BRAIN ACTIVATION AND CONNECTIVITY IN NON-DISABLED MULTIPLE SCLEROSIS PATIENTS

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. There is no cure for MS and current therapies have limited efficacy. While the majority of individuals with MS develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). The current studies combined functional MRI and diffusion tensor imaging (DTI) to elucidate brain mechanisms associated with lack of clinical disability in patients with MS. Recent evidence has implicated cortical reorganization as a mechanism to limit the clinical manifestation of the disease. Functional MRI was used to test the hypothesis that non-disabled MS patients (Expanded Disability Status Scale ≤ 1.5) show increased recruitment of cognitive control regions (dorsolateral prefrontal and anterior cingulate cortex) while performing sensory, motor and cognitive tasks. Compared to matched healthy controls, patients increased activation of cognitive control brain regions when performing non-dominant hand movements and the 2-back working memory task. Using dynamic causal modeling, we tested whether increased cognitive control recruitment is associated with alterations in connectivity in the working memory functional network. Patients exhibited similar network connectivity to that of control subjects when performing working memory tasks. We subsequently investigated the integrity of major white matter tracts to assess structural connectivity and its relation to activation and functional integration of the cognitive control system. Patients showed substantial alterations in callosal, inferior and posterior white matter tracts and less pronounced involvement of the corticospinal tracts and superior longitudinal fasciculi (SLF). Decreased structural integrity within the right SLF in patients was associated with decreased performance, and decreased activation and connectivity of the cognitive control system when performing working memory tasks. These studies suggest that patient with MS without clinical disability increase cognitive control system recruitment across functional domains and rely on preserved functional and structural connectivity of brain regions associated with this network. Moreover, the current studies show the usefulness of combining brain activation data from functional MRI and structural connectivity data from DTI to improve our understanding of brain adaptation mechanisms to neurological disease.

Evaluation of the causal pathways through which subjective norms influence mammography intention and stage of change in a national sample of women veterans

Few studies have investigated causal pathways linking psychosocial factors to each other and to screening mammography. Conflicting hypotheses exist in the theoretic literature regarding the role and importance of subjective norms, a person's perceived social pressure to perform the behavior and his/her motivation to comply. The Theory of Reasoned Action (TRA) hypothesizes that subjective norms directly affect intention; while the Transtheoretical Model (TTM) hypothesizes that attitudes mediate the influence of subjective norms on stage of change. No one has examined which hypothesis best predicts the effect of subjective norms on mammography intention and stage of change. Two statistical methods are available for testing mediation, sequential regression analysis (SRA) and latent variable structural equation modeling (LVSEM); however, software to apply LVSEM to dichotomous variables like intention has only recently become available. No one has compared the methods to determine whether or not they yield similar results for dichotomous variables. ^ Study objectives were to: (1) determine whether the effect of subjective norms on mammography intention and stage of change are mediated by pros and cons; and (2) compare mediation results from the SRA and LVSEM approaches when the outcome is dichotomous. We conducted a secondary analysis of data from a national sample of women veterans enrolled in Project H.O.M.E. (H&barbelow;ealthy O&barbelow;utlook on the M&barbelow;ammography E&barbelow;xperience), a behavioral intervention trial. ^ Results showed that the TTM model described the causal pathways better than the TRA one; however, we found support for only one of the TTM causal mechanisms. Cons was the sole mediator. The mediated effect of subjective norms on intention and stage of change by cons was very small. These findings suggest that interventionists focus their efforts on reducing negative attitudes toward mammography when resources are limited. ^ Both the SRA and LVSEM methods provided evidence for complete mediation, and the direction, magnitude, and standard errors of the parameter estimates were very similar. Because SRA parameter estimates were not biased toward the null, we can probably assume negligible measurement error in the independent and mediator variables. Simulation studies are needed to further our understanding of how these two methods perform under different data conditions. ^

Risk factors for Clostridium difficile nosocomial diarrhea in patients at the Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas

Background. Clostridium difficile is the leading cause of hospital associated infectious diarrhea and colitis. About 3 million cases of Clostridium difficile diarrhea occur each year with an annual cost of $1 billion. ^ About 20% of patients acquire C. difficile during hospitalization. Infection with Clostridium difficile can result in serious complications, posing a threat to the patient's life. ^ Purpose. The aim of this research was to demonstrate the uniqueness in the characteristics of C. difficile positive nosocomial diarrhea cases compared with C. difficile negative nosocomial diarrhea controls admitted to a local hospital. ^ Methods. One hundred and ninety patients with a positive test and one hundred and ninety with a negative test for Clostridium difficile nosocomial diarrhea, selected from patients tested between January 1, 2002 and December 31, 2003, comprised the study population. Demographic and clinical data were collected from medical records. Logistic regression analyses were conducted to determine the associated odds between selected variables and the outcome of Clostridium difficile nosocomial diarrhea. ^ Results. For the antibiotic classes, cephalosporins (OR, 1.87; CI 95, 1.23 to 2.85), penicillins (OR, 1.57; CI 95, 1.04 to 2.37), fluoroquinolones (OR, 1.65; CI 95, 1.09 to 2.48) and antifungals (OR, 2.17; CI 95, 1.20 to 3.94), were significantly associated with Clostridium difficile nosocomial diarrhea Ceftazidime (OR, 1.95; CI 95, 1.25 to 3.03, p=0.003), gatifloxacin (OR, 1.97; CI 95, 1.31 to 2.97, p=0.001), clindamycin (OR, 3.13; CI 95, 1.99 to 4.93, p<0.001) and vancomycin (OR, 1.77; CI 95, 1.18 to 2.66, p=0.006, were also significantly associated with the disease. Vancomycin was not statistically significant when analyzed in a multivariable model. Other significantly associated drugs were, antacids, laxatives, narcotics and ranitidine. Prolong use of antibiotics and an increased number of comorbid conditions were also associated with C. difficile nosocomial diarrhea. ^ Conclusion. The etiology for C. difficile diarrhea is multifactorial. Exposure to antibiotics and other drugs, prolonged antibiotic usage, the presence and severity of comorbid conditions and prolonged hospital stay were shown to contribute to the development of the disease. It is imperative that any attempt to prevent the disease, or contain its spread, be done on several fronts. ^

Pancreatic cancer deaths in Texas veterans

Background/objective. Several studies have found an increased risk of pancreatic cancer in veterans deployed to Vietnam during the Vietnam War. Diabetes, a known risk factor for pancreatic cancer, has been designated as a service-connected illness in deployed Vietnam veterans. The majority of Vietnam veterans, now between the ages of 55 to 65, have not yet reached the ages of pancreatic cancer’s greatest prevalence, ages 65 to 79. This case-control study utilized 1998 electronic Texas death certificate data for white, black and Hispanic men to explore the question of whether military service was a risk factor for deaths due to pancreatic cancer among men who died in 1998.^ Methods. The primary study included men born between 1927 and 1953, and was a matched case-control study with two control groups; 431 pancreatic cancer cases were birth-year and race-matched one case to two non-neoplastic death controls and, for the second control group, were matched 1:1 with 431 accidental death controls. The exposure was military service, recorded as “yes”, “no” or “unknown” on the death certificate. Conditional logistic regression was used for the data analysis. Logistic regression was used in two additional unmatched analyses to examine the same exposure, military service, within different birth cohorts, again using pancreatic cancer cases with non-neoplastic and accidental death controls.^ Results. For pancreatic cancer cases matched to non-neoplastic controls, the association with military service showed an elevated odds ratio (OR) of 1.40 (95% confidence interval [CI] 1.10-1.79); matched to accidental death controls, a similar association with military service was detected [OR=1.40 (95% CI 1.04-1.89)]. The association was not seen in all time periods and was greatest for those within a birth cohort specific for Vietnam Era service. For men born between 1946 and 1950, OR=1.90 (95% CI 1.03-3.50) for comparison with non-neoplastic controls and OR=1.91 (95% CI 0.9995-3.64) for accidental death controls. ^ Conclusion. In Texas, for men aged 44-71, who died in 1998, military service was associated with an approximately 40% increased risk for pancreatic cancer. For men ages 48-52, military service was associated with an approximately 90% increased risk for pancreatic cancer.^

A comparison of techniques for forecasting utilization of Veterans Affairs hospitals

This study demonstrated that accurate, short-term forecasts of Veterans Affairs (VA) hospital utilization can be made using the Patient Treatment File (PTF), the inpatient discharge database of the VA. Accurate, short-term forecasts of two years or less can reduce required inventory levels, improve allocation of resources, and are essential for better financial management. These are all necessary achievements in an era of cost-containment.^ Six years of non-psychiatric discharge records were extracted from the PTF and used to calculate four indicators of VA hospital utilization: average length of stay, discharge rate, multi-stay rate (a measure of readmissions) and days of care provided. National and regional levels of these indicators were described and compared for fiscal year 1984 (FY84) to FY89 inclusive.^ Using the observed levels of utilization for the 48 months between FY84 and FY87, five techniques were used to forecast monthly levels of utilization for FY88 and FY89. Forecasts were compared to the observed levels of utilization for these years. Monthly forecasts were also produced for FY90 and FY91.^ Forecasts for days of care provided were not produced. Current inpatients with very long lengths of stay contribute a substantial amount of this indicator and it cannot be accurately calculated.^ During the six year period between FY84 and FY89, average length of stay declined substantially, nationally and regionally. The discharge rate was relatively stable, while the multi-stay rate increased slightly during this period. FY90 and FY91 forecasts show a continued decline in the average length of stay, while the discharge rate is forecast to decline slightly and the multi-stay rate is forecast to increase very slightly.^ Over a 24 month ahead period, all three indicators were forecast within a 10 percent average monthly error. The 12-month ahead forecast errors were slightly lower. Average length of stay was less easily forecast, while the multi-stay rate was the easiest indicator to forecast.^ No single technique performed significantly better as determined by the Mean Absolute Percent Error, a standard measure of error. However, Autoregressive Integrated Moving Average (ARIMA) models performed well overall and are recommended for short-term forecasting of VA hospital utilization. ^

THE RELATIONSHIP OF PRESCRIPTION RECEIPT AND EXPECTATION OF SICK-ROLE LEGITIMATION BY AMBULATORY VETERANS

This study explored the relationship of attitudes, needs, and health services utilization patterns of elderly veterans who were identified and categorized by their expectation for and receipt of sick-role legitimation. Three prescription types (new, change, renewal) were defined as the operational variables. A population of 676 ambulatory, chronically ill (average age 60 years) veterans were sent a questionnaire (74% response rate). In addition, retrospective medical and prescription record review was performed for a 45% sample of respondents. The results were analyzed using discriminant function and regression analysis. Fewer than 20% of the veterans responding expected to receive more prescriptions than were presently prescribed, whereas over 80% expected refill authorizations. Distinct attitudinal, need, and utilization patterns were identified. ^

Posttraumatic stress disorder among veterans of the Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) wars: Psychological comorbidities, postdeployment social support and unit support

Much attention has been given to treating Operation Iraqi Freedom/Operation Enduring (OIF/OEF) Veterans with posttraumatic stress disorder (PTSD). However, little attention is given to those Veterans who do not meet diagnostic criteria for PTSD but who may still benefit from intervention. Research is needed to investigate the impact of how different racial/ethnic backgrounds, different levels of social support and comorbid mental health disorders impact OIF/OEF Veterans with varying levels of PTSD. The purpose of this dissertation is to examine the association of comorbid Axis I disorders, race/ethnicity, different levels of postdeployment social support and unit support on OIF/OEF Veterans with varying levels of PTSD. Data for this dissertation were from postdeployment screenings of OIF/OEF Veterans from a large Veterans Affairs hospital in southeast Texas. To examine the study hypotheses, we conducted multinomial logistic regressions of the clinician reported data. ^ The first article examined the prevalence of subthreshold and full levels of PTSD and compared Axis I and alcohol use comorbidity rates among 1,362 OIF/OEF Veterans with varying levels of PTSD. Results suggest that OIF/OEF Veterans with subthreshold PTSD experience similar levels of psychological distress as those with full PTSD and highlight the need to provide timely and appropriate mental health services to individuals who may not meet the diagnostic criteria for full PTSD. ^ These results suggest that OIF/OEF Veterans of all race/ethnicities can benefit from strong social support systems. Postdeployment social support was found to be a protective factor against the development of PTSD among White, Black and Hispanic veterans while deployment unit support was a protective factor only among Black Veterans. The second article investigated the association between postdeployment social support and unit support with varying levels of PTSD by race/ethnicity among 1,115 OIF/OEF Veterans. ^ The results of this study can help to formulate treatment and interventions for OIF/OEF Veterans with varying levels of PTSD and social support systems.^

Prevalence and determinants of hepatitis B co-infection among a United States Veterans Administration cohort with hepatitis C

Background and aim. Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection is associated with increased risk of cirrhosis, decompensation, hepatocellular carcinoma, and death. Yet, there is sparse epidemiologic data on co-infection in the United States. Therefore, the aim of this study was to determine the prevalence and determinants of HBV co-infection in a large United States population of HCV patients. ^ Methods. The National Veterans Affairs HCV Clinical Case Registry was used to identify patients tested for HCV during 1997–2005. HCV exposure was defined as two positive HCV tests (antibody, RNA or genotype) or one positive test combined with an ICD-9 code for HCV. HCV infection was defined as only a positive HCV RNA or genotype. HBV exposure was defined as a positive test for hepatitis B core antibodies, hepatitis B surface antigen, HBV DNA, hepatitis Be antigen, or hepatitis Be antibody. HBV infection was defined as only a positive test for hepatitis B surface antigen, HBV DNA, or hepatitis Be antigen within one year before or after the HCV index date. The prevalence of exposure to HBV in patients with HCV exposure and the prevalence of HBV infection in patients with HCV infection were determined. Multivariable logistic regression was used to identify demographic and clinical determinants of co-infection. ^ Results. Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% CI 34.5–35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV co-infection for a prevalence of 1.4% (95% CI 1.3–1.5). The independent determinants for an increased risk of HBV co-infection were male sex, positive HIV status, a history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use. Age >50 years and Hispanic ethnicity were associated with a decreased risk of HBV co-infection. ^ Conclusions. This is the largest cohort study in the United States on the prevalence of HBV co-infection. Among veterans with HCV, exposure to HBV is common (∼35%), but HBV co-infection is relatively low (1.4%). There is an increased risk of co-infection with younger age, male sex, HIV, and drug use, with decreased risk in Hispanics.^

Treatment modalities of female Operation Iraqi Freedom/Operation Enduring Freedom Veterans with posttraumatic stress disorder: A systematic review of the literature

Objective. To review professional literature regarding treatment modalities of post-traumatic stress disorder (PTSD) amongst female Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans, to assess the efficacy of these treatment options, and to summarize implications of the findings from this literature. Design. Systematic review of published literature. Data sources. Medline, Pubmed, Psycinfo. Review Methods. Articles selected for the literature review pertain to the treatment options of female OIF or OEF veterans who have a diagnosis of PTSD. In addition, other relevant articles, such as articles that discuss the prevalence of the problem, access to care, and similar treatment modalities for PTSD in other war settings, were selected for background information for the review. Results. The search strategy identified 1,305 potential journal articles, taken from thorough searches in Medline, Pubmed, and Psycinfo. These articles were then imported into Refworks. Following final screening, there were 18 articles included in the systematic review and 28 articles used as background information. The remaining articles were excluded following screening of abstract and/or full text of articles. Treatment modalities presented in these trials include: Exposure Therapy (average of 68% reduction in PTSD symptoms), Imagery Rehearsal Therapy (23% reduction), Body-Oriented Therapy (57% reduction), Electroconvulsive Therapy (35% reduction), Holographic Reprocessing (47% reduction), a self-defense training program (13% reduction), Cognitive Behavioral Therapy (65% reduction) and a variety of pharmacotherapies (antipsychotics at 81% reduction, sympatholytic drug at 100% reduction). Outcomes of the studies included in this systematic review were measured by using personal assessment of whether there was a reduction in symptoms of PTSD, based on the results in each study. Conclusion. Overall, all of the treatment modalities investigated in the systematic review proved to be somewhat effective in relieving the burden of symptoms of PTSD amongst female veterans of OIF/OEF. In addition to pharmacotherapy, which had the highest reduction in PTSD symptoms, both the Exposure Therapy and the Cognitive Behavioral Therapy techniques proved to have the most positive results. As all of the therapies had a positive effect on this population, to some degree, a study needs to be done in the future to compare and contrast the efficacy of each therapy intervention when applied to a standardized population.^