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Lung Cancer & Smoking Case Study A causal relationship between cigarette smoking and lung cancer was first suspected in the 1920s on the basis of clinical observations. To test this apparent association, numerous epidemiologic studies were undertaken between 1930 and 1960. Two studies were conducted by Richard Doll and Austin Bradford Hill in Great Britain The first was a case-control study begun in 1947 comparing the smoking habits of lung cancer patients with the smoking habits of other patients. The second was a cohort study begun in 1951 recording causes of death among British physicians in relation to smoking habits. This case study deals first with the case- control study, then with the cohort study. Data for the case-control study were obtained from hospitalized patients in London and vicinity over a 4-year period (April 1948 - February 1952). Initially, 20 hospitals, and later more, were asked to notify the investigators of all patients admitted with a new diagnosis of lung cancer. These patients were then interviewed concerning smoking habits, as were controls selected from patients with other disorders (primarily non-malignant) who were hospitalized in the same hospitals at the same time Data for the cohort study were obtained from the population of all physicians listed in the British Medical Register who resided in England and Wales as of October 1951. Information about present and past smoking habits was obtained by questionnaire. Information about lung cancer came from death certificates and other mortality data recorded during ensuing years Over 1,700 patients with lung cancer, all under age 75, were eligible for the case-control study. About 10% of these persons were not interviewed because of death, discharge, severity of illness, or inability to speak English. An additional group of patients were interviewed but later excluded when initial lung cancer diagnosis proved mistaken. The final study group included 1,530 casesTable 2 shows the frequency distribution of male cases and controls by average number of cigarettes moked per day Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer cases and matched controls with other diseases, Great Britain, 1948-1952 Daily number of cigarettes # Cases # Controls Odds Ratio 68 785 482 195 1,462 1,530 referent 1-14 15-24 25+ All smokers Total 622 498 402 1,522 1,530The next section of this case study deals with the cohort study ex-smokers were asked the amount they smoked, their method of smoking, the age they started to smoke, and, if they had stopped smoking, how long it had been since they last smoked. Nonsmokers were defined as persons who had never consistently smoked as much as one cigarette a day for as long as one year. Data for the cohort study were obtained from the population of all physicians listed in the British Medical Register who resided in England and Wales as of October 1951. Questionnaires were mailed in October 1951, to 59,600 physicians The questionnaire asked the physicians to classify themselves into one of three categories 1) current smoker, 2) ex-smoker, or 3) nonsmoker. Smokers and Usable responses to the questionnaire were received from 40,637 (68%) physicians, of whom 34,445 were males and 6,192 were females.The next section of this case study is limited to the analysis of male physician respondents, 35 vears of age or older were from cytology, bronchoscopy, or X-ray alone, and only 1% were from just case history physical examination, or death certificate The occurrence of lung cancer in physicians responding to the questionnaire was documented over a 10-year period (November 1951 through October 1961) from death certificates filed with the Registrar General of the United Kingdom and from lists of physician deaths provided by the British Medical Association. All certificates indicating that the decedent was a physician were abstracted. For each death attributed to lung cancer, medical records were reviewed to confirm the diagnosis Of 4,597 deaths in the cohort over the 10-year period, 157 were reported to have been caused by lung cancer; in 4 of the 157 cases this diagnosis could not be documented, leaving 153 confirmed deaths from lung cancer The following table shows numbers of lung cancer deaths by daily number of cigarettes smoked at the time of the 1951 questionnaire (for male physicians who were nonsmokers and current smokers only). Person-years of observation (person-years at risk) are given for each smoking category. The number of cigarettes smoked was available for 144 of the persons who died from lung cancer. Diagnoses of lung cancer were based on the best evidence available, about 70% were from biopsy, autopsy, or sputum cytology (combined with bronchoscopy or X-ray evidence): 29%Table 3. Number and rate (per 1,000 person-years) of lung cancer deaths by number of cigarettes smoked per day, Doll and Hill physician cohort study, Great Britain, 1951-1961 Daily number of Rate difference cigarettes smoked Deaths from lung cancer erson Mortality rate years at risk per 1000 erson-Vears Rate Ratio per 1000 erson-Vears 42,800 38,600 38,900 25,100 102,600 145,400 0.07 referent referent 1-14 15-24 25+ All smokers Total 23 56 62 141 144NOTE: For 19, 20, 22, and 23 you MUST show the equations along with the answers.The cohort study also provided mortality rates for cardiovascular disease among smokers and nonsmokers. The following table presents lung cancer mortality data and comparable cardiovascular disease mortality data Table 4. Mortality rates (per 1,000 person-years), rate ratios, and excess deaths from lung cancer and cardiovascular disease by smoking status, Doll and Hill physician cohort study, Great Britain, 1951-1961 Attributable risk percent Mortality rate per 1,000 person-years Non-smokers 0.07 7.32 Excess deaths per 1,000 person-years among Smokers 1.37 9.51 All 0.99 8.87 Rate ratio smokers Lung cancer 19.6 95% 23% Cardiovascular disease 2.19In calculating the attributable risk percent, the excess lung cancer deaths attributable to smoking is expressed as a percentage of all lung cancer mortality among all smokers. The attributable risk percent of 95% for smoking may be interpreted as the proportion of lung cancer deaths among smokers that could have been prevented if thev had not smoked population. From a prevention perspective, the population attributable risk percent for a given exposure can be interpreted as the proportion of cases in the entire population that would be prevented if the exposure had not occurred. The population attributable risk percent is often usecd in assessing the cost-effectiveness and cost- benefit of community-based intervention programs A similar measure, the population attributable risk percent expresses the excess lung cancer deaths attributable to smoking as a percentage of all lung cancer mortality among the entire One formula for the population attributable risk percent is PAR%-(incidence in entire population-incidence in unexposed) / Incidence in entire populationThe following table shows the relationship between smoking and lung cancer mortality in terms of the effects of stopping smoking Table 5. Number and rate (per 1,000 person-years) of lung cancer deaths for current smokers and ex- smokers by years since quitting, Doll and Hill physician cohort study, Great Britain, 1951-1961 Lung cancer deaths Rate per 1000 erson-Vears Cigarette smoking status Current smokers For ex-smokers, years since quitting: Rate Ratio 141 1.37 19.6 5 years 5-9 years 10-19 years 20+ years 0.67 0.49 0.18 0.19 9.6 7.0 2.6 2.7 Nonsmokers 0.07 1.0 (ref) Question 24: Using the rate ratios from above, what does the trend imply for the practice of public health an preventive medicine?Question 28: Which of the following criteria for causality are met by the evidence presented from these two studies? Answer 28 YES NO Strong association Consistency among studies Exposure precedes disease Dose-response effect Biologic plausibility

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Answer #1

question 24:

Trend on public health and preventive medicine:

1. Cigaratte smoking increase the risk of lung cancer.

2. Smoking also increase the risk of cardio vascular diseases.

3. Disease among exposed people are increasing..

4. Mortality rate also increasing.

28.

Answer:

Yes, cigarettes smoking will have strong association with diseases.

Strong association.

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