Recent Submissions

  • Coil embolization of a ruptured gastroduodenal artery pseudoaneurysm presenting with hemosuccus pancreaticus

    Saqib, N.U.; Ray, H.M.; DuBose, J.J. (Society for Vascular Surgery, 2020)
    Hemosuccus pancreaticus is a rare form of upper gastrointestinal bleeding that accounts for roughly 1 in 1500 cases. It is characterized by hemorrhage from the ampulla of Vater secondary to rupture of a peripancreatic pseudoaneurysm or visceral artery pseudoaneurysm. Among the visceral artery pseudoaneurysms, gastroduodenal artery pseudoaneurysms are among the rarest. In this case report, we describe a successful coil embolization of a large ruptured gastroduodenal pseudoaneurysm in a patient with massive gastrointestinal bleeding. Copyright 2019 The Author(s)
  • Optimization of a benzothiazole indolene scaffold targeting bacterial cell wall assembly

    Chauhan, J.; Fletcher, S.; de Leeuw, E.P.H.; Yu, W.; MacKerell, A.D., Jr.; Fletcher, S. (Dove Medical Press Ltd., 2020)
    Background: The bacterial cell envelope is comprised of the cell membrane and the cell wall. The bacterial cell wall provides rigidity to the cell and protects the organism from potential harmful substances also. Cell wall biosynthesis is an important physiological process for bacterial survival and thus has been a primary target for the development of antibacterials. Antimicrobial peptides that target bacterial cell wall assembly are abundant and many bind to the essential cell wall precursor molecule Lipid II. Methods: We describe the structure-to-activity (SAR) relationship of an antimicrobial peptide-derived small molecule 7771-0701 that acts as a novel agent against cell wall biosynthesis. Derivatives of compound 7771-0701 (2-[(1E)-3-[(2E)-5,6-dimethyl-3-(prop2-en-1-yl)-1,3-benzothiazol-2-ylidene]prop-1-en-1-yl]-1,3,3-trimethylindol-1-ium) were generated by medicinal chemistry guided by Computer-Aided Drug Design and NMR. Derivatives were tested for antibacterial activity and Lipid II binding. Results: Our results show that the N-alkyl moiety is subject to change without affecting functionality and further show the functional importance of the sulfur in the scaffold. The greatest potency against Gram-positive bacteria and Lipid II affinity was achieved by incorporation of a bromide at the R3 position of the benzothiazole ring. Conclusion: We identify optimized small molecule benzothiazole indolene scaffolds that bind to Lipid II for further development as antibacterial therapeutics. Copyright 2020 Chauhan et al.
  • Management of acute ischemic stroke

    Phipps, M.S.; Cronin, C.A. (BMJ Publishing Group, 2020)
    Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering the appropriate treatment, as fast as possible. Here, we review the data supporting pre-hospital and emergency stroke care, including use of emergency medical services protocols for identification of patients with stroke, intravenous thrombolysis in acute ischemic stroke including updates to recommended patient eligibility criteria and treatment time windows, and advanced imaging techniques with automated interpretation to identify patients with large areas of brain at risk but without large completed infarcts who are likely to benefit from endovascular thrombectomy in extended time windows from symptom onset. We also review protocols for management of patient physiologic parameters to minimize infarct volumes and recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke. Finally, we discuss emerging therapies and questions for future research.
  • SGLT2 Inhibitors and the Risk of Hospitalization for Fournier's Gangrene: A Nested Case - Control Study

    Wang, T.; Patel, S.M.; Koro, C.E. (Adis, 2020)
    Introduction: Based on post-marketing surveillance, concern has been raised that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may increase the risk of necrotizing fasciitis of the perineum (Fournier's gangrene, FG). As a result of the low incidence of FG, data from clinical trials may be insufficient to robustly assess this issue because of the relatively limited numbers of participants. Real-world evidence may help clarify the association between SGLT2i and FG in the type 2 diabetes (T2D) population. Methods: A nested case-control study was performed using Truven Health MarketScan(TM) databases. Each patient with T2D hospitalized for FG between 1 April 2013 (when the first SGLT2i was available) and 31 March 2018 (latest available data) was matched (on the basis of sex, age, and cohort entry date) with six controls from the same cohort. The adjusted odds ratio (OR) of hospitalization for FG was estimated for patients receiving SGLT2i compared with those receiving two or more non-SGLT2i antihyperglycemic agents (AHAs) or insulin alone using conditional logistic regression. Results: The cohort included 1,897,935 patients, with 216 hospitalized for FG (incidence rate, 5.2 events per 100,000 person-years). Patients with FG ranged from 23 to 79 years of age; 201 (93.1%) were men. Among the 216 FG cases, 9 (4.2%) were current SGLT2i users; among the1296 matched controls, 100 (7.7%) were current SGLT2i users. Approximately 93% of SGLT2i were used in combination. The adjusted OR of FG in patients treated with SGLT2i compared with patients treated with two or more non-SGLT2i AHAs or insulin alone was 0.55 [95% CI 0.25-1.18]. Conclusion: The study did not find that treatment with SGLT2i, as compared with treatment with two or more non-SGLT2i AHAs or insulin alone, was statistically significantly associated with an increased risk of hospitalization for FG. Additional studies are needed to corroborate the findings. Copyright 2020, The Author(s).
  • Alternate approach to stroke phenotyping identifies a genetic risk locus for small vessel stroke

    McArdle, P.F.; Kittner, S.J.; Mitchell, B.D. (Springer Nature, 2020)
    Ischemic stroke (IS), caused by obstruction of cerebral blood flow, is one of the leading causes of death. While neurologists agree on delineation of IS into three subtypes (cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS)), several subtyping systems exist. The most commonly used systems are TOAST (Trial of Org 10172 in Acute Stroke Treatment) and CCS (Causative Classification System for Stroke), but agreement is only moderate. We have compared two approaches to combining the existing subtyping systems for a phenotype suited for a genome-wide association study (GWAS). We used the NINDS Stroke Genetics Network dataset (SiGN, 11,477 cases with CCS and TOAST subtypes and 28,026 controls). We defined two new phenotypes: the intersect, for which an individual must be assigned the same subtype by CCS and TOAST; and the union, for which an individual must be assigned a subtype by either CCS or TOAST. The union yields the largest sample size while the intersect yields a phenotype with less potential misclassification. We performed GWAS for all subtypes, using the original subtyping systems, the intersect, and the union as phenotypes. In each subtype, heritability was higher for the intersect compared with the other phenotypes. We observed stronger effects at known IS variants with the intersect compared with the other phenotypes. With the intersect, we identify rs10029218:G>A as an associated variant with SVS. We conclude that this approach increases the likelihood to detect genetic associations in ischemic stroke. Copyright 2020, The Author(s).
  • Genome sequence of Salarchaeum sp. Strain JOR-1, an extremely halophilic archaeon from the Dead Sea

    DasSarma, P.; Martinez, F.L.; DasSarma, S.L.; DasSarma, S.; Al Madadha, M. (American Society for Microbiology, 2020)
    An extremely halophilic archaeon, Salarchaeum sp. strain JOR-1, was isolated from the east coast of the Dead Sea, Kingdom of Jordan, and sequenced using single-molecule real-time (SMRT) sequencing. The GC-rich 2.5-Mbp genome was composed of a circular chromosome and a megaplasmid. The genome contained 2,633 genes and was incorporated into HaloWeb (https://halo.umbc.edu/). Copyright 2020 Anton et al.
  • Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

    Rogers, R.; Saharia, K.; Chandorkar, A. (BioMed Central Ltd., 2020)
    Background: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. Methods: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. Results: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65–96%), and negative predictive value (NPV) was 67% (95%CI 41–87%). Conclusions: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies. Copyright 2020 The Author(s).
  • The Short- and Long-Term Impacts of Hurricane Irma on Florida Agricultural Leaders as Early Emergency Responders: The Importance of Workplace Stability

    Grattan, L.M.; Liang, Y.; Kilman, K.A. (MDPI AG, 2020)
    The impacts of hurricane-related disasters in agricultural communities include extensive losses of fields, orchards, and livestock, the recovery of which could span many years. Agricultural Extension Agents (EAs) try to manage and mitigate these losses, while simultaneously overseeing emergency shelter operations. These non-professional emergency responders face numerous potential stressors, the outcomes of which are minimally known. This study examined the short-and long-term medical and behavioral outcome of 36 University of Florida Agricultural Extension Agents within two months and one year after Hurricane Irma, Florida, USA, taking into consideration personal/home and work-related hurricane impacts. Regression analyses indicated that combined home and work hurricane impacts were associated with greater anxiety, depression, and medical symptoms controlling for age and number of prior hurricane experiences within two months of landfall. One year later, depression symptoms increased as well as the use of negative disengagement coping strategies for which stability of the work environment was protective. The findings suggest that advanced training in emergency response, organization and time management skills, time off and temporary replacement for personally impacted EAs, and workplace stability, including enhanced continuity of operations plans, represent critical elements of health prevention and early intervention for this occupational group. Copyright 2020 by the authors.
  • Detection and quantification of renal fibrosis by computerized tomography

    Cohen, E.P.; Olson, J.D.; Tooze, J.A. (Public Library of Science, 2020)
    Objectives: Reliable biomarkers for renal fibrosis are needed for clinical care and for research. Existing non-invasive biomarkers are imprecise, which has limited their utility. Methods: We developed a method to quantify fibrosis by subject size-adjusted CT Hounsfield units. This was accomplished using CT measurements of renal cortex in previously irradiated nonhuman primates. Results: Renal cortex mean CT Hounsfield units that were adjusted for body size had a very good direct correlation with renal parenchymal fibrosis, with an area under the curve of 0.93. Conclusions: This metric is a promising and simple non-invasive biomarker for renal fibrosis. Copyright 2020 Carvalho et al.
  • Cost effective, experimentally robust differential-expression analysis for human/mammalian, pathogen and dual-species transcriptomics

    Shetty, A.C.; Mattick, J.; Chung, M.; McCracken, C.; Mahurkar, A.; Fraser, C.M.; Rasko, D.A.; Bruno, V.M.; Hotopp, J.C.D. (Microbiology Society, 2020)
    As sequencing read length has increased, researchers have quickly adopted longer reads for their experiments. Here, we examine 14 pathogen or host-pathogen differential gene expression data sets to assess whether using longer reads is warranted. A variety of data sets was used to assess what genomic attributes might affect the outcome of differential gene expression analysis including: gene density, operons, gene length, number of introns/exons and intron length. No genome attribute was found to influence the data in principal components analysis, hierarchical clustering with bootstrap support, or regression analyses of pairwise comparisons that were undertaken on the same reads, looking at all combinations of paired and unpaired reads trimmed to 36, 54, 72 and 101 bp. Read pairing had the greatest effect when there was little variation in the samples from different conditions or in their replicates (e.g. little differential gene expression). But overall, 54 and 72 bp reads were typically most similar. Given differences in costs and mapping percentages, we recommend 54 bp reads for organisms with no or few introns and 72 bp reads for all others. In a third of the data sets, read pairing had absolutely no effect, despite paired reads having twice as much data. Therefore, single-end reads seem robust for differential-expression analyses, but in eukaryotes paired-end reads are likely desired to analyse splice variants and should be preferred for data sets that are acquired with the intent to be community resources that might be used in secondary data analyses. Copyright 2020 The Authors.
  • Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors

    Hardenbrook, N.J.; Krantz, B.A.; Ghosal, K. (Nature Research, 2020)
    Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-Å resolution, respectively. The first ? helix and ? strand of LF and EF unfold and dock into a deep amphipathic cleft, called the α clamp, which resides at the interface of two PA monomers. The α-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 Å, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation. Copyright 2020, The Author(s).
  • Quantitatively relating brain endothelial cell-cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

    Gray, K.M.; Huang, H.-C.; Stroka, K.M. (Springer Nature, 2020)
    BACKGROUND: The endothelial cell-cell junctions of the blood-brain barrier (BBB) play a pivotal role in the barrier's function. Altered cell-cell junctions can lead to barrier dysfunction and have been implicated in several diseases. Despite this, the driving forces regulating junctional protein presentation remain relatively understudied, largely due to the lack of efficient techniques to quantify their presentation at sites of cell-cell adhesion. Here, we used our novel Junction Analyzer Program (JAnaP) to quantify junction phenotype (i.e., continuous, punctate, or perpendicular) in response to various substrate compositions, cell culture times, and cAMP treatments in human brain microvascular endothelial cells (HBMECs). We then quantitatively correlated junction presentation with barrier permeability on both a "global" and "local" scale. METHODS: We cultured HBMECs on collagen I, fibronectin, collagen IV, laminin, fibronectin/collagen IV/laminin, or hyaluronic acid/gelatin for 2, 4, and 7 days with varying cAMP treatment schedules. Images of immunostained ZO-1, VE-cadherin, and claudin-5 were analyzed using the JAnaP to calculate the percent of the cell perimeter presenting continuous, punctate, or perpendicular junctions. Transwell permeability assays and resistance measurements were used to measure bulk ("global") barrier properties, and a "local" permeability assay was used to correlate junction presentation proximal to permeable monolayer regions. RESULTS: Substrate composition was found to play little role in junction presentation, while cAMP supplements significantly increased the continuous junction architecture. Increased culture time required increased cAMP treatment time to reach similar ZO-1 and VE-cadherin coverage observed with shorter culture, though longer cultures were required for claudin-5 presentation. Prolonged cAMP treatment (6 days) disrupted junction integrity for all three junction proteins. Transwell permeability and TEER assays showed no correlation with junction phenotype, but a local permeability assay revealed a correlation between the number of discontinuous and no junction regions with barrier penetration. CONCLUSIONS: These results suggest that cAMP signaling influences HBMEC junction architecture more than matrix composition. Our studies emphasized the need for local barrier measurement to mechanistically understand the role of junction phenotype and supported previous results that continuous junctions are indicative of a more mature/stable endothelial barrier. Understanding what conditions influence junction presentations, and how they, in turn, affect barrier integrity, could lead to the development of therapeutics for diseases associated with BBB dysfunction.
  • It's the fiber, not the fat: significant effects of dietary challenge on the gut microbiome

    Morrison, K.E.; Howard, C.D.; Bale, T.L.; Jašarević, E. (Springer Nature, 2020)
    BACKGROUND: Dietary effects on the gut microbiome play key roles in the pathophysiology of inflammatory disorders, metabolic syndrome, obesity, and behavioral dysregulation. Often overlooked in such studies is the consideration that experimental diets vary significantly in the proportion and source of their dietary fiber. Commonly, treatment comparisons are made between animals fed a purchased refined diet that lacks soluble fiber and animals fed a standard vivarium-provided chow diet that contains a rich source of soluble fiber. Despite the well-established critical role of soluble fiber as the source of short chain fatty acid production via the gut microbiome, the extent to which measured outcomes are driven by differences in dietary fiber is unclear. Further, the interaction between sex and age in response to dietary transition is likely important and should also be considered. RESULTS: We compared the impact of transitioning young adult and 1-year aged male and female mice from their standard chow diet to a refined low soluble fiber diet on gut microbiota community composition. Then, to determine the contribution of dietary fat, we also examined the impact of transitioning a subset of animals from refined low-fat to refined high-fat diet. We used a serial sampling strategy coupled with 16S rRNA marker gene sequencing to examine consequences of recurrent dietary switching on gut microbiota community dynamics. Analysis revealed that the transition from a chow diet to a refined diet that lacks soluble fiber accounted for most of the variance in community structure, diversity, and composition across all groups. This dietary transition was characterized by a loss of taxa within the phylum Bacteroidetes and expansion of Clostridia and Proteobacteria in a sex- and age-specific manner. Most notably, no changes to gut microbiota community structure and composition were observed between mice consuming either refined low- or high-fat diet, suggesting that transition to the refined diet that lacks soluble fiber is the primary driver of gut microbiota alterations, with limited additional impact of dietary fat on gut microbiota. CONCLUSION: Collectively, our results show that the choice of control diet has a significant impact on outcomes and interpretation related to diet effects on gut microbiota. As the reduction of soluble fiber may influence synthesis of microbial metabolites that are important for regulating metabolic, immune, behavioral, and neurobiological outcomes, additional studies are now needed to fully delineate the contribution of fat and fiber on the gut microbiome. Video Abtract.
  • Healthcare practitioners' views of social media as an educational resource

    Pizzuti, A.G.; Patel, K.H.; Heil, E. (Public Library of Science, 2020)
    Social media is increasingly utilized as a resource in healthcare. We sought to identify perceptions of using social media as an educational tool among healthcare practitioners. An electronic survey was distributed to healthcare administrators, nurses, nurse practitioners, pharmacists, physicians, and physician assistants f hospital systems and affiliated health science schools in Georgia, Maryland, South Carolina, and Wisconsin. Survey questions evaluated respondents' use and views of social media for educational purposes and workplace accessibility using a Likert scale (1 = strongly disagree, 5 = strongly agree). Nurses (75%), pharmacists (11%), and administrators (7%) were the most frequent respondents. Facebook® (27%), Pinterest® (17%), and Instagram® (17%) were the most frequently accessed social media platforms. Nearly 85% agreed or strongly agreed that social media can be an effective tool for educational purposes. Among those who had social media platforms, 43.0% use them for educational purposes. Pinterest® (30%), Facebook® (22%), LinkedIn® (16%), and Twitter® (14%) were most frequently used for education. About 50% of respondents had limited or no access to social media at work. Administrators, those with unlimited and limited work access, and respondents aged 20-29 and 30-39 years were more likely to agree that social media is an educational tool (OR: 3.41 (95% CI 1.31 to 8.84), 4.18 (95% CI 2.30 to 7.60), 1.66 (95% CI 1.22 to 2.25), 4.40 (95% CI 2.80 to 6.92), 2.14 (95% CI 1.53 to 3.01) respectively). Residents, physicians, and those with unlimited access were less likely to agree with allowing social media access at work for educational purposes only. Healthcare practitioners frequently utilize social media, and many believe it can be an effective educational tool in healthcare. Copyright: 2020 Pizzuti et al.
  • Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis

    Mindikoglu, A.L.; Seliger, S.L.; Raufman, J.-P. (Future Medicine Ltd., 2020)
    Aim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses. Results: The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-Acetylputrescine (AUROC = 0.9018), trans-Aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392). Conclusion: Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers. Copyright 2020 The authors.
  • A potent risk model for predicting new-onset acute coronary syndrome in patients with type 2 diabetes mellitus in Northwest China

    Lyu, J.; Li, Z.; Gong, D.-W. (Springer, 2020)
    AIMS: Type 2 diabetes mellitus (T2DM) is now very prevalent in China. Due to the lower rate of controlled diabetes in China compared to that in developed countries, there is a higher incidence of serious cardiovascular complications, especially acute coronary syndrome (ACS). The aim of this study was to establish a potent risk predictive model in the economically disadvantaged northwest region of China, which could predict the probability of new-onset ACS in patients with T2DM. METHODS: Of 456 patients with T2DM admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2019 and included in this study, 270 had no ACS, while 186 had newly diagnosed ACS. Overall, 32 demographic characteristics and serum biomarkers of the study patients were analysed. The least absolute shrinkage and selection operator regression was used to select variables, while the multivariate logistic regression was used to establish the predictive model that was presented using a nomogram. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discriminatory capacity of the model. A calibration plot and Hosmer-Lemeshow test were used for the calibration of the predictive model, while the decision curve analysis (DCA) was used to evaluate its clinical validity. RESULTS: After random sampling, 319 and 137 T2DM patients were included in the training and validation sets, respectively. The predictive model included age, body mass index, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol, serum uric acid, lipoprotein(a), hypertension history and alcohol drinking status as predictors. The AUC of the predictive model and that of the internal validation set was 0.830 [95% confidence interval (CI) 0.786-0.874] and 0.827 (95% CI 0.756-0.899), respectively. The predictive model showed very good fitting degree, and DCA demonstrated a clinically effective predictive model. CONCLUSIONS: A potent risk predictive model was established, which is of great value for the secondary prevention of diabetes. Weight loss, lowering of SBP and blood uric acid levels and appropriate control for DBP may significantly reduce the risk of new-onset ACS in T2DM patients in Northwest China. Copyright 2020, The Author(s).
  • Antimicrobial usage at a large teaching hospital in Lusaka, Zambia

    Callahan, P.; Herbert, A.; Hachaambwa, L. (Public Library of Science, 2020)
    Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.
  • Building the future for national trauma research

    Price, M.A.; Kozar, R.A.; Bulger, E.M. (BMJ Publishing Group, 2020)
    This paper describes the current funding, infrastructure growth and future state of trauma research. It also introduces a group of review articles generated from The Future of Trauma Research: Innovations in Research Methodology conference hosted by the American College of Surgeons Committee on Trauma in July 2019. Copyright Author(s) (or their employer(s)) 2020.
  • Development of peripheral eosinophilia in inflammatory bowel disease patients on infliximab treated at a tertiary pediatric inflammatory bowel disease center is associated with clinically active disease but does not result in loss of efficacy or adverse outcomes

    Zabrowski, D.; Abraham, D.; Rosenthal, G.; Kader, H. (John Wiley and Sons Inc., 2020)
    Introduction: Inflammatory bowel disease (IBD) consisting of Crohn's disease(CD) and ulcerative colitis (UC) are inflammatory conditions affecting the gastrointes-tinal tract. Infliximab (IFX) is a chimeric anti-tumor necrosis factor antibody used totreat moderate to severe IBD. Eosinophils are commonly found in chronicallyinflamed tissues in IBD. Peripheral eosinophilia (PE) was previously implicated as amarker of disease severity at diagnosis. The main aim of this study was to investigatewhether in IBD patients on IFX, development of PE is associated with adverse out-comes and poor IFX efficacy.Methods:A comprehensive retrospective chart review of IBD patients on IFX(January 2006 to July 2015) treated at a tertiary pediatric IBD center was performed.Data was collected at time specified points over a 24 month period and includeddemographics, atopy, disease severity, development of PE, human antichimeric anti-bodies (HACA), infusion reactions, cancer, psoriasis, and loss of clinical response.Results:One hundred twenty-one IBD patients starting IFX (67 male), mean age of12.4 years (range 4-22 years old), met inclusion criteria. Of them, 36.3% had?1PEepisode (CD: 25 male, 11 female; UC: 6 male, 2 female). Mean absolute eosinophilcount (AEC) did not change over time. PE was associated with clinically active dis-ease. Among patients who developed PE, adverse outcomes were not significantly dif-ferentversusthose who did not have PE.Conclusions:In a cohort of primarily pediatric IBD patients on IFX, PE was associ-ated with clinically active disease; however, PE was not related to increased incidenceof adverse outcomes or loss of drug efficacy. Copyright 2020 The Authors.
  • International ResearchKit App for Women with Menstrual Pain (Development, Access, and Engagement): Pragmatic Randomized Control Trial

    Wang, J.; D'Adamo, C.R.; Witt, C.M. (JMIR Publications, 2020)
    BACKGROUND: Primary dysmenorrhea is a common condition in women of reproductive age. A previous app-based study undertaken by our group demonstrated that a smartphone app supporting self-acupressure introduced by a health care professional can reduce menstrual pain. OBJECTIVE: This study aims to evaluate whether a specific smartphone app is effective in reducing menstrual pain in 18- to 34-year-old women with primary dysmenorrhea in a self-care setting. One group of women has access to the full-featured study app and will be compared with 2 control groups who have access to fewer app features. Here, we report the trial design, app development, user access, and engagement. METHODS: On the basis of the practical implications of the previous app-based study, we revised and reengineered the study app and included the ResearchKit (Apple Inc) framework. Behavior change techniques (BCTs) were implemented in the app and validated by expert ratings. User access was estimated by assessing recruitment progress over time. User evolution and baseline survey respondent rate were assessed to evaluate user engagement. RESULTS: The development of the study app for a 3-armed randomized controlled trial required a multidisciplinary team. The app is accessible for the target population free of charge via the Apple App Store. In Germany, within 9 months, the app was downloaded 1458 times and 328 study participants were recruited using it without external advertising. A total of 98.27% (5157/5248) of the app-based baseline questions were answered. The correct classification of BCTs used in the app required psychological expertise. CONCLUSIONS: Conducting an innovative app study requires multidisciplinary effort. Easy access and engagement with such an app can be achieved by recruitment via the App Store. Future research is needed to investigate the determinants of user engagement, optimal BCT application, and potential clinical and self-care scenarios for app use. TRIAL REGISTRATION: ClinicalTrials.gov NCT03432611; https://clinicaltrials.gov/ct2/show/NCT03432611 (Archived by WebCite at http://www.webcitation.org/75LLAcnCQ). Copyright The Authors.

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