Examination of the Effectiveness of Direct Oral Anticoagulants in Comparison to Warfarin in an Obese Population

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.

Pregnancy Outcomes among Women with Class III Obesity with Pre-diabetic Early Hemoglobin A1C

Objective We aimed to assess the risk of developing gestational diabetes mellitus (GDM) in women with a normal A1C (<5.7) compared with those with an A1C in the pre-diabetic range (5.7–6.4). Study Design This study comprises of a retrospective cohort of non-anomalous singleton pregnancies with maternal body mass index (BMI) ≥40 at a single institution from 2013 to 2017. Pregnancies with multiple gestation, late entry to care, type 1 or 2 diabetes, and missing diabetes-screening information were excluded. The primary outcome was development of GDM. Secondary outcomes included fetal growth restriction, macrosomia, gestational age at delivery, large for gestational age, delivery BMI at delivery, total weight gain in pregnancy, induction of labor, shoulder dystocia, and cesarean delivery. Bivariate statistics were used to compare demographics, pregnancy complications, and delivery characteristics of women who had an early A1C < 5.7 and A1C 5.7 to 6.4. Multivariable analyses were used to estimate the odds of the primary outcome. Results Eighty women (68%) had an early A1C <5.7 and 38 (32%) had a A1C 5.7 to 6.4. Women in the lower A1C group were less likely to be Black (45 vs. 74%, p = 0.01). No differences in other baseline demographics were observed. The median A1C was 5.3 for women with A1C < 5.7 and 5.8 for women with A1C 5.7 to 6.4 (p < 0.001). GDM was significantly more common in women with A1C 5.7 to 6.4 (3.8 vs. 24%, p = 0.002). Women with pre-diabetic range A1C had an odd ratio of 11.1 (95% CI 2.49–48.8) for GDM compared with women with a normal A1C. Conclusion Women with class III obesity and a pre-diabetic range A1C are at an increased risk for gestational diabetes when compared with those with a normal A1C in early pregnancy. Key Points

Screening Echocardiogram in High-Risk Women with Class III Obesity to Predict the Risk of Preeclampsia

Objective Women with obesity and other comorbidities such as hypertension and diabetes are at an increased risk of preeclampsia and perinatal morbidity. This study evaluates whether screening echocardiogram can identify women with obesity at a higher risk of preeclampsia. Methods We conducted a retrospective cohort study of women with class III obesity (body mass index [BMI] ≥40 kg/m2) and one or more medical comorbidities associated with an increased risk of preeclampsia (such as diabetes, hypertension, and rheumatologic disease) undergoing screening echocardiogram. Abnormal findings were defined as the presence of one or more of the following: diastolic dysfunction, ejection fraction of ≤45%, or cardiac chamber enlargement or hypertrophy. Multivariable logistic regression was used to estimate the odds ratio (OR) of gestational hypertension/mild preeclampsia, severe preeclampsia, and any preterm delivery <37 weeks associated with abnormal echocardiographic findings when controlling for potential confounders. Results Of 267 eligible women, 174 (64%) underwent screening echocardiograms. Sixty-nine women (40%) had abnormal echocardiograms. Maternal clinical characteristics were similar between women with normal echocardiographic findings and women with abnormal findings. Women with abnormal echocardiograms were more likely to have chronic hypertension (78 vs. 62%, p = 0.04) and a history of preeclampsia (27 vs. 10%, p = 0.02). After controlling for confounders, women with abnormal echocardiogram were at an increased risk of hypertensive disorders of pregnancy, OR 6.80 (95% confidence interval [CI] 3.32–13.93, p = 0.01), and in particular severe preeclampsia, OR 8.77 (95% CI 3.90–19.74, p = 0.01). Conclusion Among pregnant women with class III obesity and medical comorbidities, screening echocardiogram may help identify a subset of women at the highest risk of developing preeclampsia. Key Points

Impact of a hospital-wide computerised approach to optimise the quality of antimicrobial prescriptions in patients with severe obesity: a quasi-experimental study

Background Rates of adherence to available recommendations for dose adjustments in patients with severe obesity are generally low. Hence, antimicrobials are often underdosed in these patients. Antimicrobial stewardship programmes can improve the use of antimicrobials in hospitalised patients. The aim of the study was to analyse the impact of an antimicrobial stewardship programme based on a computerised clinical decision support system for optimal dosing and antimicrobial use in inpatients with severe obesity. Methods This quasi-experimental retrospective study using interrupted time series was conducted in an academic centre in Canada from August 2008 to June 2018. The Antimicrobial Prescription Surveillance System was implemented in August 2010 (intervention 1) and specific rules targeting patients with class III obesity (body mass index ≥ 40 kg/m2) were added in June 2014 (intervention 2). Data were collected from all hospitalised adults receiving antimicrobials which required dose adjustment for severe obesity and were stratified by body mass index. Segmented regression analysis of interrupted time series was used to evaluate the impact of the Antimicrobial Prescription Surveillance System on the proportion of inappropriate days of therapy according to posology and on antimicrobial consumption. Results Overall, 65 205 antimicrobial prescriptions (68% non-obese, 25% class I-II obesity, and 7% class III obesity) were analysed. In patients with class III obesity, the intervention was associated with a decrease in the proportion of inappropriate days of therapy (trend after the first intervention, −0.8% per 2-month period [95% CI −1.1 to −0.5], p < 0.001; intercept, 11.3% [95% CI 8.2 to 14.5], p < 0.001), which led to a reduction of 35% over an eight-year period (from pre-intervention level of 19.1%). Intervention 1 resulted in a downward trend in antimicrobial consumption, followed by an increasing trend after intervention 2. In these patients, the most frequent interventions made by pharmacists targeted posology (46%). Conclusions Antimicrobial Prescription Surveillance System had a positive impact on dosing optimisation and antimicrobial consumption in patients with class III obesity. Improving antimicrobial prescriptions in these patients is important because suboptimal dosing could be associated with unfavourable outcomes.