Objective: To examine bacterial vaginosis as an effect modifier for the association between hormonal contraception and incident HIV infection. Design: Serodiscordant couples enrolled in an open longitudinal cohort in Lusaka, Zambia from 1994 to 2012. This analysis was restricted to couples with an HIV-positive man enrolled between1994 and 2002 when a quarterly genital tract examination and HIV testing was performed. Methods: Multivariate Cox models evaluated the association between contraceptive method and HIV-acquisition, stratified by time-varying bacterial vaginosis status. Results: Among 564 couples contributing 1137.2 couple-years of observation, bacterial vaginosis was detected at 15.5% of study visits. Twenty-two of 106 seroconversions occurred during intervals after bacterial vaginosis was detected [12 on no method/nonhormonal method (nonhormonal contraception), two on injectables, eight on oral contraceptive pills (OCPs)]. Unadjusted seroincidence rates per 100 couple-years for nonhormonal contraception, injectable, and OCP users, respectively, during intervals with bacterial vaginosis were 8.3, 20.8, and 31.0 and during intervals without bacterial vaginosis were 8.2, 9.7, and 12.3. In the bacterial vaginosis-positive model, there was a significant increase in incident HIV among those using injectables (adjusted hazard ratio, aHR 6.55, 95% CI 1.14-37.77) and OCPs (aHR 5.20, 95% CI 1.68-16.06) compared with nonhormonal contraception. Hormonal contraception did not increase the hazard of HIV acquisition in bacterial vaginosis-negativ e models. These findings persisted in sensitivity analyses whenever all covariates from the nonstratified model previously published were included, whenever other genital tract findings were excluded from the model and with the addition of condom-less sex and sperm on wet-prep. Conclusion: Future research should consider a potential interaction with bacterial vaginosis whenever evaluating the impact of hormonal contraception on HIV acquisition.
Introduction: Physician burnout has received considerable attention in the literature and impacts a large number of emergency medicine physicians, but there is no standardized curriculum for wellness in resident education. A culture change is needed to educate about wellness, adopt a preventative and proactive approach, and focus on resiliency. Discussion: We describe a novel approach to wellness education by focusing on resiliency rather than the unintended endpoint of physician burnout. One barrier to adoption of wellness education has been establishing legitimacy among emergency medicine (EM) residents and educators. We discuss a change in the language of wellness education and provide several specific topics to facilitate the incorporation of these topics in resident education. Conclusion: Wellness education and a culture of training that promotes well-being will benefit EM residents. Demonstrating the impact of several factors that positively affect emergency physicians may help to facilitate alert residents to the importance of practicing activities that will result in wellness. A change in culture and focus on resiliency is needed to adequately address and optimize physician self-care.
Despite using imaging studies, tissue sampling, and serologic tests about 5-10% of surgeries done for presumed pancreatic malignancies will have benign findings on final pathology. Endoscopic ultrasound (EUS) is used with increasing frequency to study pancreatic masses. The aim of this study is to examine the effect of EUS on prevalence of benign diseases undergoing Whipple over the last decade. Patients who underwent Whipple procedure for presumed malignancy at Emory University Hospital from 1998 to 2011 were selected. Demographic data, history of smoking and drinking, history of diabetes and pancreatitis, imaging data, pathology reports, and tumor markers were extracted. 878 patients were found. 95 (10.82%) patients had benign disease. Prevalence of benign finding had increased over the recent years despite using more EUS. Logistic regression models showed that abdominal pain (OR: 5.829, 95% CI 2.681-12.674, P ≤ 0.001) and alcohol abuse (OR: 3.221, CI 95%: 1.362-7.261, P: 0.002) were predictors of benign diseases. Jaundice (OR: 0.221, 95% CI: 0.084-0.58, P: 0.002), mass (OR: 0.145, 95% CI: 0.043-0.485, P: 0.008), and ductal dilation (OR: 0.297, 95% CI 0.134-0.657, P: 0.003) were associated with malignancy. Use of imaging studies, ERCP, and EUS has not decreased the percentage of benign findings after surgery for presumed pancreatic malignancy.
Background: Uncontrolled hyperglycemia in hospitalized patients, with or without diabetes mellitus, is associated with many adverse outcomes. Resident physicians are the primary managers of inpatient glycemic control (IGC) in many academic and community medical centers; however, no validated survey tools related to their perceptions and knowledge of IGC are currently available. As identification of common barriers to successful IGC amongst resident physicians may help foster better educational interventions (ultimately leading to improvements in IGC and patient care), we sought to construct and preliminarily evaluate such a survey tool. Methods: We developed the IGC questionnaire (IGCQ) by using previously published but unvalidated survey tools related to physician perspectives on inpatient glycemic control as a framework. We administered the IGCQ to a cohort of resident physicians from the University of Mississippi Medical Center, University of Louisville, Emory University, and the University of Virginia. We then used classical test theory and Rasch Partial Credit Model analyses to preliminarily evaluate and revise the IGCQ. The final survey tool contains 16 total items and three answer-choice categories for most items. Results: Two hundred forty-six of 438 (56.2%) eligible resident physicians completed the IGCQ during various phases of development. Conclusions: We constructed and preliminarily evaluated the IGCQ, a survey tool that may be useful for future research into resident physician perceptions and knowledge of IGC. Future studies could seek to externally validate the IGCQ and then utilize the survey tool in pre- and post-intervention assessments.
by
Sudeepa Bhattacharyya;
Ahmed T. Ahmed;
Matthias Arnold;
Duan Liu;
Chunqiao Luo;
Hongjie Zhu;
Siamak Mahmoudiandehkordi;
Drew Neavin;
Gregory Louie;
Boadie Dunlop;
Mark A. Frye;
Liewei Wang;
Richard M. Weinshilboum;
Ranga R. Krishnan;
A. John Rush;
Rima Kaddurah-Daouk
Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine–homogentisic acid and methionine–tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.
by
Tariq I. Mughal;
Jason Gotlib;
Ruben Mesa;
Steffen Koschmieder;
Hanna Khoury;
Jorge E Cortes;
Tiziano Barbui;
Rüdiger Hehlmann;
Michael Mauro;
Susanne Saussele;
Jerald P. Radich;
Richard A. Van Etten;
Giuseppe Saglio;
Srdnan Verstovek;
Robert Peter Gale;
Omar Abdel-Wahab
This review is based on the presentations and deliberations at the 7th John Goldman Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN) Colloquium which took place in Estoril, Portugal on the 15th October 2017, and the 11th post-ASH International Workshop on CML and MPN which took place on the 6th-7th December 2016, immediately after the 58th American Society of Hematology Annual Meeting. Rather than present a resume of the proceedings, we have elected to address some of the topical translational research and clinically relevant topics in greater detail. We address recent updates in the genetics and epigenetics of MPN, the mechanisms of transformation by mutant calreticulin, advances in the biology and therapy of systemic mastocytosis, clinical updates on JAK2 inhibitors and other therapeutic approaches for patients with MPNs, cardiovascular toxicity related to tyrosine kinase inhibitors and the concept of treatment-free remission for patients with CML.
Mitochondrial phenotype is complex and difficult to define at the level of individual cell types. Newer metabolic profiling methods provide information on dozens of metabolic pathways from a relatively small sample. This pilot study used “top-down” metabolic profiling to determine the spectrum of metabolites present in liver mitochondria. High resolution mass spectral analyses and multivariate statistical tests provided global metabolic information about mitochondria and showed that liver mitochondria possess a significant phenotype based on gender and genotype. The data also show that mitochondria contain a large number of unidentified chemicals.
Exhaled breath condensate (EBC) has been increasingly studied as a noninvasive research method for sampling the alveolar and airway space and is recognized as a promising source of biomarkers of lung diseases. Substances measured in EBC include oxidative stress and inflammatory mediators, such as arachidonic acid derivatives, reactive oxygen/nitrogen species, reduced and oxidized glutathione, and inflammatory cytokines. Although EBC has great potential as a source of biomarkers in many lung diseases, the low concentrations of compounds within the EBC present challenges in sample collection and analysis. Although EBC is viewed as a noninvasive method for sampling airway lining fluid (ALF), validation is necessary to confirm that EBC truly represents the ALF. Likewise, a dilution factor for the EBC is needed in order to compare across subjects and determine changes in the ALF. The aims of this paper are to address the characteristics of EBC; strategies to standardize EBC sample collection and review available analytical techniques for EBC analysis.