Background: Chronic kidney disease (CKD) affects approximately 20 million Americans and is the cause of significant morbidity and mortality. Anemia, common in CKD, develops early in the disease process. It contributes to increased risk of cardiovascular disease, hospitalization, mortality, and diminishes health-related quality of life. Intravenous iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in CKD. The utilization patterns of IV iron and ESA, and their impact on hospital costs and length of stay merits investigation. Objectives: There were five general objectives of this investigation. The rate and extent of utilization of IV iron in anemic CKD patients was quantified across teaching hospitals in the US. Patient characteristics of those receiving IV iron and ESA and ESA alone were evaluated in detail. Predictors of IV iron and ESA use were determined. The impact of IV iron and ESA use was examined separately for total hospital costs and length of stay (LOS) while adjusting for confounding. Methods: This is a retrospective cohort analysis within the University Health System Consortium data warehouse. Eligible patients are those who were admitted to a hospital and received either IV iron and ESA or both at least once during the period of January 1, 2006, and December 31, 2008. Inclusion criteria include age > 18 years old with a primary or secondary diagnosis of CKD. The exposure of interest was IV iron and ESA therapy, and the outcome was the difference in total hospital costs and length of stay between patients only on ESA, and those on ESA and IV iron. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Propensity scores were used to control for confounding. A generalized estimating equations (GEE) model using a gamma distribution and log link was used to determine the adjusted hospital cost and length of stay for the IV iron and ESA and ESA alone therapy groups. Results: During the study period, 82,947 patients met all the inclusion and exclusion criteria. Of the 82,947 CKD patients on ESA therapy, only 8% (n = 6678) patients were on IV iron supplementation. Age, race, primary payer, admission status, severity of illness, dialysis status and physician specialty were identified as strong predictors of IV iron use in CKD patients. According to the multivariate model, the overall mean hospital cost for all 82,947 patients was $31,674. For patients using both IV iron and ESA (n=6678), mean costs were $34,756 compared to $31,404 for ESA users alone (n=76,269) – a difference of $3,352. The overall mean LOS for all patients was 9.75 days. For those using IV iron, the LOS was 10.71 days, and for those only using ESA, the LOS was 9.66 days– a difference of approximately 1 day. Conclusions: This inquiry is the first large multi-center investigation to quantify the impact of IV iron and ESA use on total hospital costs and LOS. Our investigation showed significant reduction in ESA doses with the use of IV iron supplementation, however, the overall prevalence of IV iron usage was low. Intravenous iron users were associated with a higher total hospital cost and longer length of stay than ESA users.

AIM: The aim of this study was to determine the expression of microbial nucleic acid receptors including Toll like receptor 9 “TLR-9”, DNA-dependent activator of interferon-regulatory factors “DAI” and absent in melanoma “AIM-2” in chronic periodontitis (P) versus healthy (H) tissues. METHODS: 33 chronic periodontitis (P) and 27 periodontally-healthy (H) gingival biopsies were included. The gene and protein expression for each receptor was determined using real-time quantitative PCR and immunohistochemistry. RESULTS: Our results revealed statistically significant up-regulation of TLR-9 (p<0.006) and DAI (p<0.001) gene expression in P tissues compared to H sites. We were also able to demonstrate significant correlation among three DNA receptors (p<0.05). Immunohistochemistry further confirmed the expression of DNA sensors in gingival tissues. CONCLUSION: This study highlights a possible role for nucleic acid sensing in periodontal inflammation. Further investigations will determine whether cytoplasmic receptors and their ligands can be targeted to improve clinical outcomes in periodontitis.

The current study examined the ability of pain-related catastrophizing to predict outcomes following non-surgical and surgical intervention for temporomandibular disorders (TMDs). The interpersonal context of pain-related catastrophizing, referred to as the communal coping model, was also examined to determine if patient perceptions of punishing and solicitous responses from significant others would moderate or mediate relations between pain catastrophizing and outcomes. The role of pain duration as a moderator of the relation between pain-related catastrophizing and perceived significant other responding was also examined. A total of 94 patients were identified for which 65 had follow-up outcomes that could be examined. Patient follow-up data were obtained at approximately two to three weeks, two to three months, and six months post-intervention. Results showed that pain-related catastrophizing was predictive of greater pain severity at all three follow-up time points after controlling for baseline levels of pain severity, depressive symptoms, sleep disturbance, and pain duration. Pain-related catastrophizing was predictive of poorer range of motion (ROM) at the initial follow-up after controlling for baseline levels of ROM, gender, and form of intervention. Pain-related catastrophizing was not associated with ROM at the second and third post-intervention follow-ups. There was no interaction between pain-related catastrophizing and perceptions of either solicitous or punishing responses in predicting post-intervention pain severity or ROM and any time point. Perceptions of significant other responses also did not mediate the relation between pain-related catastrophizing and post-intervention outcomes at any time point. Additionally, the interaction between pain duration and pain-related catastrophizing in the prediction of post-intervention pain severity or ROM was not significant at any follow-up time point. The findings indicate that pain related catastrophizing is an important predictor of pain severity following non-surgical and surgical interventions for TMDs both initially and in the long-term. Pain-related catastrophizing is related to ROM outcomes only in the short term. Perceptions of punishing and solicitous responses from significant others do not appear to play a role in these associations. The results suggest that patients with high levels of pre-intervention catastrophizing may benefit from adjunctive cognitive-behavioral intervention to attenuate post-intervention pain severity.

Chronic obstructive pulmonary disease (COPD) has a severe impact on quality of life (QOL). Using the Health Promotion Model as a guide, a cross-sectional, correlational design was used to describe relationships among individual characteristics and experiences (age, gender, race, severity of illness, resilience), behavior-specific cognitions and affect (self-efficacy, barriers, social support), behavioral outcomes (health promoting lifestyle), and QOL in this patient population. One hundred and twenty participants were recruited from three clinics at Virginia Commonwealth University Health System. In addition to a demographic survey, participants completed a 151-item questionnaire incorporating measures resilience, severity of illness, self-efficacy, and barriers to a health-promoting lifestyle, social support, lifestyle, and QOL. Spirometric evaluation of lung function and the 6-minute walking test were also completed. Structural equation modeling was used to determine the effect of nine independent variables on QOL.Participants were white (51.2%), female (63.6%), and approximately 60.5 years old. Severity of illness, characterized by symptoms and functional capacity, suggested they were not severely ill (mean = 3.18, S.D.= 2.69). They were somewhat resilient (mean = 136.01, S.D.= 23.01), had adequate social support (mean = 68.10, S.D.= 19.95), were uncertain about their competency (self-efficacy) to manage their health (mean = 24.91, S.D.= 4.92), sometimes experienced barriers (mean = 33.33, S.D.= 9.02), and sometimes included attributes of a healthy lifestyle in their lives (mean = 123.93, S.D.= 25.22). Their QOL was fair to poor (mean = 6.10, S.D.= 2.39).A series of analyses using structural equation modeling was conducted. The first model that was tested did not fit the data χ2(df = 13)= 67.989,p = 0.000, GFI = 0.895, CFI = 0.781, RMSEA = 0.189). Next, modification indices were use to reexamine for fit. Using the recommended modifications, a good fit model was obtained χ2(df = 9)=5.016, p = 0.833, GFI = 0.992, CFI = 1.0, RMSEA = 0.0); however, non-significant paths were present. An alternative model was tested and fit the data very well χ2(df=18)= 10.011, p = 0.932, GFI = 0.981, CFI = 1.0, RMSEA = 0.0). The independent variables explained about 45.1% of the variance in health-promoting lifestyle. All the variables explained 45.3% of variance in QOL. The most significant predictor of a healthy lifestyle was social support (0.383) and the most significant predictor of QOL was self-efficacy (0.364). The findings confirmed the utility of the HPM.

Obesity is a dangerous health condition affecting approximately 30% of all Americans and can be attributed to 300,000 deaths a year. Obesity has been found to disproportionately affect Blacks, Latinos, and those with lower SES. Although obesity is a problem for all age groups, its prevalence is highest among those 60-74 years of age. Studies have shown that there is an association between obesity and chronic conditions such as cardiovascular disease, arthritis, cancers, and type-2 diabetes. According to the Centers for Disease Control, chronic health conditions affect 80% of all elderly persons, many times limiting function and decreasing quality of life. This study attempted to find a relationship between obesity and chronic conditions among 1,053 elderly living in Philadelphia and 1,648 elderly living in Bucks, Chester, Delaware, and Montgomery counties. This study also examined the risk for having a chronic condition associated with living in Philadelphia compared to living in the four surrounding counties. Data from the 2002 Household Survey conducted by the Philadelphia Health Management Corporation was used to examine the relationship between obesity and chronic conditions and it was found that obesity was significantly related to having a chronic condition among elderly in both the city and suburbs. Specifically, obesity was related to diabetes, asthma, arthritis, and heart conditions for persons over 60 living in the city and suburbs with an additional association with allergies for elderly living in the city. It was also found that living in the city of Philadelphia was significantly associated with a 50% increased chance for diabetes among persons 60 and over. Future research should first be conducted to design a BMI scale that reflects the decrease in muscle and bone mass associated with aging. After a new scale is devised, research should continue to further investigate the association between obesity and various chronic conditions in the elderly.

DHEA has been determined to have medically significant activity and is the parent compound to the more active metabolites; 17α-AED, 17β-AED and 17β-AET, which exhibit strong biological activity that has been attributed to androgenic, estrogenic or anti-glucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED and 17β-AET for their ability to activate the human AR, ER and GR receptors and determine the relative androgenicity, estrogenicity and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR receptor; only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors. 17β-AED and 17α-AED, androstene epimers that produce either survival or death, were utilized to treat T98G Glioblastoma cells. We identified 26 genes oppositely regulated by 17β-AED and 17α-AED to directly affect the cellular life or death decision. Network analysis demonstrated that these 26 genes are essential to regulating three critical Glioblastoma pathways. This report, for the first time, demonstrates that naturally occurring, chemically identical adrenal hormones (17β-AED or 17α-AED) direct a cellular life or death decision through contrasting modulation of identical signaling pathways and core regulators. Chronic pressure ulcers represent a significant health problem and are characterized by hypoxia, bacterial infection, repetitive ischemia/reperfusion and altered cellular and systemic stress responses. Whole genome microarray analysis was utilized in conjunction with IPA® premiere networking software to analyze chronic wound edge tissue. IPA® network analysis identified Ubiquitin C (UBC) as the most significant network. Sixteen (16) ubiquitin C associated genes were identified to be different in the chronic pressure ulcer and normal skin control. Targeted network analysis associated core regulators to 8 UBC associated genes that are unique to chronic pressure ulcers. The identification of these genes will allow the establishment of more effective treatments for Spinal Cord Injury (SCI) patients with chronic pressure ulcers.

Introduction: Following lateral ankle sprain, many individuals experience recurrent injury and symptoms of giving-way, known as Functional Ankle Instability (FAI). It has been proposed that altered joint kinematics during activity may contribute to instability in these individuals, however research findings have been inconsistent. Objective: To capture foot and ankle kinematic data during two common tasks (walking gait and jump landing) among three groups: individuals with FAI, healthy controls and copers. Design: 3-group observational cross-sectional study. Participants: Participants included 23 individuals with a history of ≥ 1 ankle sprain and at least 2 episodes of giving-way in the past year (FAI: M±SD; age=23.30±3.84years; height=1.71±0.11m, weight=68.66±14.60kg; Cumberland Ankle Instability Tool [CAIT]=20.52±2.94, episodes of giving-way=5.81±8.42 per month), 23 subjects with no history of ankle sprain or instability in their lifetime (Controls: age=23.17±4.01years, height=1.72±0.08m, weight=68.78± 13.26kg, CAIT: 28.78±1.78), and 23 individuals with a history of a single ankle sprain and no subsequent episodes of instability (Copers: age=23.52±3.68years, height=1.72±0.07m, weight=69.57±13.94kg; CAIT: 27.74 ± 1.69). Interventions: Ten trials of natural walking gait and 10 single leg drop jumps were recorded using a ViconMX motion monitoring system (OMG, Oxford, UK) and two imbedded force plates (Bertec, Columbus, Ohio, USA). Main Outcome Measures: Forefoot and hindfoot sagittal and frontal plane angles were calculated at initial contact (IC) and toe-off (TO) of walking gait, and IC and maximal vertical ground reaction force of jump landing. Results: At walking IC, there was a significant group difference in forefoot inversion (F2,66=4.68, p=0.013). Post hoc testing revealed that individuals with FAI were significantly more inverted than controls, but copers were not significantly different from the FAI or control groups. At jump landing IC, there were significant group differences in hindfoot motion (F2,66=6.12, p=0.004). Specifically, individuals with FAI were significantly more dorsiflexed than the control or coper groups. There were no other significant group differences (all p>0.05). Conclusions: Kinematic differences exist between healthy controls, copers and individuals with FAI. Copers and individuals with FAI have both experienced ankle sprain injury, yet copers do not experience subsequent instability. Analysis of coper movement patterns compared to control and FAI groups may provide insight into coping mechanisms.

The purpose of this research was to develop and test an instrument to measure or quantify the construct of inner strength. Inner strength was synthesized into a theory based on twelve years of qualitative data from direct participant quotes, defined by Roux et al. (2002) as a central human resource that promotes well-being and healing. The inner strength questionnaire (ISQ) has undergone extensive psychometric evaluation which resulted in several versions. The third version had 37-items and was believed to have four subscales that mirrored the theoretical themes that emerged through the qualitative data. The sample was composed of 281 women with a variety of chronic health conditions including breast cancer, multiple sclerosis, diabetes, and heart disease. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were employed to assess the structure of the ISQ. Internal consistency was used to assess the reliability of each hypothesized subscale and the entire ISQ. Convergent and discriminant validity, were analyzed using the multitrait-multimethod by Campbell and Fiske (1959). For convergent validity, the entire instrument and each of the subscales was correlated with similar theoretical subscales of the Mastery of Stress Instrument (Younger, 1993). For discriminant validity, the Center for Epidemiological Studies in Depression (CESD) was correlated with the entire ISQ. Both the EFA and CFA revealed a four factor model. The four factors were labeled 1) mental, 2) connectedness, 3) knowing and searching, 4) physical. The reliability for all items on the ISQ was 0.91. The reliabilities for each of the subscales were 0.85 for mental, 0.96 for connectedness, 0.85 for knowing and searching, and 0.83 for physical. The multitrait-multimethod matrix revealed correlation coefficients for the relationship between the ISQ and MSI to be 0.55 and a correlation coefficient of -0.19 between the ISQ and the CESD.A four factor model is supported by the statistical data. Through face-to-face interviewing and input from content expert reviewers, ten items were eliminated from the 37-item (version 3) instrument to form a new version of the instrument. The new instrument supports the metasynthesis generated by Roux (2002) except for the fifth theme, entitled "new normal", which was found to be a consequence of having inner strength, not a component of inner strength.

A characteristic feature of chronic wounds is a prolonged inflammatory response as well as susceptibility to infection. Studies have shown that during the inflammatory response, there is a significant increase in the levels of neutrophil-derived enzymes. The purpose of this work was to determine whether the anionic macromolecule polystyrene sulfonate (PSS) and five of its salt forms, namely PSS-calcium, PSS-chlorhexidine, PSS-doxycycline, PSS-glutathione and PSS-silver are able to inhibit the activity of three of the enzymes whose levels are elevated in chronic wounds: elastase, cathepsin G and myeloperoxidase. In addition to the enzyme inhibition study, the various formulations’ antimicrobial properties were analyzed by evaluating their ability to inhibit the growth of three common clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumanii. It is worthy to note that the structure of PSS makes it a very flexible platform to which other molecules can be added in order to address a variety of “targets” as well as tailor quantitative strength. The results from this project showed that purified PSS and the various salt derivatives were able to inhibit elastase and cathepsin G activity. In addition, three of the therapeutic cations attached to PSS: silver, doxycycline and chlorhexidine retained their intrinsic antimicrobial properties without having an adverse effect on healthy tissue. In summary, this study demonstrated that PSS possessed an intrinsic ability to inhibit a number of proteases and that it could also be used as a delivery vehicle for other compounds with potential therapeutic value.

This diploma thesis summarizes recent knowledge about body scheme, spatial orientation and their change in context of chronic pain. The purpose of this work is to find out if chronic pain negatively affects the body scheme and spatial orientation. The thesis includes a comparative analysis of experimental measurements between the patients with Failed Back Surgery Syndrome and healthy control group. The analysis compares tasks based on spatial orientation and body scheme tests. Results show the patients' group having lower results in body scheme related tests, showing a noticeable disparity compared to the control group's test scores. These results were further supported by portion of spatial orientation based tasks, where patients' group again performed at significantly lower level than the control group. In conclusion, our thesis, along with other academic works, states that there is a correlation between chronic pain, disrupted body scheme and spatial orientation. However, at the present time it could not be determined whether the pain precedes the effect of disrupted body scheme or vice versa. Powered by TCPDF (www.tcpdf.org)