Hypogonadism in male cancer patients: A cross-sectional study

Introduction. Cancer is the second most common cause of death in the USA (2). Studies have shown a coexistence of cancer and hypogonadism (9,31,13). The majority of patients with cancer develop cachexia, which cannot be solely explained by anorexia seen in these patients. Testosterone is a male sex hormone which is known to increase muscle mass and strength, maintain cancellous bone mass, and increase cortical bone mass, in addition to improving libido, sexual desire, and fantasy (14). If a high prevalence of hypogonadism is detected in male cancer patients, and a significant difference exists in testosterone levels in cancer patients with cachexia versus those without cachexia, testosterone may be administered in future randomized trials to help alleviate cachexia. Study group and design The study group consisted of male cancer patients and non-cancer controls aged between 40 and 70 years. The primary study design was cross-sectional with a sample size of 135. The present data analysis is done on a subset convenience sample of 72 patients recruited between November 2006 and January 2010. ^ Methods. Patients aged 40-70 years with or without a diagnosis of cancer were recruited into the study. All patients with a BMI over 35, significant edema, non-melanomatous skin cancer, current alcohol or illicit drug abuse, concomitant usage of medications interfering with gonadal axis, and anabolic agents, patients on tube feeds or parenteral nutrition within 3 months prior to enrollment were excluded from the study. The study was approved by the Institutional Review Board of Baylor College of Medicine and is being conducted at the Michael E. DeBakey Veterans Affairs Medical Center at Houston. My thesis is a pilot data analysis that employs a smaller subset convenience sample of 72 patients determined by using the data available for the 72 patients (of the intended sample of 135 patients) recruited between November 2006 and January 2010. The primary aim of this analysis is to compare the proportion of patients with hypogonadism in the male cancer and non-cancer control groups, and to evaluate if a significant difference exists with respect to testosterone levels in male cancer patients with cachexia versus those without cachexia. The procedures of the study relevant to the current data analysis included blood collection to measure levels of testosterone and measurement of body weight to categorize cancer patients into cancer cachexia and cancer non-cachexia sub-groups. ^ Results. After logarithmic transformation of data of cancer and control groups, the unpaired t test with unequal variances was done. The proportion of patients with hypogonadism in the male cancer and non-cancer control groups was 47.5% and 22.7% with a Pearson chi2 statistic of 1.6036 and a p value of 0.205. Comparing the mean calculated Bioavailable testosterone in male cancer patients and non-cancer controls resulted in a t statistic of 21.83 and a p value less than 0.001. When the cancer group alone was taken, the mean free testosterone, calculated bioavailable testosterone and total testosterone levels in the cancer non-cachexia sub-group were 3.93, 5.09, 103.51 respectively and in the cancer cachexia sub-group were 3.58, 4.17, 84.08 respectively. The unpaired t test with equal variances showed that the two sub-groups had p values of 0.2015, 0.1842, and 0.4894 with respect to calculated bioavailable testosterone, free testosterone, and total testosterone respectively. ^ Conclusions. The small sample size of this exploratory study, resulting in a small power, does not allow us to draw definitive conclusions. For the given sub-sample, the proportion of patients with hypogonadism in the cancer group was not significantly different from that of patients with hypogonadism in the control group. Inferences on prevalence of hypogonadism in male cancer patients could not be made in this paper as the sub-sample is small and therefore not representative of the general population. However, there was a statistically significant difference in calculated Bioavailable testosterone levels in male cancer patients versus non-cancer controls. Analysis of cachectic and non-cachectic patients within the male cancer group showed no significant difference in testosterone levels (total, free, and calculated bioavailable testosterone) between both sub-groups. However, to re-iterate, this study is exploratory and the results may change once the complete dataset is obtained and analyzed. It however serves as a good template to guide further research and analysis.^

Family health history discussion in patient-provider encounters

Ascertaining the family health history (FHH) may provide insight into genetic and environmental susceptibilities specific to a variety of chronic diseases, including type II diabetes mellitus. However, discussion of FHH during patient-provider encounters has been limited and uncharacterized. A longitudinal, observational study was conducted in order to compare the content of FHH topics in a convenience sample of 37 patients, 13 new and 24 established. Each patient had an average of three follow-up encounters involving 6 staff physicians at the Audie L. Murphy Memorial Veterans Hospital (VHA) in San Antonio, TX from 2003 to 2005. A total of 131 encounters were analyzed in this study. The average age of the selected population was 68 years and included 35 males and two females. Transcriptions of encounters were obtained, coded and analyzed, in NVIVO 8. Of the 131 total encounters transcribed among the 37 patients, only 24 encounters (18.3%) included discussion of FHH. Additionally, the relationship between FHH discussion and discussion of self-care management (SCM) topics were assessed. In this study, providers were more likely to initiate discussion on family health history among new patients in the first encounter (ORnew = 8.55, 95% CI: 1.49–52.90). The discussion of FHH occurred sporadically in established patients throughout the longitudinal study with no apparent pattern. Provider-initiated FHH discussion most frequently had satisfactory level(s) of discussion while patient-initiated FHH discussion most frequently had minimal level(s) of discussion. FHH discussion most oftentimes involved topics of cancer and cardiovascular disease among primary-degree familial relationships. Overall, family health histories are largely, an underutilized tool in personalized preventive care.^

Role of {\it Mycobacterium avium-intracellulare\/} complex infection in AIDS mortality

Disseminated MAC (dMAC) is the third most prevalent opportunistic infection in AIDS patients. In order to understand the role MAC infection plays in affecting survival of AIDS patients, a cohort of 203 suspected dMAC veterans seen at the Houston Veterans Affairs Medical Center between August 14, 1987 and December 31, 1991 were analyzed. The criteria for suspected dMAC infection was HIV+ men having a CD4+ level $\le$200 cells/mm$\sp3,$ on zidovudine treatment $\ge$1 month and who had any of the following: (a) a confirmed respiratory MAC infection, (b) fever $\ge$101$\sp\circ\rm F$ for $\ge$48 hours, (c) unexplained weight loss of 10 lbs or $\ge$10% BW over 3 months or (d) Hgb $\le$7.5 g/dl or decrease in Hgb $\ge$3.0 g/dl, while on 500-600 mg/day AZT. The study was conducted before the commencement of an effective MAC anti-mycobacterial therapy, so the true course of MAC infection was seen without the confounder of a therapeutic regimen. Kaplan-Meier and Cox regression survival analysis was used to compare 45 MAC culture positive and 118 MAC culture negative veterans. The 1 year survival rate of veterans with documented dMAC infection was 0.37 compared to 0.50 for veterans not acquiring dMAC infection. Significant differences between subgroups were also seen with the variables: PCP prophylaxis, the AIDS indicator disease Candida esophagitis, CD4+ lymphocyte level, CD4 percent lymphocyte level, WBC level, Hgb and Hct levels. Using multivariate modeling, it was determined that PCP prophylaxis (RR = 6.12, CI 2.24-16.68) was a predictor of survival and both CD4% lymphocytes $\le$6.0% (RR = 0.33, CI 0.17-0.68) and WBC level $\le$3000 cells/mm$\sp3$ (RR = 0.60, CI 0.39-0.93) were predictors of mortality. CD4+ level $\le$50 cells/mm$\sp3$ was not a significant predictor of mortality. Although MAC culture status was a significant predictor of mortality in the univariate model, a positive dMAC culture was not a significant predictor of AIDS mortality in the multivariate model. A positive dMAC culture, however, did affect mortality in a stratified analysis when baseline laboratory values were: CD8+ lymphocytes $>$600 cells/mm$\sp3,$ Hgb $>$11.0 g/dl, Hct $>$31.0% and WBC level $>$3000 cells/mm$\sp3.$ ^

The association between CD4+ lymphocyte count and measures of body composition in HIV-infected men

Purpose. This project was designed to describe the association between wasting and CD4 cell counts in HIV-infected men in order to better understand the role of wasting in progression of HIV infection.^ Methods. Baseline and prevalence data were collected from a cross-sectional survey of 278 HIV-infected men seen at the Houston Veterans Affairs Medical Center Special Medicine Clinic, from June 1, 1991 to January 1, 1994. A follow-up study was conducted among those at risk, to investigate the incidence of wasting and the association between wasting and low CD4 cell counts. Wasting was described by four methods. Z-scores for age-, sex-, and height-adjusted weight; sex-, and age-adjusted mid-arm muscle circumference (MAMC); and fat-free mass; and the ratio of extra-cellular mass (ECM) to body-cell mass (BCM) $>$ 1.20. FFM, ECM, and BCM were estimated from bioelectrical impedance analysis. MAMC was calculated from triceps skinfold and mid-arm circumference. The relationship between wasting and covariates was examined with logistic regression in the cross-sectional study, and with Poisson regression in the follow-up study. The association between death and wasting was examined with Cox's regression.^ Results. The prevalence of wasting ranged from 5% (weight and ECM:BCM) to almost 14% (MAMC and FFM) among the 278 men examined. The odds of wasting, associated with baseline CD4 cell count $<$200, was significant for each method but weight, and ranged from 4.6 to 12.7. Use of antiviral therapy was significantly protective of MAMC, FFM and ECM:BCM (OR $\approx$ 0.2), whereas the need for antibacterial therapy was a risk (OR 3.1, 95% CI 1.1-8.7). The average incidence of wasting ranged from 4 to 16 per 100 person-years among the approximately 145 men followed for 160 person-years. Low CD4 cell count seemed to increase the risk of wasting, but statistical significance was not reached. The effect of the small sample size on the power to detect a significant association should be considered. Wasting, by MAMC and FFM, was significantly associated with death, after adjusting for baseline serum albumin concentration and CD4 cell count.^ Conclusions. Wasting by MAMC and FFM were strongly associated with baseline CD4 cell counts in both the prevalence and incidence study and strong predictors of death. Of the two methods, MAMC is convenient, has available reference population data, may be the most appropriate for assessing the nutritional status of HIV-infected men. ^

Potential role of statins as immunomodulators in pneumococcal pneumonia

Background: Mortality in pneumococcal pneumonia remains as high as 20%, and most deaths occur within the first two weeks of hospitalization despite eradication of the causative organisms by antimicrobials in the first 24 hours. An inflammatory response rather than active infection could be responsible for this early mortality. Statins have been shown to have potent immunomodulatory activity in vitro. We investigated whether there was decreased severity or improved outcome in patients who were receiving statins at the time they were admitted for pneumococcal pneumonia. ^ Methods: Patients seen at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas from January, 2000 to June, 2010 with a diagnosis of pneumococcal pneumonia were included in this retrospective cohort study. Electronic medical records were reviewed to record demographic characteristics, comorbidities, laboratory values and statin use at the time of admission. Severity of pneumonia was determined using the Pneumonia Outcomes Research Team (PORT) classification. Uni- and multivariate Cox regression was used to evaluate survival. We adjusted for all variables in the multivariate model if they were significant in the univariate model at p<0.05. ^ Results: Of 347 patients admitted for pneumococcal pneumonia, 90 (25.9%) were taking statins at the time of presentation. Patients in the statin group were older (age: 68.0±9.7 vs. 62.5±12.3 years, p<0.001) and had higher prevalence of diabetes, coronary artery disease and kidney disease (p<0.05 for each comparison). Liver disease and alcohol consumption were less prevalent among statin users (p<0.05). The PORT scores were normally distributed in both groups with statin users having higher mean scores at admission as compared to patients not on statins (108±32 vs. 96±32, p = 0.002). The Cox proportional hazard analyses, adjusted for age, comorbidities, length of stay and PORT scores, showed a significantly reduced risk of mortality among statin users at 14 days (HR: 0.39; 0.15-0.98, p=0.045), 20 days (0.35; 0.14- 0.88, p=0.03) and 30 days(0.41; 0.17-0.95, p=0.01) after presentation. ^ Conclusion: Statin use is associated with improved clinical outcomes in patients with pneumococcal pneumonia.^

The role and impact of transitional care utilization in colorectal cancer

BACKGROUND Although one out of every five gastrointestinal cancer patients needs transitional care (home-based skilled care or placement in skilled nursing or rehabilitation facilities) following treatment, few studies have examined outcomes in this population compared to patients who return home without assistance. This study has two primary goals: 1. To evaluate long-term cancer-specific outcomes in colorectal cancer patients utilizing transitional care compared to those that return home without assistance following therapy 2. To compare results using standard regression techniques and propensity scores. ^ METHODS Patients undergoing curative surgery for colorectal adenocarcinoma will be identified using data from a tertiary care Veterans Administration hospital. Survival and recurrence will then be determined from VA records and the Social Security Death Index. ^ The association between transitional care utilization and overall and disease-free survival will be evaluated using Cox proportional hazards regression to adjust for confounding factors. Predictors of transitional care utilization will be assessed using multiple logistic regression to generate a propensity score which will also be used to assess differences in survival based on transitional care use. ^ POTENTIAL SIGNIFICANCE If transitional care utilization is associated with worse survival and recurrence following therapy then it will be important to subsequently assess the mechanism in order to target interventions to improve outcomes. If there is no difference in cancer-specific outcomes, then this project can potentially highlight benefits of supportive therapy following colorectal cancer resection.^

Association of ALLHAT investigator characteristics with participant recruitment

Clinical trials are often not successful because of the inability to recruit a sufficient number of patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest antihypertensive trial ever conducted, provided highly generalized results and successful recruitment of over 42,000 participants. The overall purpose of this study was to examine the association of investigator characteristics with anti-hypertensive (AHT) participant recruitment in ALLHAT. This secondary data analyses collected data from the ALLHAT investigator profile survey and related investigator characteristics to recruitment success. The sample size was 502 investigators, with recruitment data from 37,947AHT participants. Recruitment was dichotomized by categorizing all sites with recruitment numbers at or above the overall median recruitment number of 46 as "Successful Recruitment". Frequency distributions and univariate and multivariate logistic regression were conducted. When adjusting for all other factors, Hispanic ethnicity, suburban setting, Department of Veterans Affairs Medical Centers (VAMC) site type, number of clinical site staff working on the trial, study coordinator hours per week, medical conference sessions attended, the investigator's primary goal and the likelihood that a physician will convince a patient to continue on randomized treatment, have significant impacts on the recruitment success of ALLHAT investigators. Most of the ALLHAT investigators described their primary commitment as being towards their patients and not to scientific knowledge alone. However, investigators that distinguished themselves as leaders in research had greater recruitment success than investigators who were leaders in clinical practice. ALLHAT was a highly successful trial that proved that community based cardiovascular trials can be implemented on a large scale. Exploring characteristics of ALLHAT investigators provides data that can be generalized to sponsors, sites, and others interested in maximizing clinical trial recruitment numbers. Future studies should further evaluate investigator and study coordinator factors that impact cardiovascular clinical trial recruitment success.^

Culminating experience: Initiation of cholinesterase inhibitors in an inpatient setting

We examined the practice of initiating Cholinesterase Inhibitors (ChEI) in a Veterans Affairs Medical Center. Patients hospitalized in FY 2008 and prescribed ChEI were identified. We reviewed electronic medical records, comparing those started on ChEI during hospitalization with those continuing ChEI from outpatient status. Of 282 patients receiving ChEI during hospitalization, 15.6% (44) were new-starts and 84.3% (238) were continuing medication. Median length of stay was 16 days in new-starts vs. 6 days in continuation patients (P<0.05). 38.6% new-starts were also treated for infection, which is a delirium risk factor. Chart review also suggested possible treatment for delirium by initiation of benzodiazepines and antipsychotics in 11.4% and 22.7% new-starts respectively. We observed a substantive practice of initiating ChEIs in hospitalized elderly who were at risk of delirium. Though there was no difference in 30-day mortality and readmission rates, new-starts were more likely to have a prolonged hospital stay than continuation patients.^

Characterization of a Leishmania tropica antigen that detects immune responses in Desert Storm viscerotropic leishmaniasis patients.

A chronic debilitating parasitic infection, viscerotropic leishmaniasis (VTL), has been described in Operation Desert Storm veterans. Diagnosis of this disease, caused by Leishmania tropica, has been difficult due to low or absent specific immune responses in traditional assays. We report the cloning and characterization of two genomic fragments encoding portions of a single 210-kDa L. tropica protein useful for the diagnosis of VTL in U.S. military personnel. The recombinant proteins encoded by these fragments, recombinant (r) Lt-1 and rLt-2, contain a 33-amino acid repeat that reacts with sera from Desert Storm VTL patients and with sera from L. tropica-infected patients with cutaneous leishmaniasis. Antibody reactivities to rLt-1 indicated a bias toward IgG2 in VTL patient sera. Peripheral blood mononuclear cells from VTL patients produced interferon gamma, but not interleukin 4 or 10, in response to rLt-1. No cytokine production was observed in response to parasite lysate. The results indicate that specific leishmanial antigens may be used to detect immune responses in VTL patients with chronic infections.

The Experiences of American Indian Women Warriors

This article examines the unique experiences of American Indian (AI) female veterans through a generalized qualitative study. Revealed in this study were interesting cultural insights regarding a concentrated, yet largely misunderstood, population within the U.S. military. For this study, six participants were interviewed and data were analyzed to identify common experiences of AI female veterans. The analyses revealed unique roles assumed during military service, a strengthening of cultural values, identity development, and personal empowerment as a result of AI women having served in the military. Discussion, implications, and limitations of this study are also described.

Back in Blue: The Successful Reintegration of Combat Veteran Law Enforcement Officers.

In the past ten plus years, several million national guard and reserve component military personnel have been deployed in support of the global war on terrorism. Tens of thousands of those personnel also serve as full-time law enforcement officers in police and sheriff's offices around the country. Life as a law enforcement officer is tough enough, but when combined with the psychological baggage brought on by months of war, reintegrating into civilian life and the role of a law enforcement officer can be extremely difficult. This article discusses a reintegration program specifically for law enforcement agencies that is designed to promote long-term psychological and social health in combat veteran officers. The program's costs are offset by the many assets (leadership, tactical training, etc.) these men and women bring to the department. By committing to the long-term successful reintegration of these individuals, departments enhance their own forces and improve community safety.

I'm Not Who I Thought I Was: A Contextual Resolution to the Identity Loss of Combat PTSD.

Given the historical rates of combat post-traumatic stress disorder (PTSD), one can expect 30% of soldiers returning from current military conflicts to suffer from PTSD. For these individuals, various cognitive behavioral therapies (CBT) are the most commonly employed treatments. Unfortunately, however, symptom relapse can be expected with the various CBT approaches, as traumatic memories remain. Soldiers are imbued with a militarized identity, and the identity loss experienced by those soldiers who suffer from PTSD is particularly painful for this population, as the militarized identity effectively disavows personal suffering. For this reason, many combat veterans diagnosed with post-traumatic stress disorder experience undue, prolonged suffering as they struggle to make sense of the different person they fear they have become. This paper contrasts certain versions of Western philosophy, which view the self as a fixed and reified entity with certain versions of Eastern philosophy, which view the self as more contextual and fluid, in order to illuminate the value of employing third wave behavioral treatments, specifically Acceptance and Commitment Therapy (ACT), to treat the identity loss experienced by military veterans with PTSD. ACT echoes the Buddhist principle that attachment to verbally-constructed conceptual notions of self contribute to undue suffering, and that more vital living can be achieved by assuming a more contextual and experiential perspective on identity. Research and anecdotal accounts are cited to illustrate why treatment for identity loss associated with combat PTSD should be less focused on reconstructing a historically substance-oriented self and more focused on an epistemological reorientation to a deconstructed, contextual self.

On the Edge of the World: Trauma and Twinship Selfobject Needs in Mrs. Dalloway

Alienation and aloneness appear as common themes in the experience of those impacted by trauma. Self psychology theorists, including contemporary proponents of intersubjectivity theory, have also discussed the ways in which alienation and disconnection from others permeate the experience of post-traumatic stress disorder. This discussion has highlighted the importance and centrality of twinship selfobject needs in providing a relational home for the emotional pain associated with trauma. These phenomena are especially apparent when one encounters the experiences of those combat veterans who have attempted to readjust to society upon returning home from military service. Using self psychology and intersubjectivity theory, this paper explores the ways that fiction, specifically Virginia Woolf's Mrs. Dalloway, can illuminate the ways that trauma negatively impacts twinship selfobject needs in combat veterans. In examining the character of Septimus Smith, this paper illustrates the estrangement, singularity, and alienation associated with post-traumatic stress, and how this state of being can collude with societal misunderstanding and repression to shatter the self's sense of belongingness with and connection to others.

Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse

Purpose. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. Methods. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. Results. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. Conclusions. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

Operational Stress Injuries: Impact on Family Mental Health and Well-being

This study was part of a larger scoping review and environmental scan conducted for Veterans Affairs Canada on the effects of operational stress injuries (OSIs) on the mental health and wellbeing of Veterans’ families. This paper focuses broadly on the relationships between combat (and/or deployment more generally), OSIs (primarily post-traumatic stress disorder (PTSD)), and the family. Based on the scoping review, the paper finds that existing research investigates the impacts of a Veteran’s OSI on the family, but also how various aspects of the family (such as family functioning, family support, etc.) can impact a Veteran living with an OSI.