No abstract

SummaryBackgroundOesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.MethodsThe Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FindingsBetween March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01–1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98–1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.InterpretationHigh-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FundingCancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).

No abstract

BackgroundIn endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh.MethodsThis cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011.ResultsOf 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera.The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge.ConclusionsThe findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.

A feasibility study of an oral cholera vaccine was carried out to test strategies to reach high-risk populations in urban Mirpur, Dhaka, Bangladesh. The study was cluster randomized, with three arms: vaccine, vaccine plus safe water and hand washing practice, and no intervention. High risk people of age one year and above (except pregnant woman) from the two intervention arms received two doses of the oral cholera vaccine, Shanchol™. Vaccination was conducted between 17th February and 16th April 2011, with a minimum interval of fourteen days between two doses. Interpersonal communication preceded vaccination to raise awareness amongst the target population. The number of vaccine doses used, the population vaccinated, left-out, drop out, vaccine wastage and resources required were documented. Fixed outreach site vaccination strategy was adopted as the mode of vaccine delivery. Additionally, mobile vaccination sites and mop-up activities were carried out to reach the target communities. Of the 172,754 target population, 141,839 (82%) and 123,666 (72%) received complete first and second doses of the vaccine, respectively. Dropout rate from the first to the second dose was 13%. Two complete doses were received by 123,661 participants. Vaccine coverage in children was 81%. Coverage was significantly higher in females than in males (77% vs. 66%, P<0.001). Vaccine wastage for delivering the complete doses was 1.2%. The government provided cold-chain related support at no cost to the project. Costs for two doses of vaccine per-person were US$3.93, of which US$1.63 was spent on delivery. Cost for delivering a single dose was US$0.76. We observed no serious adverse events. Mass vaccination with oral cholera vaccine is feasible for reaching high risk endemic population through the existing national immunization delivery system employed by the government.

Diarrhea remains one of the major causes of death in Bangladesh. We studied diarrheal disease risk and healthcare seeking behavior among populations at high risk for diarrhea in Dhaka, Bangladesh. Data were obtained from a cross-sectional survey conducted during April and September 2010. The prevalence of diarrhea was calculated by age-group and sex. A generalized estimating equation with logit link function was used to predict diarrheal disease risk and seeking care from a professional healthcare provider. Of 316,766 individuals, 10% were young children (<5 years). The prevalence of diarrhea was 16 per 1000 persons among all ages; young children accounted for 44 per 1000 persons. Prevalence of diarrhea was significantly higher (p=.003) among younger males (<15 years) compared to that among younger females. In contrast, prevalence of diarrhea was significantly higher (p<.0001) among older females (≥15 years) compared to that among older males. An increased risk for diarrhea was observed in young children, males, and those staying in rented houses, lower family members in the house, using non-sanitary toilets, living in the area for short times, living in a community with less educated persons, living in a community with less use of safe water source for drinking, or living close to the hospital. About 80% of those with diarrhea sought care initially from a non-professional healthcare provider. Choice of the professional healthcare provider was driven by age of the patient, educational status of the household head, and hygienic practices by the household. The study reaffirms that young children are at greater risk for diarrhea. Like other developing countries most people in this impoverished setting of Dhaka are less likely to seek care from a professional healthcare provider than from a non-professional healthcare provider, which could be attributed to a higher number of diarrheal deaths among young children in Bangladesh. Dissemination of information on health education, increasing the supply of skilled healthcare providers, and low-cost and quality healthcare services may encourage more people to seek care from professional healthcare providers, thus may help reduce child mortality in the country. Further studies are warranted to validate the results.

BackgroundCholera poses a substantial health burden to developing countries such as Bangladesh. In this study, the objective is to estimate the economic burden of cholera treatments incurred by households. The study was carried out in the context of a large vaccine trial in an urban area of Bangladesh.MethodsThe study used a combination of prospective and retrospective incidence-based cost analyses of cholera illness per episode per household. A total of 394 confirmed cholera hospitalized cases were identified and treated in the study area during June–October 2011. Households with cholera patients were interviewed within 15 days after discharge from hospitals or clinics. To estimate the total cost of cholera illness a structured questionnaire was used, which included questions on direct medical costs, non-medical costs, and the indirect costs of patients and caregivers.ResultsThe average total household cost of treatment for an episode of cholera was US$30.40. Total direct and indirect costs constituted 24.6% (US$7.40) and 75.4% (US$23.00) of the average total cost, respectively. The cost for children under 5 years of age (US$21.50) was higher than that of children aged 5–14 years (US$17.50). The direct cost of treatment was similar for male and female patients, but the indirect cost was higher for males.ConclusionOur study suggests that by preventing one cholera episode (3 days on an average), we can avert a total cost of 2,278.50 BDT (US$30.40) per household. Among medical components, medicines are the largest cost driver. No clear socioeconomic gradient emerged from our study, but limited demographic patterns were observed in the cost of illness. By preventing cholera cases, large production losses can be reduced.