Aspirin 162 mg versus 81 mg for Preeclampsia Prophylaxis in High-risk Obese Individuals: A Comparative Effectiveness Open Label Randomized Trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Time to Completion of Two-Step Screening for Gestational Diabetes and Adverse Outcomes.

OBJECTIVE: This study aimed to ascertain whether the length of time to complete the gestational diabetes mellitus (GDM) screening was associated with adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous individuals who were screened for GDM at ≥24 weeks' gestation at an academic hospital system. We compared outcomes among people who were diagnosed with GDM and completed the 3-hour glucose tolerance test (GTT) ≤14 second versus >14 days from the 1-hour glucose challenge test (GCT). The primary outcome was a composite adverse neonatal outcome of the following: large for gestational age, shoulder dystocia, birth injury, respiratory distress, hypoglycemia, or fetal/neonatal death. The secondary outcomes included several individual neonatal and maternal morbidities. Multivariable Poisson's regression models were used to evaluate the association. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. RESULTS: Among the 313 individuals who completed the two-step screening for GDM and had an 1-hour GCT ≥ 135 mg/dL; of them, 171 (54.6%) completed the 3-hour GTT ≤14 days, 142 (45.4%) completed the 3-hour GTT > 14 days. Overall rate of the primary outcome was 44.1%. After multivariable adjustment, the risk of the primary outcome was similar between people who completed the two-step method in ≤14 versus >14 days (aRR = 1.11, 95% CI = 0.81-1.52). There was no significant difference in all secondary adverse outcomes between the two groups. Subgroup analyses, limited to people diagnosed with GDM (N = 89, 23.4%), also found similar results as the full analyses. CONCLUSION: Among individuals who completed the two-step screening for GDM, completion of the 3-hour GTT within ≤14 versus ≥ 14 days was not associated with an increase rate of the adverse outcomes. KEY POINTS: · Among pregnant people in an academic practice, 50% of people with abnormal 1-hour GTT completed GDM two-step screening in 14 days.. · Longer length of time to completion of diagnostic testing for GDM was not associated with an increased rate of adverse outcomes.. · Pregnant people that were diagnosed with GDM and completed the two-step method in >14 days did not have worse perinatal outcomes..

Continuous Glucose Monitoring and Time in Range: Association with Adverse Outcomes among People with Type 2 or Gestational Diabetes Mellitus.

OBJECTIVE: Continuous glucose monitoring (CGM) has become available for women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) during pregnancy. The recommended time in range (TIR, blood glucose 70-140 mg/dL) and its correlation with adverse pregnancy outcomes in this group is unknown. Our aim was to compare maternal and neonatal outcomes in pregnant people with T2DM or GDM with average CGM TIR values >70 versus ≤ 70%. STUDY DESIGN: We conducted a retrospective cohort study of all individuals using CGM during pregnancy from January 2017 to June 2022. Individuals with type 1 diabetes mellitus, or those missing CGM or delivery data were excluded. Primary composite neonatal outcome included any of the following: large for gestational age, NICU admission, need for intravenous glucose, respiratory support, or neonatal death. Secondary outcomes included other maternal and neonatal outcomes. Regression models were used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: During the study period, 141 individuals with diabetes utilized CGM during pregnancy, with 65 (46%) meeting inclusion criteria. Of the study population, 28 (43%) had TIR ≤70% and 37 (57%) had TIR > 70%. Compared with those with TIR > 70%, the primary composite outcome occurred more frequently in neonates of individuals TIR ≤70% (71.4 vs. 37.8%, aOR: 4.8, 95% CI: 1.6, 15.7). Furthermore, individuals with TIR ≤70% were more likely to have hypertensive disorders (42.9 vs. 16.2%, OR: 3.9, 95% CI: 1.3, 13.0), preterm delivery (54 vs. 27%, OR: 3.1, 95% CI: 1.1, 9.1): , and cesarean delivery (96.4 vs. 51.4%, OR: 4.6, 95% CI: 2.2, 15.1) compared with those with TIR >70%. CONCLUSION: Among people with T2DM or GDM who utilized CGM during pregnancy, 4 out 10 individuals had TIR ≤70% and, compared with those with TIR > 70%, they had a higher likelihood of adverse neonatal and maternal outcomes. KEY POINTS: · Time in range can be utilized as a metric for pregnant patients using continuous glucose monitor.. · Time in range >70% is achievable by 6 out of 10 patients.. · Time in range below goal is associated with adverse neonatal and maternal outcomes..

Dispensing and Purchasing Antibiotics Without Prescription: A Cross-sectional Study Among Pharmacists and Patients in Beirut, Lebanon.

Antimicrobial resistance is a global public health issue, exacerbated by dispensing and purchasing antibiotics without a prescription, common in low- and middle-income countries, such as Lebanon. This study aimed to (1) describe behavioral patterns underpinning dispensing and purchasing antibiotics without a prescription among pharmacists and patients, (2) describe reasons for, and (3) attitudes toward these behaviors. A cross-sectional study targeted pharmacists and patients, respectively, identified through stratified random sampling and convenience sampling from all 12 Beirut quarters. Questionnaires assessed behavioral patterns, reasons for, and attitudes toward dispensing and purchasing antibiotics without prescription among the 2 samples. A total of 70 pharmacists and 178 patients were recruited. About a third (37%) of pharmacists supported dispensing antibiotics without a prescription, considering it acceptable; 43% of patients report getting antibiotics without a prescription. Reasons for distributing and purchasing antibiotics without prescription include financial costs associated with the drugs and convenience, coupled with inexistent law enforcement. Dispensing antibiotics without prescription was shared among a relatively high proportion of pharmacists and patients residing in Beirut. Dispensing antibiotics without prescription is common in Lebanon, where law enforcement needs to be stronger. National efforts, including anti-AMR campaigns and law enforcement, must be rapidly implemented to avoid the double disease burden, especially when old and new vaccines are available, and superbugs are making preventative public health efforts more difficult.