Association of Patient Sex and Pregnancy Status With Naloxone Administration During Emergency Department Visits

OBJECTIVE: To evaluate the association of sex and pregnancy status with rates of naloxone administration during opioid overdose-related emergency department (ED) visits using the Nationwide Emergency Department Sample (NEDS). METHODS: A retrospective cohort study was conducted using NEDS 2016 and 2017 datasets. Eligible records included men and women, 15–49 years of age, with an opioid overdose-related ED visit; records for women were stratified by pregnancy status (ICD-10 O codes). A multivariable logistic regression model was used to assess the primary outcome of naloxone administration (CPT code: J2310). Secondary outcomes included subsequent admission and mortality. A subgroup analysis compared pregnant women who did versus did not receive naloxone. RESULTS: Records from 443,714 men, 304,364 non-pregnant women, and 25,056 pregnant women were included. Non-pregnant women had lower odds for naloxone administration (1.70% vs 2.10%; aOR: 0.86(0.83–0.89)) and mortality (2.21% vs 2.99%; aOR: 0.71(0.69–0.73)) but higher odds of subsequent admission (30.22% vs 27.18%; aOR: 1.04(1.03–1.06)) compared with men. Pregnant women had lower odds for naloxone administration (0..27% vs 1.70%; aOR: 0.16(0.13–0.21)) and mortality (0.41% vs 2.21%; aOR: 0.28(0.23–0.35)) but higher odds of subsequent admission (40.50% vs 30.22%; aOR: 2.04(2.00–2.10)) compared with non-pregnant women. Pregnant women who received naloxone had higher odds of mortality (14% vs 0.39%; aOR: 6.30(2.11–18.78)) compared with pregnant women who did not receive naloxone. Pregnant women who did not receive naloxone were more likely to have Medicaid as their expected insurance payer, be in the lowest quartile of median household income for residence ZIP code, and have a concurrent mental health diagnosis compared with pregnant women who did receive naloxone. CONCLUSION: Reproductive-aged non-pregnant and pregnant women were less likely to receive naloxone during opioid overdose-related ED visits compared to reproductive-aged men. Naloxone administration for reproductive-aged women should be prioritized in the efforts to reduce opioid- and pregnancy-related morbidity and mortality in the United States

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events

Background: Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions. Methods: We compared the methods authors use to decide which AEs to include in a particular source (i.e., "selection criteria"), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications - gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion "occurring in ≥2% of participants in any treatment group," while only 5/316 (2%) AEs met the criterion "occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group." Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might "cherry-pick" AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study

Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6

The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Distinct Lgr5+ cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung.This work was supported by (J.-H.L. and J.C.) Wellcome Trust and the Royal Society (107633/Z/15/Z), European Research Council Starting Grant (679411), and the Cambridge Stem Cell Institute Core grant (07922/Z/11/Z) from Wellcome Trust and Medical Research Council; (J.-H.L.) the Hope Funds for Cancer Research; (M.P.) American Lung Association (400553); (A.R.) Howard Hughes Medical Institute, the Klarman Cell Observatory, and NCI grant 1U24CA180922; (A.R., T.T., and T.J.) the Koch Institute Core grant P30-CA14051 from the NCI; (T.T.) the National Cancer InstituteK99 CA187317, the Sigrid Juselius Foundation, the Hope Funds for Cancer Research; (T.J.) a Howard Hughes Medical Institute Investigator, a David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar; and (C.F.K.) R01 HL090136, R01 HL132266, R01 HL125821, U01 HL100402, Harvard Stem Cell Institute, Alfred and Gilda Slifka, Gail and Adam Slifka, and the CFMS Fund

Basin tectonic history and paleo-physiography of the pelagian platform, northern Tunisia, using vitrinite reflectance data

Constraining the thermal, burial and uplift/exhumation history of sedimentary basins is crucial in the understanding of upper crustal strain evolution and also has implications for understanding the nature and timing of hydrocarbon maturation and migration. In this study, we use Vitrinite Reflectance (VR) data to elucidate the paleo‐physiography and thermal history of an inverted basin in the foreland of the Atlasic orogeny in Northern Tunisia. In doing so, it is the primary aim of this study to demonstrate how VR techniques may be applied to unravel basin subsidence/uplift history of structural domains and provide valuable insights into the kinematic evolution of sedimentary basins. VR measurements of both the onshore Pelagian Platform and the Tunisian Furrow in Northern Tunisia are used to impose constraints on the deformation history of a long‐lived structural feature in the studied region, namely the Zaghouan Fault. Previous work has shown that this fault was active as an extensional structure in Lower Jurassic to Aptian times, before subsequently being inverted during the Late Cretaceous Eocene Atlas I tectonic event and Upper Miocene Atlas II tectonic event. Quantifying and constraining this latter inversion stage, and shedding light on the roles of structural inheritance and the basin thermal history, are secondary aims of this study. The results of this study show that the Atlas II WNW‐ESE compressive event deformed both the Pelagian Platform and the Tunisian Furrow during Tortonian‐Messinian times. Maximum burial depth for the Pelagian Platform was reached during the Middle to Upper Miocene, i.e. prior to the Atlas II folding event. VR measurements indicate that the Cretaceous to Ypresian section of the Pelagian Platform was buried to a maximum burial depth of ~3 km, using a geothermal gradient of 30°C/km. Cretaceous rock samples VR values show that the hanging wall of the Zaghouan Fault was buried to a maximum depth of <2 km. This suggests that a vertical km‐scale throw along the Zaghouan Fault pre‐dated the Atlas II shortening, and also proves that the fault controlled the subsidence of the Pelagian Platform during the Oligo‐Miocene. Mean exhumation rates of the Pelagian Platform throughout the Messinian to Quaternary were in the order of 0.3 mm/year. However, when the additional effect of Tortonian‐Messinian folding is accounted for, exhumation rates could have reached 0.6-0.7 mm/year

A randomized trial provided new evidence on the accuracy and efficiency of traditional vs. electronically annotated abstraction approaches in systematic reviews

Abstract Objectives Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verification ("regular verification"), and independent dual data abstraction plus adjudication ("independent abstraction"). Study Design and Setting This study is an online randomized cross-over trial with 26 pairs of data abstractors. Each pair abstracted data from six articles, two per approach. Outcomes were the proportion of errors and time taken. Results Overall proportion of errors was 17% for DAA verification, 16% for regular verification, and 15% for independent abstraction. DAA verification was associated with higher odds of errors when compared with regular verification (adjusted odds ratio [OR] = 1.08; 95% confidence interval [CI]: 0.99–1.17) or independent abstraction (adjusted OR = 1.12; 95% CI: 1.03–1.22). For each article, DAA verification took 20 minutes (95% CI: 1–40) longer than regular verification, but 46 minutes (95% CI: 26 to 66) shorter than independent abstraction. Conclusion Independent abstraction may only be necessary for complex data items. DAA provides an audit trail that is crucial for reproducible research

Outcomes of abdominoperineal resection for management of anal cancer in HIV-positive patients: a national case review

BACKGROUND: The incidence of anal cancer in human immunodeficiency virus (HIV)-positive individuals is increasing, and how co-infection affects outcomes is not fully understood. This study sought to describe the current outcome disparities between anal cancer patients with and without HIV undergoing abdominoperineal resection (APR). METHODS: A retrospective review of all US patients diagnosed with anal squamous cell carcinoma, undergoing an APR, was performed. Cases were identified using a weighted derivative of the Healthcare Utilization Project’s National Inpatient Sample (2000–2011). Patients greater than 60 years old were excluded after finding a skewed population distribution between those with and without HIV infection. Multivariable logistic regression and generalized linear modeling analysis examined factors associated with postoperative outcomes and cost. Perioperative complications, in-hospital mortality, length of hospital stay, and hospital costs were compared for those undergoing APR with and without HIV infection. RESULTS: A total of 1725 patients diagnosed with anal squamous cell cancer undergoing APR were identified, of whom 308 (17.9 %) were HIV-positive. HIV-positive patients were younger than HIV-negative patients undergoing APR for anal cancer (median age 47 years old versus 51 years old, p < 0.001) and were more likely to be male (95.1 versus 30.6 %, p < 0.001). Postoperative hemorrhage was more frequent in the HIV-positive group (5.1 versus 1.5 %, p = 0.05). Mortality was low in both groups (0 % in HIV-positive versus 1.49 % in HIV-negative, p = 0.355), and length of stay (LOS) (10+ days; 75th percentile of patient data) was similar (36.9 % with HIV versus 29.8 % without HIV, p = 0.262). Greater hospitalization costs were associated with patients who experienced a complication. However, there was no difference in hospitalization costs seen between HIV-positive and HIV-negative patients (p = 0.66). CONCLUSIONS: HIV status is not associated with worse postoperative recovery after APR for anal cancer as measured by length of stay or hospitalization cost. Further study may support APRs to be used more aggressively in HIV-positive patients with anal cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12957-016-0970-x) contains supplementary material, which is available to authorized users

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal