+1 862 207 3288 The questions in Section 1 relate to the article:
Argos M et al. Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study. The Lancet 2010; 376:252- 258.
Q1. What was the aim of this study? (1 mark)
Q2. Identify the criteria for selection into the study and discuss the advantages and disadvantages of these criteria. (5 marks)
Q3. a) Were the authors successful at minimising loss-to-follow-up? Provide data to support your answer. (3 marks)
b) Who (which groups) would be most likely to drop out? (2 marks)
Q4. What was the primary outcome of the study and how was it ascertained? (2 marks)
Q5. Comment on the advantages and disadvantages of the method of ascertainment of the outcome? (4 marks)
Q6. a) What were the exposure variables and how were they defined? (3 marks)
b) Comment on the strengths and weaknesses of the exposure variables. (5 marks)
Q7. Is there evidence that BMI is a confounder of the relationship between arsenic exposure and mortality? (2 marks)
Q8. On page 255, 3rd paragraph, the authors report the finding that “a one-quartile increase in arsenic concentration in well water was associated with a 15% increase in all-cause mortality (95% CI 1.05-1.26)”. Explain in your own words the interpretation of this 95% CI. (2 marks)
Q9. On page 255, 5th paragraph, the authors report the finding that “multivariate-adjusted Hazard Ratio (HR) for comparison of high baseline exposure to low baseline exposure was 1.46 (95% CI 1.14-1.86) for deaths occurring after follow up 1”. Explain in your own words the interpretation of the HR. (3 marks)
Q10. Did the authors observe a change in risk of death associated with changes in arsenic concentration in urine over time? Refer to or provide data to support your answer.
(2 marks)
Q11. What is the interpretation of the attributable proportion based upon well water for chronic-disease mortality of 24%? (2 marks)
Q12. Imagine you are designing a RCT to evaluate the impact on urine arsenic of an intervention to reduce arsenic exposure in well water. The intervention is the one–off addition of a chemical to remove arsenic in the water. The follow up will be 6 months.
a) Who would be your study population? (2 marks)
b) Draw a diagram to illustrate the study design. (3 marks)
c) Identify and explain one ethical issue of this study. (3 marks)
Q13. An outbreak of gastroenteritis that appears to be related to the consumption of fast food has recently occurred in Mandurah. A case-control study was undertaken and the following results found.
Food item Cases (n= 19) Controls (n=17)
Crumbed chicken 14 11
Any chicken 16 16
Egg rolls 14 3
Fried rice 14 9
a) Which food(s) do you suspect to be the cause of this outbreak? Give reasons for your answer. (5 marks)
b) Was a case-control study the best study design to use here? Explain your answer.
(4 marks)
Q14. In a matched cohort study of oral contraceptive (OC) use and breast cancer, where the exposed: non-exposed ratio was 1:1, the matched-pair findings were as follows.
No history of OC use
Breast cancer No breast cancer
Previous OC use Breast cancer 12 102
No breast cancer
32
87
a) What is the relative risk of breast cancer for those with a history of OC use? Show all working. (5 marks)
b) The 95% confidence interval for the RR is 1.1- 26.5. What does this mean in terms of possible random error in the study? (2 marks)
Q15. A new screening test for HIV in blood products was administered to 700 people with clinically proven HIV and to 900 people without HIV. The screening test was positive for 670 of the proven HIV cases and 150 of the people without HIV.
a) Calculate the sensitivity and specificity of the test. (2 marks)
b) The old screening test for HIV has a sensitivity of 80% and its specificity is 97%. Discuss if you would recommend the old or the new screening test for community based screening of blood donations? (3 marks)
Q16. A number of employees at a factory in WA have recently been diagnosed with cancer and the union has demanded an investigation into whether exposure to the factory working environment is placing their members at increased risk of cancer. You are asked to determine whether an increased risk exists and if so provide an estimate of the degree that factory workers are at risk compared with the community.
A total of 16 cases of the cancer have been diagnosed in factory workers over the last 10 years. You collect the following data from those who have had a cancer diagnosis while working at the factory over this time frame.
AGE GROUP in years PERSON YEARS AT RISK Cases
15-19 22.2 0
20-24 325.8 0
25-29 440.1 1
30-34 505.7 2
35-39 425.1 3
40-44 322.8 4
45-49 243.8 3
50-54 211.7 2
55-59 129.6 0
60-64 79.8 1
65-69 5.0 0
70-74 3.0 0
TOTAL 2714.4 16
Recent research has reported that the incident rate of the cancer in the WA population is 3330 per 100,000 person-years, with an age distribution in the community as follows:
AGE GROUP in years Age-specific IR in Western Australia (per 100,000PY)
15-19 0.283
20-24 1.646
25-29 11.770
30-34 44.110
35-39 103.474
40-44 196.288
45-49 335.884
50-54 413.418
55-59 503.016
60-64 569.476
65-69 565.352
70-74 585.785
Using the above information above, determine the age-standardised rate ratio (show all working) for cancer in the factory workers compared with the community and describe (in lay terms) what this result means. (5 marks)
Articles
252 www.thelancet.com Vol 376 July 24, 2010
Lancet 2010; 376: 252–58
Published Online
June 19, 2010
DOI:10.1016/S0140-
6736(10)60481-3
See Comment page 213
Department of Health Studies
(M Argos MPH, T Kalra MPH,
P J Rathouz PhD, B Pierce PhD,
Prof H Ahsan MD), and
Departments of Medicine and
Human Genetics and Cancer
Research Center, University of
Chicago, Chicago, IL, USA
(Prof H Ahsan); Department of
Epidemiology (M Argos,
Prof H Ahsan), and Department
of Environmental Health
Sciences (F Parvez MPH,
V Slavkovich MS,
Prof J Graziano PhD), Mailman
School of Public Health,
Columbia University, New
York, NY, USA; Department of
Environmental Medicine,
New York University, New York,
NY, USA (Y Chen PhD);
Columbia University and
University of Chicago Research
Offi ce in Bangladesh,
Mohakhali, Dhaka, Bangladesh
(T Islam MBBS, A Ahmed MBBS,
M Rakibuz-Zaman MBBS,
R Hasan MA, G Sarwar BS); and
Lamont-Doherty Earth
Observatory of Columbia
University, Palisades, NY, USA
(A van Geen PhD)
Correspondence to:
Prof Habibul Ahsan, Center for
Cancer Epidemiology and
Prevention, University of
Chicago, 5841 South Maryland
Avenue, Suite N102, Chicago,
IL 60637, USA
habib@uchicago.edu
Arsenic exposure from drinking water, and all-cause and
chronic-disease mortalities in Bangladesh (HEALS):
a prospective cohort study
Maria Argos, Tara Kalra, Paul J Rathouz, Yu Chen, Brandon Pierce, Faruque Parvez, Tariqul Islam, Alauddin Ahmed, Muhammad Rakibuz-Zaman,
Rabiul Hasan, Golam Sarwar, Vesna Slavkovich, Alexander van Geen, Joseph Graziano, Habibul Ahsan
Summary
Background Millions of people worldwide are chronically exposed to arsenic through drinking water, including
35–77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been
prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic
and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a
Bangladeshi population.
Methods In the prospective cohort Health Eff ects of Arsenic Longitudinal Study (HEALS), trained physicians
unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants
(aged 18–75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and
followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional
hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at diff erent
doses of arsenic exposure.
Findings 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for
all-cause mortality in a comparison of arsenic at concentrations of 10·1–50·0 µg/L, 50·1–150·0 µg/L, and
150·1–864·0 µg/L with at least 10·0 µg/L in well water were 1·34 (95% CI 0·99–1·82), 1·09 (0·81–1·47), and
1·68 (1·26–2·23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine.
Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have
much eff ect on the mortality rate.
Interpretation Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate.
Follow-up data from this cohort will be used to assess the long-term eff ects of arsenic exposure and how they might
be aff ected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting
health eff ects of arsenic exposure.
Funding US National Institutes of Health.
Introduction
Exposure to arsenic through groundwater has been a
major public health problem in the USA, Taiwan, Mexico,
Mongolia, Argentina, India, Chile, and Bangladesh.
WHO described the arsenic crisis in Bangladesh as “the
largest mass poisoning of a population in history”.1 An
estimated 35–77 million people in Bangladesh have been
chronically exposed to increased concentrations of
arsenic through drinking water, beginning in the 1970s
when about 10 million hand-pumped wells were installed
to provide pathogen-free groundwater for the prevention
of waterborne diseases.2,3 However, the natural
contamination of the groundwater with arsenic in these
wells was not realised until the 1990s.
Exposure to arsenic in drinking water has been
associated with several cancers; toxic eff ects on the liver,
skin, kidney, cardiovascular system, and lung; and fatal
poisoning.4–10 Dose-dependent associations have been
shown between arsenic levels in well water and cancers
of the bladder, kidney, skin, and lung.6,8,9,10 Dose-response
associations between arsenic exposure and peripheral
vascular disease have also been reported.11–13
Increased mortality rates from chronic diseases in
arsenic-exposed populations have been reported in studies
done in the USA, Chile, Argentina, Taiwan, and
Bangladesh.4,7,11,14–18 These studies were restricted, however,
to group-level data and were retrospective in design. Such
limitations—individual-level inferences based on aggregate
data and error in exposure measurement—do not resolve
doubts about the association between mortality rates and
arsenic exposure.
The Health Eff ects of Arsenic Longitudinal Study
(HEALS)19 provides a valuable opportunity for us to
investigate the association between arsenic exposure and
mortality rates using a prospective design and repeated
individual-level assessment of arsenic exposure. In this
study, we use data from the HEALS cohort to assess the
risk of all-cause and chronic-disease mortalities in
relation to chronic arsenic exposure at the individual
level through well water and repeated measurements of
