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Solid Dose Form of Metformin with Ethyl Eicosapentaenoic Acid Does Not Improve Metformin Plasma Availability  [PDF]
Jeffrey H. Burton, William D. Johnson, Frank L. Greenway
Pharmacology & Pharmacy (PP) , 2016, DOI: 10.4236/pp.2016.71005
Abstract: Background: The purpose of the study was to investigate effects of ethyl eicosapentaenoic acid on pharmacokinetics of metformin. Pharmacokinetic profiles of metformin and ethyl eicosapentaenoic acid when delivered separately or together in solid dose form were investigated and compared to determine whether the solid dose resulted in an altered metforminpharmacokinetics when given with or without food. Methods: A single-center, open-label, repeated dose study investigated the pharmacokinetic (PK) profile of metformin when administered in solid dose form with ethyl eicosapentaenoic acid compared to co-administration with icosapent ethyl, an ester of eicosapentaenoic acid and ethyl alcohol used to treat severe hypertriglyceridemia with metformin hydrochloride. Non-compartmental PK methods were used to compare area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) between patients randomized to either the ester or separate medications group under both fasting and fed conditions. Results: Using these two PK parameters, results showed that metformin availability was higher under fasting conditions when delivered separately from icosapent ethyl. There were no group differences in the fed condition. Conclusions: The solid dose form of metformin and ethyl eicosapentaenoic acid did not improve the pharmacokinetics of metformin in terms of plasma availability, suggesting that little is to be gained over the separate administration of ethyl eicosapentaenoic acid and metformin hydrochloride.
Health care utilization and costs in Saskatchewan's registered Indian population with diabetes
Sheri L Pohar, Jeffrey A Johnson
BMC Health Services Research , 2007, DOI: 10.1186/1472-6963-7-126
Abstract: Administrative databases from Saskatchewan Health were used to identify registered Indians and the general population diabetes cases and two controls for each diabetes case. Health care resource utilization (physician visits, hospitalizations, day surgeries and dialysis) and costs for these individuals in the 2001 calendar year were determined. The odds of having used each resource category, adjusted for age and location of residence, was assessed according to Registered Indian and diabetes status. The average number of encounters for each resource category and per capita healthcare expenditures were also determined.Registered Indian diabetes cases were younger than general population cases (45.7 ± 14.5 versus 58.4 ± 16.4 years, p < 0.001) and fewer were male (42.3% versus 53.2%, p < 0.001). Registered Indians were more likely to visit a physician, be hospitalized or receive dialysis than the general population, regardless of diabetes status. Diabetes increased the probability of having used all resource categories for both Registered Indians and the general population. Per capita health care expenditures for the diabetes subgroups were more than twice that of their respective controls and were 40% to 60% higher for registered Indians than the general population, regardless of diabetes status.Relative to individuals without the disease, both registered Indians and the general population with diabetes had substantially higher health care utilization and costs. Excess hospitalization and dialysis suggested that registered Indians with and without diabetes experienced greater morbidity than the general population.There are significant disparities between the health status of Aboriginal and non-Aboriginal populations in Canada, the United States, New Zealand and Australia [1-6]. Aboriginals rate their health status lower and have higher mortality, hypertension, arthritis, heart disease and diabetes rates than the general Canadian population [1,4-12]. Approximately 5% of
Effect of Surgical Complications on Quality of Life after Thoracoscopic Lobectomy for Lung Cancer  [PDF]
Sayf Gazala, Jeffrey A. Johnson, James D. Kutsogiannias, Eric L. R. Bédard
World Journal of Cardiovascular Surgery (WJCS) , 2014, DOI: 10.4236/wjcs.2014.43005
Abstract: Background: Surgical resection is the main treatment for early stage lung cancer; the benefits of surgery, however, need to be weighed against possible complications and patients’ quality of life. Methods: We performed a cohort study following patients after video assisted thoracoscopic lobectomy at our tertiary care center. Before surgery, health related quality of life was assessed using the SF-36, the QLQ30, QLQ13 and EQ5D questionnaires. Post-operatively health related quality of life was assessed at regular intervals (2, 4, 8 and 12 weeks). A research team assessed post-operative complications on a daily basis during the patients’ hospital stay. Based on the Clavien classification system, the cohort was classified as experiencing high-grade (i.e., grade III or IV) complications or not. Changes in quality of life scores over the follow-up period were compared using linear regression with generalized estimating equations. Results: Between March and September 2011, 44 eligible patients were recruited into the study. The mean age was 65 (SD 8.7) years; 55% were male. The majority (n = 31; 71%) had no or low-grade complications. Patients experiencing high-grade complications reported significantly worse outcomes in the following domains of the SF-36: Global Health, Vitality, and Physical Functioning (p < 0.05 for all). On the QLQ 30 and QLQ 13, patients with high-grade complications had worse outcomes in the dyspnea, emotional function and cognitive function scales, as well as worse shoulder and chest pain, and financial difficulties (p < 0.05 for all). Conclusions: The severity of post-operative complications after video assisted thoracoscopic lobectomy negatively impacts patient centered outcomes post-operatively.

A cross-sectional study of health-related quality of life deficits in individuals with comorbid diabetes and cancer
Samantha L Bowker, Sheri L Pohar, Jeffrey A Johnson
Health and Quality of Life Outcomes , 2006, DOI: 10.1186/1477-7525-4-17
Abstract: Data from the Public Use File of the Canadian Community Health Survey (PUF CCHS) Cycle 1.1 (September 2000–November 2001) were used for this analysis. The total sample size of the CCHS PUF is 130,880 individuals. We used the Health Utilities Index Mark 3 (HUI3) to assess HRQL in patients with: 1) comorbid diabetes and cancer, 2) diabetes alone, 3) cancer alone, and 4) no diabetes or cancer. Analysis of covariance was used to compare the mean overall HUI3 score, controlling for age, sex, marital status, body mass index (BMI), physical activity level, smoking status, education level, depression status, and other chronic conditions.We identified 113,587 individuals (87%) with complete data for the analysis. The comorbid diabetes and cancer group were older and a larger proportion reported being obese, inactive, having less than a secondary education and more chronic conditions when compared to the other three cohorts (p < 0.0001). However, the diabetes and cancer cohort was less likely to be depressed (p < 0.0001). Overall HUI3 scores were significantly lower for the diabetes and cancer group (unadjusted mean (SD): 0.67 (0.30)), compared to diabetes (0.78 (0.27)), cancer (0.78 (0.25)), and the reference group (0.89 (0.18)) (p < 0.0001). After adjusting for covariates, the comorbid diabetes and cancer group continued to have significantly lower overall HUI3 scores than the reference group (unstandardized mean difference: -0.11, 95% CI: -0.13 to -.0.09) (p < 0.0001).Individuals with diabetes and cancer had a clinically important and significantly lower HRQL than those with either condition alone. A better understanding of the relationship between diabetes and cancer, and their associated comorbidities, complications, and HRQL deficits may have important implications for prevention and management strategies.Diabetes is a chronic medical condition that affects approximately 5% of Canadians aged 20 years and older, with type 2 diabetes accounting for 90% of all diagnosed ca
A Hierarchical Modeling Framework for Multiple Observer Transect Surveys
Paul B. Conn, Jeffrey L. Laake, Devin S. Johnson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042294
Abstract: Ecologists often use multiple observer transect surveys to census animal populations. In addition to animal counts, these surveys produce sequences of detections and non-detections for each observer. When combined with additional data (i.e. covariates such as distance from the transect line), these sequences provide the additional information to estimate absolute abundance when detectability on the transect line is less than one. Although existing analysis approaches for such data have proven extremely useful, they have some limitations. For instance, it is difficult to extrapolate from observed areas to unobserved areas unless a rigorous sampling design is adhered to; it is also difficult to share information across spatial and temporal domains or to accommodate habitat-abundance relationships. In this paper, we introduce a hierarchical modeling framework for multiple observer line transects that removes these limitations. In particular, abundance intensities can be modeled as a function of habitat covariates, making it easier to extrapolate to unsampled areas. Our approach relies on a complete data representation of the state space, where unobserved animals and their covariates are modeled using a reversible jump Markov chain Monte Carlo algorithm. Observer detections are modeled via a bivariate normal distribution on the probit scale, with dependence induced by a distance-dependent correlation parameter. We illustrate performance of our approach with simulated data and on a known population of golf tees. In both cases, we show that our hierarchical modeling approach yields accurate inference about abundance and related parameters. In addition, we obtain accurate inference about population-level covariates (e.g. group size). We recommend that ecologists consider using hierarchical models when analyzing multiple-observer transect data, especially when it is difficult to rigorously follow pre-specified sampling designs. We provide a new R package, hierarchicalDS, to facilitate the building and fitting of these models.
A lesion and connectivity-based hierarchical model of chronic aphasia recovery dissociates patients and healthy controls
Erin L. Meier,Jeffrey P. Johnson,Swathi Kiran,Yue Pan
- , 2019, DOI: 10.1016/j.nicl.2019.101919
Abstract:
All-optical extravascular laser-ultrasound and photoacoustic imaging of calcified atherosclerotic plaque in excised carotid artery
Jami L. Johnson,Jeffrey Shragge,Kasper van Wijk,Mervyn Merrilees
- , 2018, DOI: 10.1016/j.pacs.2018.01.002
Abstract: Photoacoustic (PA) imaging may be advantageous as a safe, non-invasive imaging modality to image the carotid artery. However, calcification that accompanies atherosclerotic plaque is difficult to detect with PA due to the non-distinct optical absorption spectrum of hydroxyapatite. We propose reflection-mode all-optical laser-ultrasound (LUS) imaging to obtain high-resolution, non-contact, non-ionizing images of the carotid artery wall and calcification. All-optical LUS allows for flexible acquisition geometry and user-dependent data acquisition for high repeatability. We apply all-optical techniques to image an excised human carotid artery. Internal layers of the artery wall, enlargement of the vessel, and calcification are observed with higher resolution and reduced artifacts with nonconfocal LUS compared to confocal LUS. Validation with histology and X-ray computed tomography (CT) demonstrates the potential for LUS as a method for non-invasive imaging in the carotid artery
Analysis Methods for the Determination of Anthropogenic Additions of P to Agricultural Soils  [PDF]
Richard L. Haney, Virginia L. Jin, Mari-Vaughn V. Johnson, Elizabeth B. Haney, R. Daren Harmel, Jeffrey G. Arnold, Michael J. White
Open Journal of Soil Science (OJSS) , 2015, DOI: 10.4236/ojss.2015.52007
Abstract:

Phosphorus loading and measurement is of concern on lands where biosolids have been applied. Traditional soil testing for plant-available P may be inadequate for the accurate assessment of P loadings in a regulatory environment as the reported levels may not correlate well with environmental risk. In order to accurately assess potential P runoff and leaching, as well as plant uptake, we must be able to measure organic P mineralized by the biotic community in the soil. Soils with varying rates of biosolid application were evaluated for mineralized organic P during a 112-day incubation using the difference between P measured using a rapid-flow analyzer (RFA) and an axial flow Varian ICP-OES. An increase in the P mineralized from the treated soils was observed from analysis with the Varian ICP-OES, but not with the RFA. These results confirm that even though organic P concentrations have increased due to increasing biosolid application, traditional soil testing using an RFA for detection, would not accurately portray P concentration and potential P loading from treated soils.

Blunt trauma induced splenic blushes are not created equal
Clay Burlew, Lucy Z Kornblith, Ernest E Moore, Jeffrey L Johnson, Walter L Biffl
World Journal of Emergency Surgery , 2012, DOI: 10.1186/1749-7922-7-8
Abstract: During a 10-year period, we reviewed all patients transferred with blunt splenic injuries and contrast extravasation on initial postinjury CT scan.During the study period, 241 patients were referred for splenic injuries, of whom 16 had a contrast blush on initial CT imaging (88% men, mean age 35 ± 5, mean ISS 26 ± 3). Eight (50%) patients were managed without angioembolization or operation. Comparing patients with and without intervention, there was a significant difference in admission heart rate (106 ± 9 vs 83 ± 6) and decline in hematocrit following transfer (5.3 ± 2.0 vs 1.0 ± 0.3), but not in injury grade (3.9 ± 0.2 vs 3.5 ± 0.3), systolic blood pressure (125 ± 10 vs 115 ± 6), or age (38.5 ± 8.2 vs 30.9 ± 4.7). Of the 8 observed patients, 3 underwent repeat imaging immediately upon arrival with resolution of the blush. In the intervention group, 4 patients had ongoing extravasation on repeat imaging, 2 patients underwent empiric embolization, and 2 patients underwent splenectomy for physiologic indications.For blunt splenic trauma, evidence of contrast extravasation on initial CT imaging is not an absolute indication for intervention. A period of observation with repeat imaging could avoid costly, invasive interventions and their associated sequelae.A contrast blush on computed tomography (CT) scan has been identified as a risk factor for failure of nonoperative management (NOM) of splenic injuries [1-3], prompting many centers to perform routine splenic artery angioembolization in the presence of a blush [4,5]. Using evidence of contrast extravasation on CT scan as an indication for angioembolization, however, has never been subjected to rigorous analysis. In our experience, patients with splenic injuries transferred from other institutions specifically for angioembolization have often resolved the blush upon repeat imaging at our hospital. This made us question whether all postinjury splenic blushes were equivalent. Is evidence of contrast blush a mandate for
Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival
Qi Wang,Joshua L. Johnson,Nathalie Y.R Agar,Jeffrey N. Agar
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0060170
Abstract: The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS.
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