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Study objectivesTo describe patterns of outpatient antibacterial use among California Medicaid (Medi-Cal) fee-for-service system beneficiaries, and to investigate the influence of demographic factors-age, race/ethnicity, state county, and population density-on those patterns.DesignRetrospective analysis of administrative claims data.Data sourceMedi-Cal fee-for-service system claims database.PatientsAll outpatient Medi-Cal fee-for-service system beneficiaries enrolled between 2006 and 2011 who had at least one systemic antibacterial claim.Measurements and main resultsRates of antibacterial prescribing and the proportion of broad-spectrum antibacterial use were measured over the study period and among age, racial/ethnic, and geographic (county) groups. Of the 10,018,066 systemic antibacterial claims selected for analysis, antibacterial prescribing rates decreased from 542 claims/1000 beneficiaries in 2006 to 461 claims/1000 beneficiaries in 2011 (r = -0.971, p=0.0012; τ-b = -1.00, p=0.009). Among age groups, children had the highest rate of use (605 claims/1000 beneficiaries, χ(2) (2) = 320,000, p

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC incidence and mortality can be reduced through screening. However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and racial/ethnic minority groups. Increasing screening rates among underserved populations will reduce the US burden of CRC. In this commentary focusing on underserved populations, we highlight the public health impact of CRC screening, list key challenges to screening the underserved, and review promising approaches to boost screening rates. We identify four key policy and research priorities to increase screening among underserved populations: 1) actively promote the message, "the best test is the one that gets done"; 2) develop and implement methods to identify unscreened individuals within underserved population groups for screening interventions; 3) develop and implement approaches for organized screening delivery; and 4) fund and enhance programs and policies that provide access to screening, diagnostic follow-up, and CRC treatment for underserved populations. This commentary represents the consensus of a diverse group of experts in cancer control and prevention, epidemiology, gastroenterology, and primary care from across the country who formed the Coalition to Boost Screening among the Underserved in the United States. The group was organized and held its first annual working group meeting in conjunction with the World Endoscopy Organization's annual Colorectal Cancer Screening Committee meeting during Digestive Disease Week 2012 in San Diego, California.

Background Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB. Methods This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications. Results A total of 114 patients experienced GIB within 1 year, with a higher rate in the endoscopy cohort (36.4% vs. 24.8%, P=0.015). After adjusting for covariables, the endoscopy cohort remained at increased risk of GIB (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.976; P=0.032). Severe bleeding was common (47.4%). Arteriovenous malformations (48 cases) and peptic ulcer disease (17 cases) were the most identified sources of GIB. Only 1 minor adverse event occurred during preoperative endoscopy. Conclusions Our study suggests that pre-LVAD endoscopy is associated with a higher risk of GIB post LVAD, despite controlling for confounders. While this was an observational study and may not have captured all confounders, it appears that endoscopic screening may not be warranted. [ABSTRACT FROM AUTHOR]

Farnesoid X receptor (FXR) agonism is emerging as an important potential therapeutic mechanism of action for multiple chronic liver diseases. The bile acid‐derived FXR agonist obeticholic acid (OCA) has shown promise in a phase 2 study in patients with nonalcoholic steatohepatitis (NASH). Here, we report efficacy of the novel nonbile acid FXR agonist tropifexor (LJN452) in two distinct preclinical models of NASH. The efficacy of tropifexor at

Abstract Background Pancreatic cancer is projected to become the second leading cause of cancer‐related deaths by 2030. Endoscopic retrograde cholangiopancreatography (ERCP) is recommended as first‐line therapy for biliary decompression in pancreatic cancer. The aim of our study was to characterize geographic and racial/ethnic disparities in ERCP utilization among patients with pancreatic cancer. Methods Retrospective cohort study using the US Surveillance, Epidemiology, and End Results (SEER)‐Medicare database to identify patients diagnosed with pancreatic cancer from 2003‐2013. The primary outcome was receipt of ERCP, with or without stent placement, vs any non‐ERCP biliary intervention. Results Of the 36 619 patients with pancreatic cancer, 37.5% (n = 13 719) underwent an ERCP, percutaneous drainage, or surgical biliary bypass. The most common biliary intervention (82.6%) was ERCP. After adjusting for tumor location and stage, Blacks were significantly less likely to receive ERCP than Whites (aOR 0.84, 95% CI 0.72, 0.97) and more likely to receive percutaneous transhepatic biliary drainage (PTBD) (aOR 1.38, 95% CI 1.14, 1.66). Patients in the Southeast and the West were more likely to receive ERCP than those in the Northeast (Southeast aOR 1.21, 95% CI 1.04, 1.40; West aOR 1.16, 95% CI 1.01, 1.32). Conclusion Racial/ethnic and geographic disparities in access to biliary interventions including ERCP exist for patients with pancreatic cancer in the United States. Our results highlight the need for further research and policies to improve access to appropriate biliary intervention for all patients.

Abstract Background Metabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8 years in subjects with and without HIV infection determined based on the use of ART. Methods We studied 10 participants from the Osteoarthritis Initiative who received ART at baseline and 20 controls without ART, frequency matched for age, sex, race, baseline body mass index (BMI) and Kellgren & Lawrence grade. Knee abnormalities were assessed using the whole-organ magnetic resonance imaging score (WORMS) and cartilage T2 including laminar and texture analyses were analyzed using a multislice-multiecho spin-echo sequence. Signal abnormalities of the infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) were assessed separately using a semi-quantitative scoring system. Linear regression models were used in the cross-sectional analysis to compare the differences between ART/HIV subjects and controls in T2 (regular and laminar T2 values, texture parameters) and morphologic parameters (subscores of WORMS, scores for signal alterations of IPFP and SPFP). Mixed effects models were used in the longitudinal analysis to compare the rate of change in T2 and morphological parameters between groups over 8 years. Results At baseline, individuals on ART had significantly greater size of IPFP signal abnormalities (P = 0.008), higher signal intensities of SPFP (P = 0.015), higher effusion scores (P = 0.009), and lower subchondral cysts sum scores (P = 0.003) compared to the controls. No significant differences were found between the groups in T2-based cartilage parameters and WORMS scores for cartilage, meniscus, bone marrow edema patterns and ligaments (P > 0.05). Longitudinally, the HIV cohort had significantly higher global knee T2 entropy values (P = 0.047), more severe effusion (P = 0.001) but less severe subchondral cysts (P = 0.002) on average over 8 years. Conclusions Knees of individuals with HIV on ART had a more heterogeneous cartilage matrix, more severe synovitis and abnormalities of the IPFP and SPFP, which may increase the risk of incident knee osteoarthritis.

How HIV reservoirs are shaped over time on antiviral therapy is poorly understood. Here, the authors analyze the dynamics of the HIV reservoir by longitudinal proviral sequencing revealing that HIV reservoir expression can contribute to its clearance and paradoxically even to its persistence.

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.

Abstract Capture–recapture studies are widely used in ecology to estimate population sizes and demographic rates. In some capture–recapture studies, individuals may be visually encountered but not identified. For example, if individual identification is only possible upon capture and individuals escape capture, visual encounters can result in failed captures where individual identities are unknown. In such cases, the data consist of capture histories with known individual identities, and counts of failed captures for individuals with unknown identities. These failed captures are ignored in traditional capture–recapture analyses that require known individual identities. Here, we show that if animals can be encountered at most once per sampling occasion, failed captures provide lower bounds on population size that can increase the precision of abundance estimates. Analytical results and simulations indicate that visual encounter data improve abundance estimates when capture probabilities are low, and when there are few repeat surveys. We present a hierarchical Bayesian approach for integrating failed captures and auxiliary encounter data in statistical capture–recapture models. This approach can be integrated with existing capture–recapture models and may prove particularly useful for hard to capture species in data‐limited settings.

Vessel-based sonar systems that focus on the water column provide valuable information on the distribution of underwater marine organisms, but such data are expensive to collect and limited in their spatiotemporal coverage. Satellite data, however, are widely available across large regions and provide information on surface ocean conditions. If satellite data can be linked to subsurface sonar measurements, it may be possible to predict marine life over broader spatial regions with higher frequency using satellite observations. Here, we use random forest models to evaluate the potential for predicting a sonar-derived proxy for subsurface biomass as a function of satellite imagery in the California Current Ecosystem. We find that satellite data may be useful for prediction under some circumstances, but across a range of sonar frequencies and depths, overall model performance was low. Performance in spatial interpolation tasks exceeded performance in spatial and temporal extrapolation, suggesting that this approach is not yet reliable for forecasting or spatial extrapolation. We conclude with some potential limitations and extensions of this work.

ObjectiveAfrican potato (Hypoxis obtusa) is commonly used in Sub-Saharan Africa as a complementary herbal remedy for HIV-infected patients. It is unknown whether or not co-administration of African potato alters the pharmacokinetics of protease inhibitor antiretrovirals. The objective of this study was to investigate the impact of the African potato on the steady-state pharmacokinetics of ritonavir-boosted lopinavir (LPV/r).MethodsSixteen adult volunteers were administered LPV/r 400/100 mg twice a day for 14 days, followed by concomitant administration with African potato given once daily for 7 days. Lopinavir plasma exposure as estimated by the area under the concentration-time curve over the 12-h dosing interval (AUC(0-12h), AUCτ) was determined on day 14 and again on day 21. Lopinavir in plasma was analyzed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Steady-state AUCτ and the maximum concentration following dose administration (C(max)) were determined using non-compartmental methods using WinNonlin Professional version 5.2.1. Statistical analyses were performed using Stata version 12.1.ResultsCo-administration of African potato was not associated with any change in lopinavir AUCτ, C(max), or C(trough).ConclusionsAfrican potato when taken concomitantly with LPV/r is well-tolerated and not associated with clinically significant changes in lopinavir pharmacokinetics.

Study objectiveTo evaluate the pharmacokinetics of gentamicin in neonates with hypoxic ischemic encephalopathy (HIE) receiving hypothermia and to identify an empiric gentamicin dosing strategy in this population that optimizes achievement of target peak and trough concentrations.DesignPopulation pharmacokinetic study using retrospective medical record data.SettingTertiary neonatal intensive care unit.PatientsA total of 29 full-term neonates diagnosed with HIE treated with hypothermia who received gentamicin and underwent therapeutic drug monitoringMeasurement and main resultsPatient demographics and gentamicin concentration data were retrospectively collected over a 2-year period. A population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM). Using the developed model, Monte Carlo simulations were performed to evaluate the probability of achieving target peak (> 6 mg/L) and trough (< 2 mg/L) gentamicin concentrations for various potential dosing regimens. A one-compartment model best described the available gentamicin concentration data. Birthweight and serum creatinine significantly influenced gentamicin clearance. For the typical study neonate (birthweight 3.3 kg, serum creatinine 0.9 mg/dl), clearance was 0.034 L/hour/kg and volume was 0.52 L/kg. At a 24-hour dosing interval, Monte Carlo simulations predicted target gentamicin peak and trough concentrations could not be reliably achieved at any dose. At a 36-hour dosing interval, a dose of 4-5 mg/kg is predicted to achieve target gentamicin peak and trough concentrations in more than 90% of neonates.ConclusionsGentamicin clearance is decreased in neonates with HIE treated with hypothermia compared with previous reports in nonasphyxiated normothermic full-term neonates. A prolonged 36-hour dosing interval will be needed to achieve target gentamicin trough concentrations in this population. Further prospective evaluation of this dosing recommendation is needed.

BackgroundAn internal evaluation of the inpatient pharmacy order entry database (WORx) at a university hospital revealed that the nature of the reaction was documented for only 47% of patients with reported drug allergies/intolerance. Insufficient documentation of drug allergy/intolerance may result in administration of drugs that should not be prescribed. Similarly, valuable agents that should be used may not be prescribed due to an unnecessary fear of adverse drug reaction. More complete description of drug allergy/intolerance may result in more correct prescribing of medications.ObjectiveEvaluate the impact of a pharmacist-driven protocol on the quality of drug allergy/intolerance documentation.MethodsFour pre-intervention evaluations were conducted every 2 weeks documenting the completeness of drug allergy/intolerance information in the pharmacy order entry database. One week following the implementation of a pharmacist-driven protocol intended to improve the completeness of drug allergy/intolerance information, a series of 4 postintervention evaluations was repeated. Proportional analysis of pre- and postinterventional data was performed to evaluate the effectiveness of the intervention.ResultsA total of 1,686 allergies from 2,174 patients were reviewed pre and post intervention. The frequency of complete drug allergy/intolerance documentation pre intervention was 52% to 62%. Following implementation of the hospitalwide, pharmacist-driven protocol, this rate increased to 60% to 76%. Pediatric services demonstrated the most substantial improvement, increasing from 53% to 79% to 67% to 93%. Blank reaction fields decreased by 10% in both age groups.ConclusionA pharmacy-driven initiative intended to improve the completeness of drug allergy/intolerance documentation was associated with modest success. Other mechanisms, including electronic health record systems with computerized physician order entry and decision support, are needed to improve the completeness of drug allergy/intolerance information.

Patient adherence (the degree to which patients follow their therapeutic regimen as prescribed within a set period of time) and persistence (the time to treatment discontinuation, with a permissible gap) with drug therapy are essential components of HIV/AIDS treatment. Select community pharmacies offer specialized services for HIV/AIDS patients to help combat some of the barriers to adherence and persistence. We assessed adherence and persistence with antiretroviral therapy (ART) for patients using HIV-specialized pharmacies in nine cities from seven states compared to traditional community pharmacy users over a 1-year period. Data were limited to one pharmacy chain. Propensity scoring was used to obtain 1:1 matches for "Specialized" and "Traditional" pharmacy users based on age, gender, number of prescription-inferred chronic conditions (obtained by mapping a patient's prescriptions to the Medi-Span Drug Indications Database), and presence of prescription anxiety and/or depression medication, resulting in 7064 patients in each group. Proportion of days covered (PDC) was used to measure adherence. Specialized pharmacy users had a significantly greater mean (74.1% versus 69.2%, p

ObjectiveTo determine differences in patient characteristics, antiretroviral therapy (ART) regimen characteristics, and regimen refill adherence for human immunodeficiency virus (HIV)-focused pharmacy (HIV-P) versus traditional pharmacy (TP) users.DesignRetrospective cohort study.SettingCalifornia Walgreens pharmacies from May 2007 to August 2009.ParticipantsHIV-positive patients with greater than 30 days of antiretroviral prescription claims.InterventionDeidentified prescription records for patients filling any ART prescription at any California Walgreens pharmacy during the study period were assessed.Main outcome measuresART regimen refill adherence (calculated by modified medication possession ratio [mMPR]) and dichotomous measure of optimal adherence of 95% or greater.Results4,254 HIV-P and 11,679 TP users were included. Compared with TP users, HIV-P users traveled farther to pharmacies (5.03 vs. 1.26 miles, P < 0.01). A greater proportion of HIV-P users filled prescriptions for chronic diseases (35% vs. 30%) and received fixed-dose combination antiretroviral tablets (92% vs. 83%) (all P < 0.01). Median mMPR was higher for HIV-P users (90% vs. 77%, P < 0.0001). After adjusting for age, gender, insurance, medication use, and distance from pharmacy, use of HIV-P (odds ratio 1.90 [95% CI 1.72-2.08]) and fixed-dose combination antiretroviral tablets (3.34 [2.84-3.96]) were most strongly associated with having 95% or greater ART regimen refill adherence.ConclusionFor HIV-positive patients struggling with antiretroviral adherence, clinicians may consider minimizing pill burden with combination tablets and referral to an HIV-focused pharmacy.

Yersinia pestis can be transmitted by fleas during the first week after an infectious blood meal, termed early-phase or mass transmission, and again after Y. pestis forms a cohesive biofilm in the flea foregut that blocks normal blood feeding. We compared the transmission efficiency and the progression of infection after transmission by Oropsylla montana fleas at both stages. Fleas were allowed to feed on mice three days after an infectious blood meal to evaluate early-phase transmission, or after they had developed complete proventricular blockage. Transmission was variable and rather inefficient by both modes, and the odds of early-phase transmission was positively associated with the number of infected fleas that fed. Disease progression in individual mice bitten by fleas infected with a bioluminescent strain of Y. pestis was tracked. An early prominent focus of infection at the intradermal flea bite site and dissemination to the draining lymph node(s) soon thereafter were common features, but unlike what has been observed in intradermal injection models, this did not invariably lead to further systemic spread and terminal disease. Several of these mice resolved the infection without progression to terminal sepsis and developed an immune response to Y. pestis, particularly those that received an intermediate number of early-phase flea bites. Furthermore, two distinct types of terminal disease were noted: the stereotypical rapid onset terminal disease within four days, or a prolonged onset preceded by an extended, fluctuating infection of the lymph nodes before eventual systemic dissemination. For both modes of transmission, bubonic plague rather than primary septicemic plague was the predominant disease outcome. The results will help to inform mathematical models of flea-borne plague dynamics used to predict the relative contribution of the two transmission modes to epizootic outbreaks that erupt periodically from the normal enzootic background state.

Experimental inquiry-oriented science labs can be designed to have students regulate their own learning and decide when they leave class or to have the teacher regulate student learning and determine when they leave class. In this study, grades were examined relative to student exit times in a student-regulated class design. Preliminary interviews revealed four motivation strategies likely to differentially influence exit times and grades: proficiency, grade-target-A, grade-target-C, and time-limited. Students were categorized into the four groups of motivation strategies with a survey. Twenty teaching assistants teaching three lab sections each taught the stand-alone lab class. Students recorded the time they left class each week. Grades were determined as the overall percentage of points a student received in class. Results of the survey showed that the four motivation strategies were well represented in the student population, and two additional strategies were also frequently seen: a hybrid-1 between proficiency and grade-target-A, and a hybrid-2 between time-limited and grade-target-C. Grades were significantly higher for grade-target-A and hybrid-1 students, followed by time-limited, proficiency, grade-target-C, and hybrid 2. Time spent in class was not significantly different among categories. Students who chose to stay in class longer had significantly higher grades. If a grade is the goal, these results support the idea of a teacher-controlled exit time for the students in these inquiry-oriented labs. Implications are discussed.

Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing ~5x108 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.

A 2-year-old male with arginosuccinate lyase deficiency underwent left lateral segment liver transplantation complicated by “orphan duct syndrome (Celik et al., 2019) [1]” and biliary leak. After revision of the Roux-en-Y anastomosis, biliary drainage was still impaired. The excluded bile duct was diagnosed and a biliary restoration (or neo-duct) using a combined endoscopic and percutaneous approach was created by Gastroenterology and Interventional Radiology. To our knowledge, this case report represents the first combined endoscopic-percutaneous biliary restoration procedure performed in a pediatric patient.

Abstract Extreme droughts, heat waves, fires, hurricanes, floods, and landslides cause the largest losses in the United States, and globally, from natural hazards linked to weather and climate. There is evidence that the frequency of such extremes is increasing, particularly for heat waves, large fires, and intense precipitation, making better understanding of the probability and consequences of these events imperative. Further, these events are not isolated, but rather interact with each other and with other social and biophysical drivers and conditions, to amplify impacts. Less is known about the nature and strength of these interactions. Natural and social science subfields frame extreme events with different definitions and analytical approaches, often neglecting interactions and the subsequent novel extremes that can arise. Here we propose a framework for social‐environmental extremes, defined as extraordinary events that emerge from interactions among biophysical and social systems. We argue that this definition is critical because it constrains the focus to major events that are capturing societal and scientific attention because of their extreme biophysical drivers and/or the extreme social outcomes. We review how different fields approach extremes as interacting phenomena and propose a synthetic framework that allows analytical separation of the multiple drivers and responses that yield extreme events and extreme effects. We conclude with a future research agenda for understanding the extreme events that matter to society. This agenda will help to identify where, when, and why communities may have high exposure and vulnerability to social‐environmental extremes—informing future mitigation and adaptation strategies.

Background and study aims Impact of intravenous fluid administration on prophylaxis against post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been rigorously evaluated among patients at high-risk for PEP. Patients and methods Effect of volume and type of fluid administered on PEP incidence was studied through a secondary analysis of high-risk patients who underwent endoscopic retrograde cholangopancreatography (ERCP) as a part of a randomized controlled trial in which all patients received rectal indomethacin. Periprocedural fluid was defined as fluid infused during and after ERCP. Results A total 960 patients were randomized during the trial, of whom 476 (49.6 %) received periprocedural fluids (mean volume = 1245 mL [± 629]). There was a trend towards a lower incidence of PEP in patients who received periprocedural fluid vs. those who did not (5.2 % vs. 8.0 %, P = 0.079). Among those receiving fluids, those who did not develop PEP received a higher mean volume of fluid vs. who developed PEP (1012 ± 725 mL vs. 752 ± 783 mL, P = 0.036). Among 174 patients (37 %) who received LR, patients who did not develop PEP received a higher mean volume of LR vs. those who developed PEP (570 ± 559 mL vs. 329 ± 356 mL, P = 0.006). Length of hospital stay decreased as the volume of periprocedural volume administration increased (r = 0.16, P

[This corrects the article DOI: 10.1371/journal.pntd.0005276.].

Background and study aims Existing guidelines recommend continuation of aspirin therapy prior to outpatient endoscopic procedures, as it reduces peri-procedural cardiovascular events and is not associated with an increased risk of bleeding. Despite this, many patients at our institution inappropriately alter their aspirin prior to endoscopy. We sought to identify why this occurs and implement an intervention that could reduce improper aspirin alteration. Patients and methods All adult patients undergoing outpatient endoscopy at the Medical University of South Carolina were administered a survey querying demographics, aspirin use, endoscopic procedure, thromboembolic risk factors, and pre-procedural aspirin alteration, if any. An intervention involving revised written and verbal instructions as well as an automated voicemail aimed at ensuring patients adhere to guidelines was then undertaken. The same survey was administered after the intervention to assess for improved adherence. Results A total of 240 patients from the initial survey reported daily aspirin use, of which 114 (47.5 %) inappropriately altered aspirin therapy. A total of 182 patients from the post-intervention survey reported daily aspirin use, of which 66 (36.3 %) inappropriately altered aspirin therapy. This was a statistically significant reduction (P = 0.04), which included adjustments for age, sex, procedure type, and thromboembolic risk. Conclusions A high proportion of patients at our institution inappropriately alter aspirin therapy prior to outpatient endoscopy. The reasons for this behavior include patient self-direction, misguidance from staff, and instruction from other physicians. This alteration can be reduced significantly through an intervention that educates both patients and staff on continuation of aspirin therapy prior to outpatient endoscopy.