Knowledge, attitudes and practices of Canadian pediatric emergency physicians regarding short-term opioid use: a descriptive, cross-sectional survey

BACKGROUND: In the midst of the current opioid crisis, physicians are caught between balancing children\u27s optimal pain management and the risks of opioid therapy. This study describes pediatric emergency physicians\u27 practice patterns for prescribing, knowledge and attitudes regarding, and perceived barriers to and facilitators of short-term use of opioids. METHODS: We created a survey tool using published methodology guidelines and distributed it from October to December 2017 to all physicians in the Pediatric Emergency Research Canada database using Dillman\u27s tailored design method for mixed-mode surveys. We performed bivariable binomial logistic regressions to ascertain the effects of clinically significant variables (e.g., training, age, sex, degree of worry regarding severe adverse events) on use of opioids as a first-line treatment for moderate pain in the emergency department, and prescription of opioids for moderate or severe pain for at-home use in children. RESULTS: Of the 224 physicians in the database, 136 (60.7%) completed the survey (60/111 [54.1%] women; median age 44 yr). Of the 136, 74 (54.4%) had subspecialty training. Intranasally administered fentanyl was the most commonly selected opioid for first-line treatment of moderate (47 respondents [34.6%]) and severe (82 [60.3%]) pain due to musculoskeletal injury. On a scale of 0 (not worried) to 100 (extremely worried), physicians\u27 median score for worry regarding physical dependence was 6.0 (25th percentile 0.0, 75th percentile 16.0), for worry regarding addiction 10.0 (25th percentile 2.0, 75th percentile 20.0) and for worry regarding diversion of opioids 24.5 (25th percentile 14.0, 75th percentile 52.0). On a scale of 0 (not at all) to 100 (extremely), the median score for influence of the opioid crisis on willingness to prescribe opioids was 22.0 (25th percentile 8.0, 75th percentile 49.0). The top 3 reported barriers to prescribing opioids were parental reluctance (57 [41.9%]), lack of clear guidelines for pediatric opioid use (35 [25.7%]) and concern about adverse effects (33 [24.3%]). Binomial logistic regression did not identify any statistically significant variables affecting use of opioids in the emergency department or prescribed for use at home. INTERPRETATION: Emergency department physicians appeared minimally concerned about physical dependence, addiction risk and the current opioid crisis when prescribing opioids to children. Evidence-based development of guidelines and protocols for use of opioids in children may improve physicians\u27 ability to manage pain in children responsibly and adequately

Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes

To investigate the feasibility of conducting a genomic-scale protein labeling and localization study in Escherichia coli, a representative subset of 23 coding DNA sequences (CDSs) was selected for chromosomal tagging with one or more fluorescent protein genes (EGFP, EYFP, mRFP1, DsRed2). We used λ-Red recombination to precisely and efficiently position PCR-generated DNA targeting cassettes containing a fluorescent protein gene and an antibiotic resistance marker, at the C-termini of the CDSs of interest, creating in-frame fusions under the control of their native promoters. We incorporated cre/loxP and flpe/frt technology to enable multiple rounds of chromosomal tagging events to be performed sequentially with minimal disruption to the target locus, thus allowing sets of proteins to be co-localized within the cell. The visualization of labeled proteins in live E. coli cells using fluorescence microscopy revealed a striking variety of distributions including: membrane and nucleoid association, polar foci and diffuse cytoplasmic localization. Fifty of the fifty-two independent targeting experiments performed were successful, and 21 of the 23 selected CDSs could be fluorescently visualized. Our results show that E. coli has an organized and dynamic proteome, and demonstrate that this approach is applicable for tagging and (co-) localizing CDSs on a genome-wide scale

Estimates of North Atlantic ventilation and mode water formation for winters 2002–06

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 2600-2617, doi:10.1175/2009JPO3930.1.Lagrangian estimates for ventilation rates in the Gulf Stream Extension using Argo and World Ocean Circulation Experiment/Atlantic Climate and Circulation Experiment (WOCE/ACCE) float data, scatterometer (QuikSCAT) wind stress satellite observations, and altimetric [Archiving, Validation, and Interpretation of Satellite Oceanographic data (AVISO)] sea surface height (SSH) satellite observations from 2002 to 2006 are presented. Satellite winds and estimates of surface geostrophic currents allow the inclusion of the effects of currents on wind stress as well as their impact on the Ekman pumping. The presence of large surface geostrophic currents decreases the total Ekman pumping, contributing up to 20% where the Gulf Stream makes its two sharpest turns, and increases the total Ekman pumping by 10% or less everywhere else. The ageostrophic currents may be as large as 15% of the geostrophic currents, but only in proximity of the Gulf Stream. Using currents and mixed layer depths (MLDs) that are either climatological or vary from year to year, obducted water tends to originate along the Gulf Stream, while subducted water tends to originate to its south. However, using time-varying MLDs for each year, subduction varies significantly, sometimes oppositely from obduction. The 18° Water (EDW) subducts in different locations and is distributed differently each year but tends to be located in the Sargasso Sea. Vertical pumping is the only dominant factor in ventilation closer to the coast where MLDs are shallower and lighter parcels are subducted. Vertical pumping contributes up to 20% of the several hundreds of ventilated meters per year around the Gulf Stream and less elsewhere. Using a temperature- or density-based criterion for estimating the MLDs, especially along the coasts and north of 45°N, obduction estimates differ by up to 25%. The horizontal and temporal structure of the MLDs is the primary factor that controls the tens of sverdrups of ventilation (and a few sverdrups of EDW subduction)

The association between protease inhibitors and anal cancer outcomes in veterans living with HIV treated with definitive chemoradiation: a retrospective study

Background: The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. Methods: Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. Results: A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values\u3e 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p \u3c 0.01). Conclusion: The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation

High-cadence Timing of Binary Pulsars with CHIME

We performed near-daily observations of the binary pulsars PSR J0218+4232, PSR J1518+4904, and PSR J2023+2853 with the Canadian Hydrogen Intensity Mapping Experiment (CHIME). For the first time, we detected the Shapiro time delay in all three pulsar binary systems, using only 2-4 yr of CHIME/Pulsar timing data. We measured the pulsar masses to be 1.49 − 0.20 + 0.23 M ⊙, 1.470 − 0.034 + 0.030 M ⊙, and 1.50 − 0.38 + 0.49 M ⊙, respectively. The companion mass to PSR J0218+4232 was found to be 0.179 − 0.016 + 0.018 M ⊙. We constrained the mass of the neutron star companion of PSR J1518+4904 to be 1.248 − 0.029 + 0.035 M ⊙, using the observed apsidal motion as a constraint on the mass estimation. The binary companion to PSR J2023+2853 was found to have a mass of 0.93 − 0.14 + 0.17 M ⊙; in the context of the near-circular orbit, this mass estimate suggests that the companion to PSR J2023+2853 is likely a high-mass white dwarf. By comparing the timing model obtained for PSR J0218+4232 with previous observations, we found a significant change in the observed orbital period of the system of P b ̇ = 0.14 ( 2 ) × 10 − 12 ; we determined that this variation arises from “Shklovskii acceleration” due to the relative motion of the binary system, and used this measurement to estimate a distance of d = (6.7 ± 1.0) kpc to PSR J0218+4232. This work demonstrates the capability of high-cadence observations, enabled by the CHIME/Pulsar system, to detect and refine general-relativistic effects of binary pulsars over short observing timescales

Clinico-Neuropathological Findings in the Oldest Old from the Georgia Centenarian Study

Background: Centenarian studies are important sources for understanding of factors that contribute to longevity and healthy aging. Clinico-neuropathological finding is a key in identifying pathology and factors contributing to age-related cognitive decline and dementia in the oldest old. Objective: To characterize the cross-sectional relationship between neuropathologies and measures of premortem cognitive performance in centenarians. Methods: Data were acquired from 49 centenarians (≥98 years) from the Georgia Centenarian Study. Cognitive assessment from the time point closest to mortality was used (\u3c1 year for all subjects) and scores for cognitive domains were established. Neuropathologies [cerebral atrophy, ventricular dilation, atherosclerosis, cerebral amyloid angiopathy (CAA), Lewy bodies, hippocampal sclerosis (HS), hippocampal TDP-43 proteinopathy, neuritic plaque (NP) and neurofibrillary tangle (NFT) counts, Braak staging, and National Institute on Aging-Reagan Institute (NIARI) criteria for the neuropathological diagnosis of Alzheimer’s disease (AD)] were compared among subjects with different ratings of dementia. Linear regression was applied to evaluate the association between cognitive domain scores and neuropathologies. Results: Wide ranges of AD-type neuropathological changes were observed in both non-demented and demented subjects. Neocortical NFT and Braak staging were related to clinical dementia rating. Neocortical NFT and NP, Braak and NIARI staging, cerebral and ventricular atrophy, HS, CAA, and TDP-43 proteinopathy were differentially associated with poor performance in multiple cognitive domains and activities of daily living. Conclusion: AD-type pathology was associated with severe dementia and poor cognition but was not the only variable that explained cognitive impairment, indicating the complexity and heterogeneity of pathophysiology of dementia in the oldest old

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants.

Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, Integrative Fine-Mapping, to pinpoint causal SNPs for diversity outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMA\u27s superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/

Gender minority stress and access to health care services among transgender women and transfeminine people: results from a cross-sectional study in China

Background Transgender and gender diverse individuals often face structural barriers to health care because of their gender minority status. The aim of this study was to examine the association between gender minority stress and access to specific health care services among transgender women and transfeminine people in China. Methods This multicenter cross-sectional study recruited participants between January 1st and June 30th 2020. Eligible participants were 18 years or older, assigned male at birth, not currently identifying as male, and living in China. Gender minority stress was measured using 45 items adapted from validated subscales. We examined access to health care services and interventions relevant to transgender and gender diverse people, including gender affirming interventions (hormones, surgeries), human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) testing, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Multivariable regression was used to measure correlations between gender minority stress and access to health care service. Results Three hundred and twenty-four people completed a survey and data from 277 (85.5%) people were analyzed. The mean age was 29 years old (standard deviation [SD] = 8). Participants used hormones (118/277, 42.6%), gender affirming surgery (26/277, 9.4%), HIV testing (220/277, 79.4%), STI testing (132/277, 47.7%), PrEP (24/276, 8.7%), and PEP (29/267, 10.9%). Using gender affirming hormones was associated with higher levels of discrimination (adjusted odds ratio [aOR] 1.41, 95% confidence interval [CI] 1.17-1.70) and internalized transphobia (aOR 1.06, 95%CI 1.00-1.12). STI testing was associated with lower levels of internalized transphobia (aOR 0.91, 95%CI 0.84-0.98). Conclusions Our data suggest that gender minority stress is closely related to using health services. Stigma reduction interventions and gender-affirming medical support are needed to improve transgender health

The Induction of Autoimmune Arthritis and Sex differences in Mice Impact the Lung Inflammatory Response to Repetitive Inhalant Organic Dust Extract Exposures

Asthma, chronic bronchitis and COPD are common adverse respiratory health effects among persons exposed to agriculture organic dust work environments. Occupational inhalant exposures have been increasingly associated with the risk of rheumatoid arthritis (RA) disease development, particularly among males. Agriculture workers have increased risk of RA and generalized bone disease. Chronic lung disease is associated with production of characteristic autoantibodies associated with RA (e.g.anti-citrullinated antibodies), even in absence of RA disease. The mechanistic link between pulmonary inflammation and arthritis (and vice versa) remains poorly understood. Animal models are lacking.https://digitalcommons.unmc.edu/emet_posters/1004/thumbnail.jp