Publications by authors named "Christine Moore"

123 Publications

Upregulation of pERK and c-JUN by γ-tocotrienol and not α-tocopherol are essential to the differential effect on apoptosis in prostate cancer cells.

BMC Cancer 2020 May 15;20(1):428. Epub 2020 May 15.

Division of Hematology-Oncology Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Dogwood Avenue, Building 119, Johnson City, USA.

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3.

Methods: The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control.

Results: The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT.

Conclusions: c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.
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http://dx.doi.org/10.1186/s12885-020-06947-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227069PMC
May 2020

Introduction of Group Electronic Monitoring of Hand Hygiene on Inpatient Units: A Multicenter Cluster Randomized Quality Improvement Study.

Clin Infect Dis 2020 12;71(10):e680-e685

Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada.

Background: The current approach to measuring hand hygiene (HH) relies on human auditors who capture <1% of HH opportunities and rapidly become recognized by staff, resulting in inflation in performance. Group electronic monitoring is a validated method of measuring HH adherence, but data demonstrating the clinical impact of this technology are lacking.

Methods: A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections.

Results: After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47-1.99]; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1 395 450/4 544 144) to 37% (598 035/1 536 643) within 1 month, followed by consecutive incremental increases up to 53% (804 108/1 515 537) by 10 months (P < .0001). There was a trend toward reduced healthcare-associated transmission of MRSA (IRR, 0.74 [95% CI, .53-1.04]; P = .08).

Conclusions: The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.
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http://dx.doi.org/10.1093/cid/ciaa412DOI Listing
December 2020

Evaluation of a nanoscale zero-valent iron amendment as a potential tool to reduce mobility, toxicity, and bioaccumulation of arsenic and mercury from wetland sediments.

Environ Sci Pollut Res Int 2020 May 23;27(15):18757-18772. Epub 2020 Mar 23.

Department of Environmental Science, Saint Mary's University, 923 Robie Street, Halifax, NS, B3H-3C3, Canada.

Gold mining in the 1800s has led to the contamination of wetlands with introduced mercury (Hg) and geogenic arsenic (As). In situ risk management tools to reduce mobility and toxicity of Hg and As are needed to support natural restoration of impacted ecosystems. Here, we explored whether a nanoscale zero-valent iron (nZVI) slurry injected into two different contaminated wetland sediments can reduce Hg and As mobility to the overlaying water and toxicity to two aquatic invertebrates, burrowing mayflies (Hexagenia spp.) and Chinese mystery snails (Cipangopaludina chinensis). Total water Hg and As concentrations overlying both contaminated sediments were reduced by at least 75% and 88% respectively when treated with nZVI slurry. In the first sediment, juvenile snail survival increased from 75% in the untreated sediment to 100% in all nZVI treatments. The 2% nZVI treatment level was the only one with surviving mayflies (33%) and growth of juvenile snails. No snails or mayflies survived in the second sediment, regardless of nZVI treatment level. However, snails survived longer in this sediment with 4% and 8% nZVI. To improve reactivity of nZVI without increasing nZVI dose, future studies should investigate matrix-supported nZVI for reducing mobility and toxicity of As and Hg in wetland sediments.
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http://dx.doi.org/10.1007/s11356-020-08347-6DOI Listing
May 2020

Frequency of hand hygiene opportunities in patients on a general surgery service.

Am J Infect Control 2020 05 11;48(5):490-495. Epub 2020 Feb 11.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Background: Some electronic hand hygiene (HH) monitoring systems require a benchmark of HH opportunities. To establish a benchmark, we measured rates of HH opportunities among general surgery patients at a tertiary care hospital.

Methods: Trained observers recorded HH opportunities for newly admitted patients daily for up to 5 days. We used multivariable logistic regression to assess the relationship between patient variables and the HH opportunity rate. A subset of observed HH events was compared to event data from an electronic HH monitoring system.

Results: We observed 2,404 HH opportunities over 677.4 care-hours for 23 patients (median 3.25 per hour; IQR 2.2-4.7, range 0-13). Rates of HH opportunities were significantly higher on admission day 1, for sessions starting before 9 AM, and for patients without roommates. HH was performed using alcohol-based hand rub from dispensers at the door to a patient's room more often than bedside or pocket dispensers (72.7% vs 20.8% or 5.1%). Electronic dispenser event counts did not match observed event counts.

Conclusions: Our results provide a benchmark HH opportunity rate for general surgery patients, and highlight the importance of validating electronic HH event counts. Further research is needed to determine which patient factors affect HH opportunity rates.
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http://dx.doi.org/10.1016/j.ajic.2019.12.013DOI Listing
May 2020

Effects of Polyethylene Glycol-20k on Coronary Perfusion Pressure and Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest.

J Am Heart Assoc 2020 02 30;9(3):e014232. Epub 2020 Jan 30.

Weil Institute of Emergency and Critical Care Research Virginia Commonwealth University Richmond VA.

Background Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight (PEG-20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest. Methods and Results Twenty-four male rats were randomized into 4 groups: (1) PEG-20k, (2) epinephrine, (3) saline control-intravenous, and (4) saline control-intra-aortic. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. In PEG-20k and Saline-A, either PEG-20k (10% weight/volume in 10% estimated blood volume infused over 3 minutes) or saline was administered intra-aortically after 4 minutes of precordial compression. In epinephrine and placebo groups, either epinephrine (20 μg/kg) or saline placebo was administered intravenously after 4 minutes of precordial compression. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Sublingual microcirculation was measured at baseline and 1, 3, and 5 hours after return of spontaneous circulation. Myocardial function was measured at baseline and 2, 4, and 6 hours after return of spontaneous circulation. Neurologic deficit scores were recorded at 24, 48, and 72 hours after return of spontaneous circulation. Aortic infusion of PEG-20k increased coronary perfusion pressure to the same extent as epinephrine. Postresuscitation sublingual microcirculation, myocardial and cerebral function, and duration of survival were improved in PEG-20k (<0.05) compared with epinephrine (<0.05). Conclusions Aortic infusion of PEG-20k during cardiopulmonary resuscitation increases coronary perfusion pressure to the same extent as epinephrine, improves postresuscitation myocardial and cerebral function, and increases duration of survival in a rat model of cardiac arrest.
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http://dx.doi.org/10.1161/JAHA.119.014232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033902PMC
February 2020

What a Year!

World Neurosurg 2019 12 19;132:xxii. Epub 2019 Nov 19.

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http://dx.doi.org/10.1016/j.wneu.2019.09.124DOI Listing
December 2019

The utility of delta 9-tetrahydrocannabinol (THC) measures obtained from oral fluid samples in traffic safety.

Traffic Inj Prev 2019 29;20(7):667-672. Epub 2019 Jul 29.

Department of Mathematical Sciences, University of Puerto Rico at Mayagüez , Mayagüez , Puerto Rico.

Blood and/or urine are typical drug detection matrices used by law enforcement. There are some concerns about using oral fluid (OF) in the identification of drivers potentially impaired by cannabis, particularly regarding their accuracy when compared to blood. The study objectives were to (1) examine the accuracy of predicting delta 9-tetrahydrocannabinol (THC) in blood from THC measured in OF and (2) examine factors influencing prediction accuracy. Using data from the 2007 and 2013-2014 National Roadside Survey (NRS) of Alcohol and Drug Use, 7,517 drivers with known laboratory results in both OF and blood were included in this study. OF samples were collected using the Quantisal® device and analyzed at the same private laboratory in both the 2007 and 2013-2014 NRS. The Quantisal device has consistently shown to collect 1 mL ±10%. Descriptive statistical analyses were used to examine and compare the distribution of THC concentrations in OF and blood. A hurdle model was applied to examine factors influencing the accuracy of the THC predictions based on THC while accounting for the decisions of cannabis consumption. We estimated the number of true positives (TPs), false positives (FPs), true negatives (TNs), false negatives (FNs), sensitivity, specificity, and positive predicted value (PPV). This study found that THC measured in OF (THC) is a good predictor of THC measured in blood (THC), in particular when THC > 0 ng/mL is used to predict being positive for THC (THC > 0 ng/mL). However, as blood and OF concentrations depart from 0 ng/mL, the proportion of TPs (sensitivity) decreases, which might be a concern for law enforcement. The likelihood of accurately predicting THC from THC is lower for drivers who were simultaneously using cannabis and other drugs. The findings of this study are based on THC measures obtained in a laboratory, which may not be the same as those conducted by police using point-of-care devices. However, this study is unique due to its large sample of drivers obtained in similar roadside locations and times to actual law enforcement activities. Though a positive THC may assist law enforcement in probable cause for a blood draw, efforts to develop reliable methods to detect drug impairment based on OF should continue.
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http://dx.doi.org/10.1080/15389588.2019.1635690DOI Listing
July 2020

Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America.

Proc Natl Acad Sci U S A 2019 06 6;116(23):11207-11212. Epub 2019 May 6.

Department of Anthropology, The Pennsylvania State University, University Park, PA 16802

Over several millennia, various native plant species in South America have been used for their healing and psychoactive properties. Chemical analysis of archaeological artifacts provides an opportunity to study the use of psychoactive plants in the past and to better understand ancient botanical knowledge systems. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze organic residues from a ritual bundle, radiocarbon dated to approximately 1,000 C.E., recovered from archaeological excavations in a rock shelter located in the Lípez Altiplano of southwestern Bolivia. The site is located at an elevation of ∼3,900 m above sea level and contains evidence of intermittent human occupations during the last 4,000 years. Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine, including its degradation product benzoylecgonine, were identified, suggesting that at least three plants containing these compounds were part of the shamanic paraphernalia dating back 1,000 years ago, the largest number of compounds recovered from a single artifact from this area of the world, to date. This is also a documented case of a ritual bundle containing both harmine and dimethyltryptamine, the two primary ingredients of ayahuasca. The presence of multiple plants that come from disparate and distant ecological areas in South America suggests that hallucinogenic plants moved across significant distances and that an intricate botanical knowledge was intrinsic to pre-Columbian ritual practices.
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http://dx.doi.org/10.1073/pnas.1902174116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561276PMC
June 2019

Carbon dynamics, net primary productivity and human-appropriated net primary productivity across a forest-cocoa farm landscape in West Africa.

Glob Chang Biol 2019 08 6;25(8):2661-2677. Epub 2019 Jun 6.

Environmental Change Institute, School of Geography and the Environment, University of Oxford, Oxford, UK.

Terrestrial net primary productivity (NPP) is an important metric of ecosystem functioning; however, there are little empirical data on the NPP of human-modified ecosystems, particularly smallholder, perennial crops like cocoa (Theobroma cacao), which are extensive across the tropics. Human-appropriated NPP (HANPP) is a measure of the proportion of a natural system's NPP that has either been reduced through land-use change or harvested directly and, previously, has been calculated to estimate the scale of the human impact on the biosphere. Additionally, human modification can create shifts in NPP allocation and decomposition, with concomitant impacts on the carbon cycle. This study presents the results of 3 years of intensive monitoring of forest and smallholder cocoa farms across disturbance, management intensity, distance from forest and farm age gradients. We measured among the highest reported NPP values in tropical forest, 17.57 ± 2.1 and 17.7 ± 1.6 Mg C ha  year for intact and logged forest, respectively; however, the average NPP of cocoa farms was still higher, 18.8 ± 2.5 Mg C ha  year , which we found was driven by cocoa pod production. We found a dramatic shift in litterfall residence times, where cocoa leaves decomposed more slowly than forest leaves and shade tree litterfall decomposed considerably faster, indicating significant changes in rates of nutrient cycling. The average HANPP value for all cocoa farms was 2.1 ± 1.1 Mg C ha  year ; however, depending on the density of shade trees, it ranged from -4.6 to 5.2 Mg C ha  year . Therefore, rather than being related to cocoa yield, HANPP was reduced by maintaining higher shade levels. Across our monitored farms, 18.9% of farm NPP was harvested (i.e., whole cocoa pods) and only 1.1% (i.e., cocoa beans) was removed from the system, suggesting that the scale of HANPP in smallholder cocoa agroforestry systems is relatively small.
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http://dx.doi.org/10.1111/gcb.14661DOI Listing
August 2019

Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital.

PLoS One 2019 11;14(2):e0207138. Epub 2019 Feb 11.

Public Health Ontario Laboratories, Toronto, Ontario, Canada.

Background: Clostridium difficile (CD) is the leading cause of infectious health-care associated diarrhea. However, little is known regarding CD carriage and transmission amongst asymptomatic colonizers. We evaluated carriage, characterized strains and examined epidemiologic linkages in asymptomatic colonized CD patients.

Methods: Rectal swabs from asymptomatic patients admitted to the general medicine ward from April 1-June 30 2012 were collected. PCR-confirmed CD colonies were ribotyped and characterized by Modified-Multi Locus Variable Number Tandem Repeat Analysis (MMLVA).

Results: 1549-swabs were collected from 474-patients. Overall, 50/474(10.6%) were CD PCR-positive, 24/50 were colonized at admission, while 26/50 were first identified > = 72 hours after admission. Amongst the 50 CD PCR-positive patients, 90% were asymptomatically colonized and 80% of individuals carried toxigenic CD-strains, including ribotype-027 (5/45:11%). MMLVA revealed five-clusters involving 15-patients harboring toxigenic (4/5) and non-toxigenic CD strains (1/5). In two clusters, patients were CD positive on admission while in the other three clusters involving 10 patients, we observed CD transmission from asymptomatically colonized patients to 8 previously CD-negative patients.

Conclusions: We identified increasing rates of colonization during admission to medical wards. MMLVA typing effectively discriminated between strains and suggests that 20% of patients with CD colonization acquired their strain(s) from asymptomatically colonized individuals in hospital.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207138PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370182PMC
October 2019

A Cryptic Cause of Cardiac Arrest.

J Emerg Med 2019 Jan 9;56(1):e1-e4. Epub 2018 Nov 9.

Department of Pediatric Critical Care, Steven and Alexandra Cohen Children's Medical Center, New Hyde Park, New York.

Background: RIPPLY2-associated spondylocostal dysostosis is a rare disorder that leads to segmentation defects of the vertebrae. These vertebral defects can result in severe instability of the cervical spine, leading to cardiac arrest after only minor whiplash injury.

Case Report: We present the case of a healthy 7-year-old child who experienced an out-of-hospital cardiac arrest. He was reported to have profound respiratory distress and collapsed after going down a slide, without trauma. He was resuscitated in the field, and presented to the emergency department, where return of spontaneous circulation was achieved. Imaging of his cervical spine revealed multiple abnormalities. It was determined that a whiplash injury led to hypoxia and bradycardia due to the anatomic abnormalities of his cervical spine, resulting in cardiovascular collapse. He recovered fully and was later diagnosed with SCDO6, an autosomal recessive inherited disorder caused by a mutation in the RIPPLY2 gene. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Unfamiliarity of providers with this mechanism of cardiac arrest, and the rarity of the syndrome itself, make early recognition very difficult. Late diagnosis and lack of preventative measures, including immediate cervical spine stabilization, can lead to catastrophic outcomes. In patients with cardiac arrest of unclear etiology, early consideration of cervical spine immobilization and evaluation can be lifesaving.
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http://dx.doi.org/10.1016/j.jemermed.2018.09.044DOI Listing
January 2019

CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.

Nat Commun 2018 11 5;9(1):4619. Epub 2018 Nov 5.

AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, Paris, 75013, France.

Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates disturbance of critical binding and interaction motifs. Experimental assays with six of the identified mutations show that a subset directly affects ATPase activity, and all but one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a syndrome characterized by intellectual disability, macrocephaly, and impaired speech and language.
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http://dx.doi.org/10.1038/s41467-018-06014-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218476PMC
November 2018

Prevalence of antibiotic-resistant organisms in Canadian Hospitals. Comparison of point-prevalence survey results from 2010, 2012, and 2016.

Infect Control Hosp Epidemiol 2019 01 5;40(1):53-59. Epub 2018 Nov 5.

2Sunnybrook Health Sciences Centre,Toronto,Ontario,Canada.

Objective: Point-prevalence surveys for infection or colonization with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CREs), and for Clostridium difficile infection (CDI) were conducted in Canadian hospitals in 2010 and 2012 to better understanding changes in the epidemiology of antimicrobial-resistant organisms (AROs), which is crucial for public health and care management.

Methods: A third survey of the same AROs in adult inpatients in Canadian hospitals with ≥50 beds was performed in February 2016. Data on participating hospitals and patient cases were obtained using standard criteria and case definitions. Associations between ARO prevalence and institutional characteristics were assessed using logistic regression models.

Results: In total, 160 hospitals from 9 of the 10 provinces with 35,018 adult inpatients participated in the survey. Median prevalence per 100 inpatients was 4.1 for MRSA, 0.8 for VRE, 1.1 for CDI, 0.8 for ESBLs, and 0 for CREs. No significant change occurred compared to 2012. CREs were reported from 24 hospitals (15%) in 2016 compared to 10 hospitals (7%) in 2012. Routine universal or targeted admission screening for VRE decreased from 94% in 2010 to 74% in 2016. Targeted screening for MRSA on admission was associated with a lower prevalence of MRSA infection. Large hospitals (>500 beds) had higher prevalences of CDI.

Conclusion: This survey provides national prevalence rates for AROs in Canadian hospitals. Changes in infection control and prevention policies might lead to changes in the epidemiology of AROs and our capacity to detect them.
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http://dx.doi.org/10.1017/ice.2018.279DOI Listing
January 2019

Analysis of Drugs in Oral Fluid Using LC-MS/MS.

Methods Mol Biol 2019 ;1872:237-259

Toxicology Analytical Services, Immunalysis Corporation, Pomona, CA, USA.

Oral fluid analysis for drugs is increasingly used in a variety of testing areas: pain management and medication monitoring, parole and probation situations, driving under the influence of drugs (DUID), therapeutic drug monitoring, and testing for drugs in the workplace. The sample collection itself is straightforward, rapid, observable, and noninvasive, requiring no special facilities (compared to urine) or medical personnel (compared to blood). The pH of saliva is slightly acidic relative to blood; therefore, drugs which are more basic tend to be present in higher concentration in oral fluid than in blood: cocaine, amphetamines, oxycodone, tramadol, buprenorphine, methadone, and fentanyl. Conversely, acidic drugs and drugs which are strongly protein bound have lower concentrations in oral fluid than in blood: examples include benzodiazepines, barbiturates, and carisoprodol. Because of the low volume of specimen available for analysis and the drug concentrations present (generally much lower than those in urine), efficient extraction methods and sensitive confirmation procedures are necessary for routine analysis of drugs in oral fluid. In this chapter, solid-phase extraction methods are described for a variety of drugs with liquid chromatography-tandem mass spectrometry detection.
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http://dx.doi.org/10.1007/978-1-4939-8823-5_22DOI Listing
June 2019

Comparing a Statistical Model and Bayesian Approach to Establish the Design Space for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.

AAPS PharmSciTech 2018 Nov 2;19(8):3809-3828. Epub 2018 Oct 2.

School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, 20 N Pine Street, Baltimore, MD, 21201, USA.

The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer. Thirty experiments were conducted using a central composite design to optimize the coating process and map the response surface to build a design space using either statistical least squares or a Bayesian approach. The response surface was fitted using a linear two-factor interaction model with spraying temperature, curing temperature, and curing time as significant model terms. The design spaces established by the two approaches were in close agreement with the statistical least squares approach being more conservative than the Bayesian approach. The design space established for the critical process parameters using small-scale batches was tested using scale-up batches and found to be scale-independent. The robustness of the design space was confirmed across scales and was successfully utilized to establish process signature for the coating process.
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http://dx.doi.org/10.1208/s12249-018-1116-yDOI Listing
November 2018

Hand hygiene opportunities on Canadian acute-care inpatient units: A multicenter observational study.

Infect Control Hosp Epidemiol 2018 11 25;39(11):1378-1380. Epub 2018 Sep 25.

1Department of Medicine,University of Toronto,Toronto,Ontario,Canada.

In this multicenter observational study, medical and surgical inpatient rooms were randomized to receive 1 hour of continuous direct observation to determine hand hygiene opportunities (HHOs). After multivariable adjustment, HHOs were similar across inpatient units and hospitals. This estimate could serve to calibrate electronic hand hygiene monitoring systems for Canadian medical and surgical units.
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http://dx.doi.org/10.1017/ice.2018.221DOI Listing
November 2018

A Simple Approach to Pneumococcal Vaccination in Adults.

J Glob Infect Dis 2018 Jul-Sep;10(3):159-162

Department of Internal Medicine, East Tennessee State University James H. Quillen College of Medicine, Johnson City, TN, USA.

is a bacterium responsible for a spectrum of diseases including lobar pneumonia, meningitis, otitis media, and sinusitis. Invasive pneumococcal disease is responsible for significant morbidity and mortality across the world. Concerted efforts led to the development of two vaccinations, Pneumova × 23 and Prevnar 13, for the prevention of pneumococcal disease. The Advisory Committee on Immunization Practices of the US Centers for Disease Control and Prevention provides vaccination schedules for predisposed adults, but the proposed schedules remain a challenge to health-care providers. We performed a systematic review in PubMed and these specialty group websites to present the pathophysiology of pneumococcal disease, outline different pneumococcal vaccinations, and condense recommendations for vaccination administration.
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http://dx.doi.org/10.4103/jgid.jgid_88_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100338PMC
September 2018

Undifferentiated Pleomorphic Sarcoma after Pirfenidone Use: A Case Report.

Perm J 2018 ;22:17-116

Internist at East Tennessee State University in Johnson City.

Introduction: Pirfenidone was approved in 2014 for the treatment of idiopathic pulmonary fibrosis. Pirfenidone inhibits several factors such as tissue growth factor-β and platelet-derived growth factor, leading to decreased epithelial and fibroblast proliferation and collagen synthesis. The drug improves progression-free survival and is well tolerated, with minimal side effects. However, data on its long-term effects are lacking.

Case Presentation: We present a rare case in which an undifferentiated pleomorphic sarcoma developed in a 59-year-old man with idiopathic pulmonary fibrosis who was treated with pirfenidone for more than a year.

Discussion: Undifferentiated pleomorphic sarcoma, also known as malignant fibrous histiocytoma, is a soft-tissue sarcoma arising from fibroblasts. The disease presents in the extremities and the trunk of elderly patients, and rarely in the retroperitoneum. Surgical excision is the mainstay of treatment; however, recurrence is common in the form of lung and lymph node metastases. In this report we review this rare malignancy and highlight the need for postmarketing longitudinal studies to determine additional adverse effects in patients with idiopathic pulmonary fibrosis who are on pirfenidone therapy.
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http://dx.doi.org/10.7812/TPP/17-116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922964PMC
December 2018

Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review.

Perm J 2018 ;22:17-125

Internist at East Tennessee State University in Johnson City.

Introduction: Lenalidomide is an immunomodulatory drug approved by the US Food and Drug Administration in 2006 for the treatment of multiple myeloma. In 2012, the Food and Drug Administration issued a statement warning physicians of the increased risk with lenalidomide treatment of the following secondary primary malignancies: Acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma. The statement did not mention glioblastoma multiforme, a Grade 4 astrocytoma, or other high-grade astrocytomas that have been reported on rare occasions in the setting of multiple myeloma.

Case Presentation: A 72-year-old man, who had been in complete remission from multiple myeloma for 1 year after treatment that included lenalidomide, presented with confusion, headache, nausea and vomiting, and recurrent falls. A magnetic resonance image of his brain revealed a mass that on stereotactic biopsy was found to be glioblastoma multiforme.

Discussion: We present the seventh reported case of high-grade astrocytoma as a second primary malignancy in multiple myeloma and the first reported occurrence of glioblastoma multiforme after the use of lenalidomide in multiple myeloma. This report adds to the pool of cases that reveal associations between use of lenalidomide and increased risk of developing secondary primary high-grade astrocytomas in multiple myeloma.
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http://dx.doi.org/10.7812/TPP/17-125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882177PMC
December 2018

Debates in Pain Management Testing.

Clin Chem 2018 05 17;64(5):769-776. Epub 2018 Jan 17.

Vice President, Toxicology Research & Development, Immunalysis Corporation, Pomona, CA.

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http://dx.doi.org/10.1373/clinchem.2017.275693DOI Listing
May 2018

Empyema Necessitans: An Unexpected Infectious Presentation of Multiple Myeloma.

J Glob Infect Dis 2017 Oct-Dec;9(4):163-164

Department of Internal Medicine, East Tennessee State University James H. Quillen College of Medicine, Johnson City, TN, USA.

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http://dx.doi.org/10.4103/jgid.jgid_35_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750443PMC
January 2018

Urine and oral fluid drug testing in support of pain management.

Crit Rev Clin Lab Sci 2017 09 9;54(6):433-445. Epub 2017 Oct 9.

c Immunalysis Corporation , Pomona , CA , USA.

In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays.
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http://dx.doi.org/10.1080/10408363.2017.1385053DOI Listing
September 2017

Roadside drug testing: An evaluation of the Alere DDS 2 mobile test system.

Drug Test Anal 2018 Apr 9;10(4):663-670. Epub 2017 Nov 9.

Deputy District Attorney, Wyandotte County, Kansas, USA.

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action.
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http://dx.doi.org/10.1002/dta.2297DOI Listing
April 2018