What is the study design and population?
FPH 7240 – Introduction to Epidemiology
Fall 2018
Assignment 4 – Experimental Studies
Due: Thursday, October 4, 2018 at noon
Readings: This homework is based on the “Experimental Studies” chapter in Aschengrau & Seague and on the articles “Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicenter randomized controlled trial by Atkin et al.
Section A:
1. The following questions relate to the Atkin, et al. paper “Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicenter randomized controlled trial” posted along with the homework.
a) What is the study design and population?
b) What are the exposure and primary and secondary outcomes of this study?
c) Why do you think the investigators went through the step of sending out questionnaires to establish interest in screening before randomizing participants to receive an offer of a flexible sigmoidoscopy? What are the potential benefits and drawbacks of doing this?
d) On page 1625 (first full paragraph) the authors state: “Individuals reporting a strong family history of colorectal cancer (two or more close relatives), or symptoms of colorectal cancer were managed outside the trial because randomization would not have been in their interest.” Why is this the case? What is the principle the authors are adhering to here?
e) What are the hazard ratios (similar to a relative risk) of colorectal cancer incidence and of colorectal cancer mortality associated with the offer of a flexible sigmoidoscopy?
f) What are the relative risks of colorectal cancer incidence and of colorectal cancer mortality comparing those who actually received the sigmoidoscopy to the controls?
g) Which of the two sets of results above (4e or 4f) is more appropriate and why? Please state the results of the more appropriate result of the randomized study in a sentence?
Section B:
Please read the abstracts, identify the study design then provide very brief answers to the questions
Veugelers PJ , Porter GA , Guernsey DL , Casson AG : Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma. Dis Esophagus. 2006;19(5):321-8
The aim of this study was to examine the association of obesity with esophageal adenocarcinoma, and with the precursor lesions Barrett esophagus and gastroesophageal reflux disease (GERD). This case-control study included cases with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic regression methods, we compared obesity rates between cases and controls adjusting for differences in age, gender, and lifestyle risk factors. Relative to normal weight, obese individuals were at increased risk for esophageal adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27-17.9). Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95% CI 0.19-0.87), Barrett esophagus (OR 0.44, 95% CI 0.20-0.98), and esophageal adenocarcinoma (OR 0.21, 95% CI 0.06-0.77). For the more established risk factors, we confirmed that smoking was a significant risk factor for esophageal adenocarcinoma, and that increased liquor consumption was associated with GERD and Barrett esophagus. In light of the current obesity epidemic, esophageal adenocarcinoma incidence rates are expected to continue to increase. Successful promotion of healthy body weight and diets high in vitamin C may substantially reduce the incidence of this disease.
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Miyake Y , Iki M . Lack of association between water hardness and coronary heart disease mortality in Japan. Int J Cardiol. 2004 Jul;96(1):25-8
BACKGROUND: Elevated levels of water hardness are related to lower mortality from coronary heart disease (CHD) in different populations. This ecologic study assessed whether water hardness is related to lower mortality from CHD in Osaka Prefecture, with 44 municipalities, Japan. METHODS: The mortality rate from CHD per municipality was calculated based on the number of coronary deaths and midyear population in 1995. Values for water hardness in each of the municipalities were estimated based on the yearly amount of water supply per source and the yearly average of water hardness for each source in 1997. Multiple logistic regression analysis was used to control socioeconomic status and health care status in each municipality. RESULTS: In males, after adjustment for age, an inverse dose-response relationship between water hardness and mortality from CHD was significant (P for linear trend=0.004). However, this relationship virtually disappeared after further adjusting for socioeconomic status and health care status. In females, there was no material association between water hardness and coronary mortality. CONCLUSIONS: This study provides no evidence that water hardness is preventive against mortality from CHD in Japan.
2. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Bosset JF , Collette L , Calais G , Mineur L , Maingon P , Radosevic-Jelic L , Daban A , Bardet E , Beny A , Ollier JC ; EORTC Radiotherapy Group Trial 22921 . Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23.
BACKGROUND: Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival. RESULTS: We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%. CONCLUSIONS: In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control.
3. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Radnai M , Gorzo I , Urban E , Eller J , Novak T , Pal A : Possible association between mother’s periodontal status and preterm delivery. J Clin Periodontol. 2006 Sep 13; [Epub ahead of print]
Background: A case-control study was undertaken to detect whether initial chronic localized periodontitis could be a risk factor for preterm birth (PB) and fetal growth restriction. Methods: A PB case was defined if a patient had a threatening premature event during pregnancy pre-term premature rupture of membranes, or spontaneous pre-term delivery, before the 37th week of pregnancy, and/or the weight of the newborn was <2500 g. Into the PB (case) group, 77 women were allocated, while 84 were included in the control group, all of whom had delivery after the 37th gestational week and with a newborn weighing >/=2500 g. Results: A significant association was found between PB and initial chronic localized periodontitis, the criteria being bleeding at >/=50% of the examined teeth and having at least at one site at >/=4 mm probing depth (p=0.0001). The adjusted odds ratio for initial chronic localized periodontitis was 3.32, 95% CI: 1.64-6.69. The average weight of newborns of mothers with periodontitis was significantly less than that of the women without periodontitis (p=0.002). Conclusions: The results support the hypothesis that initial chronic localized periodontitis of pregnant women could lead to PB, and birth-weight reduction.
4. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Dugandzic R , Dodds L , Stieb D , Smith-Doiron M . The association between low level exposures to ambient air pollution and term low birth weight: a retrospective cohort study. Environ Health. 2006 Feb 17;5:3.
BACKGROUND: Studies in areas with relatively high levels of air pollution have found some positive associations between exposures to ambient levels of air pollution and several birth outcomes including low birth weight (LBW). The purpose of this study was to examine the association between LBW among term infants and ambient air pollution, by trimester of exposure, in a region of lower level exposures. METHODS: The relationship between LBW and ambient levels of particulate matter up to 10 um in diameter (PM10), sulfur dioxide (SO2) and ground-level ozone (O3) was evaluated using the Nova Scotia Atlee Perinatal Database and ambient air monitoring data from the Environment Canada National Air Pollution Surveillance Network and the Nova Scotia Department of Environment. The cohort consisted of live singleton births (> or =37 weeks of gestation) between January 1, 1988 and December 31, 2000. Maternal exposures to air pollution were assigned to women living within 25 km of a monitoring station at the time of birth. Air pollution was evaluated as a continuous and categorical variable (using quartile exposures) for each trimester and relative risks were estimated from logistic regression, adjusted for confounding variables. RESULTS: There were 74,284 women with a term, singleton birth during the study period and with exposure data. In the analyses unadjusted for year of birth, first trimester exposures in the highest quartile for SO2 and PM10 suggested an increased risk of delivering a LBW infant (relative risk = 1.36, 95% confidence interval = 1.04 to 1.78 for SO2 exposure and relative risk = 1.33, 95% confidence interval = 1.02 to 1.74 for PM10). After adjustment for birth year, the relative risks were attenuated somewhat and not statistically significant. A dose-response relationship for SO2 was noted with increasing levels of exposure. No statistically significant effects were noted for ozone. CONCLUSION: Our results suggest that exposure during the first trimester to relatively low levels of some air pollutants may be associated with a reduction in birth weight in term-born infants. These findings have implications for the development of effective risk management strategies to minimize the public health impacts for pregnant women.
5. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Kuper H , Adami HO , Theorell T , Weiderpass E . Psychosocial determinants of coronary heart disease in middle-aged women: a prospective study in Sweden. Am J Epidemiol. 2006 Aug 15;164(4):349-57.
A social gradient in coronary heart disease (CHD) has been documented in a variety of settings, predominantly among men. This study aimed to establish whether a social gradient in CHD existed in a group of Swedish women and whether it could be explained by established coronary risk factors or psychosocial factors. The Women’s Lifestyle and Health Cohort Study includes 49,259 women from Sweden aged 30-50 years at baseline (1991-1992), when an extensive questionnaire was completed. There was complete follow-up through linkages to national registries until the end of 2002, during which time 210 cases of incident fatal CHD or nonfatal myocardial infarction occurred. Risk of CHD was significantly inversely related to years of education, the socioeconomic status proxy (hazard ratio comparing the lowest with the highest education group = 3.3, 95% confidence interval: 2.2, 4.7). This association was reduced after adjustment for established coronary risk factors (smoking, body mass index, alcohol consumption, diabetes, hypertension, exercise; hazard ratio = 1.9, 95% confidence interval: 1.3, 2.8). Job strain and social support were weakly related to CHD and did not explain the gradient by years of education. Self-rated health was strongly related to CHD, mediated by established coronary risk factors. Results show a strong gradient in CHD by years of education explained by established coronary risk factors but not by job strain or social supp
6. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?
Peterson NB , Trentham-Dietz A , Newcomb PA , Chen Z , Hampton JM , Willett WC , Egan KM . Alcohol consumption and ovarian cancer risk in a population-based case-control study. Int J Cancer. 2006 Aug 18;119(10):2423-2427
Alcohol consumption has been investigated as a possible risk factor for ovarian cancer in several epidemiological studies, with inconsistent findings. Recent studies have suggested that the association between alcohol consumption and ovarian cancer may vary according to histologic subtype of ovarian cancer and type of alcohol consumed (e.g., wine, beer, or liquor). We examined these associations in a population-based case-control study comprised of 762 incident cases of epithelial ovarian cancer and 6,271 population controls from Massachusetts and Wisconsin aged 40-79 years. Women reported their usual alcohol consumption as young adults (20-30 years of age) and in the recent past. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. There was no significant association of ovarian cancer with increasing alcohol consumption either during ages 20-30 years (p trend 0.42) or in the recent past (p trend 0.83). Regular drinking of beer (1 drink/day or more) during ages 20-30 (OR 1.55, 95% CI 1.07-2.26), though not liquor (OR 1.35, 95% CI 0.86-2.11) or wine (OR 0.99, 95% CI 0.49-2.00), was associated with a statistically significant increase in risk of invasive tumors, whereas no significant relationships were observed for recent drinking, regardless of alcohol type. The elevated risk for early adult regular drinking was confined to serous invasive tumors (OR 1.52, 95% CI 1.01-2.30), though results for other subtypes were based on sparse data and results were imprecise. In this study, neither total alcohol consumption as a young adult nor recently was associated with an increase in the risk of ovarian cancer.
7. What study design is used?
a. What were the comparison groups?
b. Were the comparison groups chosen the basis of disease status or “exposure” status?
c. What exposure or treatment was the author primarily focused on, to describe its possible causal association with disease or outcome.
d. Does exposure (treatment) occur before disease onset (outcome)?