The cost effective management of Central Line-Associated Bloodstream Infections (CLABSIs) comparing the central line bundle to antimicrobialcoated central venous catheters: A systematic review

Central Line-Associated Bloodstream Infections (CLABSIs) are one of the most costly and preventable cases of morbidity and mortality among intensive care units (ICUs) in health care today. In 2008, the Centers for Medicare and Medicaid Services Medicare Program, under the Deficit Reduction Act, announced it will no longer reimburse hospitals for such adverse events among those related to CLABSIs. This reveals the financial burden shift onto the hospital rather than the health care payer who can now withhold reimbursements. With this weighing more heavily on hospital management, decision makers will need to find a way to completely prevent cases of CLABSI or simply pay for the financial consequences. ^ To reduce the risk of CLABSIs, several clinical, preventive interventions have been studied and even instituted including the Central Line (CL) Bundle and Antimicrobial Coated Central Venous Catheters (AM-CVCs). I carried out a formal systematic review on the topic to compare the cost-effectiveness of the Central Line (CL) Bundle to the commercially available antimicrobial coated central venous catheters (AM-CVCs) in preventing CLABSIs among critically and chronically ill patients in the U.S. Evidence was assessed for inclusion against predefined criteria. I, myself, conducted the data extraction. Ten studies were included in the review. Efficacy in reducing the mean incidence rate of CLABSI by the CL Bundle and AM-CVC interventions were compared with one another including costs. ^ The AM-CVC impregnated with antibiotics, rifampin-minocycline (AI-RM) is more clinically effective than the CL Bundle in reducing the mean rate of CLABSI per 1,000 catheter days. The lowest mean incidence rate of CLABSI per 1,000 catheter days among the AM-CVC studies was as low as zero in favor of the AI-RM. Moreover, the review revealed that the AI-RM appears to be more cost-effective than the CL Bundle. Results showed the adjusted incremental cost of the CL Bundle per ICU patient requiring a CVC to be approximately $196 while the AI-RM at only an additional cost of $48 per ICU patient requiring a CVC. ^ Limited data regarding the cost of the CL Bundle made it difficult to make a true comparison to the direct cost of the AM-CVCs. However, using the result I did have from this review, I concluded that the AM-CVCs do appear to be more cost-effective in decreasing the mean rate of CLABSI while also minimizing incremental costs per CVC than the CL Bundle. This review calls for further research addressing the cost of the CL Bundle and compliance and more effective study designs such as randomized control trials comparing the efficacy and cost of the CL Bundle to the AM-CVCs. Barriers that may face health care managers when implementing the CL Bundle or AM-CVCs include additional costs associated with the intervention, educational training and ongoing reinforcement as well as creating a new culture of understanding.^

The prevention of catheter related bloodstream infections in a pediatric population

Catheter related bloodstream infections are a significant barrier to success in many inpatient healthcare facilities. The goal of this study was to analyze and determine if an evidence based methodology to reduce the number of catheter related bloodstream infections in a pediatric inpatient healthcare facility had significant impact on the infection rate. Catheter related bloodstream infection rates were compared before and after program implementation. The patient population was selected based upon a recommendation in the 2010 National Healthcare Safety Network report on device related infections. This report indicated a need for more data on pediatric populations requiring admission to a long term care facility. The study design is a retrospective cohort study. Catheter related bloodstream infection data was gathered between 2008 and 2011. In October of 2008 a program implementation began to reduce the number of catheter related bloodstream infections. The key components of this initiative were to implement a standardized catheter maintenance checklist, introduce the usage of a chlorhexadine gluconate based product for catheter maintenance and skin antisepsis, and a multidisciplinary education plan that focused on hand hygiene and aseptic technique. The catheter related bloodstream infection rate in 2008 was 21.21 infections per 1000 patient-line days. After program implementation the 2009 catheter related bloodstream infection rate dropped to 1.11 per 1000 patient-line days. The infection rates in 2010 and 2011 were 2.19 and 1.47 respectively. Additionally, this study demonstrated that there was a potential cost savings of $620,000 to $1,240,000 between 2008 and 2009. In conclusion, an evidence based program based upon CDC guidelines can have a significant impact on catheter related bloodstream infection rates. ^

Retrospective analysis of Methicillin-Resistant Staphylococcus Aureus (MRSA) skin and Soft-Tissue Infections (SSTI) in a university hospital emergency department (ED)

Study Objective: Identify the most frequent risk factors of Community Acquired-MRSA (CA-MRSA) Skin and Soft-tissue Infections (SSTIs) using a case series of patients and characterize them by age, race/ethnicity, gender, abscess location, druguse and intravenous drug-user (IVDU), underlying medical conditions, homelessness, treatment resistance, sepsis, those whose last healthcare visit was within the last 12 months, and describe the susceptibility pattern from this central Texas population that have come into the University Medical Center Brackenridge (UMCB) Emergency Department (ED). ^ Methods: This study was a retrospective case-series medical record review involving a convenience sample of patients in 2007 from an urban public hospital's ED in Texas that had a SSTI that tested positive for MRSA. All positive MRSA cultures underwent susceptibility testing to determine antibiotic resistance. The demographic and clinical variables that were independently associated with MRSA were determined by univariate and multivariate analysis using logistic regression to calculate odds ratios (OR), 95% confidence intervals, and significance (p≤ 0.05). ^ Results: In 2007, there were 857 positive MRSA cultures. The demographics were: males 60% and females 40%, with the average age of 36.2 (std. dev. =13) the study population consisted of non-Hispanic white (42%), Hispanics (38%), and non-Hispanic black (18.8%). Possible risk factors addressed included using recreational drugs (not including IVDU) (27%) homelessness (13%), diabetes status (12.6%) or having an infectious disease, and IVDU (10%). The most frequent abscess location was the leg (26.6%), followed by the arm and torso (both 13.7%). Eighty-three percent of patients had one prominent susceptibility pattern that had a susceptibility rate for the following antibiotics: trimethoprim/sulfamethoxazole (TMP-SMX) and vancomycin had 100%, gentamicin 99%, clindamycin 96%, tetracycline 96%, and erythromycin 56%. ^ Conclusion: The ED is becoming an important area for disease transmission between the sterile hospital environment and the outside environment. As always, it is important to further research in the ED in an effort to better understand MRSA transmission and antibiotic resistance, as well as to keep surveillance for the introduction of new opportunistic pathogens into the population. ^

Cost-effectiveness of intensified interventions to control healthcare-associated MRSA infections -- A systematic literature review

Methicillin Resistant Staphylococcus aureus healthcare-associated infections (MRSA HAIs) are a major cause of morbidity in hospitalized patients. They pose great economic burden to hospitals caring for these patients. Intensified Interventions aim to control MRSA HAIs. Cost-effectiveness of Intensified Interventions is largely unclear. We performed a review of cost-effectiveness literature on Intensified Interventions , and provide a summary of study findings, the status of economic research in the area, and information that will help decision-makers at regional level and guide future research.^ We conducted literature search using electronic database PubMed, EBSCO, and The Cochrane Library. We limited our search to English articles published after 1999. We reviewed a total of 1,356 titles, and after applying our inclusion and exclusion criteria selected seven articles for our final review. We modified the Economic Evaluation Abstraction Form provided by CDC, and used this form to abstract data from studies.^ Of the seven selected articles two were cohort studies and the remaining five were modeling studies. They were done in various countries, in different study settings, and with different variations of the Intensified Intervention . Overall, six of the seven studies reported that Intensified Interventions were dominant or at least cost-effective in their study setting. This effect persisted on sensitivity testing.^ We identified many gaps in research in this field. The cost-effectiveness research in the field is mostly composed of modeling studies. The studies do not always clearly describe the intervention. The intervention and infection costs and the sources for these costs are not always explicit or are missing. In modeling studies, there is uncertainty associated with some key model inputs, but these inputs are not always identified. The models utilized in the modeling studies are not always tested for internal consistency or validity. Studies usually test the short term cost-effectiveness of Intensified Interventions but not the long results.^ Our study limitation was the inability to adjust for differences in study settings, intervention costs, disease costs, or effectiveness measures. Our study strength is the presentation of a focused literature review of Intensified Interventions in hospital settings. Through this study we provide information that will help decision makers at regional level, help guide future research, and might change clinical care and policies. ^

Risk factors for surgical site infections among patients undergoing major colon surgery in the United States 2007-2009

Background: Surgical site infections (SSIs) after abdominal surgeries account for approximately 26% of all reported SSIs. The Center for Disease Control and Prevention (CDC) defines 3 types of SSIs: superficial incisional, deep incisional, and organ/space. Preventing SSIs has become a national focus. This dissertation assesses several associations with the individual types of SSI in patients that have undergone colon surgery. ^ Methods: Data for this dissertation was obtained from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP); major colon surgeries were identified in the database that occurred between the time period of 2007 and 2009. NSQIP data includes more than 50 preoperative and 30 intraoperative factors; 40 collected postoperative occurrences are based on a follow-up period of 30 days from surgery. Initially, four individual logistic regressions were modeled to compare the associations between risk factors and each of the SSI groups: superficial, deep, organ/space and a composite of any single SSI. A second analysis used polytomous regression to assess simultaneously the associations between risk factors and the different types of SSIs, as well as, formally test the different effect estimates of 13 common risk factors for SSIs. The final analysis explored the association between venous thromboembolism (VTEs) and the different types of SSIs and risk factors. ^ Results: A total of 59,365 colon surgeries were included in the study. Overall, 13% of colon cases developed a single type of SSI; 8% of these were superficial SSIs, 1.4% was deep SSIs, and 3.8% were organ/space SSIs. The first article identifies the unique set of risk factors associated with each of the 4 SSI models. Distinct risk factors for superficial SSIs included factors, such as alcohol, chronic obstructive pulmonary disease, dyspnea and diabetes. Organ/space SSIs were uniquely associated with disseminated cancer, preoperative dialysis, preoperative radiation treatment, bleeding disorder and prior surgery. Risk factors that were significant in all models had different effect estimates. The second article assesses 13 common SSI risk factors simultaneously across the 3 different types of SSIs using polytomous regression. Then each risk factor was formally tested for the effect heterogeneity exhibited. If the test was significant the final model would allow for the effect estimations for that risk factor to vary across each type of SSI; if the test was not significant, the effect estimate would remain constant across the types of SSIs using the aggregate SSI value. The third article explored the relationship of venous thromboembolism (VTE) and the individual types of SSIs and risk factors. The overall incidence of VTEs after the 59,365 colon cases was 2.4%. All 3 types of SSIs and several risk factors were independently associated with the development of VTEs. ^ Conclusions: Risk factors associated with each type of SSI were different in patients that have undergone colon surgery. Each model had a unique cluster of risk factors. Several risk factors, including increased BMI, duration of surgery, wound class, and laparoscopic approach, were significant across all 4 models but no statistical inferences can be made about their different effect estimates. These results suggest that aggregating SSIs may misattribute and hide true associations with risk factors. Using polytomous regression to assess multiple risk factors with the multiple types of SSI, this study was able to identify several risk factors that had significant effect heterogeneity across the 3 types of SSI challenging the use of aggregate SSI outcomes. The third article recognizes the strong association between VTEs and the 3 types of SSIs. Clinicians understand the difference between superficial, deep and organ/space SSIs. Our results indicate that they should be considered individually in future studies.^

Mechanisms of adenovirus 5 E1A -mediated tumor suppression and E1A-mediated apoptosis

The adenovirus type 5 E1A gene products have numerous functions in cells, which serve as useful tools in studying the mechanisms of either oncogenesis or tumor suppression. To understand the mechanisms of E1A-mediated tumor suppression, we introduced an Ad5 E1A gene into murine melanoma cells, and characterized E1A-mediated biological functions both in vitro and in vivo. The results of the study indicated that: (i) Ad5 E1A mediated tumor suppression in rodent tumor cells; (ii) E1A-mediated tumor suppression is associated with E1A-mediated apoptosis in vivo.^ To determine which functional region(s) of E1A is(are) required for E1A-mediated apoptosis and whether E1A-mediated apoptosis is required for E1A-mediated tumor suppression, we established stable transfectants of E1A mutants, which have deletion mutation at either the N-terminal (p300-binding) or the CR2 (pRb-binding) domain or both, and then characterized biological functions both in vitro and in vivo. The results of the study indicate that the CR2 domain of E1A is required for E1A-mediated apoptosis, while the N-terminal domain of E1A is dispensable. Interestingly, either of the two domains is able to mediate tumor suppression, since mutant E1A with a single deletion at either domain still suppressed tumor growth. Importantly, deletion mutations at both the N-terminal and the CR2 domains of E1A abrogated E1A-mediated tumor suppression, suggesting both regions are required for E1A-mediated tumor suppression. The results demonstrate that E1A-mediated apoptosis is not the only mechanism for E1A-mediated tumor suppression. Thus, the N-terminal and CR2 domains of E1A mediated two independent mechanisms of tumor suppression.^ To understand the mechanism of E1A-mediated apoptosis, we examined the temporal relationship of molecular events during the apoptotic cascades after UV radiation and serum depletion in both the E1A-expressing cells and parental cells. Kinetic analysis of JNK activity indicates that the JNK pathway is greatly increased in response to UV light in E1A transfectants, suggesting that extracellular stress stimuli have been converted into intracellular stress signals with greater magnitude in E1A transfectants than those in parental cells. Thus, E1A-mediated sensitization precedes these events. As ceramide has been proposed as second messenger and upstream activator of JNK pathway for stress-induced apoptosis, we also examined the roles of ceramide in apoptosis and the relationship with JNK pathway. The results indicate that E1A transfectants do not have increased sensitivity to ceramide. Therefore, E1A-mediated sensitization to UV radiation cannot be attributed to an increased sensitivity to ceramide. Furthermore, UV-induced JNK activation correlates with UV-induced apoptosis, while lethal dose of ceramide does not activate JNK. Thus, activation of JNK pathway is independent of the ceramide pathway. In addition, E1A transfectants also have increased activation of NF-kB in response to UV. These results suggest that E1A-mediated sensitization is an early event which associates with conversion of extracellular stress stimuli into amplified intracellular signals. The mechanism of E1A-mediated sensitization and its relationship with other pathways are discussed. ^

Axl -Gas6 signaling counteracts adenovirus type 5 E1A-mediated cell growth suppression and proapoptotic activity

The adenovirus type 5 E1A (abbreviated E1A) has previously been known as an immortalization oncogene because E1A is required for transforming oncogenes, such as ras and E1B, to transform cells in primary cultures. However, E1A has also been shown to downregulate the overexpression of the Her-2/neu oncogene, resulting in suppression of transformation and tumorigenesis induced by that oncogene. In addition, E1A is able to promote apoptosis induced by anticancer drugs, irradiation, and serum deprivation. Many tyrosine kinases, such as the EGF receptor, Her-2/Neu, Src, and Axl are known to play a role in oncogenic signals in transformed cells. To study the mechanism underlying the E1A-mediated tumor-suppressing function, we exploited a modified tyrosine kinase profile assay (Proc. Natl. Acad. Sci, 93, 5958–5962, 1996) to identify potential tyrosine kinases regulated by E1A. RT-PCR products were synthesized with two degenerate primers derived from the conserved motifs of various tyrosine kinases. A tyrosine kinase downregulated by E1A was identified as Axl by analyzing the Alu I-digested RT-PCR products. We isolated the DNA fragment of interest, and found that E1A negatively regulated the expression of the transforming receptor tyrosine kinase Axl at the transcriptional level. To study whether downregulation of the Axl receptor is involved in E1A-mediated growth suppression, we transfected axl cDNA into E1A-expressing cells (ip1-E1A) to establish cells that overexpressed Axl (ip1-E1A-Axl). The Axl ligand Gas6 triggered a greater mitogenic effect in these ip1-E1A-Axl cells than in the control cells ip1-E1A and protected the Axl-expressing cells from serum deprivation-induced apoptosis. Further study showed that Akt is required for Axl-Gas6 signaling to prevent ip1-E1A-Axl cells from serum deprivation-induced apoptosis. These results indicate that downregulation of the Axl receptor by E1A is involved in E1A-mediated growth suppression and E1A-induced apoptosis, and thereby contributes to E1A's anti-tumor activities. ^

Population-based cross -sectional survey on intestinal helminth infections with a focus on taeniasis among residents of El Paso, Texas and Ciudad Juarez, Mexico

Few studies have been conducted on the epidemiology of enteric infectious diseases of public health importance in communities along the United States-Mexico border, and these studies typically focus on bacterial and viral diseases. The epidemiology of intestinal helminth infections along the border has not recently been explored, and there are no published reports for El Paso and Ciudad Juarez, both of which are high traffic urban areas along the Texas-Mexico border. The purpose of this research project was to conduct a cross-sectional epidemiologic survey for enteric helminths of medical importance along the Texas-Mexico border region of El Paso and Ciudad Juarez and to evaluate risk factors for exposure to these parasites. In addition, an emphasis was placed on the zoonotic tapeworm, Taenia solium. This tapeworm is especially important in this region because of the increasing incidence of neurocysticercosis, a severe disease spread by carriers of intestinal T. solium. Fecal samples were collected from individuals of all ages in a population-based cross-sectional household survey and evaluated for the presence of helminth parasites using fecal flotations. In addition, a Taenia coproantigen enzyme linked immunosorbent assay (ELISA) was performed on each stool sample to identify tapeworm carriers. A standardized questionnaire was administered to identify risk factors and routes of exposure for enteric helminth infections with additional questions to assess risk factors specific for taeniasis. The actual prevalence of taeniasis along the Texas-Mexico border was unknown, and this is the first population-based study performed in this region. Flotations were performed on 395 samples and four (1%) were positive for helminths including Ascaris, hookworms and Taenia species. Immunodiagnostic testing demonstrated a prevalence of 2.9% (11/378) for taeniasis. Based on the case definition, a 3% (12/395) prevalence of taeniasis was detected in this area. In addition, statistical analyses indicate that residents of El Paso are 8.5 times more likely to be a tapeworm carrier compared to residents of Juarez (PR=8.5, 95% CI=2.35, 30.81). This finding has important implications in terms of planning effective health education campaigns to decrease the prevalence of enteric helminths in populations along the Texas-Mexico border. ^