Survival of gastrointestinal and stromal tumor patients at UT M.D. Anderson Cancer Center

Objective. Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract with spindled cell, epithelioid, or occasionally pleomorphic morphology. The primary objective of this paper is to describe the demographic and clinical characteristics and survival among GIST patients registered at the University of Texas M.D. Anderson Cancer Center (MDACC). ^ Methods. This cohort study includes 783 consecutive patients diagnosed with GIST from 1995 to 2007. Demographic, clinical and survival information were obtained from the MDACC cancer registry. ^ Statistical Analysis. Kaplan-Meier survival curves, univariate and multivariate Cox proportional hazards analysis were conducted to estimate survival and identify prognostic clinical factors associated with survival. Results. The age at diagnosis of MDACC GIST cases ranged from 17 to 91 with a mean of 57 years and a male-to-female ratio of 1.3:1. The racial distribution was whites 77%, African-Americans 9.5%, Hispanics 9.3% and other races 4.2%. Fifty per cent of the GISTs arose from stomach, 35% small intestine, 7% retroperitoneal space, 6% colorectal and 2% were omentum and mesentery. About half of the tumors were less than 10 cm in size. Fifty eight per cent of the tumors were localized whereas 36% were metastatic. MDACC GIST patients were generally comparable to SEER patients, but, on the average, were 7 years younger than SEER patients and were predominantly whites. ^ Stratification of 783 GIST cases by year of diagnosis based on the introduction of imatinib treatment in 2000 revealed that 60% of the GIST cases were first diagnosed between 2000 and 2007 whereas, 40% were first diagnosed between 1995 and 1999. There was a significant difference between the two cohorts in the distribution of race, GIST symptom, tumor size, tumor site, and stage of the tumor at diagnosis. The 1- and 5-year survival was 93% and 59% in the 1995–2007 cohort. Multivariate Cox regression analysis identified age at diagnosis (p<0.001), female sex (p=0.047), tumor size (p=0.07), multiple cancers (p=0.002), and GIST diagnosed between 2000 and 2007 (p<0.001) were significantly associated with survival. Approximately, 58% of the cases were treated with imatinib whereas 42% did not receive imatinib in 2000–2005 cohort. There was a significant difference in survival between imatinib and non-imatinib groups and in the distribution of tumor size categories, stage of the tumor at diagnosis and cancers before the diagnosis of GIST. The 1- and 5-year survival for imatinib patients was 99% and 73% and was 91% and 63% for non-imatinib patients. Multivariate Cox regression analysis of the 2000–2007 cohort identified, age at diagnosis and tumor stage as possible prognostic factors associated with survival.^

Hepatitis C and human immunodeficiency virus infections in injecting drug users in drug treatment centers in Vietnam

Background. Injecting drug users (IDUs) are at risk of infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Independently, each of these viruses is a serious threat to health, with HIV ravaging the body’s immune system, and HCV causing cirrhosis, liver cancer and liver failure. Co-infection with HIV/HCV weakens the response to antiretroviral therapy in HIV patients. IDUs with HIV/HCV co-infection are at a 20 times higher risk of having liver-related morbidity and mortality than IDUs with HIV alone. In Vietnam, studies to ascertain the prevalence of HIV have found high rates, but little is known about their HCV status. ^ Purpose. To measure the prevalence of HCV and HIV infection and identify factors associated with these viruses among IDUs at drug treatment centers in northern Vietnam. ^ Methods. A cross-sectional study was conducted from November 2007 to February 2008 with 455 injecting drug users aged 18 to 39 years, admitted no more than two months earlier to one of four treatment centers in Northern Vietnam (Hatay Province) (response rate=95%). Participants, all of whom had completed detoxification and provided informed consent, completed a risk assessment questionnaire and had their blood drawn to test for the presence of antibody-HCV and antibody-HIV with enzyme immuno assays. Univariate and multivariable logistic regression models were utilized to explore the strength of association using HIV, HCV infections and HIV/HCV co-infection as outcomes and demographic characteristics, drug use and sexual behaviors as factors associated with these outcomes. Unadjusted and adjusted odds ratios and 95% confidence intervals were calculated. ^ Results. Among all IDU study participants, the prevalence of HCV alone was 76.9%, HIV alone was 19.8%. The prevalence of HIV/HCV co-infection was 92.2% of HIV-positive and 23.7% of HCV-positive respondents. No sexual risk behaviors for lifetime, six months or 30 days prior to admission were significantly associated with HCV or HIV infection among these IDUs. Only duration of injection drug use was independently associated with HCV and HIV infection, respectively. Longer duration was associated with higher prevalence. Nevertheless, while HCV infection among IDUs who reported being in their first year of injecting drugs were lower than longer time injectors, their rates were still substantial, 67.5%. ^ Compared with either HCV mono-infection or HIV/HCV non-infection, HIV/HCV co-infection was associated with the length of drug injection history but was not associated with sexual behaviors. Higher education was associated with a lower prevalence of HIV/HCV co-infection. When compared with HIV/HCV non-infection, current marriage was associated with a lower prevalence of HIV/HCV co-infection. ^ Conclusions. HCV was prevalent among IDUs from 18 to 39 years old at four drug treatment centers in northern Vietnam. Co-infection with HCV was predominant among HIV-positive IDUs. HCV and HIV co-infection were closely associated with the length of injection drug history. Further research regarding HCV/HIV co-infection should include non-injecting drug users to assess the magnitude of sexual risk behaviors on HIV and HCV infection. (At these treatment centers non-IDUs constituted 10-20% of the population.) High prevalence of HCV prevalence among IDUs, especially among HIV-infected IDUs, suggests that drug treatment centers serving IDUs should include not only HIV prevention education but they should also include the prevention of viral hepatitis. In addition, IDUs who are HIV-positive need to be tested for HCV to receive the best course of therapy and achieve the best response to HIV treatment. These data also suggest that because many IDUs get infected with HCV in the first year of their injection drug career, and because they also engaged in high risk sexual behaviors, outreach programs should focus on harm reduction, safer drug use and sexual practices to prevent infection among drug users who have not yet begun injecting drugs and to prevent further spread of HCV, HIV and co-infection. ^

11beta-hydroxysteroid dehydrogenases as regulators of pulmonary corticosterone during the granulomatous response to trehalose 6,6'-dimycolate

Protection against Mycobacterium tuberculosis requires development and maintenance of granulomatous lesions, a feature considered to be the pathological hallmark of Tuberculosis (TB) disease. Upon encountering Mtb or mycobacterial antigens, specifically trehalose 6,6'-dimycolate (TDM), a strong local pro-inflammatory response is initiated. Systemic production of anti-inflammatory glucocorticoids (GCs) is also induced. Emergence of these antagonists at the inflammatory foci is counterproductive to development of the granulomatous structure and detrimental to host protection against TB. Therefore, it was hypothesized that local enzymatic regulation of GCs occurs locally at the site of granulomatous inflammation. The experiments described here strongly suggest that 11β-hydroxysteroid dehydrogenases (11βHSDs) shuttle GCs between active and inert forms during the acute granulomatous response, supporting the net reduction of corticosterone. The patterns of GC and 11βHSD regulation were specific to the lung (the site of inflammation) and were not observed in other tissues. Furthermore, 11βHSD2, which decreases corticosterone concentrations, was not expressed in models of dysregulated granulomatous inflammation. These findings suggest that cellular exposure to local active GC concentrations is restricted via 11βHSDs as a mechanism to initiate and maintain granuloma formation. The information derived from the experiments outlined in this dissertation provides a better understanding of the events required for establishment and maintenance of the protective granulomatous response. As a practical consequence, exploiting 11βHSD2 modulation of GCs at the site of Mtb infection may lead to improvement of Tuberculosis treatment strategies.^

Prevalence and risk factors for polyomavirus reactivation in solid-organ transplantation

Background. Polyomavirus reactivation is common in solid-organ transplant recipients who are given immunosuppressive medications as standard treatment of care. Previous studies have shown that polyomavirus infection can lead to allograft failure in as many as 45% of the affected patients. Hypothesis. Ubiquitous polyomaviruses when reactivated by post-transplant immunosuppressive medications may lead to impaired renal function and possibly lower survival prospects. Study Overview. Secondary analysis of data was conducted on a prospective longitudinal study of subjects who were at least 18 years of age and were recipients of liver and/or kidney transplant at Mayo Clinic Scottsdale, Arizona. Methods. DNA extractions of blinded urine and blood specimens of transplant patients collected at Mayo Clinic during routine transplant patient visits were performed at Baylor College of Medicine using Qiagen kits. Virologic assays included testing DNA samples for specific polyomavirus sequences using QPCR technology. De-identified demographic and clinical patient data were merged with laboratory data and statistical analysis was performed using Stata10. Results. 76 patients enrolled in the study were followed for 3.9 years post transplantation. The prevalence of BK virus and JC virus urinary excretion was 30% and 28%. Significant association was observed between JC virus excretion and kidney as the transplanted organ (P = 0.039, Pearson Chi-square test). The median urinary JCV viral loads were two logs higher than those of BKV. Patients that excreted both BKV and JCV appeared to have the worst renal function with a mean creatinine clearance value of 71.6 millimeters per minute. A survival disadvantage was observed for dual shedders of BKV and JCV, log-rank statistics, p = 0.09; 2/5 dual-shedders expired during the study period. Liver transplant and male sex were determined to be potential risk factors for JC virus activation in renal and liver transplant recipients. All patients tested negative for SV40 and no association was observed between polyomavirus excretion and type of immunosuppressive medication (tacrolimus, mycophenolate mofetil, cyclosporine and sirolimus). Conclusions. Polyomavirus reactivation was common after solid-organ transplantation and may be associated with impaired renal function. Male sex and JCV infection may be potential risk factors for viral reactivation; findings should be confirmed in larger studies.^

The role of AKT-mediated phosphorylation in suppression of MAD1 and the development of new approach in protein complex detection

MAX dimerization protein 1 (MAD1) is a basic-helix-loop-helix transcription factors that recruits transcription repressor such as HDAC to suppress target genes transcription. It antagonizes to MYC because the promoter binding sites for MYC are usually also serve as the binding sites for MAD1 so they compete for it. However, the mechanism of the switch between MYC and MAD1 in turning on and off of genes' transcription is obscure. In this study, we demonstrated that AKT-mediated MAD1 phosphorylation inhibits MAD1 transcription repression function. The association between MAD1 and its target genes' promoter is reduced after been phosphorylated by AKT; therefore, consequently, allows MYC to occupy the binding site and activates transcription. Mutation of such phosphorylation site abrogates the inhibition from AKT. In addition, functional assays demonstrated that AKT suppressed MAD1-mediated transcription repression of its target genes hTERT and ODC. Cell cycle and cell growth were also been released from inhibition by MAD1 in the presents of AKT. Taken together, our study suggests that MAD1 is a novel substrate of AKT and AKT-mediated MAD1 phosphorylation inhibits MAD1function; therefore, activates MAD1 target genes expression. ^ Furthermore, analysis of protein-protein interaction is indispensable for current molecular biology research, but multiplex protein dynamics in cells is too complicated to be analyzed by using existing biochemical methods. To overcome the disadvantage, we have developed a single molecule level detection system with nanofluidic chip. Single molecule was analyzed based on their fluorescent profile and their profiles were plotted into 2 dimensional time co-incident photon burst diagram (2DTP). From this 2DTP, protein complexes were characterized. These results demonstrate that the nanochannel protein detection system is a promising tool for future molecular biology. ^

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

The relationship between premature rupture of the membranes and sepsis in preterm neonates

This investigation was designed as a hospital-based, historical cohort study. The objective of the study was to determine the association between premature rupture of the membranes (PROM) and its duration on neonatal sepsis, infection, and mortality. Neonates born alive with gestational ages between 25 and 35 weeks from singleton pregnancies complicated by PROM were selected. Each of the 507 neonates was matched on gestational age, gender, ethnicity, and month of birth with a neonate without the complication of PROM.^ Data were abstracted from deliveries between January 1979 and December 1985 describing the mother's demographics, labor and delivery treatments and complications, the neonate's demographics, infection status, and medical care. The matched pairs analysis reveals a significant increase in risk of neonatal sepsis (RR = 3.5) and neonatal infection (RR = 2.4) among preterm births complicated by PROM, with a PROM exposure contributing an excess 4 to 5 cases of sepsis per 100 infants (RD = 0.04 for infection and RD = 0.05 for sepsis). Generally PROM remains an important risk factor for sepsis and infection when controlling for various other characteristics, and the risk difference remains constant.^ PROM was not significantly associated with neonatal mortality (RR = 1.02). There is an increase in risk difference for mortality associated with PROM among septic and infected infants, but it is not significant.^ A clear increase in risk of sepsis and infection from PROM occurs when durations of PROM are long (more than 48 hours), e.g., for sepsis the RR is 2.42 for short durations and RR is 6.0 for long durations. No such risk with long duration appears for neonatal mortality.^ This study indicates the importance of close observation of neonates with PROM for sepsis and infection so treatment can be initiated early. However, prematurity is the major risk for sepsis and the practice of early delivery to avoid prolonged durations of PROM does not alter the magnitude of risk. The greatest protection against these infection complications was provided when the neonate weighed over 1500 grams or had more than 33 weeks gestation. ^

Perinatal mortality and quality of care at the National Institute of Perinatology: A 3-year analysis

Quality of medical care has been indirectly assessed through the collection of negative outcomes. A preventable death is one that could have been avoided if optimum care had been offered. The general objective of the present project was to analyze the perinatal mortality at the National Institute of Perinatology (located in Mexico City) by social, biological and some available components of quality of care such as avoidability, provider responsibility, and structure and process deficiencies in the delivery of medical care. A Perinatal Mortality Committee data base was utilized. The study population consisted of all singleton perinatal deaths occurring between January 1, 1988 and June 30, 1991 (n = 522). A proportionate study was designed.^ The population studied mostly corresponded to married young adult mothers, who were residents of urban areas, with an educational level of junior high school or more, two to three pregnancies, and intermediate prenatal care. The mean gestational age at birth was 33.4 $\pm$ 3.9 completed weeks and the mean birthweight at birth was 1,791.9 $\pm$ 853.1 grams.^ Thirty-five percent of perinatal deaths were categorized as avoidable. Postnatal infection and premature rupture of membranes were the most frequent primary causes of avoidable perinatal death. The avoidable perinatal mortality rate was 8.7 per 1000 and significantly declined during the study period (p $<$.05). Preventable perinatal mortality aggregated data suggested that at least part of the mortality decline for amenable conditions was due to better medical care.^ Structure deficiencies were present in 35% of avoidable deaths and process deficiencies were present in 79%. Structure deficiencies remained constant over time. Process deficiencies consisted of diagnosis failures (45.8%) and treatment failures (87.3%), they also remained constant through the years. Party responsibility was as follows: Obstetric (35.4%), pediatric (41.4%), institutional (26.5%), and patient (6.6%). Obstetric responsibility significantly increased during the study period (p $<$.05). Pediatric responsibility declined only for newborns less than 1500 g (p $<$.05). Institutional responsibility remained constant.^ Process deficiencies increased the risk for an avoidable death eightfold (confidence interval 1.7-41.4, p $<$.01) and provider responsibility ninety-fivefold (confidence interval 14.8-612.1, p $<$.001), after adjustment for several confounding variables. Perinatal mortality due to prematurity, barotrauma and nosocomial infection, was highly preventable, but not that due to transpartum asphyxia. Once specific deficiencies in the quality of care have been identified, quality assurance actions should begin. ^

Risk factors of pneumonia in traumatic spinal-cord-injured patients

Pneumonia is a well-documented and common respiratory infection in patients with acute traumatic spinal cord injuries, and may recur during the course of acute care. Using data from the North American Clinical Trials Network (NACTN) for Spinal Cord Injury, the incidence, timing, and recurrence of pneumonia were analyzed. The two main objectives were (1) to investigate the time and potential risk factors for the first occurrence of pneumonia using the Cox Proportional Hazards model, and (2) to investigate pneumonia recurrence and its risk factors using a Counting Process model that is a generalization of the Cox Proportional Hazards model. The results from survival analysis suggested that surgery, intubation, American Spinal Injury Association (ASIA) grade, direct admission to a NACTN site and age (older than 65 or not) were significant risks for first event of pneumonia and multiple events of pneumonia. The significance of this research is that it has the potential to identify patients at the time of admission who are at high risk for the incidence and recurrence of pneumonia. Knowledge and the time of occurrence of pneumonias are important factors for the development of prevention strategies and may also provide some insights into the selection of emerging therapies that compromise the immune system. ^

Anal warts and their predictors among HIV-infected women

Human papillomavirus (HPV) is a necessary cause of cervical cancer and is also strongly associated with anal cancer. While different factors such as CD4+ cell count, HIV RNA viral load, smoking status, and cytological screening results have been identified as risk factors for the infection of HPV high-risk types and associated cancers, much less is known about the association between those risk factors and the infection of HPV low-risk types and anogential warts. In this dissertation, a public dataset (release P09) obtained from the Women's Interagency HIV Study (WIHS) was used to examine the effects of those risk factors on the size of the largest anal warts in HIV-infected women in the United States. Linear mixed modeling was used to address this research question. ^ The prevalence of anal warts at baseline for WIHS participants was higher than other populations. Incidence of anal warts in HIV-infected women was significantly higher than that of HIV-uninfected women [4.15 cases per 100 person-years (95% CI: 3.83–4.77) vs. 1.30 cases per 100 person-years (95% CI: 1.00–1.58), respectively]. There appeared to be an inverse association between the size of the largest anal wart and CD4+ cell count at baseline visit, however it was not statistically significant. There was no association between size of the largest anal wart and CD4+ cell count or HIV RNA viral load over time among HIV-infected women. There was also no association between the size of the largest anal wart and current smoking over time in HIV-infected women, even though smokers had larger warts at baseline than non-smokers. Finally, even though a woman with Pap smear results of ASCUS/LGSIL was found to have an anal wart larger than a woman with normal cervical Pap smear results the relationship between the size of the largest anal wart with cervical Pap smear results over time remains unclear. ^ Although the associations between these risk factors and the size of the largest anal wart over time in HIV-infected women could not be firmly established, this dissertation poses several questions concerning anal wart development for further exploration: (1) the role of immune function (i.e., CD4+ cell count), (2) the role of smoking status and the interaction between smoking status with other risk factors (e.g., CD4+ cell count or HIV RNA viral load), (3) the molecular mechanism of smoking on anal warts over time, (4) the potential for development of a screening program using anal Pap smear in HIV-infected women, and (5) how cost-effective and efficacious would an anal Pap smear screening program be in this high-risk population. ^

Development and Implementation of the Use of Optically Stimulated Luminescent Detectors in the Radiological Physics Center Anthropomorphic Quality Assurance Phantoms

The Radiological Physics Center (RPC) uses both on-site and remote reviews to credential institutions for participation in clinical trials. Anthropomorphic quality assurance (QA) phantoms are one tool the RPC uses to remotely audit institutions, which include thermoluminescent dosimeters (TLDs) and radiochromic film. The RPC desires to switch from TLD as the absolute dosimeter in the phantoms, to optically stimulated luminescent dosimeters (OSLDs), but a problem lies in the angular dependence exhibited by the OSLD. The purpose of this study was to characterize the angular dependence of OSLD and establish a correction factor if necessary, to provide accurate dosimetric measurements as a replacement for TLD in the QA phantoms. A 10 cm diameter high-impact polystyrene spherical phantom was designed and constructed to hold an OSLD to study the angular response of the dosimeter under the simplest of circumstances for both coplanar and non-coplanar treatment deliveries. OSLD were irradiated in the spherical phantom, and the responses of the dosimeter from edge-on angles were normalized to the response when irradiated with the beam incident normally on the surface of the dosimeter. The average normalized response was used to establish an angular correction factor for 6 MV and 18 coplanar treatments, and for 6 MV non-coplanar treatments specific to CyberKnife. The RPC pelvic phantom dosimetry insert was modified to hold OSLD, in addition to the TLD, adjacent to the planes of film. Treatment plans of increasing angular beam delivery were developed, three in Pinnacle v9.0 (4-field box, IMRT, and VMAT) and one in Accuray’s MultiPlan v3.5.3 (CyberKnife). The plans were delivered to the pelvic phantom containing both TLD and OSLD in the target volume. The pelvic phantom was also sent to two institutions to be irradiated as trials, one delivering IMRT, and the other a CyberKnife treatment. For the IMRT deliveries and the two institution trials, the phantom also included film in the sagittal and coronal planes. The doses measured from the TLD and OSLD were calculated for each irradiation, and the angular correction factors established from the spherical phantom irradiations were applied to the OSLD dose. The ratio of the TLD dose to the angular corrected OSLD dose was calculated for each irradiation. The corrected OSLD dose was found to be within 1% of the TLD measured dose for all irradiations, with the exception of the in-house CyberKnife deliveries. The films were normalized to both TLD measured dose and the corrected OSLD dose. Dose profiles were obtained and gamma analysis was performed using a 7%/4 mm criteria, to compare the ability of the OSLD, when corrected for the angular dependence, to provide equivalent results to TLD. The results of this study indicate that the OSLD can effectively be used as a replacement for TLD in the RPC’s anthropomorphic QA phantoms for coplanar treatment deliveries when a correction is applied for the dosimeter’s angular dependence.

Does prior receipt of a rifamycin antibiotic increase the risk of acquiring an infection due to a rifamycin-resistant strain of Clostridium difficile?

Objectives. To examine the association between prior rifamycin exposure and later development of C. difficile infection (CDI) caused by a rifamycin-resistant strain of C. difficile , and to compare patient characteristics between rifamycin-resistant strains of C. difficile infection and rifamycin-susceptible strains of C. difficile infection. ^ Methods. A case-control study was performed in a large university-affiliated hospital in Houston, Texas. Study subjects were patients with C. difficile infection acquired at the hospital with culture-positive isolates of C. difficile with which in vitro rifaximin and rifampin susceptibility has been tested. Prior use of rifamycin, demographic and clinical characteristics was compared between case and control groups using univariate statistics. ^ Results. A total of 49 C. difficile strains met the study inclusion criteria for rifamycin-resistant case isolates, and a total of 98 rifamycin-susceptible C. difficile strains were matched to case isolates. Of 49 case isolates, 12 (4%) were resistant to rifampin alone, 12 (4%) were resistant to rifaximin alone, and 25 (9%) were resistant to both rifampin and rifaximin. There was no significant association between prior rifamycin use and rifamycin-resistant CDI. Cases and controls did not differ according to demographic characteristics, length of hospital stay, known risk factors of CDI, type of CDI-onset, and pre-infection medical co-morbidities. Our results on 37 rifaximin-resistant isolates (MIC ≥32 &mgr;g/ml) showed more than half of isolates had a rifaximin MIC ≥256 &mgr;g/ml, and out of these isolates, 19 isolates had MICs ≥1024 &mgr;g/ml. ^ Conclusions. Using a large series of rifamycin-non-susceptible isolates, no patient characteristics were independently associated with rifamycin-resistant CDI. This data suggests that factors beyond previous use of rifamycin antibiotics are primary risk factors for rifamycin-resistant C. difficile. ^

An assessment of post-disaster psychological stress in hazardous waste operations and emergency response (HAZWOPER) workers

Personnel involved in natural or man-made disaster response and recovery efforts may be exposed to a wide variety of physical and mental stressors that can exhibit long-lasting and detrimental psychopathological outcomes. In a disaster situation, huge numbers of "secondary" responders can be involved in contaminant clean-up and debris removal and can be at risk of developing stress-related mental health outcomes. The Occupational Safety and Health Administration (OSHA) worker training hierarchy typically required for response workers, known as "Hazardous Waste Operations and Emergency Response" (HAZWOPER), does not address the mental health and safety concerns of workers. This study focused on the prevalence of traumatic stress experienced by secondary responders that had received or expressed interest in receiving HAZWOPER training through the National Institute of Environmental Health Sciences Worker Education and Training Program (NIEHS WETP). ^ The study involved the modification of two preexisting and validated survey tools to assess secondary responder awareness of physical, mental, and traumatic stressors on mental health and sought to determine if a need existed to include traumatic stress-related mental health education in the current HAZWOPER training regimen. The study evaluated post-traumatic stress disorder (PTSD), resiliency, mental distress, and negative effects within a secondary responder population of 176 respondents. Elevated PTSD levels were seen in the study population as compared to a general responder population (32.9% positive vs. 8%-22.5% positive). Results indicated that HAZWOPER-trained disaster responders were likely to test positive for PTSD, whereas, untrained responders with no disaster experience and responders who possessed either training or disaster experience only were likely to test PTSD negative. A majority (68.75%) of the population tested below the mean resiliency to cope score (80.4) of the average worker population. Results indicated that those who were trained only or who possessed both training and disaster work experience were more likely to have lower resiliency scores than those with no training or experience. There were direct correlations between being PTSD positive and having worked at a disaster site and experiencing mental distress and negative effects. However, HAZWOPER training status does not significantly correlate with mental distress or negative effect. ^ The survey indicated clear support (91% of respondents) for mental health education. The development of a pre- and post-deployment training module is recommended. Such training could provide responders with the necessary knowledge and skills to recognize the symptomology of PTSD, mental stressors, and physical and traumatic stressors, thus empowering them to employ protective strategies or seek professional help if needed. It is further recommended that pre-deployment mental health education be included in the current HAZWOPER 24- and 40-hour course curriculums, as well as, consideration be given towards integrating a stand-alone post-deployment mental health education training course into the current HAZWOPER hierarchy.^

Data quality in trauma transfusion studies and the impact of missing data on predicting massive transfusion

Maximizing data quality may be especially difficult in trauma-related clinical research. Strategies are needed to improve data quality and assess the impact of data quality on clinical predictive models. This study had two objectives. The first was to compare missing data between two multi-center trauma transfusion studies: a retrospective study (RS) using medical chart data with minimal data quality review and the PRospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study with standardized quality assurance. The second objective was to assess the impact of missing data on clinical prediction algorithms by evaluating blood transfusion prediction models using PROMMTT data. RS (2005-06) and PROMMTT (2009-10) investigated trauma patients receiving ≥ 1 unit of red blood cells (RBC) from ten Level I trauma centers. Missing data were compared for 33 variables collected in both studies using mixed effects logistic regression (including random intercepts for study site). Massive transfusion (MT) patients received ≥ 10 RBC units within 24h of admission. Correct classification percentages for three MT prediction models were evaluated using complete case analysis and multiple imputation based on the multivariate normal distribution. A sensitivity analysis for missing data was conducted to estimate the upper and lower bounds of correct classification using assumptions about missing data under best and worst case scenarios. Most variables (17/33=52%) had <1% missing data in RS and PROMMTT. Of the remaining variables, 50% demonstrated less missingness in PROMMTT, 25% had less missingness in RS, and 25% were similar between studies. Missing percentages for MT prediction variables in PROMMTT ranged from 2.2% (heart rate) to 45% (respiratory rate). For variables missing >1%, study site was associated with missingness (all p≤0.021). Survival time predicted missingness for 50% of RS and 60% of PROMMTT variables. MT models complete case proportions ranged from 41% to 88%. Complete case analysis and multiple imputation demonstrated similar correct classification results. Sensitivity analysis upper-lower bound ranges for the three MT models were 59-63%, 36-46%, and 46-58%. Prospective collection of ten-fold more variables with data quality assurance reduced overall missing data. Study site and patient survival were associated with missingness, suggesting that data were not missing completely at random, and complete case analysis may lead to biased results. Evaluating clinical prediction model accuracy may be misleading in the presence of missing data, especially with many predictor variables. The proposed sensitivity analysis estimating correct classification under upper (best case scenario)/lower (worst case scenario) bounds may be more informative than multiple imputation, which provided results similar to complete case analysis.^

The risk prediction for SPM and its impact on the survival in patients with head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth common malignancy in the world, with high rates of developing second primary malignancy (SPM) and moderately low survival rates. This disease has become an enormous challenge in the cancer research and treatments. For HNSCC patients, a highly significant cause of post-treatment mortality and morbidity is the development of SPM. Hence, assessment of predicting the risk for the development of SPM would be very helpful for patients, clinicians and policy makers to estimate the survival of patients with HNSCC. In this study, we built a prognostic model to predict the risk of developing SPM in patients with newly diagnosed HNSCC. The dataset used in this research was obtained from The University of Texas MD Anderson Cancer Center. For the first aim, we used stepwise logistic regression to identify the prognostic factors for the development of SPM. Our final model contained cancer site and overall cancer stage as our risk factors for SPM. The Hosmer-Lemeshow test (p-value= 0.15>0.05) showed the final prognostic model fit the data well. The area under the ROC curve was 0.72 that suggested the discrimination ability of our model was acceptable. The internal validation confirmed the prognostic model was a good fit and the final prognostic model would not over optimistically predict the risk of SPM. This model needs external validation by using large data sample size before it can be generalized to predict SPM risk for other HNSCC patients. For the second aim, we utilized a multistate survival analysis approach to estimate the probability of death for HNSCC patients taking into consideration of the possibility of SPM. Patients without SPM were associated with longer survival. These findings suggest that the development of SPM could be a predictor of survival rates among the patients with HNSCC.^