Trends in antenatal corticosteroid administration: did our timing improve?

OBJECTIVES: We aimed to analyze trends in the rate of effective antenatal corticosteroid prophylaxis (ACS) administrations across a spectrum of typical diagnoses associated with preterm birth. METHODS: In this retrospective study we utilized delivery data after ACS from 2014 to 2020 at Charité Berlin, Germany. We evaluated the rate of effective ACS administrations defined as ≤10 days between last dose of ACS and delivery as well as the rate of post-ACS births on/after 37 + 0 weeks. We explored conditions associated with high rates of ineffective ACS administrations (>10 days before delivery). We analyzed the trend of ACS-effectiveness during the study period in the overall cohort and in placental dysfunction and cervical insufficiency diagnoses. RESULTS: The overall rate of effective ACS administrations was 42 % (709/1,672). The overall percentage of deliveries after/at 37 + 0 weeks following ACS administration was 19 % (343). Placenta previa, twin pregnancy and isthmocervical insufficiency were associated with ineffective ACS (19-34 % effective i.e. ≤10 days before delivery). The overall ratio of effective ACS applications rose over time (p=0.002). Over the course of this study ACS effectiveness increased in placental dysfunction and isthmocervical insufficiency diagnoses (p=0.028; p=0.001). CONCLUSIONS: Compared to a previous publication we found a decrease of post-ACS deliveries after/at 37 + 0 weeks (19 vs. 27 %). Ineffective ACS administrations are still frequent in patients with placenta previa, twin pregnancy and isthmocervical insufficiency. It remains to be investigated in future trials if the introduction of new diagnostic tools such as soluble Fms-like tyrosinkinase-1/placental growth factor (sFlt-1/PlGF) testing and placental alpha-microglobulin-1 (PAMG-1) testing directly led to an increased ACS effectiveness.

The CHANGED Score-A New Tool for the Prediction of Insulin Dependency in Gestational Diabetes.

Gestational diabetes (GDM) is a frequent complication during pregnancy. We aimed to develop a score to predict future insulin dependency in gestational diabetes (GDM). Data from 1611 patients from Charité Berlins gestational diabetes clinic from 2015 to 2022 were utilized. A stepwise backwards regression, including patient characteristics obtained at the initial presentation, was performed. Predictors examined included age, fasting blood glucose level, blood glucose levels one and two hours after oral glucose tolerance test, pre-pregnancy BMI, number of previous pregnancies and births, and fetal sex. The ideal cutoff value between high and low risk for insulin dependency was assessed and the score was internally validated. There were 1249 (77.5%) women diagnosed with dietary GDM and 362 (22.5%) were diagnosed with insulin-dependent GDM. The CHarité AssessmeNt of GEstational Diabetes (CHANGED) Score achieved an area under the curve of 0.77 (95% confidence interval 0.75-0.80; 0.75 in internal validation). The optimal cutoff value was calculated at a score value of 9 (72% sensitivity, 69% specificity). We developed an easily applicable tool to accurately predict insulin dependency in gestational diabetes. The CHANGED Score is routinely available and can potentially improve maternal and fetal outcomes.

Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM).

OBJECTIVES: Gestational diabetes (GDM) is a common complication during pregnancy that is strongly associated with adverse fetal and maternal outcomes. Advanced maternal age (≥35 years) is a known risk factor for GDM. Studies advocate that GDM comprises distinctive metabolic entities, suggesting an individualized approach based on early pregnancy characteristics (such as 75 g oGTT values, maternal age, obstetric history). METHODS: The oGTT blood glucose levels of 1,664 women were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated postprandial hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values after glucose application. These three subtypes were analysed regarding baseline characteristics as well as fetal and maternal outcome in the context of maternal age. RESULTS: This analysis reveals that the 75 g oGTT levels and maternal age can distinguish metabolic phenotypes in women with GDM. The overall rate of insulin therapy required was higher in women from the GDM-CH group and increased with maternal age (31.7 %, 38.2 %, <35 years, ≥35-39 years respectively, vs. total insulin rate 22.3 %, p-value <0.001). Women ≥35 years displayed a significantly higher caesarean delivery (CD) rate (<35 years 34.6 %, 38.4 %, 41.1 % vs. ≥35 years 54.8 %, 47.6 %, 46.5 %, GDM-IFH, GDM-IPH, GDM-CH respectively, p-value <0.001). CONCLUSIONS: Women with fasting hyperglycemia, especially those with combined hyperglycemia and advanced maternal age (AMA) display a higher risk for unfavorable perinatal outcome. A categorization based on oGTT values and maternal age, as well as other characteristics can facilitate a basis for clinical risk stratification. Women at risk should receive an individualized and intensified perinatal care as well as interventional therapies.

Glucose Levels of the Oral Glucose Tolerance Test (oGTT) Can Predict Adverse Pregnancy Outcomes in Women with Gestational Diabetes (GDM).

OBJECTIVES AND BACKGROUND: Gestational diabetes (GDM) is a common pregnancy complication defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1 h 50 g oGCT (oral glucose challenge test) followed by a 2 h 75 g oGTT if the first was pathological. This analysis examines the correlation of 75 g oGTT glucose levels and fetomaternal outcome. METHODS: Data from 1664 patients from a gestational diabetes consultation clinic at the Charité University Hospital in Berlin, Germany, were analyzed retrospectively from 2015 to 2022. The 75 g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values, after glucose application. These subtypes were compared based on their baseline characteristics as well as fetal and maternal outcome. RESULTS: GDM-IFH and GDM-CH women displayed higher pre-conceptional BMI and required insulin therapy more frequently (p < 0.001). The GDM-IFH group was at higher risk of having a primary cesarean section (p = 0.047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p = 0.013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p < 0.001) and birth weight percentiles (p < 0.001) and were at increased risk of being large for gestational age (LGA) (p = 0.004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p = 0.027) or with low fetal weight <30th percentile (p = 0.003). CONCLUSION: This analysis shows a strong association between the glucose response pattern in the 75 g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach to prenatal care after a GDM diagnosis.

Effects of night surgery on postoperative mortality and morbidity: a multicentre cohort study.

BACKGROUND: Surgery at night (incision time 17:00 to 07:00 hours) may lead to increased postoperative mortality and morbidity. Mechanisms explaining this association remain unclear. METHODS: We conducted a multicentre retrospective cohort study of adult patients undergoing non-cardiac surgery with general anaesthesia at two major, competing tertiary care hospital networks. In primary analysis, we imputed missing data and determined whether exposure to night surgery affects 30-day mortality using a mixed-effects model with individual anaesthesia and surgical providers as random effects. Secondary outcomes were 30-day morbidity and the mediating effect of blood transfusion rates and provider handovers on the effect of night surgery on outcomes. We further tested for effect modification by surgical setting. RESULTS: Among 350 235 participants in the primary imputed cohort, the mortality rate was 0.9% (n=2804/322 327) after day and 3.4% (n=940/27 908) after night surgery. Night surgery was associated with an increased risk of mortality (ORadj 1.26, 95% CI 1.15 to 1.38, p<0.001). In secondary analyses, night surgery was associated with increased morbidity (ORadj 1.41, 95% CI 1.33 to 1.48, p<0.001). The proportion of patients receiving intraoperative blood transfusion and anaesthesia handovers were higher during night-time, mediating 9.4% (95% CI 4.7% to 14.2%, p<0.001) of the effect of night surgery on 30-day mortality and 8.4% (95% CI 6.7% to 10.1%, p<0.001) of its effect on morbidity. The primary association was modified by the surgical setting (p-for-interaction<0.001), towards a greater effect in patients undergoing ambulatory/same-day surgery (ORadj 1.81, 95% CI 1.39 to 2.35) compared with inpatients (ORadj 1.17, 95% CI 1.02 to 1.34). CONCLUSIONS: Night surgery was associated with an increased risk of postoperative mortality and morbidity. The effect was independent of case acuity and was mediated by potentially preventable factors: higher blood transfusion rates and more frequent provider handovers.

The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

BACKGROUND: Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. METHODS: Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. RESULTS: Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. CONCLUSIONS: These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

Incidence, Prediction, and Causes of Unplanned 30-Day Hospital Admission After Ambulatory Procedures.

BACKGROUND: Unanticipated hospital admission is regarded as a measure of adverse perioperative patient care. However, previously published studies for risk prediction after ambulatory procedures are sparse compared to those examining readmission after inpatient surgery. We aimed to evaluate the incidence and reasons for unplanned admission after ambulatory surgery and develop a prediction tool for preoperative risk assessment. METHODS: This retrospective cohort study included adult patients undergoing ambulatory, noncardiac procedures under anesthesia care at 2 tertiary care centers in Massachusetts, United States, between 2007 and 2017 as well as all hospitals and ambulatory surgery centers in New York State, United States, in 2014. The primary outcome was unplanned hospital admission within 30 days after discharge. We created a prediction tool (the PREdicting admission after Outpatient Procedures [PREOP] score) using stepwise backward regression analysis to predict unplanned hospital admission, based on criteria used by the Centers for Medicare & Medicaid Services, within 30 days after surgery in the Massachusetts hospital network registry. Model predictors included patient demographics, comorbidities, and procedural factors. We validated the score externally in the New York state registry. Reasons for unplanned admission were assessed. RESULTS: A total of 170,983 patients were included in the Massachusetts hospital network registry and 1,232,788 in the New York state registry. Among those, the observed rate of unplanned admission was 2.0% (3504) and 1.7% (20,622), respectively. The prediction model showed good discrimination in the training set with C-statistic of 0.77 (95% confidence interval [CI], 0.77-0.78) and satisfactory discrimination in the validation set with C-statistic of 0.71 (95% CI, 0.70-0.71). The risk of unplanned admission varied widely from 0.4% (95% CI, 0.3-0.4) among patients whose calculated PREOP scores were in the first percentile to 21.3% (95% CI, 20.0-22.5) among patients whose scores were in the 99th percentile. Predictions were well calibrated with an overall ratio of observed-to-expected events of 99.97% (95% CI, 96.3-103.6) in the training and 92.6% (95% CI, 88.8-96.4) in the external validation set. Unplanned admissions were most often related to malignancy, nonsurgical site infections, and surgical complications. CONCLUSIONS: We present an instrument for prediction of unplanned 30-day admission after ambulatory procedures under anesthesia care validated in a statewide cohort comprising academic and nonacademic hospitals as well as ambulatory surgery centers. The instrument may be useful in identifying patients at high risk for 30-day unplanned hospital admission and may be used for benchmarking hospitals, ambulatory surgery centers, and practitioners.

Calabadion 1 selectively reverses respiratory and central nervous system effects of fentanyl in a rat model.

BACKGROUND: We hypothesised that Calabadion 1, an acyclic cucurbit[n]uril molecular container, reverses fentanyl-induced respiratory depression and dysfunction of the CNS. METHODS: Experiments were conducted in male Sprague-Dawley rats. A constant-rate i.v. infusion of fentanyl (12.5 or 25 µg kg-1 over 15 min) was administered followed by an i.v. bolus of Calabadion 1 (0.5-200 mg kg-1) or placebo. The primary outcome was reversal of ventilatory and respiratory depression, assessed by pneumotachography and arterial blood gas analysis, respectively. Key secondary outcomes were effects on fentanyl-induced central nervous dysfunction quantified by righting reflex, balance beam test, and electromyography (EMG). RESULTS: Calabadion 1 reversed fentanyl-induced respiratory depression across the endpoints minute ventilation, pH, and Paco2 (P=0.001). Compared with placebo, Calabadion 1 dose dependently (P for trend <0.001) reversed fentanyl-induced hypoventilation {81.9 [5.1] (mean [standard error of the mean]) vs 45.5 [12.4] ml min-1; P<0.001}, acidosis (pH 7.43 [0.01] vs 7.28 [0.04]; P=0.005), and hypercarbia (Paco2 43.4 [1.6] vs 63.4 [8.1] mm Hg; P=0.018). The effective Calabadion 1 doses required to reverse respiratory depression by 50% and 90% (ED50Res and ED90Res) were 1.7 and 15.6 mg kg-1, respectively. Higher effective doses were needed for recovery of righting reflex (ED50CNS: 9.6 mg kg-1; ED90CNS: 86.1 mg kg-1), which was accelerated by Calabadion 1 (4.6 [0.3] vs 9.0 [0.7] min; P<0.001). Calabadion 1 also significantly accelerated recovery of full functional mobility and reversal of muscle rigidity. CONCLUSIONS: Calabadion 1 selectively and dose dependently reversed the respiratory system and CNS side-effects of fentanyl.