Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradicating Helicobacter pylori (H. pylori) infection than five-day concomitant and ten-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses and thus may be suitable for eradication programs in low-resource settings. Studies are limited from Latin America, however, where the burden of H. pylori-associated diseases is high. Methods We randomised 1463 men and women ages 21–65 selected from general populations in Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites) who tested positive for H. pylori by a urea breath test (UBT) to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); five days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or five days of lansoprazole and amoxicillin followed by five of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by UBT six–eight weeks after randomisation. Findings In intention-to-treat analyses, the probability of eradication with standard therapy was 82·2%, which was 8·6% higher (95% adjusted CI: 2·6%, 14·5%) than with concomitant therapy (73·6%) and 5·6% higher (95% adjusted CI: −0·04%, 11·6%) than with sequential therapy (76·5%). In analyses limited to the 1314 participants who adhered to their assigned therapy, the probabilities of eradication were 87·1%, 78·7%, and 81·1% with standard, concomitant, and sequential therapies, respectively. Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to five-day concomitant or ten-day sequential four-drug regimens as empiric therapy for H. pylori among diverse Latin American populations. Funding Bill & Melinda Gates Foundation and US National Institutes of Health.

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Human arsenic methylation efficiency has been consistently associated with arsenic-induced disease risk. Interindividual variation in arsenic methylation profiles is commonly observed in exposed populations, and great effort has been put into the study of potential determinants of this variability. Among the factors that have been evaluated, body mass index (BMI) has not been consistently associated with arsenic methylation efficiency, however an underrepresentation of the upper BMI distribution was commonly observed in these studies. This study investigated potential factors contributing to variations in the metabolism of arsenic, with specific interest in the effect of BMI where more than half of the population was overweight or obese. We studied 624 adult women exposed to arsenic in drinking water from three independent populations. Multivariate regression models showed that higher BMI, arsenic (+3 oxidation state) methyltransferase (AS3MT) genetic variant 7388, and higher total urinary arsenic, were significantly associated with low percentage of urinary arsenic excreted as monomethylarsonic acid (%uMMA) or high ratio between urinary dimethylarsinic acid and uMMA (uDMA/uMMA); while AS3MT genetic variant M287T was associated with high %uMMA and low uDMA/uMMA. The association between BMI and arsenic methylation efficiency was also evident in each of the three populations when studied separately. This strong association observed between high BMI and low %uMMA and high uDMA/uMMA underscores the importance of BMI as a potential arsenic-associated disease risk factor, and should be carefully considered in future studies associating human arsenic metabolism and toxicity.

Background Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations. Methods We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing human epidermal growth factor receptor 2 positive (HER2+) tumors and triple negative breast cancer (TNBC) to luminal A tumors was conducted. Results Compared to women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC (odds ratio [OR], 0.61; 95% CI, 0.39–0.95), whereas those with ≥ 3 full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10–2.55). A lower odds of TNBC was shown for longer menstruation duration, whether prior to first pregnancy (OR, 0.78; 95% CI, 0.65–0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69–0.91 per 10 years). Patients who reported breastfeeding for >12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24–3.68). Associations comparing HER2+ to luminal A tumors were weak or non-existent except for the interval between last full-term pregnancy and breast cancer diagnosis. Conclusions Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles. Impact Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.