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In order to examine the association of smoking cigarettes with a lower tar and nicotine yield to peptic ulcer disease, a common disease associated in past studies with cigarette smoking. We used questionnaire information provided by 9009 current regular cigarette smokers. The percentage who ever had peptic ulcer disease in smokers whose current cigarette yielded 0.00-0.81, 0.81-0.99, 1.00-1.27 and 1.28 + milligrams of nicotine per cigarette were 8.5, 9.2, 9.2 and 9.5, respectively . The percentages who ever has peptic ulcer in smokers whose current cigarette yielded 0.0-11.9, 12.0-15.9, 16.0-18.9 and 19.0+ milligrams of tar per cigarette were 8.6, 9.1, 8.9 and 10.8 per 100, respectively. In contrast, the percentages who ever had peptic ulcer disease increased with the smoking of a greater number of cigarettes, being 5.9, 8.8, 9.0, 11.8 and 10.5 in smokers of less than 10, 10-19, 20-29, 30-39 and 40+ cigarettes, respectively. In multiple logistic regression analyses, peptic ulcer disease was significantly (p = 0.002) associated with number of cigarettes (RR = 1.12 per 10 cigarettes; 95% CI 1.08, 1.16), age and sex. There was no significant association (both p's less than 0.10) either with the current cigarette's tar yield (RR = 1.09 per 10 milligrams; 95% CI 0.96, 1.25) or with its nicotine yield (RR = 1.15 per milligram; 95% CI 0.94, 1.42).

Analysis of data from the Walnut Creek Contraceptive Drug Study showed a significant increase in risk of venous thromboembolic disease in the absence of surgery, trauma, malignancy, pregnancy, and the puerperium for women with a previous history of thromboembolism, hypertension, diabetes, varicose veins, gallbladder disease, and cigarette smoking. Education, marital status, parity, use of noncontraceptive estrogens, and obesity were not associated with an increase in risk of the disease. When only cases of the disease in the absence of all known predisposing causes (idiopathic cases) were analyzed, both oral contraceptive use and smoking remained as independent risk factors; there was no evidence of a positive interaction between them.

The California Automated Mortality Linkage System (CAMLIS), established in 1981 to facilitate the conduct of follow-up studies in the State of California, employs a combination of deterministic and probabilistic linkage decision criteria to perform the death clearance function. The system was evaluated against four traditional death clearance procedures and the performance of each procedure measured in terms of measures of sensitivity and specificity. Only one procedure was associated with a specificity lower than 0.99; for that one, the specificity was 0.93. There was much greater fluctuation in the observed sensitivity levels. In one of the procedures, CAMLIS demonstrated a sensitivity of 0.97 versus 0.79 for the Social Security Administration. A comparison against the National Death Index (NDI) produced sensitivities of 0.89 for CAMLIS and 0.94 for the NDI. An assessment of manual search procedures using a file of Japanese names produced a CAMLIS sensitivity measure of 0.92 compared with 0.93 for the manual search. Another manual search procedure using microfiche copies of the state death index produced a CAMLIS sensitivity of 0.97; in this evaluation, the sensitivity of the manual search was defined as 1.0. Another measure of performance of a death clearance procedure is its predictive value in identifying a person who has died; CAMLIS generated predictive values in these evaluations that ranged from 0.93 through 0.99, contrasted with the NDI value of 0.59.

To study the association between smoking cigarettes with a low yield of tar and nicotine (tar less than 15.0 mg per cigarette and nicotine less than 1.0 mg) and respiratory disease, we reviewed the medical records of 4,610 current, regular cigarette smokers and 2,035 persons who had never used any form of tobacco and who were enrolled in a smoking study. In the year after recruitment to the study, the percentage of subjects with pneumonia or influenza was lower in female but not in male smokers of low-yield cigarettes. The percentage of subjects with any disease of the respiratory tract was lower in both male and female smokers of low-yield cigarettes. In multiple logistic regression analyses in which tar was included as a continuous variable and in which we also controlled for age, sex, race, and number of cigarettes smoked per day, smoking lower tar cigarettes was associated with lower risk for pneumonia or influenza, but not with the risk for other acute respiratory infections, other diseases of the upper respiratory tract, chronic obstructive pulmonary disease and allied conditions, or all respiratory diseases considered as a group. In other multiple logistic regression analyses, in which we controlled for age, race, and sex, smokers of low-yield cigarettes had a higher risk for pneumonia or influenza and chronic obstructive pulmonary disease when compared with subjects who had never used tobacco. We conclude that, with regard to pneumonia and influenza seen in an outpatient setting, smoking low-yield cigarettes is probably less hazardous than smoking high-yield cigarettes, but it still represents a considerable hazard compared with not smoking cigarettes at all.

The effect of postmenopausal estrogen use on mortality is an important and controversial subject. To address it, we analyzed data from a ten- to 13-year mortality follow-up of the 3437 women enrolled in the Walnut Creek Contraceptive Drug Study who never used either estrogens or oral contraceptives and the 2656 women who used estrogens but not oral contraceptives. By 1983, 109 estrogen users and 110 nonusers had died. After adjusting for age, mortality in estrogen users (1.64 per 1000 woman-years) was lower than in nonusers (2.06 per 1000 woman-years) for all categories of cause of death except cancer. The lower mortality from accidents, suicide, and homicide in estrogen users has no plausible biologic explanation, and the observation suggests that life-style differences between estrogen users and nonusers account at least in part for their lower mortality. On the other hand, the observation that the relative risk of mortality due to cardiovascular disease was 0.5 in estrogen users, after adjustment for age and other cardiovascular disease risk factors, is suggestive.

By univariate analysis of patients with membraneous nephropathy, terminal renal failure was associated with male sex, a large amount of proteinuria, low serum albumin concentration, low creatinine clearance rate, high serum creatinine concentration, and high systolic blood pressure, but was not associated with age or prednisone treatment. In a multivariate life table analysis that controlled for all these factors simultaneously, the risk of developing terminal renal failure was significantly independently associated only with sex, serum albumin concentration, and prednisone treatment, being higher in men, lower in those treated with prednisone, and inversely related to serum albumin. Except for the minimal electron-dense deposition, the electron microscopic findings had no predictive value.

In a large cohort of women, the risk of subarachnoid haemorrhage was significantly associated both with cigarette smoking and with use of oral contraceptives (O.C.S.). The risk of cigarette smokers was 5.7 times that of non-smokers; for current users of O.C.S. the risk was 6.5 times that of non-users. The risk in women who both smoked cigarettes and used O.C.S was 22 times that of women who neither smoked nor used O.C.S. Past use of O.C.S was also significantly associated with increased risk of subarachnoid haemorrhage, the relative risk being 5.3. There was some evidence that risk may increase with duration of O.C. use. In this series no significant associations were found between occurrence of subarachnoid haemorrhage and history of hypertension or of migraine headache.

To study the relation of method of delivery to perinatal mortality, we examined information from the deliveries of 1593 breech infants weighing 1000 g or more born in 1976 and 1977. In none of the birthweight groups 1000 g or more was neonatal mortality significantly different between infants delivered vaginally compared with those delivered by cesarean section, although the number of deaths was small. In all the birthweight groups, perinatal mortality was higher in breeches delivered vaginally, but the differences were because all of the infants who died before labor were delivered vaginally. Total mortality (intrapartum plus neonatal deaths) in infants who survived to labor was not significantly different in breech infants delivered by one or the other method at any birthweight. These data suggest that routine cesarean delivery for infants 1000 g or more who are in the breech presentation may not be justified from the standpoint of mortality.

To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation.

Using questionnaire information provided by 4.385 vasectomized and 13,155 matched, non-vasectomized men, we found no significant differences between them for a large number of symptoms and diseases, including those of the cardiovascular system. After taking into account differences in their martial status, past smoking habits, and physical activity at work, significant statistical associations of vasectomy with joint pain or swelling, back trouble, and a history of kidney or bladder infection persisted. Our data are inconsistent with the occurrence of large increases in the risks of many important diseases in vasectomized humans.

To determine the relation of smoking low yield cigarettes (tar yield less than 15.0 mg and nicotine yield less than 1.0 mg per cigarette) to the number of cigarettes smoked per day, we analysed information provided on self-administered questionnaires by 7706 current, regular cigarette smokers. The mean age at starting to smoke and the mean number of years of smoking were not consistently different in smokers of low yield compared with smokers of high yield cigarettes. In contrast, at all ages in both men and women, smokers of low yield cigarettes smoked significantly more cigarettes per day than smokers of high yield cigarettes. The differences in the number of cigarettes smoked per day between smokers of low and high yield cigarettes were small--about 3 cigarettes per day in men and about 1 1/2 cigarettes per day in women. However, these small differences might translate to the smoking of as many as one billion more packs of cigarettes per year in the United States alone. The potential beneficial effect of the smoking of cigarettes whose yield per cigarette is lower must be weighed against a possible adverse effect of the smoking of more cigarettes if the relation between smoking low yield cigarettes and smoking more cigarettes is causal.

To determine the association of duration of warfarin anticoagulant therapy after hospitalization for venous thromboembolism with the probability of recurrent thromboembolism and with the risks of hemorrhage, medical records of 2,422 patients hospitalized in 1970 through 1980 with pulmonary embolism, thrombophlebitis, or both were reviewed. Multivariate life-table analyses were performed for 370 patients who had positive results of venography or pulmonary angiography, or who had lung scanning evidence of a "high probability" of pulmonary embolism and no history of the disease. For these patients, warfarin therapy for more than six weeks was not associated with a lower risk of recurrent thromboembolism when compared with warfarin therapy for one through six weeks (risk of recurrence for seven to 26 weeks of treatment 0.8; 95 percent confidence limits 0.3 and 2.5; risk of recurrence for more than 26 weeks of treatment 1.1; 95 percent confidence limits 0.4 and 3.1). The longer the warfarin therapy, the higher the risk of medically important complications from therapy. From one week through five years, the probability of major hemorrhage increased almost linearly: 10 percent for 12 weeks, 18 percent at one year, 26 percent at two years, and 41 percent at five years. This study suggests that intensive, long-term warfarin anticoagulation, in patients with a first episode of venous thromboembolism and no predisposing condition, is associated with more toxicity than efficacy and should be abandoned.

Information from examinations of 62,541 adults enrolled in a study of smoking from 1979 through 1982 in Oakland, California, was used to explore the associations of various measures of intensity of smoking with the leukocyte count and to try to determine whether there was a persistent effect of smoking cigarettes on the leukocyte count. In current, regular cigarette smokers, leukocyte counts were higher in smokers of a large number of cigarettes and were associated with smoking cigarettes with a high tar and nicotine yield, deep inhalation of the cigarette smoke, and a longer duration of smoking. There was an association of past smoking with a high leukocyte count independent of age, sex, and race. In past smokers of cigarettes who used no other form of tobacco, the leukocyte count was related to time since quitting, smokers who had quit more recently having higher leukocyte counts. The study shows that a high leukocyte count is associated consistently with various measures of intensity of cigarette smoking. Moreover, it appears that smoking has an effect on the leukocyte count that persists after quitting. Delineation of the physiologic basis for the acute and chronic effects of cigarette smoking on the leukocyte count might lead eventually to a better understanding of the mechanisms for regulation of granulopoiesis and the release and destruction of leukocytes.

We previously showed that the risk of major hemorrhage in patients with venous thromboembolism treated with warfarin was strongly related to duration of anticoagulant therapy. We here report the results of a more detailed analysis of factors other than duration of warfarin therapy associated with the risk of hemorrhage in these patients. Almost 7% of patients had a major hemorrhage on warfarin and an additional 23.7% had at least one minor bleeding episode. Age, female sex, and congestive heart failure were associated with small increases in the risk of major hemorrhage but not with the risk of minor bleeding. A prothrombin time ratio greater than 2.5 was associated with a fourteen-fold increase in the risk of a major hemorrhage (95% CI 5.1, 42.7), but major hemorrhages occurred in patients on warfarin at all measured values of the prothrombin time ratio. Taken together with the findings from our previous analysis, the study suggests that prevention of bleeding in patients on warfarin would best be accomplished by minimizing the duration of warfarin therapy, by scrupulous monitoring of the prothrombin time ratio, and by considering the "therapeutic range" for the prothrombin time ratio to be somewhat less than 2.0-2.5.

A pilot study of more than 400 clinical faculty was conducted in spring 1985 by the Division of Family and Community Medicine, University of California, San Francisco, to identify physicians interested in participating in collaborative research. Six different approaches to collaborative research were defined, and the respondents indicated their "enthusiasm" to each of the approaches and the methodologies that each would involve. Based on response to mail and phone surveys, it is estimated that 40 percent of the clinical faculty have some interest in collaborative research. Their preferences for the approaches were: (1) randomized trials, 63 percent; (2) surveys of patients, 60 percent; (3) evaluation of physician practices, 59 percent; (4) referral of patients for research conducted elsewhere, 54 percent; (5) research involving chart review, 53 percent; and (6) research involving a change in clinical practice, 38 percent. Thus, there is preference for more complex types of studies, but this can create a dilemma for those who wish to stimulate research among unproven investigators.

In its 1982 report on toxic shock syndrome, the institute of Medicine, Washington, DC, identified population-based studies of the incidence of toxic shock syndrome over time based on hospital records as being a high priority for further research. We conducted such a study using records of hospitalizations in Northern California Kaiser-Permanente Medical Care Program facilities for the period from 1972 through 1983 among women and men aged 15 through 34 for illnesses considered possibly to be toxic shock syndrome. Of 6,688 hospitalizations reviewed, 54 were considered definite cases of toxic shock syndrome, and an additional nine were considered probable toxic shock syndrome. Four definite cases of toxic shock syndrome occurred in men, and 50 in women. The overall incidence of definite hospitalized toxic shock syndrome in men was 0.1 per 100,000 person-years, and in women 1.5 per 100,000 person-years. In women, an increase in the incidence of toxic shock syndrome was apparent by 1977; the rate peaked in 1980, decreased slightly in 1981 and 1982, and then almost doubled again in 1983. The temporal trend in the incidence of hospitalized toxic shock syndrome in women in the years 1977 through 1982 is consistent with the best available information on patterns of use of tampons containing higher-absorbency materials. The sharp increase in the incidence of hospitalized toxic shock syndrome in 1983 remains unexplained.

A case-control study of low birthweight among residents of high risk areas of Alameda County was conducted in 1983. The relation of 13 variables to low birthweight was assessed using a multiple logistic regression analysis. A six-fold increase in the risk of low birthweight was found in association with financial problems during the current pregnancy, controlling for differences in race, certain poor health habits, complications of pregnancy, and several other factors between cases and controls.