Deep Remission at 1 Year Prevents Progression of Early Crohn's Disease.

BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

Criminal arrests associated with reduced regional brain volumes in an adult population with documented childhood lead exposure.

Childhood lead exposure interferes with brain maturation, which adversely impacts cognitive and behavioral development. Lower intelligence scores, impairments in decision making, and increased rates of delinquent and criminal behavior are adverse outcomes linked to childhood lead absorption. The present study examined the relationships between childhood blood lead concentrations, structural brain volume, and measures of adult criminality. We hypothesized that increased rates of criminal arrests in adulthood would be inversely correlated with regional gray and white matter volumes, especially prefrontal areas responsible for decision making and self-control. We obtained childhood blood lead histories and anatomical magnetic resonance imaging from a subset of the longitudinally followed birth cohort known as the Cincinnati Lead Study. Criminality data for cohort participants were extracted from public databases. Voxel based morphometry was used to examine spatial differences in regional gray and white matter volumes associated with childhood blood lead concentrations and measures of adult criminality, respectively. Conjunction analyses allowed for the exploratory evaluation of common regions of volume change. Childhood blood lead concentrations were inversely associated with gray and white matter volume in the frontal, parietal and temporal lobes. Gray matter volumes were also inversely associated with criminal arrests with key regions within the cingulate, precuneus, several frontal gyri and the supplementary motor area. Conjunction analyses identified regions in the anterior cingulate, frontal gray matter and supplementary motor area associated with childhood lead absorption and criminality. The results from this study suggest that reduced brain volumes in regions responsible for cognition and emotional regulation are associated with childhood lead exposure and criminal arrests.

The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK.

BACKGROUND: Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. METHODS: Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. RESULTS: All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. CONCLUSION: The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks.

Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure.

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes.

The prevalence of discrimination across racial groups in contemporary America: Results from a nationally representative sample of adults.

A large body of social science research is devoted to understanding the causes and correlates of discrimination. Comparatively less effort has been aimed at providing a general prevalence estimate of discrimination using a nationally representative sample. The current study is intended to offer such an estimate using a large sample of American respondents (N = 14,793) while also exploring perceptions regarding why respondents felt they were discriminated against. The results provide a broad estimate of self-reported discrimination experiences-an event that was only reported by about one-quarter of all sample members-across racial and ethnic categories.

Aggregate-level lead exposure, gun violence, homicide, and rape.

CONTEXT: An increasing body of research has linked the geographic distribution of lead with various indicators of criminal and antisocial behavior. OBJECTIVE: The current study, using data from an ongoing project related to lead exposure in St. Louis City, MO, analyzed the association between aggregate blood lead levels and specific indicators violent crime within the city. DESIGN: Ecological study. SETTING: St. Louis, Missouri. EXPOSURE MEASURE: Blood lead levels. MAIN OUTCOME MEASURE: Official reports of violent crimes were categorized as 1) crimes involving a firearm (yes/no), 2) assault crimes (with or without a firearm), 3) robbery crimes (with or without a firearm), 4) homicides and 5) rape. RESULTS: With the exception of rape, aggregate blood-lead levels were statistically significant predictors of violent crime at the census tract level. The risk ratios for each of the outcome measures were as follows: firearm crimes 1.03 (1.03-1.04), assault crimes 1.03 (1.02-1.03), robbery crimes 1.03 (1.02-1.04), homicide 1.03 (1.01, 1.04), and rape 1.01 (0.99-1.03). CONCLUSIONS: Extending prior research in St. Louis, results suggest that aggregated lead exposure at the census tract level predicted crime outcomes, even after accounting for important sociological variables. Moving forward, a more developed understanding of aggregate level crime may necessitate a shift toward studying the synergy between sociological and biological risk factors such as lead exposure.

Refinements in acute dietary exposure assessments for chlorpyrifos.

Food pesticide residue data are used by the U.S. Environmental Protection Agency (EPA) to determine potential dietary risk from chronic and acute exposures. An acute dietary risk assessment determines the pesticide exposure resulting from a single-day consumption of food, and uses stepwise refinement of residue estimates to better judge actual exposures. All exposure refinements use estimates of the fraction of crops treated and food residues measured increasingly closer to the point of actual food consumption, without changes in the pesticide uses. Exposure distributions at all levels of data refinement were extremely right skewed. At the highest level evaluated, estimated exposures at the 99.9th percentile were 0.00087 mg/kgBW/day compared to 0.2648 mg/kgBW/day at the tolerance level for children 1-6 years, theoretically the highest-exposed population sub-group. The estimated exposure at the 99.9th percentile of the U.S. population was approximately twice the exposure at the 99th percentile and 33 times the exposure at the 90th percentile. This evaluation showed the calculated exposure at the highest tier of assessment was 300 times lower than the tolerance level assessment for children 1-6 years at the 99.9th percentile. Reduction in exposure estimates between these tiers was due to a combination of the following factors: food residue measurements in a specially designed market-basket study, government-sponsored monitoring data, probabilistic methodologies, market share information, and food processing data. This case study demonstrates that an improved understanding of the uncertainties of acute dietary exposure from pesticides is possible by using well-established statistical tools and applying them to comprehensive exposure information, including residue monitoring data, consumption data, and pesticide use information.

A comparison of crop and non-crop plants as sensitive indicator species for regulatory testing.

The effectiveness of regulatory non-target plant testing using crop species to predict the phytotoxicicity of herbicides to non-crop species was evaluated for eleven herbicides. These herbicides were representative of eight chemical classes and six modes of action. Data for non-crop plants from pre-emergence and post-emergence efficacy screening studies were compared with those for the most sensitive crop species defined by regulatory tests conducted to meet US EPA requirements. Testing under pre-emergence conditions for ten compounds indicated that for five of the compounds (K-815910, trifluralin, pyridyloxy A, pyridyloxy B and cyanazine), the most sensitive crop species was more sensitive than all the non-crop species evaluated. For metsulfuron-methyl, chlorimuron-ethyl, hexazinone and bromacil, only one of the non-crop species evaluated was more sensitive than the most sensitive crop species from regulatory tests. Data for the tenth compound, chloroacetamide, showed that four of 32 non-crop species tested in efficacy screens had at least one rate at which greater visual effects were observed than were observed for the most sensitive crop response in a regulatory test. The results of post-emergence exposure comparisons for five of the compounds (pyridyloxy A, cloransulam-methyl, chlorimuron-ethyl, cyanazine and hexazinone) indicated that the most sensitive crop species were more sensitive than all the non-crop species evaluated. Data for pyridyloxy B, metsulfuron-methyl and bromacil indicated that only one of the non-crop species evaluated was more sensitive than the most sensitive crop species. For trifluralin, three of the eight non-crop species were more sensitive than the most sensitive crop species. Data for K-815910 indicated that four of the fourteen non-crop species tested were marginally more sensitive than the most sensitive crop, but were within the same range of sensitivity. These results indicate that the current regulatory test batteries and methods using crop species effectively provide suitable sensitive indicator plants for the eleven diverse herbicides evaluated. This comparison indicates that crop species sensitivity to test substances is likely to be representative of non-crop herbaceous species response, regardless of chemical class, mode of action and magnitude or route of exposure.

'What really annoys me is people take it like it's a disability', epilepsy, disability and identity among people of Pakistani origin living in the UK.

This paper reports on a study of Pakistani people with epilepsy. It explores their attitudes towards their condition, others' attitudes, its impact on their lives, and the extent to which they considered themselves as disabled. Epilepsy was variously interpreted within biomedical, folk and religious paradigms. In line with popular understandings, participants associated disability with stable, permanent and visible physical impairments and did not consider themselves as disabled. However, they also recognised a social dimension to their experience. Much of the distress and disadvantage they experienced was socially determined, both through direct prejudice and discrimination, and indirectly through a fear of others' negative reactions. However, the invisible and unpredictable nature of epilepsy meant that they could conceal their condition and thereby mitigate its social effects. 'Disability' was not experienced as a static and permanent state but as a potential identity that was both contingent and contested. The literature portrays people moving from biomedical to social interpretations of disability. However, the tensions experienced by people in the study were more between competing religious interpretations of their condition and, to some extent, between religious and medical approaches. Conceptions of disability, which are presented in the literature as antagonistic and mutually exclusive, were experienced as different dimensions reflecting the complexity of experience. The paper concludes by suggesting that for many people, for whom disability is an ambiguous, contingent and contested identity, public self-identification as disabled is an unrealistic goal. Rather than conceiving of disability as primarily physical or primarily social, it would be better construed as a complex interweaving of multiple factors--physical, environmental, socio-cultural and psychological factors.

Budesonide and mesalazine in active Crohn's disease: a comparison of the effects on quality of life.

OBJECTIVES: Controlled ileal release budesonide and slow release mesalazine are both used to treat mild to moderate active Crohn's disease, although data show that budesonide is more effective in inducing remission. When comparing different treatment options, the effects of agents on health-related quality of life must be considered as well as efficacy. In this study, we sought to compare the effects of budesonide and mesalazine on the health-related quality of life of patients with active Crohn's disease. METHODS: The study included 182 patients with Crohn's Disease Activity Index scores between 200 and 400. Patients were randomized in a double blind, double dummy, multicenter study to receive 9 mg of budesonide, once daily (n = 93), or 2 g of mesalazine, b.i.d. (n = 89), for 16 wk. Quality of life was assessed at baseline and after 2, 4, 8, 12, and 16 wk of treatment using the Psychological General Well-Being index. In addition, a physician's global evaluation was used to assess how symptoms affected patients' normal activities. RESULTS: Patients treated with budesonide experienced significantly greater improvement in Psychological General Well-Being scores than the group treated with mesalazine after 2, 8, 12, and 16 wk. All components of this index showed greater improvements in the budesonide-treated group than in the mesalazine group at 12 and 16 wk. The physician's global evaluation showed significantly greater improvements in the budesonide group than in the mesalazine group at all visits. CONCLUSION: Budesonide (9 mg once daily) improves health-related quality of life to a greater extent than mesalazine (2 g b.i.d.) in patients with mild to moderate active Crohn's disease.