The relationship between leadership practices and a medication safety regime

Errors in healthcare are commonplace and have significant impact on mortality, morbidity, and costs. Other high-risk industries are credited with strong safety records. These successes are due in part to a strong, committed organizational culture and their leadership. A consistent pattern of effective leadership behaviors; creating change, establishing a vision and strategic actions, and enabling and inspiring the organization's members to act, is present in these high-risk industries. This research examined the relationship between leadership practices and a medication safety regime. The hypothesis is strong leadership practices have a positive relationship with the degree of sophistication of a medication safety program (safety performance). Leadership was used as a surrogate for organizational culture and was measured in this research through the Kouzes and Posner's Leadership Practices Inventory. The Institute of Medicine's 14 Selected Strategies to Improve Medication Safety was used to measure the development of a medication safety regime. Leadership practices towards safety were assessed by surveying 2,478 critical care Registered Nurses in the greater Houston area. A response rate of 19% was achieved. Thirteen hospitals participated in the medication safety regime assessment. Data from 386 RN respondents from 53 institutions provided an overall description of unit (ICU) and organization (hospital) leader's practices towards safety. There is some recognition of the medical error problem and that leaders exhibit moderate levels of leadership practices to promote safety. There were no differences noted in unit and hospital leaders' behaviors, with the exception that unit leaders promote change and enable staff to act more often than hospital leaders. There were no statistically significant relationships between overall leadership, or individual leadership practices and the organization's safety performance. There was a significant relationship between leadership and safety performance when other factors in organizational culture were considered. Teaching and Magnet hospitals also exhibited stronger behaviors towards safety. Organizational culture, as measured by academic affiliation and Magnet recognition, is strongly related to safety performance as measured by the degree of development of a medication safety regime. ^

Role of the cyclin dependent kinase-4 in normal and neoplastic proliferation

In the last few years, our laboratory has studied the regulatory mechanisms of proliferation and differentiation in epidermal tissues. Our results showed differences in the roles of cyclin dependent-kinases 4 and 6, and the three D-type cyclins, during normal epidermal proliferation and neoplastic development. Thus, to elucidate the role of the different cell cycle regulators, we developed transgenic mice that overexpress CDK4 (K5-CDK4), or their cognate D-type cyclins, in epithelial tissues. The most severe phenotype was observed in K5-CDK4 animals that developed dermal fibrosis, epidermal hyperplasia and hypertrophy. Forced expression of CDK4 in the epidermal basal cell layer increased the malignant conversion of skin papillomas to squamous cell carcinomas (SCC). Contrastingly, lack of CDK4 completely inhibited tumor development, suggesting that CDK4 is required in this process. Biochemical studies demonstrated that p21 Cip1 and p27Kip1 inhibitors are sequestered by CDK4 resulting in indirect activation of Cyclin E/CDK2, implicating the non-catalytic activity of CDK4 in deregulation of the cell cycle progression. ^ It has been proposed that the proliferative and oncogenic role of Myc is linked to its ability to induce the transcription of CDK4, cyclin D1, and cyclin D2 in vitro. Deregulation of Myc oncogene has been found in several human cancers. Also it has been demonstrated that CDK4 has the ability to functionally inactivate the product of the tumor suppressor gene Rb, providing a link between Myc and the CDK4/cyclin D1/pRb/p16 pathway in some malignant tumors. Here, we sought to determine the role of CDK4 as a mediator of Myc activities by developing a Myc overexpressing mouse nullizygous for CDK4. We demonstrated that lack of CDK4 results in reduced keratinocyte proliferation and epidermal thickness in K5-Myc/CDK4-null mice. In addition, complete reversion of tumor development was observed. All together, this work demonstrates that CDK4 acts as an oncogene independent of the D-type cyclin levels and it is an important mediator of the tumorigenesis induced by Myc. In addition, we showed that the sequestering activity of CDK4 is critical for the development of epidermal hyperplasia during normal proliferation, malignant progression from papillomas to squamous cell carcinomas, and tumorigenesis induced by Myc. ^

A qualitative analysis of leadership styles and the selection of quality improvement in primary care practice

In the Practice Change Model, physicians act as key stakeholders, people who have both an investment in the practice and the capacity to influence how the practice performs. This leadership role is critical to the development and change of the practice. Leadership roles and effectiveness are an important factor in quality improvement in primary care practices.^ The study conducted involved a comparative case study analysis to identify leadership roles and the relationship between leadership roles and the number and type of quality improvement strategies adopted during a Practice Change Model-based intervention study. The research utilized secondary data from four primary care practices with various leadership styles. The practices are located in the San Antonio region and serve a large Hispanic population. The data was collected by two ABC Project Facilitators from each practice during a 12-month period including Key Informant Interviews (all staff members), MAP (Multi-method Assessment Process), and Practice Facilitation field notes. This data was used to evaluate leadership styles, management within the practice, and intervention tools that were implemented. The chief steps will be (1) to analyze if the leader-member relations contribute to the type of quality improvement strategy or strategies selected (2) to investigate if leader-position power contributes to the number of strategies selected and the type of strategy selected (3) and to explore whether the task structure varies across the four primary care practices.^ The research found that involving more members of the clinic staff in decision-making, building bridges between organizational staff and clinical staff, and task structure are all associated with the direct influence on the number and type of quality improvement strategies implemented in primary care practice.^ Although this research only investigated leadership styles of four different practices, it will offer future guidance on how to establish the priorities and implementation of quality improvement strategies that will have the greatest impact on patient care improvement. ^

Structural and functional studies of the human integrin $\alpha 4\beta 1$ (CD49d/CD29)

The integrin receptor $\alpha 4\beta 1$ is a cell surface heterodimer involved in a variety of highly regulated cellular interactions. The purpose of this dissertation was to identify and characterize unique structural and functional properties of the $\alpha 4\beta 1$ molecule that may be important for adhesion regulation and signal transduction. To study these properties and to establish a consensus sequence for the $\alpha 4$ subunit, cDNA encoding $\alpha 4$ was cloned and sequenced. A comparison with previously described human $\alpha 4$ sequences identified several substitutions in the $5\prime$ and $3\prime$ untranslated regions, and a nonsynonymous G to A transition in the coding region, resulting in a glutamine substitution for arginine. Further analysis of this single nucleotide substitution indicated that two variants of the $\alpha 4$ subunit exist, and when compared with three ancestrally-related species, the new form cloned in our laboratory was found to be evolutionarily conserved.^ The expression of $\alpha 4$ cDNA in transfected K562 erythroleukemia cells, and subsequent studies using flow cytofluorometric, immunochemical, and ligand binding/blocking analyses, confirmed $\alpha 4\beta 1$ as a receptor for fibronectin (FN) and vascular cell adhesion molecule-1 (VCAM-1), and provided a practical means of identifying two novel monoclonal antibody (mAb) binding epitopes on the $\alpha 4\beta 1$ complex that may play important roles in the regulation of leukocyte adhesion.^ To investigate the association of $\alpha 4\beta 1$-mediated adhesion with signals involved in the spreading of lymphocytes on FN, a quantitative method of analysis was developed using video microscopy and digital imaging. The results showed that HPB-ALL $(\alpha 4\beta 1\sp{\rm hi},\ \alpha 5\beta 1\sp-)$ cells could adhere and actively spread on human plasma FN, but not on control substrate. Many cell types which express different levels of the $\alpha 4\beta 1$ and $\alpha 5\beta 1$ FN binding integrins were examined for their ability to function in these events. Using anti-$\alpha 4$ and anti-$\alpha 5$ mAbs, it was determined that cell adhesion to FN was influenced by both $\beta 1$ integrins, while cell spreading was found to be dependent on the $\alpha 4\beta 1$ complex. In addition, inhibitors of phospholipase A$\sb2$ (PLA$\sb2$), 5-lipoxygenases, and cyclooxygenases blocked HPB-ALL cell spreading, yet had no effect on cell adhesion to FN, and the impaired spreading induced by the PLA$\sb2$ inhibitor cibacron blue was restored by the addition of exogenous arachidonic acid (AA). These results suggest that the interaction of $\alpha 4\beta 1$ with FN, the activation of PLA$\sb2,$ and the subsequent release of AA, may be involved in lymphocyte spreading. ^

Primary lung cancer after breast cancer: The role of radiation therapy and cigarette smoking

The magnitude of the interaction between cigarette smoking, radiation therapy, and primary lung cancer after breast cancer remains unresolved. This case control study further examines the main and joint effects of cigarette smoking and radiation therapy (XRT) among breast cancer patients who subsequently developed primary lung cancer, at The University of Texas M. D. Anderson Cancer Center (MDACC) in Houston, Texas. Cases (n = 280) were women diagnosed with primary lung cancer between 1955 and 1970, between 30–89 years of age, who had a prior history of breast cancer, and were U.S. residents. Controls (n = 300) were randomly selected from 37,000 breast cancer patients at MDACC and frequency matched to cases on age at diagnosis (in 5-year strata), ethnicity, year of breast cancer diagnosis (in 5-year strata), and had survived at least as long as the time interval for lung cancer diagnosis in the cases. Stratified analysis and unconditional logistic regression modeling were used to calculate the main and joint effects of cigarette smoking and radiation treatment on lung cancer risk. Medical record review yielded smoking information on 93% of cases and 84% of controls, and among cases 45% received XRT versus 44% of controls. Smoking increased the odds of lung cancer in women who did not receive XRT (OR = 6.0, 95%CI, 3.5–10.1) whereas XRT was not associated with increased odds (OR = 0.5, 95%CI, 0.2–1.1) in women who did not smoke. Overall the odds ratio for both XRT and smoking together compared with neither exposure was 9.00 (9 5% CI, 5.1–15.9). Similarly, when stratifying on laterality of the lung cancer in relation to the breast cancer, and when the time interval between breast and lung cancers was >10 years, there was an increased odds for both smoking and XRT together for lung cancers on the same side as the breast cancer (ipsilateral) (OR = 11.5, 95% CI, 4.9–27.8) and lung cancers on the opposite side of the breast cancer (contralateral) (OR= 9.6, 95% CI, 2.9–0.9). After 20 years the odds for the ipsilateral lung were even more pronounced (OR = 19.2, 95% CI, 4.2–88.4) compared to the contralateral lung (OR = 2.6, 95% CI, 0.2–2.1). In conclusion, smoking was a significant independent risk factor for lung cancer after breast cancer. Moreover, a greater than multiplicative effect was observed with smoking and XRT combined being especially evident after 10 years for both the ipsilateral and contralateral lung and after 20 years for the ipsilateral lung. ^

Trends in anti-tuberculosis drug resistance from 2003--2007 at Pham Ngoc Thach tuberculosis and lung disease hospital, Ho Chi Minh City, Vietnam

Vietnam is one of the countries with the highest prevalence and incidence of tuberculosis (TB) in the world (1). Although Vietnam has had many successes in TB control, it still faces the challenge of drug resistant and multidrug-resistant tuberculosis (MDR-TB). MDR-TB appears to be relatively stable, but data on MDR-TB continues to be scarce and routine testing of all isolates for drug susceptibility is not performed under Vietnam's National Tuberculosis Program (6). Pham Ngoc Thach Hospital (PNT), the leading tuberculosis and lung disease hospital in Ho Chi Minh City, serves as a reference hospital and laboratory for both Ho Chi Minh City and the Southern Vietnam region. This study is an unmatched, nested case-control study consisting of a secondary analysis of a previously created dataset composed of drug susceptibility and basic demographic data from a cohort of patients diagnosed with tuberculosis at PNT from 2003 through 2007 in order to calculate the prevalence of resistance among acid-fast bacilli smear-positive patients. The susceptibility records for the years 2003-2004 were not representative of the entire population, but over the years 2005-2007 the investigator found a decrease in resistance to all primary TB drugs on which records were available, as well as MDR-TB. Overall, females showed a higher proportion of resistance to TB drugs than males, and females had a greater likelihood of presenting with MDR-TB than males (OR=1.77). Persons 35-54 had greater likelihood of having MDR-TB than younger and older age groups. Among the population with HIV data, HIV-positivity was associated with greater likelihood of MDR-TB (OR=1.70, 95% CI=0.97-3.11). This study shows that rates of TB drug resistance are high, but declining, in one of Vietnam's largest TB hospitals, and that females and HIV-positive individuals are possible high-risk groups in this population.^

HIV disclosure decisions and social support among African-American women in Houston, Texas

African Americans make up 12.3% of the population but account for over half of the new HIV cases and 39% of the AIDS cases in 2003 (Centers for Disease Control and Prevention [CDC], 2003). African American women in particular accounted for 64% of these cases of HIV and 60% of the AIDS cases (Leigh & Huff, 2003). This study contributed to the knowledge about the disclosure process of women living with HIV/AIDS by documenting the relationship between social support and the disclosure process in the African American HIV/AIDS population.^ The study aims were to: (1) discuss the participants' self concept of support; (2) describe the common characteristics of the disclosure process; and (3) evaluate the common characteristics of support sought in a potential disclosure source. The ethnographic qualitative methodology was utilized to elicit participant narratives of HIV disclosure and social support. The researcher utilized a key informant interview methodology building on existing social and organizational relationships (Krueger, 1994) to gain access to the population. ^ Semi-structured interviews are a widely used and accepted qualitative research method for use with hard to reach populations and sensitive topics. Ten participants completed a 45 to 60 minute, one on one semi-structured interview covering social support and disclosure variables. Inclusion and exclusion criteria included: (1) self identified as a person living with HIV/AIDS; (2) African American); (3) female; (4) age 18-64 years old, (5) residence in Houston or surrounding counties.^ Themes generated from the interviews were (1) nondisclosure, (2) experiences with disclosure, (3) timing, (4) disclosure sources, and (5) coping. The themes suggest African American women living with HIV/AIDS come from different lifestyles but share similar experiences. Women utilize different strategies such as deciphering whom to trust and determining how much information to divulge in order to protect themselves or others.^ Although the sample group was small for this study, the results inform us about the various experiences each woman goes through as it relates to social support and disclosure and that each woman has to customize her response to the type of support she is receiving and her personal attitude about her disease.^

The relationship between surgical residents' perception of leadership and patient safety culture

Introduction. Patient safety culture is the integration of interrelated practices that once developed is supported by both the culture and leadership of the organization (Sagan, 1993). The purpose of this study is to describe and examine the relationship between surgical residents’ perception of their leadership and the resulting organizational safety culture within their clinical setting. This assessment is important to understanding the extent that leadership style affects the perception of the safety culture.^ Methods. A secondary dataset was used which included data from 68 surgical residents from two survey instruments, Organizational Description Questionnaire (ODQ) and Patient Safety Climate In Healthcare Organizations (PSCHO) Survey. Multiple regressions followed by hierarchical regressions with the introduction of the Post Graduate Year (PGY) variable examined the association between the leadership styles, Transactional and Transformational and the organizational safety culture variables, Overall Emphasis on Safety, Senior management engagement, Organizational resources for safety. Independent t-tests were conducted to assess whether males and females differ among the organizational safety culture variables and either leadership style.^ Results. The surgical residents perceived their organizational leadership to have greater emphasis placed on transformational leadership culture style relative to transactional leadership culture style. The only significant association found was between Transformational leadership and Organizational resources for safety. PGY had no significant effect on the leadership or the safety culture perceived. No significant difference was found between females and males in regards to the safety culture or the leadership style.^ Discussion. These results have implications as they support the premise for the study which is surgical residents perceive their existing leadership and organizational culture to be more transformational in nature than transactional. Significance was found between the leadership perceived and one of the safety culture variables, Organizational resources for safety. The foundation for this association lies in the fact that surgical residents are the personnel which are a part of the organizational resources. Although PGY differentiation did not seem to play a difference in the leadership perceived this could be attributed to the small sample size. No gender difference were found which supports the assumption that within such a highly specialized group such as surgical residents there is no gender differences since the highly specialized field draws a certain type of person with distinct characteristics. In future research these survey tools can be used to gauge the survey audiences’ perception and safety interventions can be developed based on the results. ^

Development and Characterization of an in vitro Four-species Anaerobic Dental Biofilm Model

Dental caries is the most common chronic disease worldwide. It is characterized by the demineralization of tooth enamel caused by acid produced by cariogenic dental bacteria growing on tooth surfaces, termed bacterial biofilms. Cariogenesis is a complex biological process that is influence by multiple factors and is not attributed to a sole causative agent. Instead, caries is associated with multispecies microbial biofilm communities composed of some bacterial species that directly influence the development of a caries lesion and other species that are seemingly benign but must contribute to the community in an uncharacterized way. Clinical analysis of dental caries and its microbial populations is challenging due to many factors including low sensitivity of clinical measurement tools, variability in saliva chemistry, and variation in the microbiota. Our laboratory has developed an in vitro anaerobic biofilm model for dental carries to facilitate both clinical and basic research-based analyses of the multispecies dynamics and individual factors that contribute to cariogenicity. The rational for development of this system was to improve upon the current models that lack key elements. This model places an emphasis on physiological relevance and ease of maintenance and reproducibility. The uniqueness of the model is based on integrating four critical elements: 1) a biofilm community composed of four distinct and representative species typically associated with dental caries, 2) a semi-defined synthetic growth medium designed to mimic saliva, 3) physiologically relevant biofilm growth substrates, and 4) a novel biofilm reactor device designed to facilitate the maintenance and analysis. Specifically, human tooth sections or hydroxyapatite discs embedded into poly(methyl methacrylate) (PMMA) discs are incubated for an initial 24 hr in a static inverted removable substrate (SIRS) biofilm reactor at 37°C under anaerobic conditions in artificial saliva (CAMM) without sucrose in the presence of 1 X 106 cells/ml of each Actinomyces odontolyticus, Fusobacterium nucleatum, Streptococcus mutans, and Veillonella dispar. During days 2 and 3 the samples are maintained continually in CAMM with various exposures to 0.2% sucrose; all of the discs are transferred into fresh medium every 24 hr. To validate that this model is an appropriate in vitro representation of a caries-associated multispecies biofilm, research aims were designed to test the following overarching hypothesis: an in vitro anaerobic biofilm composed of four species (S. mutans, V. dispar, A. odontolyticus, and F. nucleatum) will form a stable biofilm with a community profile that changes in response to environmental conditions and exhibits a cariogenic potential. For these experiments the biofilms as described above were exposed on days 2 and 3 to either CAMM lacking sucrose (no sucrose), CAMM with 0.2% sucrose (constant sucrose), or were transferred twice a day for 1 hr each time into 0.2% sucrose (intermittent sucrose). Four types of analysis were performed: 1) fluorescence microscopy of biofilms stained with Syto 9 and hexidium idodine to determine the biofilm architecture, 2) quantitative PCR (qPCR) to determine the cell number of each species per cm2, 3) vertical scanning interferometry (VSI) to determine the cariogenic potential of the biofilms, and 4) tomographic pH imaging using radiometric fluorescence microscopy after exposure to pH sensitive nanoparticles to measure the micro-environmental pH. The qualitative and quantitative results reveal the expected dynamics of the community profile when exposed to different sucrose conditions and the cariogenic potential of this in vitro four-species anaerobic biofilm model, thus confirming its usefulness for future analysis of primary and secondary dental caries.