Catalytic antibody response to the Staphylococcus aureus virulence factor Efb

Staphylococcus aureus is a globally prevalent pathogen that can cause a wide variety of acute and chronic diseases in both adults and children, in both immune susceptible populations and healthy individuals. Its ability to cause persistent infections has been linked to multiple immune evasion strategies, including Efb-mediated complement inhibition. As new multi-drug-resistant strains emerge, therapeutic alternatives to traditional antibiotics must be developed. These experiments assessed the ability of healthy patient immunoglobulin to cleave Efb and disable the complement-inhibitory properties of Efb in vitro. Levels of immunoglobulin-mediated Efb catalysis varied both between immunoglobulin isoform/isotype and between individuals. Serum IgG showed the strongest catalytic activity of the immunoglobulin isotypes tested. Additionally, IgG hydrolyzed the virulence factor in a way that enabled only minimal binding to the complement component C3b, effectively blocking Efb-mediated inhibition of complement lysis. Salivary IgA and serum IgM did not block Efb-mediated inhibition of complement. Catalytic IgG selectively cleaved Efb and showed no cleavage of a variety of other proteins tested. Catalytic activity of IgG was inhibited by serine protease inhibitors, but not by other protease inhibitors, suggesting a serine-protease mechanism of catalysis. It is proposed that varying concentrations and activity levels of catalytic IgG between healthy individuals and those with current or recurrent S. aureus infections in both adult and pediatric populations be studied in order to assess the potential effectiveness of passive immunization therapy with catalytic monoclonal IgG. ^

A literature review of the use of DDT to fight malaria

Background. First synthesized in 1874, dichlorodiphenyltrichloroethane (DDT) was not used until the second half of World War II after its insecticidal properties were discovered in 1939. For decades DDT has been used globally with the intent of eradicating malaria. This began in 1955 when the eighth World Health Assembly launched a global campaign selecting DDT as the chemical of choice for the eradication of malaria. The United States banned DDT use in 1972 partially due to the publication of “Silent Spring” by Rachel Carson in 1962 which suggested that DDT was harmful to the environment, wildlife and is a carcinogen. ^ Objectives. To critically review the literature on DDT, and evaluate its importance in malaria prevention and control. Methods: The design of this systematic literature review is a narrative summary and evaluation of the papers reviewed. The data came from searches using PubMed and MEDLINE which are free and publicly available databases. Inclusive criteria that were considered during the search are English language peer reviewed journal articles published in the last 20 years. The keywords were: “insecticidal and agricultural use of DDT”, “human impact of malaria”, “economic impact of malaria”, “benefits of DDT”, “effects of DDT”, “importance of malaria control”, and alternatives to DDT for malaria control. ^ Results. Malaria continues to be one of the most common infectious diseases and creates a tremendous global public health problem. WHO recommends DDT for malaria vector control because compared to other pesticides, it is the most persistent in indoor spraying. ^ Conclusion. Indoor spraying of DDT in malaria endemic areas may cause increased exposure of the chemical to humans; however I conclude that the overall benefits outweigh the risks because more lives are saved due to fewer infections with malaria.^

A Bayesian approach to estimating the intraclass correlation coefficient

A Bayesian approach to estimating the intraclass correlation coefficient was used for this research project. The background of the intraclass correlation coefficient, a summary of its standard estimators, and a review of basic Bayesian terminology and methodology were presented. The conditional posterior density of the intraclass correlation coefficient was then derived and estimation procedures related to this derivation were shown in detail. Three examples of applications of the conditional posterior density to specific data sets were also included. Two sets of simulation experiments were performed to compare the mean and mode of the conditional posterior density of the intraclass correlation coefficient to more traditional estimators. Non-Bayesian methods of estimation used were: the methods of analysis of variance and maximum likelihood for balanced data; and the methods of MIVQUE (Minimum Variance Quadratic Unbiased Estimation) and maximum likelihood for unbalanced data. The overall conclusion of this research project was that Bayesian estimates of the intraclass correlation coefficient can be appropriate, useful and practical alternatives to traditional methods of estimation. ^

Commentary on "Child Welfare Waivers: The Stakes for Families"

The purpose of this piece is to provide commentary of an article, Child Welfare Waivers: The Stakes for Your State, that discusses the recent reauthorization of the Title IV-E Child Welfare Waivers. The article provides an overview of funds available to the states for child welfare programs and their intended purpose and restrictions placed on use. As structured, the present system rewards states monetarily for maintaining foster care. Research from waiver programs shows promising results for improved outcomes at the same or lower financial cost by utilizing safe, proven alternatives to the current foster care system. Waiver funds also protect the financial commitment to child welfare because state legislative budget slashing in this area will result in the loss of Federal funding. The independent analysis required with the grant of a waiver must be maintained to provide ongoing analysis and oversight of the increase spending flexibility. Stakeholders must be aware of the program and its results and use these funds as an opportunity to assess new concepts and apply programs best suited to the needs of children in their state. Allowing those “on the ground” to determine appropriate programming and careful result assessment may be the best means for protecting children, preserving families and doing both in a manner that makes the most efficient use of available resources.

Effects of exercise with oxygen prebreathe for decompression risk reduction

Astronauts performing extravehicular activities (EVA) are at risk for occupational hazards due to a hypobaric environment, in particular Decompression Sickness (DCS). DCS results from nitrogen gas bubble formation in body tissues and venous blood. Denitrogenation achieved through lengthy staged decompression protocols has been the mainstay of prevention of DCS in space. Due to the greater number and duration of EVAs scheduled for construction and maintenance of the International Space Station, more efficient alternatives to accomplish missions without compromising astronaut safety are desirable. ^ This multi-center, multi-phase study (NASA-Prebreathe Reduction Protocol study, or PRP) was designed to identify a shorter denitrogenation protocol that can be implemented before an EVA, based on the combination of adynamia and exercise enhanced oxygen prebreathe. Human volunteers recruited at three sites (Texas, North Carolina and Canada) underwent three different combinations (“PRP phases”) of intense and light exercise prior to decompression in an altitude chamber. The outcome variables were detection of venous gas embolism (VGE) by precordial Doppler ultrasound, and clinical manifestations of DCS. Independent variables included age, gender, body mass index, oxygen consumption peak, peak heart rate, and PRP phase. Data analysis was performed both by pooling results from all study sites, and by examining each site separately. ^ Ten percent of the subjects developed DCS and 20% showed evidence of high grade VGE. No cases of DCS occurred in one particular PRP phase with use of the combination of dual-cycle ergometry (10 minutes at 75% of VO2 peak) plus 24 minutes of light EVA exercise (p = 0.04). No significant effects were found for the remaining independent variables on the occurrence of DCS. High grade VGE showed a strong correlation with subsequent development of DCS (sensitivity, 88.2%; specificity, 87.2%). In the presence of high grade VGE, the relative risk for DCS ranged from 7.52 to 35.0. ^ In summary, a good safety level can be achieved with exercise-enhanced oxygen denitrogenation that can be generalized to the astronaut population. Exercise is beneficial in preventing DCS if a specific schedule is followed, with an individualized VO2 prescription that provides a safety level that can then be applied to space operations. Furthermore, VGE Doppler detection is a useful clinical tool for prediction of altitude DCS. Because of the small number of high grade VGE episodes, the identification of a high probability DCS situation based on the presence of high grade VGE seems justified in astronauts. ^

Molecular mechanisms of response in gastrointestinal stromal tumors treated with imatinib mesylate

Gastrointestinal stromal tumors (GIST) represent 80% of sarcoma arising from the GI tract. The inciting event in tumor progression is mutation of the kit or, rarely, platelet derived growth factor receptor-α (PDGFR) gene. These mutations encode ligand independent, constitutively active proteins: Kit or PDGFR. ^ These tumors are notoriously chemo and radio resistant. Historically, patients with advanced disease realized a median overall survival of 9 months. However, with modern management of GIST with imatinib mesylate (Novartis), a small molecule inhibitor of the Kit, PDGFR, and Abl tyrosine kinases, patients now realize a median overall survival greater than 30 months. However, almost half of patients present with surgically resectable GIST and the utility of imatinib in this context has not been prospectively studied. Also, therapeutic benefit of imatinib is variable from patient to patient and alternative targeted therapy is emerging as potential alternatives to imatinib. Thus, elucidating prognostic factors for patients with GIST in the imatinib-era is crucial to providing optimal care to each particular patient. Moreover, the exact mechanism of action of imatinib in GIST is not fully understood. Therefore, physicians find difficulty in accurately predicting which patient will benefit from imatinib, how to assess response to therapy, and the time at which to assess response. ^ I have hypothesized that imatinib is tolerable and clinically beneficial in the context of surgery, VEGF expression and kit non-exon 11 genotypes portend poor survival on imatinib therapy, and imatinib's mechanism of action is in part due to anti-vascular effects and inhibition of the Kit/SCF signaling axis of tumor-associated endothelial cells. ^ Results herein demonstrate that imatinib is safe and increases the duration of disease-free survival when combined with surgery. Radiographic and molecular (namely, apoptosis) changes occur within 3 days of imatinib initiation. I illustrate that non-exon 11 mutant genotypes and VEGF are poor prognostic factors for patients treated with imatinib. These findings may allow for patient stratification to emerging therapies rather than imatinib. I show that imatinib has anti-vascular effects via inducing tumor endothelial cell apoptosis perhaps by abrogation of the Kit/SCF signaling axis. ^

The Emergency Department: Rising wait times, costs, and possible remedies

Emergency Departments (EDs) and Emergency Rooms (ERs) are designed to manage trauma, respond to disasters, and serve as the initial care for those with serious illnesses. However, because of many factors, the ED has become the doorway to the hospital and a “catch-all net” for patients including those with non-urgent needs. This increase in the population in the ED has lead to an increase in wait times for patients. It has been well documented that there has been a constant and consistent rise in the number of patients that frequent the ED (National Center for Health Statistics, 2002); the wait time for patients in the ED has increased (Pitts, Niska, Xu, & Burt, 2008); and the cost of the treatment in the ER has risen (Everett Clinic, 2008). Because the ED was designed to treat patients who need quick diagnoses and may be in potential life-threatening circumstances, management of time can be the ultimate enemy. If a system was implemented to decrease wait times in the ED, decrease the use of ED resources, and decrease costs endured by patients seeking care, better outcomes for patients and patient satisfaction could be achieved. The goal of this research was to explore potential changes and/or alternatives to relieve the burden endured by the ED. In order to explore these options, data was collected by conducting one-on-one interviews with seven physicians closely tied to a Level 1 ED (Emergency Room physicians, Trauma Surgeons and Primary Care physicians). A qualitative analysis was performed on the responses of one-on-one interviews with the aforementioned physicians. The interviews were standardized, open-ended questions that probe what makes an effective ED, possible solutions to improving patient care in the ED, potential remedies for the mounting problems that plague the ED, and the feasibility of bringing Primary Care Physicians to the ED to decrease the wait times experienced by the patient. From the responses, it is clear that there needs to be more research in this area, several areas need to be addressed, and a variety of solutions could be implemented. The most viable option seems to be making the ED its own entity (similar to the clinic or hospital) that includes urgent clinics as a part of the system, in which triage and better staffing would be the most integral part of its success.^

A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

Policy analysis of Texas Senate Bill 532 and the regulation of nurse practitioners in the convenience care model

Background. Retail clinics, also called convenience care clinics, have become a rapidly growing trend since their initial development in 2000. These clinics are coupled within a larger retail operation and are generally located in "big-box" discount stores such as Wal-mart or Target, grocery stores such as Publix or H-E-B, or in retail pharmacies such as CVS or Walgreen's (Deloitte Center for Health Solutions, 2008). Care is typically provided by nurse practitioners. Research indicates that this new health care delivery system reduces cost, raises quality, and provides a means of access to the uninsured population (e.g., Deloitte Center for Health Solutions, 2008; Convenient Care Association, 2008a, 2008b, 2008c; Hansen-Turton, Miller, Nash, Ryan, Counts, 2007; Salinsky, 2009; Scott, 2006; Ahmed & Fincham, 2010). Some healthcare analysts even suggest that retail clinics offer a feasible solution to the shortage of primary care physicians facing the nation (AHRQ Health Care Innovations Exchange, 2010). ^ The development and performance of retail clinics is heavily dependent upon individual state policies regulating NPs. Texas currently has one of the most highly regulated practice environments for NPs (Stout & Elton, 2007; Hammonds, 2008). In September 2009, Texas passed Senate Bill 532 addressing the scope of practice of nurse practitioners in the convenience care model. In comparison to other states, this law still heavily regulates nurse practitioners. However, little research has been conducted to evaluate the impact of state laws regulating nurse practitioners on the development and performance of retail clinics. ^ Objectives. (1). To describe the potential impact that SB 532 has on retail clinic performance. (2). To discuss the effectiveness, efficiency, and equity of the convenience care model. (3). To describe possible alternatives to Texas' nurse practitioner scope of practice guidelines as delineated in Texas Senate Bill 532. (4). To describe the type of nurse practitioner state regulation (i.e. independent, light, moderate, or heavy) that best promotes the convenience care model. ^ Methods. State regulations governing nurse practitioners can be characterized as independent, light, moderate, and heavy. Four state NP regulatory types and retail clinic performance were compared and contrasted to that of Texas regulations using Dunn and Aday's theoretical models for conducting policy analysis and evaluating healthcare systems. Criteria for measurement included effectiveness, efficiency, and equity. Comparison states were Arizona (Independent), Minnesota (Light), Massachusetts (Moderate), and Florida (Heavy). ^ Results. A comparative states analysis of Texas SB 532 and alternative NP scope of practice guidelines among the four states: Arizona, Florida, Massachusetts, and Minnesota, indicated that SB 532 has minimal potential to affect the shortage of primary care providers in the state. Although SB 532 may increase the number of NPs a physician may supervise, NPs are still heavily restricted in their scope of practice and limited in their ability to act as primary care providers. Arizona's example of independent NP practice provided the best alternative to affect the shortage of PCPs in Texas as evidenced by a lower uninsured rate and less ED visits per 1,000 population. A survey of comparison states suggests that retail clinics thrive in states that more heavily restrict NP scope of practice as opposed to those that are more permissive, with the exception of Arizona. An analysis of effectiveness, efficiency, and equity of the convenience care model indicates that retail clinics perform well in the areas of effectiveness and efficiency; but, fall short in the area of equity. ^ Conclusion. Texas Senate 532 represents an incremental step towards addressing the problem of a shortage of PCPs in the state. A comparative policy analysis of the other four states with varying degrees of NP scope of practice indicate that a more aggressive policy allowing for independent NP practice will be needed to achieve positive changes in health outcomes. Retail clinics pose a temporary solution to the shortage of PCPs and will need to expand their locations to poorer regions and incorporate some chronic care to obtain measurable health outcomes. ^

INTAKE VARIABLES AS PREDICTORS OF ASSESSMENT AND REFERRAL PROCEDURE OUTCOMES IN EMPLOYEE ASSISTANCE PROGRAMS

While reported prevalence rates of troubled employees vary considerably, even conservative estimates indicate a major public health problem. For example, alcohol and drug related problems alone cost U.S. industry more than 45 billion dollars annually.^ Of the alternatives available to deal with these problems, e.g., dismissal or disciplinary actions, the most viable and cost effective are employee assistance programs (EAP), designed to provide professional assistance to employees experiencing alcohol, drug, emotional or personal crisis.^ The principal component of an EAP is that of assessment and referral, and this study was developed to determine which EAP client intake variables are the most efficacious predictors of assessment and referral procedures.^ Although, specific client intake variables were statistically significant the discriminant classification analysis was demonstrably inadequate. Nevertheless, the identification of A/R procedure phases which were not efficacious, as well as EAP client populations for whom services were not effective, were extremely valuable discernments. Identifying the less efficacious components of the A/R process provided an opportunity to recommend alternatives to current program procedures and practices, which may ameliorate program effectiveness. ^