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Moral injury is a complex phenomenon characterized by spiritual, psychological, and moral distress caused by actions or acts of omission inconsistent with an individual’s moral and ethical values. We present two cases from an ongoing randomized controlled trial of a spiritually integrated structured intervention delivered by chaplains for individuals suffering from moral injury. Chaplains met with Veterans for twelve 50-min sessions that each focused on a specific domain of moral injury. Participants were asked to complete validated scales assessing symptoms of moral injury and PTSD, including the PTSD Checklist for DSM-5 (PCL-5), Moral Injury Symptom Scale-Military Version Short Form, and Moral Injury Symptom Scale-Military Version Long Form. We report on two Veterans who completed the intervention and demonstrated significant improvement in moral injury and PTSD symptoms.

Gout is one of the most common and complex causes of arthritis that can affect anyone.1,2 It is one of the most ancient medical conditions known going back to references in Egypt in 2640 BC and Hippocrates writing about it in 400 BC.3–5 Gout occurs when there are deposits of urate monosodium crystals in the synovial fluid and other tissues causing the inflammation and intense pain of a gout attack. Urate monosodium crystals usually are associated with long-term hyperuricemia that is triggered by several genetic factors as well as environmental factors such as the overconsumption of rich purine diets, alcohol, obesity, obesity-related disease, kidney disease, and certain medications.1,6–13 Risk factors for older patients include low-dose aspirin, alcohol abuse, decreased renal function, and prolonged use of diuretics.14,15 Advanced gout, also known as gouty tophi, are large, visible (masses) made up of urate crystals.5,16,17 The tophus is a cardinal sign and usually develops after 5–10 years of chronic undertreated gout with the olecranon bursa being one of the most affected areas.5,16,17 Formation is caused by elevated serum uric acid levels due to neglected and poorly controlled gout.18,19 Gouty tophi can develop anywhere. It can develop in peri-articular soft tissues, sub-articular regions around bones, tendon sheaths, bursas, articular cartilage, and synovial tissues around flexor tendons.17,20 Gouty tophi have been identified in vocal cords, myocardium, heart valves, eyes, spinal cord, pancreatic tail, breast, penis, with a propensity to affect the helix of the ear.17,21,22 However, patients with multiple gouty tophi rarely are encountered because hyperuricemia can be treated effectively. The differential diagnosis of gouty tophi is broad, even though gout can be diagnosed clinically by elevated serum uric acid level; however, the concentration of serum uric acid may be within the normal limits and yet gouty tophi still can be developed.23–25 This case was a patient who developed multiple gouty tophi over an extended period of time with increasing size of the masses while on medical treatment for his gout. The one mass of unique interest developed over the superficial anterior tibia just distal to the tibial tubercle and not in the patellar tendon, which is uncommon.

Objective: We investigated two hypotheses: First, incident CHD, defined as myocardial infarction or definite angina, leads to faster long-term cognitive decline. Second, among those with CHD, treatment with CABG surgery or PCI leads to slower long-term cognitive decline. Methods: The Cardiovascular Health Study is a cohort of US adults aged 65+. Global cognitive ability was assessed annually up to 9 times from 1990 to 1998 with the 100-point Modified Mini-Mental State Examination (3MS). We estimated trajectories of 3MS scores in the absence of stroke, adjusting for demographics, health behaviors, and comorbidities. For hypothesis 1, we compared 3MS trajectory after incident CHD with 3MS trajectory in the absence of CHD, censoring at first receipt of CABG/PCI. For hypothesis 2, among participants with CHD, we compared 3MS trajectory after first receipt of CABG/PCI with 3MS trajectory without CABG/PCI. Results: For hypothesis 1, of 4,122 participants, 398 had incident CHD during a mean of 5.9 years of follow-up. Figure Panel A shows model-predicted mean 3MS trajectories without CHD (blue) and after incident CHD (red) diagnosed at ages 70, 75, 80, or 85. Model-predicted 3MS score declined faster after incident CHD, especially for CHD diagnosed at age 80 or later. For example, after incident CHD at age 85, predicted 5-year decline in mean 3MS score through age 90 was 13.9 points (95% CI: 11.0, 16.7) versus 8.9 points (95% CI: 8.1, 9.7) among those without CHD. For hypothesis 2, of 1,183 participants who had prevalent or incident CHD, 118 had their first CABG/PCI during a mean of 4.1 years of follow-up. Model-predicted 3MS score declined faster after first receipt of CABG/PCI ( Figure Panel B ). Conclusions: Older adults diagnosed with incident CHD had faster average cognitive decline than those without CHD. However, treatment with CABG/PCI did not slow cognitive decline among those with CHD. This finding may be due to adverse effects of CABG/PCI on brain health or CABG/PCI recipients having more severe CHD or more cerebral atherosclerosis.

Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex.

Clinical Scenario:Eating disorders in female athletes are a commonly underdiagnosed condition. Better screening tools for eating disorders in athletic females could help increase diagnosis and help athletes get the treatment they need.Focused Clinical Question:Should screening tools be used to detect eating disorders in female athletes?Summary of Key Findings:The literature was searched for studies that included information regarding the sensitivity and specificity of screening tools for eating disorders in female athletes. The search returned 5 possible articles related to the clinical question; 3 studies met the inclusion criteria (2 cross-sectional studies, 1 cohort study) and were included. All 3 studies reported sensitivity and specificity for the Athletic Milieu Direct Questionnaire version 2, the Brief Eating Disorder in Athletes Questionnaire version 2, and the Physiologic Screening Test to Detect Eating Disorders Among Female Athletes. All 3 studies found that the respective screening tool was able to accurately identify female athletes with eating disorders; however, the screening tools varied in sensitivity and specificity values.Clinical Bottom Line:There is strong evidence to support the use of screening tools to detect eating disorders in female athletes. Screening tools with higher sensitivity and specificity have demonstrated a successful outcome of determining athletes with eating disorders or at risk for developing an eating disorder.Strength of Recommendation:There is grade A evidence available to demonstrate that screening tools accurately detect female athletes at risk for eating disorders.

Using a sample of 256 juvenile offenders who were randomly assigned to treatment or control groups, this study evaluates a cognitive-behavioral program that combines cognitive training, goal setting, and a phone-coach follow-up. The training involved six classroom sessions where participants received instruction and help in creating individualized goals. After attending the classes, participants received automated phone calls twice a day for up to a year. During the year following the program, the treatment and control groups were not significantly different in whether or not they were rearrested or in total rearrests. However, the total number of calls received had a significant negative association with whether or not they were rearrested for a felony and with the total number of felony rearrests.

OBJECTIVE To demonstrate the effectiveness of a Diabetes Prevention Program-inspired 12-month behavioral intervention for patients with severe mental illness (SMI) and medication-associated obesity. METHOD This randomized, controlled, parallel, superiority study screened 225 volunteers from November 2005 to August 2008 at the VA Greater Los Angeles Healthcare System. 122 outpatients with DSM-IV-diagnosed SMI taking antipsychotic medications who had ≥ 7% weight gain or body mass index (BMI) > 25 were randomized by computer-generated number to Lifestyle Balance treatment intervention (n = 60) or usual care control (n = 62) groups. Clinical raters were masked to randomization. Treatment intervention included weekly classes and individual counseling for 8 weeks, food and exercise diaries, rewards, caregiver consultations, and monthly booster classes and counseling for 1 year. Controls received self-help materials and visited at equivalent intervals without formal classes or counseling. Outcomes were changes in anthropometric measurements, psychiatric symptoms, health knowledge, and glucose, hemoglobin A1c, and lipid levels. RESULTS Our intention-to-treat analysis found significant differences in predicted trajectory of mean weight change between the groups over 12 months (P < .01), with treatment participants expected to lose an average 4.6 kg, while control participants would gain an average 0.6 kg. BMI and body fat percentage followed the same pattern. Both groups demonstrated statistically significant improvements in health knowledge quiz scores over time (P = .006), without significant difference between groups. CONCLUSIONS Treatment was more effective than usual care control in treating medication-associated obesity, independent of SMI diagnosis, antipsychotic medication, and knowledge gained, suggesting that behavioral interventions are effective in SMI patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00344500.

Caused by the parasitic nematodes Toxocara canis and cati, toxocariasis in humans can result in covert toxocariasis, ocular toxocariasis, visceral larval migrans, and neurotoxocariasis. A common infection, toxocariasis exposure varies widely within and between countries, with a previous estimate of Toxocara seroprevalence using data from 1988 to 1994 in the United States of approximately 13%. Age, poverty, sex, educational attainment, ethnicity, and region have been associated with Toxocara seroprevalence. In this study, we sought to determine the seroprevalence of and factors associated with Toxocara seropositivity in the United States using data from the National Health and Nutrition Examination Survey from 2011 to 2014 to provide a more recent estimate of Toxocara seroprevalence in the United States. We found an overall Toxocara seroprevalence of 5.1%. Increasing age, male sex, low educational attainment, low income, and immigration status each was associated with Toxocara seropositivity. Mexican Americans had reduced odds of exposure. These findings show that exposure to Toxocara continues in the United States and that several demographic factors influence the risk of exposure.

Veterans with mental illness tend to have shorter life spans and suboptimal physical health because of a variety of factors. These factors include poor nutrition, being overweight, and smoking cigarettes. Nonphysical contributors that may affect quality of life are the stigma associated with mental illness, social difficulties, and spiritual crises. Current mental health treatment focuses primarily on the delivery of medication and evidence-based psychotherapies, which may not affect all the above areas of a Veteran's life as they focus primarily on improving psychological symptoms. Clinicians may find greater success using integrative, comprehensive, multifaceted programs to treat these problems spanning the biological, psychological, social, and spiritual domains. These pilot studies test an adjunctive, holistic, behavioral approach to treat mental illness. This pilot work explores the hypotheses that engagement in a greater number of therapeutic lifestyle changes (TLCs) leads to improvement in quality of life, reduction of psychiatric symptoms, and weight loss.Institutional Review Boards for human subjects at the Veterans Affairs (VA) Greater Los Angeles and Long Beach Healthcare Systems approved pilot study activities at their sites. Pilot Study 1 was a prospective survey study of Veterans with mental illness, who gained weight on an atypical antipsychotic medication regimen, participating in a weight management study. At each session of the 1-year study, researchers asked a convenience sample of 55 Veterans in the treatment arm whether they engaged in each of the eight TLCs: exercise, nutrition/diet, stress management and relaxation, time in nature, relationships, service to others, religious or spiritual involvement, and recreation. Pilot Study 2 applied the TLC behavioral intervention and examined 19 Veterans with mental illness, who attended four classes about TLCs, received individual counseling over 9 weeks, and maintained journals to track TLC practice. Besides weekly journals, researchers also collected prospective data on quality of life, psychiatric symptoms, vitals, and anthropometric measurements. In both studies, investigators tested for main effects of the total number of TLCs practiced and study week using mixed-effects linear models with independent intercepts by participant.In Study 1, engagement in more TLC behaviors was significantly associated with higher ratings of quality of life, as well as greater weight loss for each additional type of TLC practiced. In Study 2, TLC practice increased significantly over 9 weeks, and was significantly associated with improvements in quality of life and diastolic blood pressure.Counseling Veterans to practice TLCs provides a holistic adjunct to current treatments for mental illness. TLCs may confer multiple benefits upon Veterans with mental illness, enhancing quality of life and well-being along with weight management efforts. As these were pilot studies, the samples sizes were relatively small and a control group was lacking. Our findings may have broader implications supporting a holistic approach in both primary and mental health care settings. Future research will expand this work to address its weaknesses and examine the cost differential between this holistic approach and traditional mental health treatment.

The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.

Weight gain and other metabolic sequelae of antipsychotic medications can lead to medication non-adherence, reduced quality of life, increased costs, and premature mortality. Of the approaches to address this, behavioral interventions are less invasive, cost less, and can result in sustained long-term benefits. We investigated behavioral weight management interventions for veterans with mental illness across four medical centers within the Veterans Affairs (VA) Healthcare System. We conducted a 12-month, multi-site extension of our previous randomized, controlled study, comparing treatment and control groups. Veterans (and some non-veteran women) diagnosed with mental illness, overweight (defined as having a BMI over 25), and required ongoing antipsychotic therapy. One group received “Lifestyle Balance” (LB; modified from the Diabetes Prevention Program) consisting of classes and individual nutritional counseling with a dietitian. A second group received less intensive “Usual Care” (UC) consisting of weight monitoring and provision of self-help. Participants completed anthropometric and nutrition assessments weekly for 8 weeks, then monthly. Psychiatric, behavioral, and physical assessments were conducted at baseline and months 2, 6, and 12. Metabolic and lipid laboratory tests were performed quarterly. Participants in both groups lost weight. LB participants had a greater decrease in average waist circumference [F(1,1244) = 11.9, p

Background: Second-generation antipsychotic medications have proven effective for individuals with serious mental illness (SMI) but may cause weight gain and other metabolic sequelae. Investigators designed and assessed a 12-month behavioral intervention for overweight/obese patients with SMI called “Lifestyle Balance” (LB), based on the Diabetes Prevention Program (DPP), which was tested at 4 VA sites.

Background: The delivery of mental health care is shifting to one that is patient-centered and recovery-oriented, with the goal of increasing quality of life. These pilot studies test an adjunctive, holistic, behavioral approach to treating serious mental illness (SMI) and medication-associated weight gain; investigators hypothesized that engagement in a greater number of therapeutic lifestyle changes (TLCs) leads to improvement in quality of life, reduction of psychiatric symptoms, and weight loss.

BackgroundInfectious diseases might affect cognitive aging and dementia risk, possibly via neuroinflammation. Similarly, risk factors for cardiovascular and cerebrovascular diseases are associated with cognitive function and dementia. We hypothesized that cardiovascular risk factors moderate the association of exposure to infectious diseases with cognitive function.MethodsWe studied 5662 participants aged 20 to 59 years from the third National Health and Nutrition Examination Survey (1988-1994) in the United States. We used linear regression to investigate whether the Framingham general cardiovascular risk index moderated the association of infection burden based on exposure to eight different infectious diseases with cognitive functioning as measured by the Symbol Digit Substitution, Serial Digit Learning, and Reaction Time tests.ResultsThe multiplicative interaction between the infection-burden index and the cardiovascular-risk index was associated with performance on the Symbol Digit Substitution (B = .019 [95% CI: .008, .031], p < .001) but not on the Serial Digit Learning (B = .034 [95% CI: -.025, .094]) or for Reaction Time (B = -.030 [95% CI: -.848, .787]). Participants with a lower cardiovascular risk appeared to be more resilient against the potential adverse effects of higher infection burden on the Symbol Digit Substitution task.ConclusionsParticipants at zero risk for a cardiovascular event in the next 10 years had no differences in processing speed with increasing exposure to infectious disease, whereas participants with higher risk for a cardiovascular event had worse processing speed with increased exposure to infectious disease.

Purpose Posttraumatic stress disorder (PTSD) is an important clinical problem, but little is known about PTSD in rural, nonclinical populations. To better understand PTSD in rural areas, we examined the prevalence and risk and protective factors in urban, rural, and highly rural communities in Montana for both subclinical posttraumatic stress symptoms (PTSS) and PTSD. Methods We compared the prevalence of PTSS and PTSD in urban, rural, and highly rural communities in bivariate and multivariable regression analyses using self-reported cross-sectional survey data from the Montana Health Matters study (N = 3,512), a state-representative household-based survey done in 2010-2011. We also explore potential risk and protective factors for PTSS and PTSD and whether risk and protective factors for each differ by rurality. Findings There were no differences in the level of PTSS by rurality in bivariate or multivariate models, and the bivariate relationship between rurality and PTSD became nonsignificant in a multivariate model. Only locus of control was predictive for PTSS; however, gender, age, marital status, income, employment status, community fit, locus of control, and religiosity were associated with PTSD. Some risk and protective factors operate differently by rurality. Conclusions Although our findings are subject to weaknesses common to cross-sectional data and are based on questionnaire reports, it appears that there are different risk and protective factors for PTSS and PTSD, suggesting that PTSD may be qualitatively different from PTSS. Furthermore, differences in risk and protective factors across urban and rural communities suggest more attention is needed to understand PTSD in rural communities.

Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.

Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplasma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G antibody (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999-2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81-1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96-1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85-1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98-1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4+ T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

The aim of this study was to determine how laser in situkeratomileusis (LASIK) affects quality of life (QOL) and to identify factors that may affect satisfaction after LASIK. A total of 104 patients with a mean age of 29±6, treated with LASIK for myopia and astigmatism, were enrolled in a prospective study. High (90%) and low (10%) contrast visual acuity (CVA) were measured under photopic and scotopic conditions before surgery and at 3 months later. A multidimensional QOL scale (Institute for Eye Research multidimensional QOL scale), which assesses psychological characteristics, personality traits, cosmesis, frequency, and tolerance to disturbing visual and ocular symptoms, and overall satisfaction with vision correction, was also used. Paired rank tests were used to compare preoperative and postoperative vision and QOL scores. Correlations and a multiple linear regression were used to describe the relationship between CVA, QOL, and satisfaction after LASIK. Significant postoperative changes included increased satisfaction following LASIK (P

To assess pre-operative visual function, psychological factors, personality traits and satisfaction in myopic patients seeking laser-assisted in situkeratomileusis (LASIK). Eligible patients seeking LASIK (n=183) and successful contact lens wearers (n=23) not interested in LASIK completed the Institute for Eye Research Quality of Life (QOL) Scale. Of the 183 patients seeking LASIK who completed the QOL instrument before LASIK, 30 declined the procedure and 153 underwent LASIK. One hundred and two patients who underwent LASIK attended their 3-month post-operative follow-up appointment and 51 patients failed to present for their post-operative follow-up appointment. Multiple comparisons (One-way Analysis of Variance (ANOVA)) were conducted to determine differences in visual function, psychological factors, personality traits and satisfaction between patient groups. Successful soft contact lens (SCL) wearers reported better functional vision (P=0.001), felt more attractive (P=0.007), had a lower frequency of disturbing visual and ocular symptoms (P=0.027) and higher overall satisfaction with their current optical correction (P

Background Participation in cancer clinical trials has been shown to increase overall survival with minimal increase in cost, but enrollment in adult cancer clinical trials remains low. One factor limiting enrollment is lack of insurance coverage, but this barrier should be reduced under the 2010 Patient Protection and Affordable Care Act (ACA), which includes a provision requiring coverage for clinical trial participation as of 2014. Methods To assess the number of Kansas adults aged 19–64, newly covered with health insurance for participation in oncology clinical trials as a result of the ACA, a cross sectional design using extracted data from the 2012 American Community Survey, Public Use Microdata Sample to estimate the number of individuals covered by insurance and data from the 2014 Department of Health and Human Services Health Insurance Marketplace enrollment to estimate those newly enrolled through ACA. Results In 2014, there was an estimated increase of 3% (54,397; 95% CI: 44,149–64,244) for a total of 72% (1,171,041) of Kansans aged 19 to 64 with health insurance coverage for clinical trial participation. Conclusion Three main factors limit the effectiveness of the ACA provisions in expanding clinical trial coverage: 1) ‘grandfathered’ self-funded employer plans not subject to state Employee Retirement Income Security Act (ERISA) regulations, 2) Medicaid coverage limits not addressed under the ACA, 3) populations that remain uninsured. Kansas saw a negligible increase in insurance coverage as a result of the ACA thus lack of insurance coverage is likely to remain a concern for cancer patients.

The ascarid nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) may infect humans resulting in toxocariasis. A prior study associated species of Toxocara Stiles, 1905 with cognitive deficits in children. To determine if a similar association between toxocariasis and cognition exists in adults, we analysed a large dataset from the United States' Center for Disease Control's National Health and Nutrition Examination Survey. We used linear-regression and multivariate models to examine the association between toxocariasis as assessed by the presence of anti-Toxocara IgG antibodies and three measures of cognitive function - simple reaction time (SRT), symbol-digit substitution (SDS) and serial-digit learning (SDL) in 4 279 adults aged 21 to 59 years. Toxocara seroprevalence did not vary with age or blood-lead concentration but did vary with gender, ethnicity, educational attainment and poverty-to-income ratio. Controlling for gender, age, blood-lead concentration, educational attainment, ethnic background and the poverty-to-income ratio, we found that toxocariasis predicted worse performance on the SDS but not on the SRT or the SDL. Moreover, there were significant interactions between toxocariasis and age, gender and educational attainment. In conclusion, toxocariasis appears to be associated with decreased cognitive function. Interactions between toxocariasis and gender, age and educational attainment further suggest that certain groups may be more susceptible than others to the cognitive dysfunction associated with toxocariasis in adults.

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.

Background A recent study reviewed phase III trials of first-line advanced non-small cell lung cancer (NSCLC) conducted from 1981 to 2010, and provided trends in the study outcome. However, such trials have never been analyzed in detail for design and stratification factors. Methods Phase III studies of systemic treatment for first-line advanced or metastatic NSCLC published in English literature between 1981 and 2010 were identified. Characteristics, including sample size, number of trials, region, rate of meeting accrual goal, primary endpoint, type of phase III, interim analysis, allocation method, and stratification factors, were determined for each decade. Results A total of 162 studies met the criteria. The number of studies and sample size increased over the three decades. The primary endpoint was reported more frequently in recent decades, and non-overall survival endpoints were chosen in European and Asian studies. Interim analysis was conducted more commonly during the 2000s. Allocation method was rarely reported throughout the three decades. The number of stratification factors increased significantly from one in 1980s to three in 2000s. Performance status, stage, and institution were most frequently selected, and at least one of the three factors was used in most of the studies in the 2000s. However, there are many other stratification factors that were used infrequently. Conclusions Despite Consolidated Standards of Reporting Trials guidelines, allocation method has rarely been reported. The choice of stratification factor remains inconsistent across studies.

OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.

Using a cross-sectional comparison group design, 4,746 ethnically diverse middle and high school students from 31 public schools in a metropolitan area were surveyed about their health, emotional factors (self-esteem, depressive symptoms, and suicidality), and behaviors (tobacco, alcohol, and drug use). Based on regression analyses that adjusted for gender, race, school level, and socioeconomic status, adolescents with chronic health conditions were significantly more likely to report depressive symptoms and low self-esteem than adolescents without chronic health conditions; they were almost twice as likely to have considered suicide and over 3½ times more likely to have attempted suicide. They also reported greater use of cigarettes, marijuana, and illicit drugs. Given the extent of behavioral and emotional problems among adolescents with chronic health conditions, appropriate referrals and mental health services for these adolescents are warranted.

Objective To explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function. Methods We used data obtained from the 1999–2000 continuous National Health and Nutrition Examination Survey produced by the United States’ Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III. We then tested for interactions between each of the folate-cycle factors and Helicobacter pylori in the prediction of cognitive function. Results Although Helicobacter pylori seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not associated with performance on the digit symbol coding task, Helicobacter pylori seropositivity interacted with 5-methyltetrahydrofolate concentration to predict performance on the digit symbol coding task. The Helicobacter pylori seropositive group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate concentration decreased. Conclusion The interaction between Helicobacter pylori seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might impair aspects of cognitive function.

Male DNA, of presumed fetal origin, can be detected in the maternal circulation decades after delivery and is referred to as fetal microchimerism (FM). We previously found quantitatively greater FM in the circulation of women with the autoimmune disease scleroderma (SSc) than of healthy women. However, it is unknown whether this difference is due to intact circulating cells or free DNA released from breakdown in disease-affected tissues. To distinguish the origin of FM, we developed a real-time quantitative polymerase chain reaction (PCR) assay for the Y-chromosome–specific sequenceDYS14, and tested 114 women in peripheral blood mononuclear cells (PBMCs) and/or plasma. Fifty-seven controls and 57 SSc patients were studied, 48 and 43 of whom, respectively, had given birth to at least one son. Circulating FM was quantitatively greater in PBMCs from SSc patients (n = 39; range, 0.0-12.5 male genome–equivalent cells per million maternal cells), compared with healthy women (n = 39; range, 0.0-4.4; P = .03). In contrast, there was no difference between patients (n = 25) and controls (n = 22) in plasma, and no evidence of free DNA. FM was enriched among T lymphocytes compared with PBMCs (P = .01) in controls (n = 14), but not in SSc patients (n = 14); the latter finding was most likely due to immunosuppressive medications. In conclusion, this real-time quantitative assay showed that quantitative differences in the circulation of women with SSc are due to cells and not to free DNA. As FM was not uncommon in healthy women, including among T cells, and because graft-versus-host disease has similarities to SSc, these results also suggest that FM merits investigation in pheresis products used for stem cell transplantation.

The transport of alanine by system A is an important source of carbons for the synthesis of glucose in the liver. Here, we show that the mRNA encoding the ubiquitously expressed isoform of the rat system A transporter (SAT2) is dramatically increased in liver following streptozotocin-induced diabetes. This increase in SAT2 mRNA is intensified in the gluconeogenic periportal hepatocytes and also in hepatocytes surrounding the central vein. SAT3, the more abundant system A mRNA isoform present in liver, is restricted to perivenous hepatocytes and is also increased following this treatment but to a much lesser extent than SAT2 mRNA. SN1, an abundant system N mRNA isoform expressed in both perivenous and periportal hepatocytes, is not affected by streptozotocin treatment. A pharmacological dose of glucagon also increased both SAT2 and SAT3 mRNA levels in liver while SN1 mRNA levels remained unaffected. These results indicate that the increase in system A activity observed in liver following experimentally induced diabetes or glucagon treatment is due to the selective increase in mRNAs encoding system A transporters.

Weight gain and worsening metabolic parameters are often side effects of antipsychotic medications used by individuals with severe mental illness. To address this, a randomized, controlled research study of a behavioral weight management program for individuals with severe mental illness was undertaken to assess its efficacy. Patients unable to meet weight loss goals during the first portion of the year-long study were given the option of using meal replacement shakes in an effort to assist with weight loss. Specific requirements for use of meal replacement shakes were specified in the study protocol; only five patients were able to use the shakes in accordance with the protocol and lose weight while improving metabolic parameters. Case studies of two subjects are presented, illustrating the challenges and obstacles they faced, as well as their successes. Taking responsibility for their own weight loss, remaining motivated through the end of the study, and incorporating the meal replacement shakes into a daily routine were factors found in common with these patients. Use of meal replacements shakes with this population may be effective.

Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

Background Accutane® a teratogenic prescription drug licensed to treat severe, recalcitrant nodular acne. First-trimester pregnancy exposure can cause major birth defects. The manufacturer began a Pregnancy Prevention Program (PPP) in 1988; however, exposed pregnancies continue to occur. In 1996, the manufacturer began a direct-to-consumer advertising campaign, raising concerns of more exposed pregnancies. Methods We examined trends in Accutane use by reproductive-aged women. We also interviewed a series of 14 women in California who had recent Accutane-exposed pregnancies to identify opportunities for prevention. Results The estimated number of Accutane prescriptions for reproductive-aged women has more than doubled in the past 10 years; it is the most widely used teratogenic drug in the United States, with approximately 2.5 per 1,000 reproductive-aged women exposed to Accutane in 1999. One-half of the women interviewed reported seeing an advertisement for prescription acne treatment before taking Accutane. Eight of the 14 women used no contraception at the time of the exposed pregnancy; 13 of the 14 women did not use two forms of contraception. Four of the 14 women did not have pregnancy tests before starting Accutane. None reported seeing all PPP components, and four saw only the information on the pill packet. These 14 pregnancies resulted in four live infants who had no apparent birth defects, one live-born infant with multiple defects, four spontaneous abortions, and five induced abortions. Conclusions The increase in Accutane use observed among females may be exacerbated by advertising. Physicians and patients must use more caution with teratogenic prescription drugs. Teratology 64:142–147, 2001. Published 2001 Wiley-Liss, Inc.

A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis.

Each year spina bifida and anencephaly, the two most common forms of neural-tube defects, occur in 1 in 1000 pregnancies in the United States1 and an estimated 300,000 or more newborns worldwide.2 Although these severe conditions have been recognized since antiquity, never before has progress been so fast and substantive, particularly in the area of prevention. The results of randomized trials indicate that at least half the cases of neural-tube defects could be prevented if women consumed sufficient amounts of the B vitamin folic acid before conception and during early pregnancy.3,4 Elsewhere in this issue of the Journal, Berry . . .

Immunocytochemistry for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) was used to examine the expression of these linked cholinergic markers in human basal forebrain, including cases with early stages of Alzheimer's disease (AD). Previous neurochemical studies have measured decreased ChAT activity in terminal fields, but little change or even increased levels of VAChT. To determine total cholinergic neuron numbers in the nucleus basalis of Meynert (nbM), stereologic methods were applied to tissue derived from three groups of individuals with varying levels of cognition: no cognitive impairment (NCI), mild cognitive impairment (MCI), and early-stage Alzheimer's disease (AD). Both markers were expressed robustly in nucleus basalis neurons and across all three groups. On average, there was no significant difference between the number of ChAT- (210,000) and VAChT- (174,000) immunopositive neurons in the nbM per hemisphere in NCI cases for which the biological variation was calculated to be 17%. There was approximately a 15% nonsignificant reduction in the number of cholinergic neurons in the nbM in the AD cases with no decline in MCI cases. The number of ChAT- and VAChT-immunopositive neurons was shown to correlate significantly with the severity of dementia determined by scores on the Mini-Mental State Examination, but showed no relationship to apolipoprotein E allele status, age, gender, education, or postmortem interval when all clinical groups were combined or evaluated separately. These data suggest that cholinergic neurons, and the coexpression of ChAT and VAChT, are relatively preserved in early stages of AD. J. Comp. Neurol. 411:693–704, 1999. © 1999 Wiley-Liss, Inc.

Purpose: We examined maternal smoking and oral contraceptive use as possible risk factors in the genesis of cases of trisomy 21 of maternal origin. This is the first epidemiological study to categorize cases of trisomy 21 by parent of origin and timing of the meiotic error before assessing possible risk factors. Methods: We used chromosome 21-specific DNA markers to assign origin to each case. Structured interviews were employed to deter-mine maternal smoking and oral contraceptive use around conception. Results: The odds ratio (OR) for maternal smoking was significantly increased among younger mothers (OR = 2.98; 95% CI = 1.01–8.87), but only in a particular subset of meiotically-derived cases. The combined use of cigarettes and oral contraceptives increased the risk further (OR = 7.62; 95% CI = 1.63–35.6); however, oral contraceptive use alone was not a significant risk factor. Conclusion: Our results indicate that categorizing cases of trisomy 21 by parent and timing of the meiotic error allows more precision in identifying risk factors and may shed light on mechanisms of meiotic nondisjunction.

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MeImAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1–5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.

In the northern provinces of China, the birth prevalence rate of neural tube defects (NTDs) is among the highest in the world-at about 6 per 1,000 births in rural areas. A unique population-based birth defects surveillance system in which photographs are taken of infants with selected external birth defects was implemented in two provinces in northern China and two provinces in southern China where NTD rates approximate those in the United States. In the period from March 1992 through December 1993, 660 infants with NTDs were identified by the surveillance project from a birth cohort of 251,567. We compared data from the two surveillance areas in China with data from a low-prevalence area in the United States to determine if the pattern of NTD types differs. Based on birth prevalence rates of NTDs from the Metropolitan Atlanta Congenital Defects Program, the observed to expected ratios for two types of NTDs are markedly increased at 80.8 for craniorachischisis and 25.0 for iniencephaly. Rates of these two NTDs in the southern provinces are increased to a lesser degree with observed to expected ratios of 7.1 for craniorachischisis and 2.7 for iniencephaly. The pattern of NTDs in northern China shows an increase in types that are rare in low-prevalence areas such as metropolitan Atlanta. Increased awareness of varying patterns of NTDs in different populations may have important implications for identifying etiologic and pathogenetic mechanisms of NTDs.

Objective. Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. Methodology. The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. Results. Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. Conclusions. The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.