Self-Reported Pain in Male and Female Iraq/Afghanistan-Era Veterans: Associations with Psychiatric Symptoms and Functioning

Objective. To examine pain symptoms and co-occurring psychiatric and functional indices in male and female Iraq/Afghanistan-era veterans. Design. Self-reported data collection and interviews of Iraq/Afghanistan-era veterans who participated in a multisite study of postdeployment mental health. Setting. Veterans were enrolled at one of four participating VA sites. Subjects. Two thousand five hundred eighty-seven male and 662 female Iraq/Afghanistan-era veterans. Methods. Nonparametric Wilcoxon rank tests examined differences in pain scores between male and female veterans. Chi-square tests assessed differences between male and female veterans in the proportion of respondents endorsing moderate to high levels of pain vs no pain. Multilevel regression analyses evaluated the effect of pain on a variety of psychiatric and functional measures. Results. Compared with males, female veterans reported significantly higher mean levels of headache (P \u3c 0.0001), muscle soreness (P \u3c 0.008), and total pain (P \u3c 0.0001), and were more likely to report the highest levels of headache (P \u3c 0.0001) and muscle soreness (P \u3c 0.0039). The presence of pain symptoms in Iraq/Afghanistan-era veterans was positively associated with psychiatric comorbidity and negatively associated with psychosocial functioning. There were no observed gender differences in psychiatric and functional indices when levels of pain were equated. Conclusions. Although female Iraq/Afghanistan-era veterans reported higher levels of pain than male veterans overall, male and female veterans experienced similar levels of psychiatric and functional problems at equivalent levels of reported pain. These findings suggest that pain-associated psychological and functional impacts are comparable and consequential for both male and female veterans

Cognitive mediators of the effect of peer victimization on loneliness

The impact of stress on psychological adjustment may be mediated by cognitive interpretations (i.e., appraisals) of events for individuals. Defining characteristics of loneliness suggest that appraisals of blame, threat, and perceived control may be particularly important in this domain. AIMS: To evaluate the extent to which cognitive appraisals (perceived control, threat, and blame) can mediate the effect of peer victimization on loneliness. SAMPLE: One hundred and ten children (54 boys, 56 girls) aged 8-12 years attending mainstream schools in Scotland. METHOD: Self-report measures of peer victimization, appraisal, and loneliness. RESULTS: Perceived control partially mediated the effects of peer victimization on loneliness, but neither blame nor threat were mediators. All three measures of control were significantly associated with loneliness at the bivariate level, but only perceived control was significant when the appraisals were entered as predictors in a hierarchical multiple linear regression. CONCLUSIONS: The results highlight the importance of research designs assessing multiple categories of appraisal. Furthermore, they suggest that intervention efforts aiming to combat feelings of loneliness within a peer victimization context should address children's appraisals of perceived control

Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001

Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. Furthermore, clozapine increases pregnenolone in rodent hippocampus, possibly contributing to its superior efficacy. We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot randomized, placebo-controlled, double-blind trial. Following a 2-week single-blind placebo lead-in, patients were randomized to pregnenolone (fixed escalating doses to 500 mg/day) or placebo, for 8 weeks. Primary end points were changes in BACS and MCCB composite and total SANS scores. Of 21 patients randomized, 18 completed at least 4 weeks of treatment (n = 9/group). Pregnenolone was well tolerated. Patients receiving pregnenolone demonstrated significantly greater improvements in SANS scores (mean change = 10.38) compared with patients receiving placebo (mean change = 2.33), p = 0.048. Mean composite changes in BACS and MCCB scores were not significantly different in patients randomized to pregnenolone compared with placebo. However, serum pregnenolone increases predicted BACS composite scores at 8 weeks in the pregnenolone group (rs = 0.81, p = 0.022). Increases in allopregnanolone, a GABAergic pregnenolone metabolite, also predicted BACS composite scores (rs = 0.74, p = 0.046). In addition, baseline pregnenolone (rs = −0.76, p = 0.037), pregnenolone sulfate (rs = − 0.83, p = 0.015), and allopregnanolone levels (rs = −0.83, p = 0.015) were inversely correlated with improvements in MCCB composite scores, further supporting a possible role for neurosteroids in cognition. Mean BACS and MCCB composite scores were correlated (rs = 0.74, p <0.0001). Pregnenolone may be a promising therapeutic agent for negative symptoms and merits further investigation for cognitive symptoms in schizophrenia

Decrease in Incidence of Colorectal Cancer Among Individuals 50 Years or Older After Recommendations for Population-based Screening

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) in the United States is increasing among adults younger than 50 years, but incidence has decreased among older populations after population-based screening was recommended in the late 1980s. Blacks have higher incidence than whites. These patterns have prompted suggestions to lower the screening age for average-risk populations or in blacks. At the same time, there has been controversy over whether reductions in CRC incidence can be attributed to screening. We examined age-related and race-related differences in CRC incidence during a 40-year time period. METHODS: We determined the age-standardized incidence of CRC from 1975 through 2013 by using the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We calculated incidence for 5-year age categories (20-24 years through 80-84 years and 85 years or older) for different time periods (1975-1979, 1980-1984, 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010-2013), tumor subsite (proximal colon, descending colon, and rectum), and stages at diagnosis (localized, regional, and distant). Analyses were stratified by race (white vs black). RESULTS: There were 450,682 incident cases of CRC reported to the SEER registries during the entire period (1975-2013). Overall incidence was 75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the decreases in incidence between the time periods of 1980-1984 and 2010-2013 were limited to the screening-age population (ages 50 years or older). Between these time periods, there was 40% decrease in incidence among whites compared with 26% decrease in incidence among blacks. Decreases in incidence were greater for cancers of the distal colon and rectum, and reductions in these cancers were greater among whites than blacks. CRC incidence among persons younger than 50 years decreased slightly between 1975-1979 and 1990. However, among persons 20-49 years old, CRC incidence increased from 8.3/100,000 persons in 1990-1994 to 11.4/100,000 persons in 2010-2013; incidence rates in younger adults were similar for whites and blacks. CONCLUSIONS: On the basis of an analysis of the SEER cancer registries from 1975 through 2013, CRC incidence decreased only among individuals 50 years or older between the time periods of 1980-1984 and 2010-2013. Incidence increased modestly among individuals 20-49 years old between the time periods of 1990-1994 and 2010-2013. The decision of whether to recommend screening for younger populations requires a formal analysis of risks and benefits. Our observed trends provide compelling evidence that screening has had an important role in reducing CRC incidence

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures

BACKGROUND: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy

Investigator experiences with financial conflicts of interest in clinical trials

<p>Abstract</p> <p>Background</p> <p>Financial conflicts of interest (fCOI) can introduce actions that bias clinical trial results and reduce their objectivity. We obtained information from investigators about adherence to practices that minimize the introduction of such bias in their clinical trials experience.</p> <p>Methods</p> <p>Email survey of clinical trial investigators from Canadian sites to learn about adherence to practices that help maintain research independence across all stages of trial preparation, conduct, and dissemination. The main outcome was the proportion of investigators that reported full adherence to preferred trial practices for all of their trials conducted from 2001-2006, stratified by funding source.</p> <p>Results</p> <p>844 investigators responded (76%) and 732 (66%) provided useful information. Full adherence to preferred clinical trial practices was highest for institutional review of signed contracts and budgets (82% and 75% of investigators respectively). Lower rates of full adherence were reported for the other two practices in the trial preparation stage (avoidance of confidentiality clauses, 12%; trial registration after 2005, 39%). Lower rates of full adherence were reported for 7 practices in the trial conduct (35% to 43%) and dissemination (53% to 64%) stages, particularly in industry funded trials. 269 investigators personally experienced (n = 85) or witnessed (n = 236) a fCOI; over 70% of these situations related to industry trials.</p> <p>Conclusion</p> <p>Full adherence to practices designed to promote the objectivity of research varied across trial stages and was low overall, particularly for industry funded trials.</p