Effect of the emergence of community acquired methicillin resistant Staphylococcus aureus on microbial resistance patterns seen during a seven year study of minocycline/rifampin catheter use

Background. Health care associated catheter related blood stream infections (CRBSI) represent a significant public health concern in the United States. Several studies have suggested that precautions such as maximum sterile barrier and use of antimicrobial catheters are efficacious at reducing CRBSI, but there is concern within the medical community that the prolonged use of antimicrobial catheters may be associated with increased bacterial resistance. Clinical studies have been done showing no association and a significant decrease in microbial resistance with prolonged minocycline/rifampin (M/R) catheter use. One explanation is the emergence of community acquired methicillin resistant Staphylococcus aureus (MRSA), which is more susceptible to antibiotics, as a cause of CRBSI.^ Methods. Data from 323 MRSA isolates cultured from cancer patients at The University of Texas MD Anderson Cancer center from 1997-2007 displaying MRSA infection were analyzed to determine whether there is a relationship between resistance to minocycline and rifampin and prolonged wide spread use of minocycline (M/R) catheters. Analysis was also conducted to determine whether there was a significant change in the prevalence community acquired MRSA (CA-MRSA) during this time period and if this emergence act as a confounder masquerading the true relationship between microbial resistance and prolonged M/R catheter use.^ Results. Our study showed that the significant (p=0.008) change in strain type over time is a confounding variable; the adjusted model showed a significant protective effect (OR 0.000281, 95% CI 1.4x10 -4-5.5x10-4) in the relationship between MRSA resistance to minocycline and prolonged M/R catheter use. The relationship between resistance to rifampin and prolonged M/R catheter use was not significant.^ Conclusion. The emergence of CA-MRSA is a confounder and in the relationship between resistance to minocycline and rifampin and prolonged M/R catheter use. However, despite the adjustment for the more susceptible CA-MRSA the widespread use of M/R catheters does not promote microbial resistance. ^

Age -period -cohort analysis: An extension of Cox's lifetable regression with time -dependent covariates

It is well known that an identification problem exists in the analysis of age-period-cohort data because of the relationship among the three factors (date of birth + age at death = date of death). There are numerous suggestions about how to analyze the data. No one solution has been satisfactory. The purpose of this study is to provide another analytic method by extending the Cox's lifetable regression model with time-dependent covariates. The new approach contains the following features: (1) It is based on the conditional maximum likelihood procedure using a proportional hazard function described by Cox (1972), treating the age factor as the underlying hazard to estimate the parameters for the cohort and period factors. (2) The model is flexible so that both the cohort and period factors can be treated as dummy or continuous variables, and the parameter estimations can be obtained for numerous combinations of variables as in a regression analysis. (3) The model is applicable even when the time period is unequally spaced.^ Two specific models are considered to illustrate the new approach and applied to the U.S. prostate cancer data. We find that there are significant differences between all cohorts and there is a significant period effect for both whites and nonwhites. The underlying hazard increases exponentially with age indicating that old people have much higher risk than young people. A log transformation of relative risk shows that the prostate cancer risk declined in recent cohorts for both models. However, prostate cancer risk declined 5 cohorts (25 years) earlier for whites than for nonwhites under the period factor model (0 0 0 1 1 1 1). These latter results are similar to the previous study by Holford (1983).^ The new approach offers a general method to analyze the age-period-cohort data without using any arbitrary constraint in the model. ^

Analysis of Mycobacterium tuberculosis in the state of Texas for rifampin resistance using molecular beacons

Mycobacterium tuberculosis, a bacillus known to cause disease in humans since ancient times, is the etiological agent of tuberculosis (TB). The infection is primarily pulmonary, although other organs may also be affected. The prevalence of pulmonary TB disease in the US is highest along the US-Mexico border, and of the four US states bordering Mexico, Texas had the second highest percentage of cases of TB disease among Mexico-born individuals in 1999 (CDC, 2001). Between the years of 1993 and 1998, the prevalence of drug-resistant (DR) TB was 9.1% among Mexican-born individuals and 4.4% among US-born individuals (CDC, 2001). In the same time period, the prevalence of multi-drug resistant (MDR) TB was 1.4% among Mexican-born individuals and 0.6% among US-born individuals (CDC, 2001). There is a renewed urgency in the quest for faster and more effective screening, diagnosis, and treatment methods for TB due to the resurgence of tuberculosis in the US during the mid-1980s and early 1990s (CDC, 2007a), and the emergence of drug-resistant, multidrug-resistant, and extremely drug-resistant tuberculosis worldwide. Failure to identify DR and MDR-TB quickly leads to poorer treatment outcomes (CDC, 2007b). The recent rise in TB/HIV comorbidity further complicates TB control efforts. The gold standard for identification of DR-TB requires mycobacterial growth in culture, a technique taking up to three weeks, during which time DR/MDR-TB individuals harboring resistant organisms may be receiving inappropriate treatment. The goal of this study was to determine the sensitivity and specificity of real-time quantitative polymerase chain reaction (qPCR) using molecular beacons in the Texas population. qPCR using molecular beacons is a novel approach to detect mycobacterial mutations conferring drug resistance. This technique is time-efficient and has been shown to have high sensitivity and specificity in several populations worldwide. Rifampin (RIF) susceptibility was chosen as the test parameter because strains of M. tuberculosis which are resistant to RIF are likely to also be MDR. Due to its status as a point of entry for many immigrants into the US, control efforts against TB and drug-resistant TB in Texas is a vital component of prevention efforts in the US as a whole. We show that qPCR using molecular beacons has high sensitivity and specificity when compared with culture (94% and 87%, respectively) and DNA sequencing (90% and 96%, respectively). We also used receiver operator curve analysis to calculate cutoff values for the objective determination of results obtained by qPCR using molecular beacons. ^

NONLINEAR TIME SERIES/SYSTEM ANALYSIS (STATE-SPACE, DYNAMICS, INTERVENTION, RESILIENCE, KALMAN)

A discussion of nonlinear dynamics, demonstrated by the familiar automobile, is followed by the development of a systematic method of analysis of a possibly nonlinear time series using difference equations in the general state-space format. This format allows recursive state-dependent parameter estimation after each observation thereby revealing the dynamics inherent in the system in combination with random external perturbations.^ The one-step ahead prediction errors at each time period, transformed to have constant variance, and the estimated parametric sequences provide the information to (1) formally test whether time series observations y(,t) are some linear function of random errors (ELEM)(,s), for some t and s, or whether the series would more appropriately be described by a nonlinear model such as bilinear, exponential, threshold, etc., (2) formally test whether a statistically significant change has occurred in structure/level either historically or as it occurs, (3) forecast nonlinear system with a new and innovative (but very old numerical) technique utilizing rational functions to extrapolate individual parameters as smooth functions of time which are then combined to obtain the forecast of y and (4) suggest a measure of resilience, i.e. how much perturbation a structure/level can tolerate, whether internal or external to the system, and remain statistically unchanged. Although similar to one-step control, this provides a less rigid way to think about changes affecting social systems.^ Applications consisting of the analysis of some familiar and some simulated series demonstrate the procedure. Empirical results suggest that this state-space or modified augmented Kalman filter may provide interesting ways to identify particular kinds of nonlinearities as they occur in structural change via the state trajectory.^ A computational flow-chart detailing computations and software input and output is provided in the body of the text. IBM Advanced BASIC program listings to accomplish most of the analysis are provided in the appendix. ^

Clostridium difficile infection (CDI) in HIV-positive patients

The main aim of this study was to look at the association of Clostridium difficile infection (CDI) and HIV. A secondary goal was to look at the trend of CDI-related deaths in Texas from 1999-2011. To evaluate the coinfection of CDI and HIV, we looked at 2 datasets provided by CHS-TDSHS, for 13 years of study period from 1999-2011: 1) Texas death certificate data and 2) Texas hospital discharge data. An ancillary source of data was national level death data from CDC. We did a secondary data analysis and reported the age-adjusted death rates (mortality) and hospital discharge frequencies (morbidity) for CDI, HIV and for CDI+HIV coinfection.^ Since the turn of the century, CDI has reemerged as an important public health challenge due to the emergence of hypervirulent epidemic strains. From 1999-2011, there has been a significant upward trend in CDI-related death rates; in the state of Texas alone, CDI mortality rate has increased 8.7 fold in this time period at the rate of 0.2 deaths per year per 100,000 individuals. On the contrary, mortality due to HIV has decreased by 46% and has been trending down. The demographic groups in Texas with the highest CDI mortality rates were elderly aged 65+, males, whites and hospital inpatients. The epidemiology of C. difficile has changed in such a way that it is not only staying confined to these traditional high-risk groups, but is also being increasingly reported in low-risk populations such as healthy people in the community (community acquired C. difficile), and most recently immunocompromised patients. Among the latter, HIV can worsen the adverse health outcomes of CDI and vice versa. In patients with CDI and HIV coinfection, higher mortality and morbidity was found in young & middle-aged adults, blacks and males, the same demographic population that is at higher risk for HIV. As with typical CDI, the coinfection was concentrated in the hospital inpatients. Of all the CDI-related deaths in USA from 1999-2010, in the 25-44 year age group, 13% had HIV infection. Of all CDI-related inpatient hospital discharges in Texas from 1999-2011, in patients 44 years and younger, 17% had concomitant HIV infection. Therefore, HIV is a possible novel emerging risk factor for CDI.^

Sex Trafficking of Minors in the U.S.: Implications for Policy, Prevention and Research

Context: Information currently available on the trafficking of minors in the U.S. for commercial sexual exploitation includes approximations of the numbers involved, risk factors that increase the likelihood of victimization and methods of recruitment and control. However, specific characteristics about this vulnerable population remain largely unknown. Objective: This article has two distinct purposes. The first is to provide the reader with an overview of available information on minor sex trafficking in the U.S. The second is to present findings and discuss policy, research, and educational implications from secondary data analysis of 115 cases of minor sex trafficking in the U.S. Design: Minor sex trafficking cases were identified through two main venues - a review of U.S. Department of Justice press releases of human trafficking cases and an online search of media reports. Searches covered the time period from October 28, 2000, which coincided with the passage of the VTVPA through October 31, 2009. Cases were included in analysis if the incident involved at least one victim under the age of 18, occurred in the U.S., and at least one perpetrator had been arrested, indicted, or convicted. Results: A total of 115 separate incidents involving at least 153 victims were located. These occurrences involved 215 perpetrators, with the majority of them having been convicted (n = 117, 53.4%), The number of victims involved in a single incident ranged from 1 to 9. Over 90% of victims were female who ranged in age from 5 to 17 years. There were more U.S. minor victims than those from other countries. Victims had been in captivity from less than 6 months to 5 years. Minors most commonly fell into exploitation through some type of false promise indicated (16.3%, n = 25), followed by kidnapping (9.8%, n = 15). Over a fifth of the sample (22.2%, n = 34) were abused through two commercial sex practices, with almost all (94.1%, n = 144) used in prostitution. One of every five victims (24.8%, n = 38) had been advertised on an Internet website. Conclusions: Results of a review of known information about minor sex trafficking and findings from analysis of 115 incidents of the sex trafficking of youth in the U.S. indicate a need for stronger legislation to educate various professional groups, more comprehensive services for victims, stricter laws for pimps and traffickers, and preventive educational interventions beginning at a young age.

Change Detection Memory in Rhesus Monkeys and Humans

Visual short-term memory (VSTM) is the storage of visual information over a brief time period (usually a few seconds or less). Over the past decade, the most popular task for studying VSTM in humans has been the change detection task. In this task, subjects must remember several visual items per trial in order to identify a change following a brief delay interval. Results from change detection tasks have shown that VSTM is limited; humans are only able to accurately hold a few visual items in mind over a brief delay. However, there has been much debate in regard to the structure or cause of these limitations. The two most popular conceptualizations of VSTM limitations in recent years have been the fixed-capacity model and the continuous-resource model. The fixed-capacity model proposes a discrete limit on the total number of visual items that can be stored in VSTM. The continuous-resource model proposes a continuous-resource that can be allocated among many visual items in VSTM, with noise in item memory increasing as the number of items to be remembered increases. While VSTM is far from being completely understood in humans, even less is known about VSTM in non-human animals, including the rhesus monkey (Macaca mulatta). Given that rhesus monkeys are the premier medical model for humans, it is important to understand their VSTM if they are to contribute to understanding human memory. The primary goals of this study were to train and test rhesus monkeys and humans in change detection in order to directly compare VSTM between the two species and explore the possibility that direct species comparison might shed light on the fixed-capacity vs. continuous-resource models of VSTM. The comparative results suggest qualitatively similar VSTM for the two species through converging evidence supporting the continuous-resource model and thereby establish rhesus monkeys as a good system for exploring neurophysiological correlates of VSTM.

Calcification of a collagen-liposome complex

The purpose of the study was to evaluate in vitro calcification potential among liposomes composed of phospholipids with variations in fatty acid chains and polar head groups. The liposome was also modified by utilizing mixed phospholipids, incorporation of different types of protein to the liposome, or complexing with various collagen preparations. The samples were then incubated in a metastable calcium phosphate solution for the proposed time period. Calcium and phosphate uptake were measured. Resulting precipitates were processed for x-ray diffraction and electron microscopy. Acidic phospholipid, Dioleoylphosphatidic acid and mixed phospholipids, Dioleoylphosphatidic acid/Dipalmitoylphosphatidylethanolamine liposomes calcified at a faster rate and to a greater degree than other phospholipids tested. The incorporation of polylysine, fibronectin, bone protein, or the complexing with collagen decreased the rate and amount of calcification. Electron microscopy demonstrated the similarity of the calcified collagen-liposome complex to the natural calcification matrix. These preparations may be used as a model to study the role of membrane lipids and collagen-phospholipid during the process of calcification.^ The in vivo study was designed to determine whether the potential existed for the promotion of bone healing by the synthetic liposome-collagen complex. The implant materials were modified to provide decreased antigenicity, biocompatability while maintaining their bone conduction properties. The samples were placed subcutaneously and/or subperiosteally and/or in 8 mm calvarium defects of adult rats. Histological and immunological studies demonstrated that the implant itself retained minimal antigenicity and did not inhibit bone formation. However, modification of the implant may contain the bone induction property and be utilized to stimulate bony healing. ^

Regulation of the gastrin-releasing peptide/bombesin receptor

Gastrin-releasing peptide (GRP) and other bombesin-like peptides stimulate hormone secretion and cell proliferation by binding to specific G-protein-coupled receptors. Three studies were performed to identify potential mechanisms involved in GRP/bombesin receptor regulation.^ Although bombesin receptors are localized throughout the gastrointestinal tract, few gastrointestinal cell lines are available to study bombesin action. In the first study, the binding and function of bombesin receptors in the human HuTu-80 duodenal cancer cell line were characterized. ($\sp{125}$I-Tyr$\sp4$) bombesin bound with high affinity to a GRP-preferring receptor. Bombesin treatment increased IP$\sb3$ production, but had no effect on cell proliferation. Similar processing of ($\sp{125}$I-Tyr$\sp4$) bombesin and of GRP-receptors was observed in HuTu-80 cells and Swiss 3T3 fibroblasts, a cell line which mitogenically responds to bombesin. Therefore, the lack of a bombesin mitogenic effect in HuTu-80 cells is not due to unusual processing of ($\sp{125}$I-Tyr$\sp4$) bombesin or rapid GRP-receptor down-regulation.^ In the second study, a bombesin antagonist was developed to study the processing and regulatory events after antagonist binding. As previously shown, receptor bound agonist, ($\sp{125}$I-Tyr$\sp4$) bombesin, was rapidly internalized and degraded in chloroquine-sensitive compartments. Interestingly, receptor-bound antagonist, ($\sp{125}$I-D-Tyr$\sp6$) bombesin(6-13)PA was not internalized, but degraded at the cell-surface. In contrast to bombesin, (D-Tyr$\sp6$) bombesin(6-13)PA treatment did not cause receptor internalization. Together these results demonstrate that receptor regulation and receptor-mediated processing of antagonist is different from that of agonist.^ Bombesin receptors undergo acute desensitization. By analogy to other G-protein-coupled receptors, a potential desensitization mechanism may involve receptor phosphorylation. In the final study, $\sp{32}$P-labelled Swiss 3T3 fibroblasts and CHO-mBR1 cells were treated with bombesin and the GRP-receptor was immunoprecipitated. In both cell lines, bombesin treatment markedly stimulated GRP-receptor phosphorylation. Furthermore, bombesin-stimulated GRP-receptor phosphorylation occurred within the same time period as bombesin-stimulated desensitization, demonstrating that these two processes are correlated.^ In conclusion, these studies of GRP-receptor regulation further our understanding of bombesin action and provide insight into G-protein-coupled receptor regulation in general. ^

The effects of population density on the spread of disease

The objective of this study is to identify the relationship between population density and the initial stages of the spread of disease in a local population. This study proposes to concentrate on the question of how population density affects the distribution of the susceptible individuals in a local population and thus affects the spread of the disease, measles. Population density is measured by the average of the number of contacts with susceptible individuals by each individual in the population during a fixed-length time period. The term “contact with susceptible individuals” means sufficient contact between two people for the disease to pass from an infectious person to a susceptible person. The fixed-length time period is taken to be the average length of time an infected person is infectious without symptoms of the disease. For this study of measles, the time period will be seven days. ^ While much attention has been given to modeling the entire epidemic process of measles, attempts have not been made to study the characteristics of contact rates required to initiate an epidemic. This study explores the relationship between population density, given a specific herd immunity rate in the population, and initial rate of the spread of the disease by considering the underlying distribution of contacts with susceptibles by the individuals in the population. ^ This study does not seek to model an entire measles epidemic, but to model the above stated relationship for the local population within which the first infective person is introduced. This study describes the mathematical relationship between population density parameters and contact distribution parameters. ^ The results are displayed in graphs that show the effects of different population densities on the spread of disease. The results support the idea that the number of new infectives is strongly related to the distribution of susceptible contacts. The results also show large differences in the epidemic measures between populations with densities equal to four versus three. ^

The transformation of a health care system: An ecology perspective

Beginning in the early 1980s, the health care system experienced momentous realignments. Fundamental changes in structures of traditional health care organizations, shifts in authority and relationships of professionals and institutions, and the increasing influence of managed care contributed to a relatively stable industry entering into a state of turbulence. The dynamics of these changes are recurring themes in the health services literature. The purpose of this dissertation was to examine the content of this literature over a defined time period and within the perspective of a theory of organizational change. ^ Using a theoretical framework based upon the organizational theory known as Organizational Ecology, secondary data from the period between 1983 and 1994 was reviewed. Analysis of the literature identified through a defined search methodology was focused upon determining the manner in which the literature characterized changes that were described. Using a model constructed from fundamentals of Organizational Ecology with which to structure an assessment of content, literature was summarized for the manner and extent of change in specific organizational forms and for the changes in emphasis by the environmental dynamics directing changes in the population of organizations. Although it was not the intent of the analysis to substantiate causal relationships between environmental resources selected as the determinants of organizational change and the observed changes in organizational forms, the structured review of content of the literature established a strong basis for inferring such a relationship. ^ The results of the integrative review of the literature and the power of the appraisal achieved through the theoretical framework constructed for the analysis indicate that there is considerable value in such an approach. An historical perspective on changes which have transformed the health care system developed within a defined organizational theory provide a unique insight into these changes and indicate the need for further development of such an analytical model. ^

THE INHIBITORY EFFECTS OF VSV INFECTION ON MULV PRODUCTION OCCUR BETWEEN SYNTHESIS AND RELEASE OF MULV GENOMIC RNA

The inhibitory effects of VSV infection on MuLV production were investigated using the VSV temperature-sensitive mutants t1B17(I & V), tsT1026(I), tsG22(II), and ts052(II). At the permissive temperature, all four mutants suppressed the release of virion-associated MuLV gRNA by approximately 98% within 0.5 to 2.5 hr post infection. At the restrictive temperature and in the absence of cell killing, infection with t1B17(I & V) inhibited the release of MuLV gRNA, while tsT1026(I) and tsG22(II) did not. In contrast, ts052(II) inhibited the release of MuLV gRNA and induced cell killing. During the same time period and at either temperature, all four mutants did not suppress either MuLV-associated protein release or intracellular MuLV sRNA synthesis. These results indicate that VSV inhibits MULV gRNA release at a level somewhere between the synthesis and release of newly synthesized gRNA.^

For-profit business safety interventions: A systematic, descriptive review of the literature

The purpose of this research was to determine if principles from organizational theory could be used as a framework to compare and contrast safety interventions developed by for-profit industry for the time period 1986–1996. A literature search of electronic databases and manual search of journals and local university libraries' book stacks was conducted for safety interventions developed by for-profit businesses. To maintain a constant regulatory environment, the business sectors of nuclear power, aviation and non-profits were excluded. Safety intervention evaluations were screened for scientific merit. Leavitt's model from organization theory was updated to include safety climate and renamed the Updated Leavitt's Model. In all, 8000 safety citations were retrieved, 525 met the inclusion criteria, 255 met the organizational safety intervention criteria, and 50 met the scientific merit criteria. Most came from non-public health journals. These 50 were categorized by the Updated Leavitt's Model according to where within the organizational structure the intervention took place. Evidence tables were constructed for descriptive comparison. The interventions clustered in the areas of social structure, safety climate, the interaction between social structure and participants, and the interaction between technology and participants. No interventions were found in the interactions between social structure and technology, goals and technology, or participants and goals. Despite the scientific merit criteria, many still had significant study design weaknesses. Five interventions tested for statistical significance but none of the interventions commented on the power of their study. Empiric studies based on safety climate theorems had the most rigorous designs. There was an attempt in these studies to address randomization amongst subjects to avoid bias. This work highlights the utility of using the Updated Leavitt's Model, a model from organizational theory, as a framework when comparing safety interventions. This work also highlights the need for better study design of future trials of safety interventions. ^

Texas Department of Health organizational structure changes: A reflection of public health policy and agency expansion, September 1, 1946--June 30, 1994

The premise of this study is that changes in the agency's organizational structure reflect changes in government public health policy. Based on this premise, this study tracks the changes in the organizational structure and the overall expansion of the Texas Department of Health to understand the evolution of changing public health priorities in state policy from September 1, 1946 through June 30, 1994, a period of growth and new responsibilities. It includes thirty-seven observations of organizational structure as depicted by organizational charts of the agency and/or adapted from public documents. ^ The major questions answered are, what are the changes in the organizational structure, why did they occur and, what are the policy priorities reflected in these changes in and across the various time periods. ^ The analysis of the study included a thorough review of the organizational structure of the agency for the time-span of the study, the formulation of the criteria to be used in ascertaining the changes, the delineation of the changes in the organizational structure and comparison of the observations sequentially to characterize the change, the discovery of reasons for the structural changes (financial, statutory - federal and state, social and political factors), and the determination of policy priorities for each time period and their relation to the expansion and evolution of the agency. ^ The premise that the organizational structure of the agency and the changes over time reflect government public health policy and agency expansion was found to be true. ^

Youth population's health issues in Comal County, Texas

This study assesses adolescent's health issues in Comal County, TX. Adolescents are defined as youth between the ages of 12 to 17 years of age, who resided in Comal County during the time period of 2000 to 2007. The analysis focused on high risk behaviors including use of gateway drugs—tobacco and alcohol; illegal substance use; and reproductive health related indicators, including sexual activity, sexually transmitted diseases, and pregnancy. This study is based on the primary and secondary data collected as part of the 2008 Comal County Community Assessment. It compares findings from the primary data sources to extant data from four secondary data sources including: (1) The Centers for Disease Control & Prevention (national) Healthy People 2010; (2) The Centers for Disease Control & Prevention, Youth Risk Behavior Surveillance Survey, 2007; (3) The Texas Department of State Health Services, 2000 to 2007; and The Pride Survey (Local and Statewide). The methods are drawn from the literature on "rapid epidemiologic appraisal" (Annett H. & Rifkin S. B., 1988). The study focus on corroborating the perceptions, subjective concerns, opinions and beliefs of the Comal County key stakeholders and community participants with qualitative and quantitative indicators of health and well being. The value of this approach is to inform community leaders using a public health perspective and evidence in their decisions about priority setting and resources allocation activities for prevention of high risk behaviors and promotion of adolescent health and well being. ^