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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 eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy., Methods: Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437., Findings: 1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). 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 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations., Funding: Bill & Melinda Gates Foundation, US National Institutes of Health., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Evidence that aspirin and other non-steroidal anti-inflammatory drugs reduce risk for colorectal cancer has prompted interest in their ability to prevent other cancers. We aimed to find out what effect over-the-counter analgesics have on risk of ovarian cancer., Methods: In a case-control study we compared use of over-the-counter analgesics by 563 women from eastern Massachusetts and New Hampshire, USA, who had epithelial ovarian cancer with 523 women from the general population. We calculated exposure odds ratios to estimate the effect of over-the-counter analgesics on ovarian cancer risk. Use of over-the-counter analgesics was assessed through interviews and defined as use at least once a week continuously for at least 6 months., Findings: The odds ratio for risk of ovarian cancer for aspirin use was 0.75 (95% CI 0.52-1.10), that for ibuprofen was 1.03 (0.64-1.64), and that for paracetamol was 0.52 (0.31-0.86), after adjusting for age, study centre, education, religion, parity, oral contraceptive use, and menstrual, arthritic, or headache pain. Relative to no use, the lower risk of ovarian cancer associated with paracetamol was more apparent for use on a daily basis, 0.39 (0.21-0.74), for more than 10 years of use, 0.40 (0.19-0.88), or for more than 20 tablet years defined as (tablets per day x years of use), 0.45 (0.20-0.99)., Interpretation: In our data, there was a statistically significant inverse association between paracetamol use and ovarian cancer risk. There was a modest but non-significant inverse association with aspirin use and ovarian cancer and no association with ibuprofen use. Experimental studies in rodents demonstrating uterine and ovarian atrophy at high doses of paracetamol and decreased ovarian-cyst formation at lower doses suggest a biological basis for our observations.

beta-Carotene has been studied widely as a potential cancer-preventing agent. Recent studies found that subjects who took beta-carotene supplements orally had increases in their serum concentrations of alpha-carotene and lycopene that were large (> 150% increase) and significantly greater than such increases in subjects who received placebo and that similar supplementation was associated with a decrease of approximately 37% in plasma lutein concentrations. A biologic interaction between beta-carotene and other carotenoids was suggested. We measured concentrations of retinol, alpha-tocopherol, and five carotenoids in serum specimens from a random sample of subjects enrolled in a clinical trial of the use of antioxidant vitamins in preventing colonic adenomas. We used serum specimens obtained at enrollment and after the subjects took placebo (n = 54) or 25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis, baseline serum concentrations of the analytes, sex, body mass index, diet, smoking status, and age were associated with variable changes in some analytes over the 4-y period but supplementation with beta-carotene was related only to a mean increase in serum beta-carotene itself of 151%. We excluded with 95% confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%, and a decrease in lutein > 14.7% in subjects given beta-carotene. These results confirm previous findings that supplementation with beta-carotene given orally does not alter serum concentrations of retinol or alpha-tocopherol. The findings also indicate that beta-carotene supplementation, which results in a moderate increase in serum beta-carotene concentration, does not significantly change serum concentrations of other carotenoids.

We examined time trends and geographical variations in the detection and treatment of prostate cancer in USA, based on information from white men aged 50 to 79 who resided in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program of the United States National Cancer Institute. Prostate-cancer incidence and treatment rates were determined for the 9 population-based cancer registries which participate in the SEER program. Prostate-cancer mortality rates were assessed from data compiled by the National Center for Health Statistics. Prostate cancer incidence rates increased by 6.4% per year between 1983 and 1989. The increase appeared to be due to detection of early-stage disease; there was no increase in the incidence rate of metastatic cancer. Incidence rates varied widely among the SEER program areas: in 1989 from 267.9 per 100,000 in Connecticut to 606.8 in Seattle. Radical prostatectomy rates more than tripled between 1983 and 1989 in the SEER areas as a whole. Among men aged 70-79, the rate of prostatectomy increased by nearly 35% per year. There was a five-fold variation among SEER areas in radical prostatectomy rates in 1989, with a low of 43.4 per 100,000 in Connecticut and a high of 224.4 in Seattle. Prostate cancer mortality rates did not increase during the period of study; there was little variation among areas in prostate-cancer mortality rates, and no apparent correlation between the incidence and mortality rates for an area. Increases in rates of prostate cancer incidence and prostate surgery have occurred in the United States without clear evidence that screening and prostectomy are effective in reducing mortality. Moreover, much of the growth in incidence and radical prostatectomy rates has occurred among older men, who appear least likely to benefit from early detection and surgery of occult prostate cancer.

We studied within-person variation over time in serum concentrations of five carotenoids. In a diurnal study involving 33 subjects, only the 1700 h blood samples demonstrated carotenoid concentrations different from the original 0800 values. Correlations between serum concentrations of the same carotenoids drawn 1 d apart ranged from 0.93 to 0.98. In a seasonal study involving 29 subjects, no systematic trends were observed for serum concentrations of these carotenoids. Correlations between concentrations of the same carotenoids drawn 1 y apart ranged from 0.57 to 0.82. Concentrations of different carotenoids within an individual tended to be correlated with each other. Obtaining one blood sample from subjects is a relatively imprecise way to estimate their usual serum concentrations of carotenoids. If an epidemiological study was to be based on only one determination of serum carotenoids, within-person variability in serum concentrations would attenuate true regression coefficients by 4-13% and would increase the required numbers of study subjects by 19-65%.

We studied the relationship between eight variables, including age, sex, baseline plasma beta-carotene (BC) concentration, and smoking status and the increase in plasma BC in 582 subjects receiving oral supplementation with 50 mg BC/d. Median plasma BC concentrations after 1 y of supplementation increased from 335 nmol/L at entry to 3163 nmol/L. Changes in plasma BC concentrations ranged widely from -313 to 16,090 nmol/L (median 2721 nmol/L). Multivariate analysis revealed that the subject's plasma BC concentration before supplementation was the most important indicator of the amount of increase after supplementation. Nonsmokers, women, and leaner subjects all had larger increases in plasma concentrations although the statistical model could account for relatively little of the variability in subjects' plasma response to BC supplementation (R2 = 0.14). We conclude that between-subject variability in response to daily supplementation with oral BC is very large and that the best predictor of this response is the initial plasma BC concentration.

We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies.

We describe a randomized clinical trial of oral beta-carotene (50 mg/day) for preventing nonmelanoma skin cancer. It is a multicenter study conducted at sites in California, Minnesota, and New Hampshire. This report describes the design of the study, baseline characteristics of the 1805 randomized patients, changes in their plasma beta-carotene and retinol levels after 1 year of treatment, and plans for statistical analyses. Important features of this study are (1) a high proportion of potential subjects were found to be ineligible or chose not to enter the study, (2) the study agent is readily available over the counter and in common foods, and (3) nonmelanoma skin cancer is a relatively minor health concern for most patients. These considerations necessitated intensive efforts to encourage compliance with the study regimen. There are also some unusual statistical features of the study. One is that the study outcome is routinely assessed only at annual examinations, so the precise time of failure cannot be identified. Also, a secondary goal of the study is to determine whether beta-carotene decreases the average number of new skin cancers per patient per year, and there are no established statistical methods for analysis of data in this situation. Alternative approaches to the analysis are discussed.