Catherine Ley

Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial.

Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H. pylori infection prevents this cancer remains unknown. In a randomized, double-blind, placebo-controlled trial of H. pylori eradication, we determined whether treatment for H. pylori decreases gastric cancer risk, using preneoplastic conditions as surrogate markers. A total of 248 healthy volunteers (age >40 years) randomly received H. pylori treatment (omeprazole, amoxicillin, clarythromycin; n = 122) or matched placebo (n = 126) for 1 week. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification. Outcome measures were both a consensus “worst biopsy” diagnosis and a weighted index score that incorporated degrees of severity of preneoplasia from all biopsies. We compared change in these outcomes over time between the two treatment groups. H. pylori cure rates for compliant subjects in the treatment arm were 79.2% and 75.7% at 6 weeks and 1 year, respectively. No statistically significant change in the worst biopsy diagnosis was observed from 6 weeks to 1 year between placebo and treated subjects (for improvement/worsening, placebo, 19.4%/10.5%; treatment, 22.5%/8.3%; P = 0.74). Change in index score was favorably greater in treatment compared with placebo subjects (intention-to-treat analysis, P = 0.03); this finding was particularly evident in the antrum. H. pylori eradication gave more favorable gastric histopathologies over 1 year than no treatment. Such incomplete regression suggests but does not prove that eradication of H. pylori decreases cancer risk.

Prevalence and Incidence of Herpes Simplex Virus Type 2 Infection among Male Zimbabwean Factory Workers

Stored sera from a cohort of 2397 male factory workers in Harare, Zimbabwe, were screened for herpes simplex virus type 2 (HSV-2)-specific antibodies, to estimate the prevalence and incidence of genital herpes infection and to assess the relation between HSV-2 and human immunodeficiency virus (HIV) acquisition. The prevalence of HSV-2 at enrollment was 39.8%. Correlates of HSV-2 seropositivity were HIV seropositivity, marital status, history of sexually transmitted disease (STD), older age, and higher income. The incidence of HSV-2 seroconversion during follow-up was 6.2/100 person-years. Correlates of HSV-2 seroconversion were enrollment while HIV-positive or seroconversion during follow-up, reported genital ulcer, history of STD, and number of sex partners. No evidence was found that HSV-2 infection was more likely to precede HIV or vice versa. HSV-2 and HIV seropositivity are strong markers for high-risk sexual behavior. Improved interventions targeted to populations in which the incidence of either viral infection is high are needed.

Interobserver variability in application of the revised sydney classification for gastritis

The Sydney classification for gastritis provides guidelines for histological grading of gastric biopsies. In an ongoing study of gastric preneoplastic lesions in Chiapas, Mexico, 7 biopsies from 150 patients (4 from the antrum and 3 from the body) were obtained during endoscopy and studied histologically. The first 74 endoscopy specimens were read independently by 2 general surgical pathologists. We assessed diagnostic concordance using kappa statistics. The 2 pathologists then jointly reviewed biopsies about which they had disagreed to reach a final diagnosis. A second group of 76 endoscopies was subsequently evaluated independently by the 2 pathologists, and concordance was again assessed. In the first group of biopsies, we found low concordance rates (Heliobacter pylori 0.59, acute inflammation 0.22, intestinal metaplasia 0.60, and atrophy 0.04). In the second group, of independently reviewed cases, there was better concordance (H pylori 0.77, acute inflammation 0.50, intestinal metaplasia 0.70, and atrophy 0.64). We presumed that use of the Sydney classification would result in minimal interpretational differences achieving ideal kappas greater than 0.80. Because pathology results are based on subjective interpretation of this classification, complete diagnostic agreement is practically impossible. Concordance by general surgical pathologists after joint review of cases was similar to that obtained by gastrointestinal pathologists.

Maternal prepregnancy body mass index and risk of spontaneous preterm birth.

BACKGROUND Findings from studies examining risk of preterm birth associated with elevated prepregnancy body mass index (BMI) have been inconsistent. METHODS Within a large population-based cohort, we explored associations between prepregnancy BMI and spontaneous preterm birth across a spectrum of BMI, gestational age, and racial/ethnic categories. We analysed data for 989,687 singleton births in California, 2007-09. Preterm birth was grouped as 20-23, 24-27, 28-31, or 32-36 weeks gestation (compared with 37-41 weeks). BMI was categorised as <18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0-34.9 (obese I); 35.0-39.9 (obese II); and ≥ 40.0 (obese III). We assessed associations between BMI and spontaneous preterm birth of varying severity among non-Hispanic White, Hispanic, and non-Hispanic Black women. RESULTS Analyses of mothers without hypertension and diabetes, adjusted for age, education, height, and prenatal care initiation, showed obesity categories I-III to be associated with increased risk of spontaneous preterm birth at 20-23 and 24-27 weeks among those of parity 1 in each race/ethnic group. Relative risks for obese III and preterm birth at 20-23 weeks were 6.29 [95% confidence interval (CI) 3.06, 12.9], 4.34 [95% CI 2.30, 8.16], and 4.45 [95% CI 2.53, 7.82] for non-Hispanic Whites, non-Hispanic Blacks, and Hispanics, respectively. A similar, but lower risk, pattern was observed for women of parity ≥ 2 and preterm birth at 20-23 weeks. Underweight was associated with modest risks for preterm birth at ≥ 24 weeks among women in each racial/ethnic group regardless of parity. CONCLUSIONS The association between womens prepregnancy BMI and risk of spontaneous preterm birth is complex and is influenced by race/ethnicity, gestational age, and parity.

Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES

Background Triclosan—a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies—has the potential to alter both gut microbiota and endocrine function and thereby affect body weight. Methods We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003–2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures—either presence vs. absence or quartiles of triclosan—we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations. Results Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified. Conclusions Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.

C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction.

PURPOSE C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI). METHODS Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP. RESULTS In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections. CONCLUSIONS Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status.

Patients with crohn’s disease are unaware of the risks that smoking has on their disease

Smoking, both in quantity and duration, increases the risk of recurrent Crohn’s disease (CD) and the need for surgical treatment of CD. This study assessed awareness among patients with CD of the risks of smoking on their disease. We distributed self-administered questionnaires to 714 CD patients under follow-up at the University Hospital Birmingham, United Kingdom. We asked the patients eight multiplechoice (yes/uncertain/no) questions about the effects of smoking on health and on CD. We also determined relevant patient demographics, smoking history, and medical history. A total of 312 patients completed the questionnaire. Patients acknowledged the dangers of smoking on overall health (91.5%), lung cancer (89.6%), lung disease (90.8%), and cardiovascular disease (85.3%). Employed, educated, and homeowning patients demonstrated significantly more recognition of these smoking risks. Conversely, few patients recognized that smoking increases the risks of development of CD (9.5%) and of reoperation for CD (12.0%). Moreover, few patients recognized that both the quantity of cigarettes smoked (11.4%) and the duration of smoking (17.4%) increase the risk of reoperation. Patients with CD are unaware of the risks that smoking has on their disease, indicating a need for increased patient education with regard to the effects of smoking on CD.

Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome

Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans. ABSTRACT Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans.

Perceived risks and benefits of HIV testing, and predictors of acceptance of HIV counselling and testing among pregnant women in Zimbabwe

This project evaluated perceived risks and benefits and determined predictors of acceptance of voluntary HIV counselling and testing (VCT) among pregnant women in Zimbabwe. One hundred and seventy pregnant women attending an urban antenatal clinic were surveyed. Implications of a negative or positive HIV test result and of telling a partner or community members that one is HIV positive were queried. Forty women (23.5%) consented to VCT, and 16 (40%) were HIV positive. Women who saw VCT as lower risk (odds ratio [OR] = 2.3, 95% confidence interval [CI] [1.1–5.0]) and women who had had a stillbirth or child die (OR = 0.4, 95% CI [0.16–0.97]) were more likely to consent. Prenatal HIV VCT offers the best opportunity for prevention of mother-to-child transmission of HIV; however, less than 25% of women consented. If such interventions are to be successful, attention must be directed towards developing culturally appropriate strategies to address womens concerns and improve future acceptance of VCT in Zimbabwe.

Validation of Spanish language dyspepsia questionnaire.

No dyspepsia-specific questionnaire currently exists in Spanish. The Spanish Language Dyspepsia Questionnaire (SLDQ) was developed based on Rome dyspepsia criteria, other questionnaires, and common symptoms. Self-reported normal and dyspeptic volunteers (N = 63) in Chiapas, Mexico, participated in a validation study. We assessed intra- and interrater reliability by test–retest studies and established validity by both correlation to the Short Form-36 (SF-36) and comparison of scores between normals and dyspeptics. The total SLDQ score showed a wide distribution (range 0–78, mean 23.7 ± 21.9). Internal reliability of the SLDQ was high (Cronbachs α = 0.93). Intra- and interrater reliability were excellent (scores from the first and second interviews not statistically different; P = 0.94; intraclass correlation coefficient = 0.96). SLDQ scales correlated appropriately with the SF-36. The SLDQ distinguished self-classified normals from dyspeptics (P < 0.001). The SLDQ fills the unmet need for a valid, reproducible, and multidimensional Spanish-language instrument to measure dyspepsia. Additionally, we have made suggestions for the development of symptom-quantifying questionnaires.