitalization was compared to a matched cohort that did not receive these drugs. The primary endpoint was incidence of DCI. Secondary outcomes included modified Rankin score (mRS) at discharge, discharge destination, and mortality at 6 weeks from discharge. The two groups were compared using univariate analysis. P < 0.05 was considered significant. RESULTS: There was no significant difference in the incidence of DCI (15.8% vs. 16.9%, p = 1), discharge mRS (mRS 0-3: 51.3% vs. 45.1%, p = 0.59), discharge disposition (Home: 43.6% vs. 44.4, p = 0.47), or mortality (0% vs. 9.2%; p = 0.074) between the melatonin/ramelteon and non-melatonin groups. CONCLUSION: The use melatonin had no effect on DCI but may improve mortality in aSAH subjects. Prospective studies using a larger cohort are warranted to validate these findings.

Development and validation of a simple and sensitive LC-MS/MS method for quantification of ampicillin and sulbactam in human plasma and its application to a clinical pharmacokinetic study.

Ampicillin-sulbactam is a broad-spectrum combination antibiotic used for a variety of clinical applications, including as a prophylactic agent to reduce the risk of surgical site infection. The pharmacokinetics of ampicillin-sulbactam after redosing during prolonged surgeries remains incompletely understood. In anticipation of further studying the intra-operative pharmacokinetics of this drug, we have developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of ampicillin and sulbactam. The plasma samples were prepared using a simple protein precipitation method. Gradient chromatographic elution was used to separate analytes, and MS/MS analysis was performed in negative ionization mode for both analytes via multiple reaction monitoring (MRM). All validation parameters were evaluated under a good laboratory practice (GLP) environment. For both ampicillin and sulbactam, the lower limit of quantitation (LLOQ) was established as 0.25 µg/mL. The calibration curve ranged from 0.25 to 200 µg/mL for ampicillin and 0.25-100 µg/mL for sulbactam. Inter- and intra-day precisions for both analytes were ≤11.5 % for quality controls and ≤17.4 % for LLOQ; accuracies ranged from -11.5 to 12.5% for 3 quality control levels and -18.1-18.7% for LLOQ. In addition to sensitivity, accuracy and precision, 13 other parameters were also validated for both analytes, and the results met the acceptance criteria. Our method was successfully applied to quantify ampicillin and sulbactam concentrations in patients undergoing surgery.