Host risk factors for rifamycin-resistant clostridium difficile infection: A case control study

Objective. To evaluate the host risk factors associated with rifamycin-resistant Clostridium difficile (C. diff) infection in hospitalized patients compared to rifamycin-susceptible C.diff infection.^ Background. C. diff is the most common definable cause of nosocomial diarrhea affecting elderly hospitalized patients taking antibiotics for prolonged durations. The epidemiology of Clostridium difficile associated disease is now changing with the reports of a new hypervirulent strain causing hospital outbreaks. This new strain is associated with increased disease severity and mortality. The conventional therapy for C. diff includes metronidazole and vancomycin but high recurrence rates and treatment failures are now becoming a major concern. Rifamycin antibiotics are being developed as a new therapeutic option to treat C. diff infection after their efficacy was established in a few in vivo and in vitro studies. There are some recent studies that report an association between the hypervirulent strain and emerging rifamycin resistance. These findings assess the need for clinical studies to better understand the efficacy of rifamycin drugs against C. diff.^ Methods. This is a hospital-based, matched case-control study using de-identified data drawn from two prospective cohort studies involving C. diff patients at St Luke's Hospital. The C. diff isolates from these patients are screened for rifamycin resistance using agar dilution methods for minimum inhibitory concentrations (MIC) as part of Dr Zhi-Dong Jiang's study. Twenty-four rifamycin-rifamycin resistant C. diff cases were identified and matched with one rifamycin susceptible C. diff control on the basis of ± 10 years of age and hospitalization 30 days before or after the case. De-identified data for the 48 subjects was obtained from Dr Kevin Garey's clinical study at St Luke's Hospital enrolling C. diff patients. It was reviewed to gather information about host risk factors, outcome variables and relevant clinical characteristic.^ Results. Medical diagnosis at the time of admission (p = 0.0281) and history of chemotherapy (p = 0.022) were identified as a significant risk factor while hospital stay ranging from 1 week to 1 month and artificial feeding were identified as an important outcome variable (p = 0.072 and p = 0.081 respectively). Horn's Index assessing the severity of underlying illness and duration of antibiotics for cases and controls showed no significant difference.^ Conclusion. The study was a small project designed to identify host risk factors and understand the clinical implications of rifamycin-resistance. The study was underpowered and a larger sample size is needed to validate the results.^

Household risk factors and the health and nutritional status of children in rural Honduras

During this cross-sectional study, both quantitative and qualitative research methods were used to elucidate the role that household environment and sanitation play in the nutritional status of children in a rural Honduran community. Anthropometric measurements were taken as measures of nutritional status among children under five years of age, while interviews regarding the household environment were conducted with their primary caregivers. Community participatory activities were conducted with primary caregivers, and results from water quality testing were analyzed for E. coli contamination. Anthropometric results were compared using the 1977 NCHS Growth Charts and the 2006 WHO Child Growth Standard to examine the implications of using the new WHO standard. The references showed generally good or excellent agreement between z-score categories, except among height-for-age classifications for males 24-35.9 months and weight-for-age classifications for males older than 24 months. Comparing the proportion of stunted, underweight, and wasted children, using the WHO standard generally resulted in higher proportions of stunting, lower underweight proportions, and higher overweight proportions. Logistic regression was used to determine which household and sanitation factors most influenced the growth of children. Results suggest only having water from a spring, stream, or other type of surface water as the primary source of drinking water is a significant risk factor for stunting. A protective association was seen between the household wealth index and stunting. Through participatory activities, the community provided insight on health issues important for improving child health. These activities yielded findings to be harnessed as a powerful resource to unify efforts for change. The qualitative findings were triangulated with the quantitative interview and water testing results to provide intervention recommendations for the community and its primary health care clinic. Recommendations include educating the community on best water consumption practices and encouraging the completion of at least some primary education for primary caregivers to improve child health. It is recommended that a community health worker program be developed to support and implement community interventions to improve water use and household sanitation behaviors and to encourage the involvement of the community in targeting and guiding successful interventions. ^

School screening for tuberculosis in high risk areas of Texas

Screening for latent tuberculosis infection (LTBI) is an integral component of an effective tuberculosis control strategy, but one that is often relegated to the lowest priority. In a state with higher than national average rates of tuberculosis, due consideration should be given to LTBI screening. Recent large scale contact investigations in the middle school of Del Rio, Texas, raised questions about the status of school screening for LTBI. An evidence based approach was used to evaluate school screening in high risk areas of Texas. A review of the literature revealed that the current recommendations for LTBI screening in children is based on administration of a risk factor questionnaire that should be based on the four main risk factors for LTBI in children that have been identified. Six representative areas in Texas were identified for evaluation of the occurrence of contact investigations in schools for the period of 2006 to 2009 and any use of school screening programs. Of the five reporting areas that responded, only one utilized a school screening program; this reporting area had the lowest percentage of contact investigations occurring in schools. Contact investigations were most common in middle schools and least common in elementary schools. In metropolitan areas, colleges represented up to 42.9% of contact investigations. The number of contact investigations has increased from 2006 to 2008. This report represents a small sample, and further research into the frequency, distribution and risk for contact investigations in schools and the efficacy of screening programs should be done. ^

Risk factors for encephalitis and death from West Nile virus infection: An analysis of hospitalized cases in Houston, Texas from 2002--2008

We conducted a nested case-control study to determine the significant risk factors for developing encephalitis from West Nile virus (WNV) infection. The purpose of this research project was to expand the previously published Houston study of 2002–2004 patients to include data on Houston patients from four additional years (2005–2008) to determine if there were any differences in risk factors shown to be associated with developing the more severe outcomes of WNV infection, encephalitis and death, by having this larger sample size. A re-analysis of the risk factors for encephalitis and death was conducted on all of the patients from 2002–2008 and was the focus of this proposed research. This analysis allowed for the determination to be made that there are differences in the outcome in the risk factors for encephalitis and death with an increased sample size. Retrospective medical chart reviews were completed for the 265 confirmed WNV hospitalized patients; 153 patients had encephalitis (WNE), 112 had either viral syndrome with fever (WNF) or meningitis (WNM); a total of 22 patients died. Univariate logistic regression analyses on demographic, comorbidities, and social risk factors was conducted in a similar manner as in the previously conducted study to determine the risk factors for developing encephalitis from WNV. A multivariate model was developed by using model building strategies for the multivariate logistic regression analysis. The hypothesis of this study was that there would be additional risk factors shown to be significant with the increase in sample size of the dataset. This analysis with a greater sample size and increased power supports the hypothesis in that there were additional risk factors shown to be statistically associated with the more severe outcomes of WNV infection (WNE or death). Based on univariate logistic regression results, these data showed that even though age of 20–44 years was statistically significant as a protecting effect for developing WNE in the original study, the expanded sample lacked significance. This study showed a significant WNE risk factor to be chronic alcohol abuse, when it was not significant in the original analysis. Other WNE risk factors identified in this analysis that showed to be significant but were not significant in the original analysis were cancer not in remission > 5 years, history of stroke, and chronic renal disease. When comparing the two analyses with death as an outcome, two risk factors that were shown to be significant in the original analysis but not in the expanded dataset analysis were diabetes mellitus and immunosuppression. Three risk factors shown to be significant in this expanded analysis but were not significant in the original study were illicit drug use, heroin or opiate use, and injection drug use. However, with the multiple logistic regression models, the same independent risk factors for developing encephalitis of age and history of hypertension including drug induced hypertension were consistent in both studies.^

Early life risk factors and puberty implications for cancer prevention

Earlier age at puberty is a known risk factor for breast cancer and suspected to influence prostate cancer; yet few studies have assessed early life risk factors for puberty. The overall objectives was to determine the relationship between birth-weight-for-gestational-age (BWGA), weight gain in infancy and pubertal status in girls and boys at 10.8 and 11.8 years and who were born of preeclamptic (PE) and normotensive (NT) mothers. Data for this study were collected from hospital and public health medical records and at a follow-up visit at 10.8 and 11.8 years for girls and boys, respectively. We used stratified analysis and multivariable logistic regression modeling to assess effect measure modifier and to determine the relationship between BWGA, weight gain in infancy and childhood and pubertal status, respectively. ^ There was no difference in the relationship between BWGA and pubertal status by maternal PE status for girls and boys; however, there was a non-significant increase in the odds of having been born small-for-gestational-age (SGA) in girls who were pubertal for breast or pubic hair Tanner stage 2+ compared to those who B1 or PH1. In contrast, boys who were pubertal for genital and pubic hair Tanner stage 2+ had lower odds of having been born SGA than those who were prepubertal for G1 or PH1. ^ In girls who were pubertal for breast development, the odds of having gained one additional unit SD for weight was highest between 3 to 6 months and 6-12 months for those who were B2+ vs. B1. For pubic hair development, weight gain between 6-12 months had the greatest effect for girls of PE mothers only. In boys, there were no statistically significant associations between weight gain and genital Tanner stage at any of the intervals; however, weight gain between 3-6 months did affect pubic hair tanner stage in boys of NT mothers. This study provide important evidence regarding the role of SGA and weight gain at specific age intervals on puberty; however, larger studies need to shed light on modifiable exposures for behavioral interventions in pregnancy, postpartum and in childhood.^

Dietary patterns and risk of pancreatic cancer in a hospital-based case-control study

Background. It is important to understand the association between diet and risk of pancreatic cancer in order to better understand the etiology of pancreatic cancer.^ Objectives. Describe the dietary patterns of cases of adenocarcinoma of the pancreas and non-cancer controls and evaluate the odds of having a healthy eating pattern among cases and non-cancer controls.^ Design and Methods. An ongoing hospital-based case-control study was conducted in Houston, Texas from 2000-2008 with 678 pancreatic adenocarcinoma cases and 724 controls. Participants completed a food frequency questionnaire and a risk factor questionnaire. Dietary patterns were derived by principal component analysis and associations between dietary patterns and pancreatic cancer risk were assessed using unconditional logistic regression.^ Results. Two dietary patterns were derived: fruit-vegetable and high fat-meat. There were no statistically significant associations between the fruit-vegetable pattern and pancreatic cancer. An inverse association was seen between the high fat-meat pattern and pancreatic cancer risk when comparing those in the upper intake quintile to those scoring in the lowest quintile after adjusting for demographic and risk factor variables (OR=0.67, p=0.03). In sex-stratified analysis adjusted for demographic and risk factor variables, females scoring in the upper intake quintile of the fruit-vegetable pattern had a 49% lower risk of pancreatic cancer compared to females scoring in the lowest quintile (OR=0.51, p=0.03). An inverse relationship was also seen for the high fat-meat pattern when comparing females in the upper intake quintile to females in the lowest quintile (OR=0.50, p=0.03). In males, neither dietary pattern was significantly associated with pancreatic cancer.^ Conclusions. The current findings for the fruit-vegetable pattern are similar to those of previous studies and support the hypothesis that there is an inverse association between a “healthy” diet (comprised of fruits, vegetables, and whole grains) and risk of having pancreatic cancer (in females only). However, the inverse relationship with the high fat-meat pattern and risk of pancreatic cancer is contrary to other results. Further research on dietary patters and pancreatic cancer risk may lead to better understanding of the etiologic cause of pancreatic cancer.^

Cardiovascular disease risk factors in Hispanic children identified through a diabetic proband

Prevalence and mortality rates for non-insulin dependent (Type II) diabetes mellitus are two to five times greater in the Mexican-American population than in the general U.S. population. Diabetes has been associated with risk factors which increases the likelihood of developing atherosclerosis. Relatives of noninsulin dependent diabetic probands are at increased risk of developing diabetes; and offspring of diabetic parents are at greater risk. Elevation in risk factor levels clearly began to develop prior to adulthood. Therefore an excess of these risk factors are expected among offspring and relatives of diabetics.^ The purposes of this study were to describe levels of risk factors within a group of Mexican American children who were identified through a diabetic proband, and to determine if there was a relationship between risk factor levels and heritability. Data from three hundred and seventy-six children and adolescents between the ages of 7 and 13 years, inclusively, were analyzed. These children were identified through a diabetic proband who participated in the Diabetes Alert Study. This study group was compared to a representative sample of Mexican American children, who participated in the Hispanic Health and Nutrition Examination Survey.^ For females, there were statistically significant associations between upper body fat distribution and increased systolic and diastolic blood pressure after adjusting for age and measures of fatness. Body mass index was positively related to and explained a significant portion of the variability in systolic blood pressure, total cholesterol, and HDL-cholesterol, for males only. No relationship was found between degree of relationship to the diabetic proband and risk factor levels. The most likely explanations for this were insufficient sample size to detect differences, and/or incomplete ascertainment of pedigree information.^ Although there was evidence that these Mexican American children are fatter and have more central fat distribution than non-Hispanic children, there is no evidence of increased risk for diabetes and/or cardiovascular disease at these ages. ^

A case-control study to identify risk factors for preterm labor in Colorado Springs, Colorado

The study objectives were to determine risk factors for preterm labor (PTL) in Colorado Springs, CO, with emphasis on altitude and psychosocial factors, and to develop a model that identifies women at high risk for PTL. Three hundred and thirty patients with PTL were matched to 460 control patients without PTL using insurance category as an indirect measure of social class. Data were gathered by patient interview and review of medical records. Seven risk groups were compared: (1) Altitude change and travel; (2) Psychosocial ((a) child, sexual, spouse, alcohol and drug abuse; (b) neuroses and psychoses; (c) serious accidents and injuries; (d) broken home (maternal parental separation); (e) assault (physical and sexual); and (f) stress (emotional, domestic, occupational, financial and general)); (3) demographic; (4) maternal physical condition; (5) Prenatal care; (6) Behavioral risks; and (7) Medical factors. Analysis was by logistic regression. Results demonstrated altitude change before or after conception and travel during pregnancy to be non-significant, even after adjustment for potential confounding variables. Five significant psychosocial risk factors were determined: Maternal sex abuse (p = 0.006), physical assault (p = 0.025), nervous breakdown (p = 0.011), past occupational injury (p = 0.016), and occupational stress (p = 0.028). Considering all seven risk groups in the logistic regression, we chose a logistic model with 11 risk factors. Two risk factors were psychosocial (maternal spouse abuse and past occupational injury), 1 was pertinent to maternal physical condition ($\le$130 lbs. pre-pregnancy weight), 1 to prenatal care ($\le$10 prenatal care visits), 2 pertinent to behavioral risks ($>$15 cigarettes per day and $\le$30 lbs. weight gain) and 5 medical factors (abnormal genital culture, previous PTB, primiparity, vaginal bleeding and vaginal discharge). We conclude that altitude change is not a risk factor for PTL and that selected psychosocial factors are significant risk factors for PTL. ^

A CASE-CONTROL STUDY OF RISK FACTORS FOR ECTOPIC PREGNANCY (ROCHESTER, MINNESOTA, OBSTETRICS)

A population-based case-control study of risk factors for ectopic pregnancy has been conducted. The investigation includes 274 cases diagnosed in Rochester, Minnesota residents from 1935 through 1982, and 548 matched controls selected from live birth deliveries. Risk factor information documented prior to the last index menstrual period was obtained via medical record abstract for 22 potential risk factor variables.^ Univariate matched analyses revealed nine variables with significantly elevated odds ratios (ORs). Following conditional logistic regression for matched sets, four variables remained as significant risk factors for ectopic pregnancy. These risk factors with ORs and 95% confidence intervals (Cls) were: current intrauterine device use (OR = 13.7, Cl = 1.6 - 120.6), infertility (OR = 2.6, Cl = 1.6 - 4.2), pelvic inflammatory disease (OR = 3.3, Cl = 1.6 - 6.6), and tubal surgery (OR = 4.5, Cl = 1.5 - 13.9). After adjusting for these four major risk factors, the following variables did not have statistically significant ORs: abdominal/pelvic surgery (OR = 2.0), acute appendicitis (OR = 2.0), anovulation (OR = 1.2), clomiphene citrate use during the index conception (OR = 3.5), induced abortion (OR = 2.1), in utero exposure to diethylstilbestrol (OR = 1.6), myomas (OR = 0.7), ovarian cysts (OR = 1.0), and past intrauterine device use (OR = 1.2). ^

Effect of smoking on the association between periodontitis and incidence of coronary heart disease: The Atherosclerosis Risk in Communities Study

Multiple studies have shown an association between periodontitis and coronary heart disease due to the chronic inflammatory nature of periodontitis. Also, studies have indicated similar risk factors and patho-physiologic mechanisms for periodontitis and CHD. Among these factors, smoking has been the most discussed common risk factor and some studies suggested the periodontitis - CHD association to be largely a result of confounding due to smoking or inadequate adjustment for it. We conducted a secondary data analysis of the Dental ARIC Study, an ancillary study to the ARIC Study, to evaluate the effect of smoking on the periodontitis - CHD association using three periodontitis classifications namely, BGI, AAP-CDC, and Dental-ARIC classification (Beck et al 2001). We also compared these results with edentulous ARIC participants. Using Cox proportional hazard models, we found that the individuals with the most severe form of periodontitis in each of the three classifications (BGI: HR = 1.56, 95%CI: 1.15 – 2.13; AAP-CDC: HR = 1.42, 95%CI: 1.13 – 1.79; and Dental-ARIC: HR = 1.49, 95%CI: 1.22 – 1.83) were at a significantly higher risk of incident CHD in the unadjusted models; whereas only BGI-P3 showed statistically significant increased risk in the smoking adjusted models (HR = 1.43, 95%CI: 1.04 – 1.96). However none of the categories in any of the classifications showed significant association when a list of traditional CHD risk factors was introduced into the models. On the other hand, edentulous participants showed significant results when compared to the dentate ARIC participants in the crude (HR = 1.56, 95%CI: 1.34 – 1.82); smoking adjusted (HR = 1.39, 95%CI: 1.18 – 1.64) age, race and sex adjusted (HR = 1.52, 95%CI: 1.30 – 1.77); and ARIC traditional risk factors (except smoking) adjusted (HR = 1.27, 95%CI: 1.02 – 1.57) models. Also, the risk remained significantly higher even when smoking was introduced in the age, sex and race adjusted model (HR = 1.38, 95%CI: 1.17 – 1.63). Smoking did not reduce the hazard ratio by more than 8% when it was included in any of the Cox models. ^ This is the first study to include the three most recent case definitions of periodontitis simultaneously while looking at its association with incident coronary heart disease. We found smoking to be partially confounding the periodontitis and coronary heart disease association and edentulism to be significantly associated with incident CHD even after adjusting for smoking and the ARIC traditional risk factors. The difference in the three periodontitis classifications was not found to be statistical significant when they were tested for equality of the area under their ROC curves but this should not be confused with their clinical significance.^

Interferon-gamma release assays for latent tuberculosis infection in child and young adult candidates or recipients of tumor necrosis factor inhibitor therapy

Background. Inhibition of tumor necrosis factor (TNF) is associated with progression of latent tuberculosis infection (LTBI) to active disease. LTBI screening prior to starting TNF inhibitor therapy is recommended. Blood tests, collectively known as interferon-gamma release assays (IGRAs), offer a means other than the tuberculin skin test (TST) of screening for LTBI. However, in the setting of immune compromise, anergy may limit the clinical utility of IGRAs. ^ Methods. A cross-sectional study was conducted in children and young adults ≤ 21 years of age who were cared for at Texas Children's Hospital in Houston, TX, during 2011 and who were candidates for, or were receiving, tumor necrosis factor (TNF)-inhibitor therapy. All subjects answered a risk factor questionnaire and were tested for LTBI by two commercially available IGRAs (QuantiFERON-Gold In-Tube assay and the T-SPOT.TB assay), along with the TST. T-cell phenotypes were evaluated through flow cytometry, both at baseline and after antigen stimulation. ^ Results. Twenty-eight subjects were enrolled. All were TST negative and none were IGRA positive. Results were negative for the 27 subjects who were tested with QuantiFERON-Gold In-Tube. However, 26% of subjects demonstrated anergy in the T-SPOT.T. Patients with T-SPOT. TB anergy had lower quantitative IFN-γ responses to mitogen in the QFT assay—the mean IFN-γ level to mitogen in patients without T-SPOT.TB anergy was 9.84 IU/ml compared to 6.91 IU/ml in patients with T-SPOT.TB anergy (P = 0.046). Age and use of TNF inhibitors, corticosteroids, or methotrexate use were not significantly associated with T-SPOT.TB anergy. Antigen stimulation revealed depressed expression of intracellular IFN-γ in subjects with T-SPOT. TB anergy. ^ Conclusions. The frequency of anergy in this population is higher than would be expected from studies in adults. There appears to be inappropriate IFN-γ responses to antigen in subjects with T-SPOT. TB anergy. This immune defect was detected by the T-SPOT. TB assay but not by the QuantiFERON-Gold In-Tube assay. Further data are needed to clarify the utility of IGRAs in this population.^

HIV prevalence and contextual risk-factors among injection drug users in Harris County, Texas

Injection drug use is the third most frequent risk factor for new HIV infections in the United States. A dual mode of exposure: unsafe drug using practices and risky sexual behaviors underlies injection drug users' (IDUs) risk for HIV infection. This research study aims to characterize patterns of drug use and sexual behaviors and to examine the social contexts associated with risk behaviors among a sample of injection drug users. ^ This cross-sectional study includes 523 eligible injection drug users from Houston, Texas, recruited into the 2009 National HIV Behavioral Surveillance project. Three separate set of analyses were carried out. First, using latent class analysis (LCA) and maximum likelihood we identified classes of behavior describing levels of HIV risk, from nine drug and sexual behaviors. Second, eight separate multivariable regression models were built to examine the odds of reporting a given risk behavior. We constructed the most parsimonious multivariable model using a manual backward stepwise process. Third, we examined whether HIV serostatus knowledge (self-reported positive, negative, or unknown serostatus) is associated with drug use and sexual HIV risk behaviors. ^ Participants were mostly male, older, and non-Hispanic Black. Forty-two percent of our sample had behaviors putting them at high risk, 25% at moderate risk, and 33% at low risk for HIV infection. Individuals in the High-risk group had the highest probability of risky behaviors, categorized as almost always sharing needles (0.93), seldom using condoms (0.10), reporting recent exchange sex partners (0.90), and practicing anal sex (0.34). We observed that unsafe injecting practices were associated with high risk sexual behaviors. IDUs who shared needles had higher odds of having anal sex (OR=2.89, 95%CI: 1.69-4.92) and unprotected sex (OR=2.66, 95%CI: 1.38-5.10) at last sex. Additionally, homelessness was associated with needle sharing (OR=2.24, 95% CI: 1.34-3.76) and cocaine use was associated with multiple sex partners (OR=1.82, 95% CI: 1.07-3.11). Furthermore, twenty-one percent of the sample was unaware of their HIV serostatus. The three groups were not different from each other in terms of drug-use behaviors: always using a new sterile needle, or in sharing needles or drug preparation equipment. However, IDUs unaware of their HIV serostatus were 33% more likely to report having more than three sexual partners in the past 12 months; 45% more likely to report to have unprotected sex and 85% more likely to use drug and or alcohol during or before at last sex compared to HIV-positive IDUs. ^ This analysis underscores the merit of LCA approach to empirically categorize injection drug users into distinct classes and identify their risk pattern using multiple indicators and our results show considerable overlap of high risk sexual and drug use behaviors among the high-risk class members. The observed clustering pattern of drug and sexual risk behavior among this population confirms that injection drug users do not represent a homogeneous population in terms of HIV risk. These findings will help develop tailored prevention programs.^

Risk factors for inflammatory breast cancer

Background: Inflammatory breast cancer (IBC) is rare and accounts for 2.5% of all invasive breast cancers. The 5-year survival rates are significantly lower than for other types of breast cancer, highlighting the significance of cancer prevention in IBC. The comprehensive multi-disciplinary team Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at University of Texas MD Anderson Cancer Center treats the largest number of Inflammatory Breast patients in a single center. Because of this unique center, large patient resources, and good medical and epidemiological records, we were able to conduct the largest single center case-control and case-case study on IBC. Methods: We identified 246 patients diagnosed with IBC and 397 cancer free patients seen at the Dan L Duncan Cancer Prevention Clinic. Breast cancer reproductive risk factors and lifestyle risk factors were compared between tumor subtypes of IBC patients (Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+), Human Epidermal Growth Factor 2 positive (HER2+)), and (ER -/PR-/HER2-)) and cancer free controls. Results: Breastfeeding was the only significant risk factor (p<0.01) between tumor subtypes in IBC patients. In the case-control study that included all IBC patients and cancer free patients the descriptive statistics indicate significant difference in BMI, history of smoking, number of children, age of first pregnancy, any breastfeeding and total time breastfeeding (p<0.05). No differences were found in the frequency of other breast cancer risk factors. Conclusion: The associations determined between cancer free controls and IBC patients have identified previously unknown risk factors for IBC. The risk factors identified by the case control study suggest BMI, history of smoking, and the protective effect of breastfeeding as potential modifiable risk factors that can be used to decrease the incidence of IBC. Impact: These results highlight the importance of evaluating epidemiologic risk factors of IBC, which could lead to the identification of distinct etiologic pathways that could be targeted for prevention.^

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.^

Ultraviolet radiation modulates the immune system through the platelet -activating factor receptor

Ultraviolet radiation plays a critical role in the induction of non-melanoma skin cancer. UV radiation is also immune suppressive. Moreover, UV-induced systemic immune suppression is a major risk factor for skin cancer induction. Previous work had shown that UV exposure in vivo activates a cytokine cascade involving PGE2, IL-4, and IL-10 that induces immune suppression. However, the earliest molecular events that occur immediately after UV-exposure, especially those upstream of PGE2, were not well defined. To determine the initial events and mediators that lead to immune suppression after a pathological dose of UV, mouse keratinocytes were analyzed after sunlamp irradiation. It is known that UV-irradiated keratinocytes secrete the phospholipid mediator of inflammation, platelet-activating factor (PAF). Since PAF stimulates the production of immunomodulatory compounds, including PGE2, the hypothesis that UV-induced PAF activates cytokine production and initiates UV-induced immune suppression was tested. Both UV and PAF activated the transcription of cyclooxygenase (COX)-2 and IL-10 reporter gene constructs. A PAF receptor antagonist blocked UV-induced IL, 10 and COX-2 transcription. PAF mimicked the effects of UV in vivo and suppressed delayed-type hypersensitivity (DTH), and immune suppression was blocked when UV-irradiated mice were injected with a PAF receptor antagonist. This work shows that UV generates PAF-like oxidized lipids, that signal through the PAF receptor, activate cytokine transcription, and induce systemic immune suppression. ^