Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.

BACKGROUND: Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. OBJECTIVE: The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. METHODS: We analyzed 150 Web sites retrieved from a search for the three most popular herbs: ginseng, ginkgo and St. John's wort and their purported uses on the ten most commonly used search engines. The presence of technical quality criteria as well as potentially harmful statements (commissions) and vital information that should have been mentioned (omissions) was recorded. RESULTS: Thirty-eight sites (25%) contained statements that could lead to direct physical harm if acted upon. One hundred forty five sites (97%) had omitted information. We found no relationship between technical quality criteria and potentially harmful information. CONCLUSIONS: Current technical quality criteria do not identify potentially harmful CAM information online. Consumers should be warned to use other means of validation or to trust only known sites. Quality criteria that consider the uniqueness of CAM must be developed and validated.

Evaluating the prevalence, content and readability of complementary and alternative medicine (CAM) web pages on the internet.

Complementary and alternative medicine (CAM) use is growing rapidly. As CAM is relatively unregulated, it is important to evaluate the type and availability of CAM information. The goal of this study is to deter-mine the prevalence, content and readability of online CAM information based on searches for arthritis, diabetes and fibromyalgia using four common search engines. Fifty-eight of 599 web pages retrieved by a "condition search" (9.6%) were CAM-oriented. Of 216 CAM pages found by the "condition" and "condition + herbs" searches, 78% were authored by commercial organizations, whose pur-pose involved commerce 69% of the time and 52.3% had no references. Although 98% of the CAM information was intended for consumers, the mean read-ability was at grade level 11. We conclude that consumers searching the web for health information are likely to encounter consumer-oriented CAM advertising, which is difficult to read and is not supported by the conventional literature.

A study of the relationship between physical activity and cardiovascular fitness and coronary heart disease risk factors in female adolescents

The association of measures of physical activity with coronary heart disease (CHD) risk factors in children, especially those for atherosclerosis, is unknown. The purpose of this study was to determine the association of physical activity and cardiovascular fitness with blood lipids and lipoproteins in pre-adolescent and adolescent girls.^ The study population was comprised of 131 girls aged 9 to 16 years who participated in the Children's Nutrition Research Center's Adolescent Study. The dependent variables, blood lipids and lipoproteins, were measured by standard techniques. The independent variables were physical activity measured as the difference between total energy expenditure (TEE) and basal metabolic rate (BMR), and cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg). TEE was measured by the doubly-labeled water (DLW) method, and BMR by whole-room calorimetry. Cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg), was measured on a motorized treadmill. The potential confounding variables were sexual maturation (Tanner breast stage), ethnic group, body fat percent, and dietary variables. A systematic strategy for data analysis was used to isolate the effects of physical activity and cardiovascular fitness on blood lipids, beginning with assessment of confounding and interaction. Next, from regression models predicting each blood lipid and controlling for covariables, hypotheses were evaluated by the direction and value of the coefficients for physical activity and cardiovascular fitness.^ The main result was that cardiovascular fitness appeared to be more strongly associated with blood lipids than physical activity. An interaction between cardiovascular fitness and sexual maturation indicated that the effect of cardiovascular fitness on most blood lipids was dependent on the stage of sexual maturation.^ A difference of 760 kcal/d physical activity (which represents the difference between the 25th and 75th percentile of physical activity) was associated with negligible differences in blood lipids. In contrast, a difference in 10 ml/min/kg of VO$\rm\sb{2max}$ or cardiovascular fitness (which represents the difference between the 25th and 75th percentile in cardiovascular fitness) in the early stages of sexual maturation was associated with an average positive difference of 15 mg/100 ml ApoA-1 and 10 mg/100 ml HDL-C. ^

Impact of oral contraceptives on weight, body composition, and cardiovascular disease risk factors in women age 18--30 years participating in a 15-week exercise program

Objective. To assess differences in body weight, body composition, total cholesterol, blood pressure, and blood glucose between OC users and non-users age 18-30 y before and after a 15-week cardiovascular exercise program in Houston, TX from 2003 to 2007.^ Study Design. Secondary analysis of prospective data. ^ Study Subjects. 453 Non-Hispanic white (NHW), Hispanic, and African American (AA) women age 18-30 y with no previous live birth, a history of menstruating, no use of other hormonal contraceptives or medications, no menopause or hysterectomy, and no current pregnancies.^ Measurements. Demographic data, medication use, and menstrual history were assessed via self-administered questionnaires at baseline. Anthropometric and laboratory measures were taken at baseline and 15-weeks. ^ Data Analysis. Linear regression assessed the association between OC use and study variables at baseline, and the change in study variables from baseline to 15-weeks. Logistic regression assessed the association between OC use and CVD risk. Each analysis was also stratified by race/ethnicity. ^ Results. At baseline, OC users had higher total cholesterol (p<.0005) and were above cholesterol risk cut points for CVD (OR=4.3, 95% CI=2.4-7.7) compared to non-users. At baseline, OC use was also associated with higher diastolic blood pressure (p=.018) compared to non-users, primarily in non-Hispanic whites (p=.007). OC use was associated with lower blood glucose compared to non-users in Hispanics only (p=.008). OC use was associated with absolute change in diastolic blood pressure (p=.044) and total cholesterol (p=.003). There was evidence that OC use may affect individuals differently based on race/ethnicity for certain obesity and CVD risk factors.^ Conclusions. OC users and non-users responded similarly to a 15-week cardiovascular exercise program. Exceptions included a greater change in diastolic blood pressure and total cholesterol among NHW and Hispanic OC users compared to non-users after exercise intervention. At baseline, OC use was associated with diastolic blood pressure and was most strongly associated with increased levels of total cholesterol. OC users were at greater risk of having total cholesterol above CVD risk cut points than non-users.^

Environmental tobacco smoke exposure, respiratory and cardiovascular health in restaurant and bar workers in Mexico

Environmental tobacco smoke (ETS) is a well established health hazard, being causally associated to lung cancer and cardiovascular disease. ETS regulations have been developed worldwide to reduce or eliminate exposure in most public places. Restaurants and bars constitute an exception. Restaurants and bar workers experience the highest ETS exposure levels across several occupations, with correspondingly increased health risks. In Mexico, previous exposure assessment in restaurants and bars showed concentrations in bars and restaurants to be the highest across different public and workplaces. Recently, Mexico developed at the federal level the General Law for Tobacco Control restricting indoors smoking to separated areas. AT the local level Mexico City developed the Law for the Protection of Non-smokers Health, completely banning smoking in restaurants and bars. Studies to assess ETS exposure in restaurants and bars, along with potential health effects were required to evaluate the impact of these legislative changes and to set a baseline measurement for future evaluations.^ A large cross-sectional study conducted in restaurants and bars from four Mexican cities was conducted from July to October 2008, to evaluate the following aims: Aim 1) Explore the potential impact of the Mexico City ban on ETS concentrations through comparison of Mexico City with other cities. Aim 2). Explore the association between ETS exposure, respiratory function indicators and respiratory symptoms. Aim 3). Explore the association between ETS exposure and blood pressure and heart rate.^ Three cities with no smoking ban were selected: Colima (11.5% smoking prevalence), Cuernavaca (21.5% smoking prevalence) and Toluca (27.8% smoking prevalence). Mexico City (27.9% smoking prevalence), the only city with a ban at the time of the study, was also selected. Restaurants and bars were randomly selected from municipal records. A goal of 26 restaurants and 26 bars per city was set, 50% of them under 100 m2. Each establishment was visited during the highest occupancy shift, and managers and workers answered to a questionnaire. Vapor-phase nicotine was measured using passive monitors, that were activated at the beginning and deactivated at the end of the shift. Also, workers participated at the beginning and end of the shift in a short physical evaluation, comprising the measurement of Forced Expiratory Volume in the first second (FEV1) and Peak Expiratory Flow (PEF), as well as blood pressure and heart rate.^ A total of 371 establishments were invited, 219 agreed to participate for a 60.1% participation rate. In them, 828 workers were invited, 633 agreed to participate for a 76% participation rate. Mexico City had at least 4 times less nicotine compared to any of the other cities. Differences between Mexico City and other cities were not explained by establishment characteristics, such as ventilation or air extraction. However, differences between cities disappeared when ban mechanisms, such as policy towards costumer's smoking, were considered in the models. An association between ETS exposure and respiratory symptoms (cough OR=1.27, 95%CI=1.04, 1.55) and respiratory illness (asthma OR=1.97, 95%CI=1.20, 3.24; respiratory illness OR=1.79, 95%CI=1.10, 2.94) was observed. No association between ETS and phlegm, wheezing or respiratory infections was observed. No association between ETS and any of the spirometric indicators was observed. An association between ETS exposure and increased systolic and diastolic blood pressure at the end of the shift was observed among non-smokers (systolic blood pressure beta=1.51, 95%CI=0.44, 2.58; diastolic blood pressure beta=1.50, 95%CI=0.72, 2.28). The opposite effect was observed in heavy smokers, were increased ETS exposure was associated with lower blood pressure at the end of the shift (systolic blood pressure beta=1.90, 95%CI=-3.57, -0.23; diastolic blood pressure beta=-1.46, 95%CI=-2.72, -0.02). No association in light smokers was observed. No association for heart rate was observed. ^ Results from this dissertation suggest Mexico City's smoking ban has had a larger impact on ETS exposure. Ventilation or air extraction, mechanisms of ETS control suggested frequently by tobacco companies to avoid smoking bans were not associated with ETS exposure. This dissertation suggests ETS exposure could be linked to changes in blood pressure and to increased respiratory symptoms. Evidence derived from this dissertation points to the potential negative health effects of ETS exposure in restaurants and bars, and provides support for the development of total smoking bans in this economic sector. ^

Metabolic syndrome and cardiovascular mortality among participants of the hypertension detection and follow-up program

Metabolic Syndrome (MetS) is a clustering of cardiovascular (CV) risk factors that includes obesity, dyslipidemia, hyperglycemia, and elevated blood pressure. Applying the criteria for MetS can serve as a clinically feasible tool for identifying patients at high risk for CV morbidity and mortality, particularly those who do not fall into traditional risk categories. The objective of this study was to examine the association between MetS and CV mortality among 10,940 American hypertensive adults, ages 30-69 years, participating in a large randomized controlled trial of hypertension treatment (HDFP 1973-1983). MetS was defined as the presence of hypertension and at least two of the following risk factors: obesity, dyslipidemia, or hyperglycemia. Of the 10,763 individuals with sufficient data available for analysis, 33.2% met criteria for MetS at baseline. The baseline prevalence of MetS was significantly higher among women (46%) than men (22%) and among non-blacks (37%) versus blacks (30%). All-cause and CV mortality was assessed for 10,763 individuals. Over a median follow-up of 7.8 years, 1,425 deaths were observed. Approximately 53% of these deaths were attributed to CV causes. Compared to individuals without MetS at baseline, those with MetS had higher rates of all-cause mortality (14.5% v. 12.6%) and CV mortality (8.2% versus 6.4%). The unadjusted risk of CV mortality among those with MetS was 1.31 (95% confidence interval [CI], 1.12-1.52) times that for those without MetS at baseline. After multiple adjustment for traditional risk factors of age, race, gender, history of cardiovascular disease (CVD), and smoking status, individuals with MetS, compared to those without MetS, were 1.42 (95% CI, 1.20-1.67) times more likely to die of CV causes. Of the individual components of MetS, hyperglycemia/diabetes conferred the strongest risk of CV mortality (OR 1.73; 95% CI, 1.39-2.15). Results of the present study suggest MetS defined as the presence of hypertension and 2 additional cardiometabolic risk factors (obesity, dyslipidemia, or hyperglycemia/diabetes) can be used with some success to predict CV mortality in middle-aged hypertensive adults. Ongoing and future prospective studies are vital to examine the association between MetS and cardiovascular morbidity and mortality in select high-risk subpopulations, and to continue evaluating the public health impact of aggressive, targeted screening, prevention, and treatment efforts to prevent future cardiovascular disability and death.^

Quality of life, symptom experience, and use of complementary and alternative medicine among women with ovarian cancer

The objectives of this dissertation were to determine the quality of life in women with ovarian cancer and the association of their physical and emotional well-being with the number of symptoms, duration of symptoms, and the scores of common symptoms of ovarian cancer; to study the prevalence of complementary and alternative medicine techniques for symptom relief and its association with the number of symptoms, age, education, insurance, comorbidity, and satisfaction with medical care they received, and their pre-diagnostic experience of symptoms.^ This study was based on a secondary data analysis of a study of early detection of ovarian cancer. A sample of 139 women with ovarian cancer was recruited and was administered a questionnaire comprised of questions on their quality of life, their symptoms and what they did about the symptoms, whether they used any complementary and alternative medicine techniques, and other medical conditions they had. Out of this sample, 53 patients underwent in-depth interviews relating to their symptoms before the diagnosis and their experiences with the health care system leading to the ovarian cancer diagnosis. ^ In article #1, ovarian cancer patients were observed to have significantly poorer quality of life on all subscales and summary scores except pain, compared to that of the general population of US women. Physical well-being scores were negatively associated with the number of symptoms before diagnosis and a significant negative association of comorbidity index was observed with physical well-being. Higher education and increase in time since diagnosis was found to have better physical scores. Emotional well-being scores showed marginally significant associations with number of symptoms and bloating. ^ In article #2, a thematic content analysis of the ovarian cancer patients’ interviews revealed that on recognition of their symptoms women first assumed their symptoms to be a normal transient occurrence due to a pre-existing disease condition, or due to some other disease. A series of misattributions of their symptoms on their and their doctors’ part impacted their health care seeking.In article #3, a significantly greater likelihood of CAM use with an increase in the number of symptoms was observed.^ Based on the foregoing results, it is important to educate women on possible signs of ovarian cancer and also to educate doctors about the results of current research regarding ovarian cancer diagnosis. This will help to avoid a delay in getting a diagnosis and improve women’s quality of life. It emphasizes the diagnosis of ovarian cancer in earlier stages by more sensitive screening techniques. This study emphasizes the importance of consideration of comorbidity in any quality of life research. Additionally, educating women in the safe use of CAM techniques carries immense significance because the efficacy and safety of many of the currently advertized CAM products has not been scientifically validated. Further research is needed to confirm the findings of this study. ^

MARITAL STATUS AND CARDIOVASCULAR RISK (SERUM, CHOLESTEROL, CIGARETTE, SMOKING, BLOOD, PRESSURE, SYSTOLIC)

There were three purposes of this study. The first was to describe the association between stable marital status and serum cholesterol, systolic blood pressure and cigarette smoking. The second purpose was to determine whether individuals who were married at one point and became widowed or divorced/separated had higher serum cholesterol, higher systolic blood pressure or were more likely to smoke prior to the change in marital status compared with individuals who did not change marital status. The third purpose was to determine whether the changes in marital status described above were related to increases in serum cholesterol or in cigarette smoking behavior. The rationale for the study was to determine whether previously reported associations between marital status categories and cardiovascular mortality may be mediated through higher values of risk correlates for cardiovascular disease among unmarried individuals.^ The study group selected for this dissertation was a sample from the Hypertension Detection and Follow-up Program (HDFP) population. The HDFP population was aged 30-69 years at the initial visit and included blacks and whites, males and females. The population was followed five years after the initial visit and periodic measurements of serum cholesterol, blood pressure and cigarette smoking behavior were obtained.^ Serum cholesterol was not associated with stable marital status category or with marital status prior to change. Changes in serum cholesterol were associated with marital status categories after change but the serum cholesterol values deceased rather than increased. Married individuals were shown to have higher serum cholesterol values compared with unmarried. Selection of the HDFP population may have influenced an ability to detect a significant association between marital status and serum cholesterol but it is doubtful that use of a general population would alter the direction of the association.^ Systolic blood pressure was significantly higher at the initial visit among unmarried white males and females compared with their married counterparts. No association between systolic blood pressure was found among black males or females. Those individuals who were married at the initial visit who experienced a change in marital status were found to have higher systolic blood pressure prior to the change in marital status. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

Understanding mental illness in Nigeria: Bringing culture and traditional medicine into mental health policy

One of the major challenges in treating mental illness in Nigeria is that the health care facilities and mental health care professionals are not enough in number or well equipped to handle the burden of mental illness. There are several barriers to treatment for individual Nigerians which include the following: such as the lack of understanding of the root causes of mental illness, lack of financial support to get mental treatment, lack of social support (family, friends, neighbors), the fear of stigmatization concerning being labeled as mentally ill or being in association with the mentally ill, and the consultation of traditional native healers who may be unknowingly prolonging illness, rather than addressing and treating them due to lack of formal education and standardization of their treatments. Another barrier is the non-health nature of the mental health services in Nigeria. Traditional healers are essentially the mental health system. The elderly, women, and children are the most vulnerable groups in times of strife and hardships. Their mental well-being must be taken into account as well as their special needs in times of personal or societal crisis. ^ Nigerian mental health policy is geared toward forming a mental health system, but in actuality only a mental illness care system is the observed result of the policy. The government of Nigeria has drafted a mental health policy, yet its actual implementation into the Nigerian health infrastructure and society waits to be materialized. The limited health legislation or policy implementations tend to favor those who have access to these urban areas and the facilities' health services. Nigerians living in rural areas are at a disadvantage; many of them may not even be aware of services available to help them understand and treat mental illness. Perhaps, government driven health interventions geared toward mental illness in rural areas would reach an underserved Nigerians and Africans in general. Issues with political instability and limited infrastructure often hinder crucial financial resources and legislation from reaching the people that are truly in need of governmental leadership in regards to mental health policy.^ Traditional healers are a severely untapped resource in the treatment of mental illness within the Nigerian population. They are abundant within Nigerian communities and are meeting a real need for the mentally ill. However, much can be done to remove the barriers that prevent the integration of traditional healers within the mental health system and improve the quality of care they administer within the population. Mental illness is almost exclusively coped with through traditional medicine practices. Mobilization and education from each strata of Nigerian society and government as well as input from the medical community can improve how traditional medicine is utilized as a treatment for clinical illness and help alleviate the heavy burden of mental illness in Nigeria. Currently, there is no existing policy making structure for a working mental health system in Nigeria, and traditional healers are not taken into account in any formulation of mental health policy. Advocacy for mental illness is severely inadequate due to fear of stigmatization, with no formally recognized national of regional mental health association.^

The relationship of obesity and cardiovascular disease

Aim. To review published literature on the relationship of obesity and cardiovascular disease.^ Methods. To look at all the studies published on the topic from 2005.^ Results. In the studies done prior to 2011, body mass index and in particular waist to hip ratio (51.57) was found to be associated with coronary heart disease. But, this relationship was challenged by the latest Lancet 2011meta-analysis 1 which concluded that singly or in combination, body-mass index, waist circumference, and waist-to-hip ratio did not importantly improve prediction of first-onset cardiovascular disease when additional information exists on blood pressure, history of diabetes, and cholesterol measures were available. Furthermore, they also found long-term reproducibility of BMI to be superior to that of waist-to-hip ratio (or waist circumference). Interestingly, body mass index in later childhood and early adult life showed positive association with coronary heart disease later in life 2. In US female health professionals 3 increasing body mass index was found to be associated with increased coronary heart disease risk. Overall 4, physical activity was found to be independently associated with fewer risk factors, less coronary artery disease, and fewer adverse events in women. Finally, obesity was found to be associated with increased overall cardiovascular mortality and coronary heart disease mortality 5.^ Conclusions. There is insufficient data to draw guidelines regarding parameters of obesity affecting cardiovascular disease. But there is data to support that lower body mass index would lead to decreased cardiovascular disease mortality. And physical activity has a direct association with less coronary artery disease in women.^

Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Evaluation of androgenicity, abdominal adiposity, blood pressure and types of ovulatory patterns in a sample of women with menstrual irregularities

Objective: To determine the prevalence of and the relationships between the degree and source of hyperandrogenemia, ovulatory patterns and cardiovascular disease risk indicators (blood pressure, indices or amount of obesity and fat distribution) in women with menstrual irregularities seen at endocrinologists' clinic. Design: A cross-sectional study design. Participants: A sample of 159 women with menstrual irregularities, aged 15-44, seen at endocrinologists' clinic. Main Outcome Measures: androgen levels, body mass index (BMI), waist-hip ratio (WHR), systolic and diastolic blood pressure (SBP & DBP), source of androgens, ovulatory activity. Results: The prevalence of hyperandrogenemia was 54.7% in this study sample. As expected, women with acne or hirsutism had an odds ratio 12.5 (95%CI = 5.2-25.5) times and 36 (95%CI = 12.9-99.5) times more likely to have hyperandrogenemia than those without acne or hirsutism. The main findings of this study were the following: Hyperandrogenemic women were more likely to have oligomenorrheic cycles (OR = 3.8, 95%CI = 1.5-9.9), anovulatory cycles (OR = 6.6, 95%CI = 2.8-15.4), general obesity (BMI $\ge$ 27) (OR = 6.8, 95%CI = 2.2-27.2) and central obesity (WHR $\ge$ 127) (OR = 14.5, 95%CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women with non-suppressible androgens had a higher mean BMI (29.3 $\pm$ 8.9) than those with suppressible androgens (27.9 $\pm$ 7.9); the converse was true for abdominal adiposity (WHR). Hyperandrogenemic women had a 2.4 odds ratio (95%CI = 1.0-6.2) for an elevated SBP and a 2.7 odds ratio (95%CI = 0.8-8.8) for elevated DBP. When age differences were accounted for, this relationship was strengthened and further strengthened when sources of androgens were controlled. When the differences in BMI were controlled, the odds ratio for elevated SBP in hyperandrogenemic women increased to 8.8 (95%CI = 1.1-69.9). When the age, the source of androgens, the amount of obesity and the type of obesity were controlled, hyperandrogenemic women had 13.5 (95%CI = 1.1-158.9) odds ratio for elevated SBP. Conclusions: In this study population, the presence of menstrual irregularities are highly predictive for the presence of elevated androgens. Women with elevated androgens have a high risk for obesity, more specifically for central obesity. The androgenemic status is an independent predictor of blood pressure elevation. It is probable that in the general population, the presence of menstrual irregularities are predictive of hyperandrogenemia. There is a great need for a population study of the prevalence of hyperandrogenemia and for longitudinal studies in hyperandrogenemic women (adrenarche to menopause) to investigate the evolution of these relationships. ^

Study of length of stay in the cardiovascular intensive care unit

Coronary artery bypass graft (CABG) surgery is among the most common operations performed in the United States and accounts for more resources expended in cardiovascular medicine than any other single procedure. CABG surgery patients initially recover in the Cardiovascular Intensive Care Unit (CVICU). The post-procedure CVICU length of stay (LOS) goal is two days or less. A longer ICU LOS is associated with a prolonged hospital LOS, poor health outcomes, greater use of limited resources, and increased medical costs. ^ Research has shown that experienced clinicians can predict LOS no better than chance. Current CABG surgery LOS risk models differ greatly in generalizability and ease of use in the clinical setting. A predictive model that identified modifiable pre- and intra-operative risk factors for CVICU LOS greater than two days could have major public health implications as modification of these identified factors could decrease CVICU LOS and potentially minimize morbidity and mortality, optimize use of limited health care resources, and decrease medical costs. ^ The primary aim of this study was to identify modifiable pre-and intra-operative predictors of CVICU LOS greater than two days for CABG surgery patients with cardiopulmonary bypass (CPB). A secondary aim was to build a probability equation for CVICU LOS greater than two days. Data were extracted from 416 medical records of CABG surgery patients with CPB, 50 to 80 years of age, recovered in the CVICU of a large teaching, referral hospital in southeastern Texas, during the calendar year 2004 and the first quarter of 2005. Exclusion criteria included Diagnosis Related Group (DRG) 106, CABG surgery without CPB, CABG surgery with other procedures, and operative deaths. The data were analyzed using multivariate logistic regression for an alpha=0.05, power=0.80, and correlation=0.26. ^ This study found age, history of peripheral arterial disease, and total operative time equal to and greater than four hours to be independent predictors of CVICU LOS greater than two days. The probability of CVICU LOS greater than two days can be calculated by the following equation: -2.872941 +.0323081 (age in years) + .8177223 (history of peripheral arterial disease) + .70379 (operative time). ^

Investigations of stress responses in Saccharomyces cerevisiae: Transcriptional control and heat shock protein function

The baker's yeast, Saccharomyces cerevisiae responds to the cytotoxic effects of elevated temperature (37-42°C) by activating transcription of ∼150 genes, termed heat shock genes, collectively required to compensate for the abundance of misfolded and aggregated proteins and various physiological modifications necessary for the cell to survive and grow at heat shock temperatures. An intriguing facet of the yeast heat shock response is the remarkable similarity it shares with the global remodeling that occurs in mammalian cells in response to numerous pathophysiological conditions including cancer and cardiovascular disease and thus provides an ideal model system. I have therefore investigated several novel features of stress signaling, transcriptional regulation, and physiology. Initial work focused on the characterization of SYM1, a novel heat shock gene in yeast which was demonstrated to be required for growth on the nonfermentable carbon source ethanol at elevated temperature, and to be the functional ortholog of the mammalian kidney disease gene, Mpv17. Additional work addressed the role of two proteins, the Akt-related kinase, Sch9, and Sse1, the yeast Hsp110 protein chaperone homolog, in signaling by protein kinase A, establishing Sse1 as a critical negative regulator of this pathway. Furthermore, I have demonstrated a role for Sse1 in biogenesis and stability of the stress-response transcription factor, Msn2; a finding that has been extended to include a select subset of additional high molecular weight proteins, suggesting a more global role for this chaperone in stabilizing the cellular proteome. The final emphasis of my doctoral work has included the finding that celastrol, a compound isolated from the plant family Celasfraceae, a component of traditional Chinese herbal medicine, can activate heat shock transcription factor (Hsf1) in yeast and mammalian cells through an oxidative stress mechanism. Celastrol treatment simultaneously activates both heat shock and oxidative stress response pathways, resulting in increased cytoprotection. ^