Characterization of Early Small Bowel Obstructions Following Elective Bariatric Surgery.

PURPOSE: Small bowel obstruction (SBO) after bariatric surgery is an uncommon but important complication. We sought to characterize bariatric surgery patients who developed SBO, to compare 30-day complications, and to determine the influence of patient and procedure factors on the development of SBO. METHODS AND MATERIALS: All data was extracted from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database using the 2020 operative year. Multivariable logistic regression modelling was used to determine the influence of patient and operative factors on the development of SBO. RESULTS: Of a total of 142 111 patients, 408 (0.3%) were identified as having developed an SBO. SBO patients were older (45.7 ± 11.5 vs. 43.5 ± 11.9 years; p = 0.0002), of reduced BMI (43.6 ± 6.8 vs. 45.1 ± 7.7; p = 0.0001), and more likely to be of female sex (92.2% vs. 81.1%; p < 0.0001). At 30 days post-operation, serious complications were increased in SBO patients. Roux-en-Y gastric bypass (RYGB) was the largest independent predicator of the development of SBO (OR 11.91; 95% CI 8.92-15.90; p < 0.0001). With regard to patient factors, COPD (OR 2.60; 95% CI 1.54-4.38; p < 0.0001) and prior DVT (OR 2.37; 95% CI 1.49-3.77; p < 0.0001) were found to be independently predictive of the development of SBO. Additionally having a lower BMI and being of female sex were found to be independently predictive. CONCLUSION: SBO occurred in approximately 0.3% of MBSAQIP cases. SBO is associated with serious outcome measures and patients of female sex and reduced index BMI, and those undergoing RYGB may be at an increased risk.

Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation.

BACKGROUND: Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. OBJECTIVES: The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. DESIGN: This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011-2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). RESULTS: There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68-4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74-3.38), and hypertension (ARR:1.92, 95% CI: 1.37-2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15-7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62-4.67), and hypertension (ARR:2.18, 95% CI:1.28-3.72). No significant differences were found for obesity or diabetes. CONCLUSION: These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Characterization of Pre- and Postpandemic 30-Day Follow-Up After Elective Bariatric Surgery: a Retrospective MBSAQIP Analysis of 834,646 Patients.

BACKGROUND: Effects of the COVID-19 pandemic on rates of early postoperative follow-up after bariatric surgery are poorly understood. Our study characterizes 30-day follow-up after bariatric surgery prior to COVID-19 (years 2015-2019) and during the pandemic of COVID-19 (year 2020) and evaluates general predictive factors of short-term follow-up. METHODS: Data was extracted from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data registry from 2015 to 2020. Cohorts were divided into pre-pandemic and pandemic years and patients with and without 30-day follow-up. Multivariable logistic regression analysis was used to identify general factors independently predictive of 30-day follow-up. The primary aim was to evaluate the impact of the COVID-19 pandemic on short-term 30-day follow-up adherence. A secondary outcome was to characterize general short-term postoperative 30-day follow-up associated with elective bariatric surgery and identify independent predictors of 30-day follow-up among bariatric surgery patients using multivariable logistic regression analysis. RESULTS: A total of 834,646 patients were identified. Follow-up rates significantly increased in the COVID era in 2020 (p < 0.0001). Patients who achieved 30-day follow-up were older and had an increased burden of medical comorbidities, including non-insulin and insulin-dependent diabetes mellitus, hypertension, dyslipidemia, as well as increased BMI compared to patients lacking follow-up. The cohort with successful 30-day follow-up was more likely to receive gastric bypass and had increased rates of metabolic comorbidities. After adjusting for comorbidities, the greatest independent predictors of follow-up were the 2020 COVID-19 era year, Asian race, black race, and gastroesophageal reflux disease. CONCLUSIONS: After adjusting for comorbidities, the 2020 COVID-19 era year was one of the greatest predictors of follow-up after bariatric surgery. Postoperative follow-up rates after elective bariatric surgery are excellent at > 95% and increased during the 2020 COVID-19 era year. Several independent predictors of follow-up were identified which may help in development of strategies aimed to mitigate lack of postoperative follow-up.

Hypoalbuminemia Predicts Serious Complications Following Elective Bariatric Surgery.

PURPOSE: The aims of this study were to (1) characterize the prevalence of hypoalbuminemia (HA), (2) compare complication rates among HA and non-HA patients, and (3) determine the influence of HA on postoperative complications and 30-day mortality among bariatric surgery patients. MATERIALS AND METHODS: Data was extracted from the MBSAQIP registry from 2015 to 2018. A presurgical serum albumin level of [Formula: see text] 3.5 g/dL was used to organize the patient population into HA and non-HA cohorts. Bivariate analysis and multivariable logistic regression modeling were used. RESULTS: Of 590,971 patients, 42,618 (7.2%) were identified as having serum albumin levels [Formula: see text] 3.5 g/dL. HA patients were younger (44.0 + / - 11.9 vs. 44.5 + / - 12.0 years; p < 0.0001), were of increased BMI (48.5 + / - 9.0 kg/m2 vs. 45.1 + / - 7.7 kg/m2; p < 0.0001), and had a lower baseline functional status (1.6% vs. 1.0% dependent or partially dependent; p < 0.0001). HA patients had more anastomotic leaks (0.46% vs. 0.38%; p = 0.02), deep surgical site infections (0.37% vs. 0.24%; p < 0.0001), and composite serious complications (4.4% vs. 3.3%; p < 0.0001). At 30-day post-operation, complications including need for reintervention (1.6% vs. 1.2%; p < 0.0001), readmission (4.8% vs. 3.7%; p < 0.0001), and mortality (0.14% vs. 0.086%; p = 0.001) were all more prevalent among HA patients. After functional status, HA was the strongest modifiable predictor of serious complications but was not predictive of 30-day mortality. CONCLUSION: We identified HA as one of the greatest modifiable factors predictive of serious complications. Adoption of strategies to identify and improve preoperative serum albumin levels may reduce overall serious complications among elective bariatric surgery patients.

A 15-Year Population-Based Investigation of Sexual Assault Cases Across the Province of Ontario, Canada, 2002-2016.

Objectives. To estimate the population-level frequencies and standardized rates of sexual assault cases in the province of Ontario, Canada.Methods. We conducted a 15-year retrospective analysis (2002-2016) of sexual assault cases by linking 5 provincial administrative health databases. We defined sexual assault by an algorithm of 23 International Classification of Diseases, 10th Revision, and physician billing codes. We calculated age- and sex-stratified standardized rates per 100 000 census population, and we used age- and sex-stratified Poisson regressions to determine annual rate ratios.Results. Between 2002 and 2016, there were 52 780 incident cases of sexual assault in Ontario at a rate of 27.38 per 100 000 population. The highest rates were found among females aged 15 to 19 years (187 per 100 000) and 20 to 24 years (127 per 100 000). Among males, the highest rates were observed among children aged 0 to 4 years (41 per 100 000) and 5 to 9 years (29 per 10 000). Among males and females, the annual rate ratio increased among those aged 15 years and older and decreased among those aged 14 years and younger.Conclusions. Sexual assault was documented across all age groups and sexes, from children to elders, with high standardized rates among adolescents and children.

Incidence Rate of Post-Kidney Transplant Infection: A Retrospective Cohort Study Examining Infection Rates at a Large Canadian Multicenter Tertiary-Care Facility.

BACKGROUND: Reducing post-operative infections among kidney transplant patients is critical to improve long-term outcomes. With shifting disease demographics and implementation of new transplantation protocols, frequent evaluation of infection rate and type is necessary. OBJECTIVE: Our objectives were to assess the incidence and types of post-operative infections in kidney transplant recipients at a large tertiary-care facility and determine sample sizes needed for future intervention trials. DESIGN: Retrospective cohort study. SETTING: The Ottawa Hospital, Ottawa, Ontario. PATIENTS: Adult kidney transplant patients, N = 142. MEASUREMENTS: Demographic data, transplant protocol, infections up to 2 years following transplantation. METHODS: Infections within 2 years following transplantation in all kidney transplant recipients between January 2011 and December 2012 were reviewed. Sample sizes were determined using all-cause infection rates and infection-free survival data. RESULTS: Of 142 patients, 44 (31.0%) had at least one infection. The incidence of infection was 36.2 per 100 patient-years by 2 years post-transplant. A total of 32 (22.5%) patients had 56 infection-related hospitalizations with 73.2% occurring in the first year. In the first 2 years, urinary tract infections had the highest incidence (18.1 per 100 patient-years) followed by skin (3.9 per 100 patient-years), cytomegalovirus (3.9 per 100 patient-years), and bacteremia (3.9 per 100 patient-years). Results indicate that 206 patients per study arm would be needed to show a 30% reduction in the 2-year incidence of infection post-transplantation. LIMITATIONS: Infection rates may be slightly underestimated due to the relatively short 2-year follow-up; however, the highest infection-risk period was captured within this time frame. CONCLUSIONS: Infections post-kidney transplant are still common, particularly urinary tract infections. They are associated with significant morbidity and hospitalization. Given the feasible sample sizes calculated in this study, intervention trials are indicated to further reduce infection rates within the first 2 years post-kidney transplantation.

CONTEXTE: La réduction du nombre d'infections post-opératoires contractées par les receveurs d'une greffe rénale est essentielle pour améliorer leurs résultats à long terme. Compte tenu de l'évolution démographique de la maladie et de la mise en œuvre de nouveaux protocoles de transplantation, l'évaluation fréquente des taux d'infections et des types d'infections est nécessaire. OBJECTIFS: Nous voulions identifier les types d'infections post-opératoires touchant les receveurs d'une greffe rénale et mesurer leur incidence dans un important centre de soins tertiaires. Nous souhaitions également établir la taille de l'échantillon adéquat pour procéder à des études interventionnelles futures. TYPE D'ÉTUDE: Une étude de cohorte rétrospective. CADRE: L'Hôpital d'Ottawa, en Ontario. SUJETS: Des adultes receveurs d'une greffe rénale (n=142). MESURES: Les données démographiques des patients, le protocole de transplantation appliqué lors de l'intervention et les infections contractées dans les deux ans suivant la greffe. MÉTHODOLOGIE: Ont été examinées toutes les infections contractées dans les deux ans suivant l'intervention chez tous les receveurs d'une greffe rénale entre janvier 2011 et décembre 2012. La taille de l'échantillon adéquat pour une étude interventionnelle a été déterminée à l'aide des données sur le taux d'infections toutes causes et le taux de survie sans infections. RÉSULTATS: Des 142 patients retenus pour l'étude, 44 (31,0 %) avaient contracté au moins une infection au cours de la période de suivi. L'incidence des infections se situait à 36,2 par 100 années-patients deux ans après la greffe. Un total de 32 patients (22,5 %) avait contracté 56 infections liées à l'hospitalisation, dont 73,2 % étaient survenues dans la première année. Dans les deux ans suivant la greffe, les infections des voies urinaires se sont avérées les plus prévalentes (18,1 par 100 années-patients), suivies des infections cutanées (3,9 par 100 années-patients), des infections par cytomégalovirus (3,9 par 100 années-patients) et des bactériémies (3,9 par 100 années-patients). Les résultats indiquent que 206 sujets par bras d'étude seraient nécessaires pour démontrer une réduction de 30 % de l'incidence des infections au cours des deux ans suivant une greffe rénale. LIMITES: Les taux d'infections pourraient être sous-estimés compte tenu de la durée relativement courte du suivi (deux ans). Par contre, la durée du suivi couvrait la période où le risque de contracter une infection est le plus élevé. CONCLUSION: Les infections consécutives à une greffe rénale sont encore fréquentes, particulièrement les infections des voies urinaires, et sont associées à plus de morbidité et à un important taux d'hospitalisation. La taille de l'échantillon adéquat étant facilement réalisable, des études interventionnelles sont indiquées pour réduire davantage les taux d'infections contractées au cours des deux ans suivant une greffe rénale.

Food Effect on Rosuvastatin Disposition and Low-Density Lipoprotein Cholesterol.

Rosuvastatin is commonly prescribed for the treatment of hypercholesterolemia and hepatic transporter-mediated accumulation in the liver enhances its efficacy. Current guidelines indicate no preference for fed or fasted rosuvastatin administration. We investigated the association between food intake and rosuvastatin disposition in healthy subjects and low-density lipoprotein cholesterol (LDL-C)-lowering effects among patients taking rosuvastatin. We demonstrate that administration with food resulted in a near 40% reduction of rosuvastatin exposure in healthy Asian (n = 12) and Caucasian (n = 11) subjects. Higher rosuvastatin concentrations in Asian subjects also correlated with higher allele frequency of ABCG2 c.421C>A. In mice, a greater rosuvastatin liver:plasma ratio was noted when administered with food. Among rosuvastatin patients (n = 156), there was no difference in dose needed to reach target LDL-C, measured LDL-C, or lathosterol concentrations, when administered in a fed or fasting state. Therefore, taking rosuvastatin with food could reduce systemic concentrations, and subsequent myopathy risk, without compromising LDL-C-lowering benefit.

Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant?

Drug transporters are becoming increasingly recognized as relevant to the drug development process. This may be a reflection of increasing target complexity and the need for high-affinity interaction with drug targets that minimize off-target side effects. Moreover, as new molecular entities (NMEs) become larger in size and amphipathic in nature, interaction with drug transporters, both uptake as well as efflux, becomes increasingly likely. In some cases transporters may limit the absorption or organ-specific entry of NMEs, whereas in other cases transporters may enhance their absorption or tissue accumulation. Indeed, in some cases, transporters may prove to be a therapeutic target. Accordingly, a better understanding of potentially clinically relevant drug transporter polymorphisms earlier in the drug development process is highly desirable. In this review we examine key transporters that are important to the absorption, distribution, and excretion of a large number of drugs in clinical use. Importantly, we provide our assessment of the potential impact of known polymorphisms in such transporters and discuss whether there is sufficient evidence to incorporate these polymorphisms in the drug development process.

Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis.

PURPOSE OF REVIEW: This article evaluates the link between trimethylamine-N-oxide (TMAO) and bile acids and the consequent impact on the development of atherosclerosis. RECENT FINDINGS: Elevation in plasma TMAO concentrations is associated with an increased risk of cardiovascular disease in many different patient cohorts. In addition to the recently identified direct effects of TMAO on the development of atherosclerosis, other components involved in TMAO metabolism may also have an impact. Furthermore, the relationship between TMAO and bile acid regulation is emerging as a possible mediator of atherosclerosis. SUMMARY: Studies that are emerging highlight the mechanistic relationship of TMAO to the development atherosclerosis in addition to its role as disease biomarker. The interplay between TMAO and bile acid metabolism mediated through multiple factors, such as the gut microbiome, farnesoid X receptor signaling, and flavin monooxygenase 3 activity may help identify another pathway by which atherosclerosis occurs. In this review, we discuss the most recent data regarding atherosclerosis, TMAO, and bile acid metabolism.