Robert J. Lipnick

Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis

Although thrombolysis with streptokinase has been compared with heparin anticoagulation for treating acute proximal deep venous thrombosis in several randomized trials, no individual study has had a sample of sufficient size to determine with adequate power both efficacy and safety. Therefore, results were pooled from six randomized studies in which phlebography was used to confirm the diagnosis and to assess therapy. Thrombolysis was achieved 3.7 times more often among patients treated with streptokinase than among patients treated with heparin (95 percent confidence limits 2.5, 5.7; p less than 0.0001). Only three studies allowed comparison of these drugs for major bleeding complications, which were 2.9 times greater with streptokinase than with heparin (95 percent confidence limits 1.1, 8.1; p = 0.04). Thus, in aggregate, streptokinase-treated patients achieved thrombolysis but also seemed to experience major bleeding complications more frequently than those assigned at random to receive heparin. Future trials of sufficient sample size should be undertaken to evaluate efficacy and safety. Such trials, which should include newer fibrinolytic agents, are necessary to determine optimal therapy for acute proximal deep venous thrombosis.

Moderate alcohol and decreased cardiovascular mortality in an elderly cohort

The data from case control and cohort studies are generally consistent with the hypothesis that moderate alcohol consumption has an inverse relationship with coronary heart disease (CHD).‘.’ However, several prospective studies have failed to show a significant association between alcohol consumption and CHD. In the Tecumseh Community Health Study,5 the risk of myocardial infarction in men aged 45 to 49 at entry into the study did not vary across three levels of alcohol (never drinkers, less than or equal to 4 oz absolute alcohol per week, greater than 4 oz absolute alcohol per week). In the Los Angeles Heart Study, drinkers had lower rates of CHD than nondrinkers, although this relationship was not statistically significant. Morris et al.” failed to find any relationship between alcohol consumption and risk of CHD in London busmen; Doyle et a1.7 found no relationship in New York civil servants, as did Grieg et a1.8 in a study of Belfast men. From a public health perspective, it is necessary to consider not only CHD, but all-cause mortality. Some prospective studies have shown an inverse relationship between moderate alcohol consumption

Smoking behavior among participants in the nurses' health study.

We analyzed smoking behavior of 91,651 married female nurses, aged 30-55 years in 1976. The prevalence of smoking was similar among all birth cohorts. The largest percentage increase in starting to smoke occurred between ages 15 and 25 years; by age 25, 50 per cent had started smoking. The cessation rate was lowest in earlier birth cohorts and among nurses starting to smoke at earlier ages. The cessation rate increased substantially between 1963-73 compared with the period 1948-58.

A case-control study of risk indicators among women with premenopausal and early postmenopausal breast cancer.

Among 714 premenopausal and 130 postmenopausal breast cancer cases matched with 8440 controls for age in years and menopausal status, risk indicators for breast cancer were similar, although most associations were stronger in the premenopausal women. Compared with nulliparous women, the relative risk (RR) for those with first birth before age 25 years was 0.7 (95% confidence limits [CL] from 0.5 to 0.9) among premenopausal women, and 0.7 (0.4–1.4) for postmenopausal women. In the premenopausal cases, a history of breast cancer in a sister gave a RR of 3.0 (2.1–4.1) and in a mother 1.9 (1.4–2.5), whereas for the postmenopausal women the RRs were 1.4 (0.6–3.1) and 13 (0.6–2.6), respectively. Fibrocystic breast disease was also a significant predictor of subsequent breast cancer in the premenopausal and postmenopausal women. In relation to women having a single birth, premenopausal women with six or more births had a risk of breast cancer of 0.6 (0.4–1.0), which was present even after adjustment for age at first birth.

Interruption of the inferior vena cava by clip or filter

Interruption of the inferior vena cava is usually performed with either external clipping or transvenous filter placement. For patients unable to tolerate general anesthesia and laparotomy, the advantages of transvenous filters rather than clips are obvious. However, for some patients, the use of either clips or filters is possible. In general, retrospective observational studies of inferior vena caval interruption have not adequately accounted for baseline patient characteristics such as age, presence of cancer, and history of prior venous thromboembolism. These confounding factors can independently affect subsequent rates of both recurrent embolism and overall mortality. A comparative, controlled, prospective evaluation of inferior vena caval clipping versus transvenous filter placement among patients who are appropriate candidates for either procedure has not been undertaken. It is suggested that, among patients with good long-term prognoses, a randomized controlled trial would be necessary to help determine whether clipping or transvenous filter placement is more efficacious.

Vitamin A and risk of cancer

Although cancer is a leading cause of death in the United States today, it may be largely avoidable. This optimism derives from several types of epidemiologic studies, including observations of the differing international cancer mortality rates as well as international comparisons of cancer rates for different sites. In addition, migrant studies usually find that the cancer rates of migrants approach those of the host population within one to two generations. These observations support the theory that as a determinant of cancer, environment is a stronger factor than genetics. Doll and Peto (1) estimated that in the United States, tobacco is implicated in nearly a third of all cancer deaths while those factors which have generated the most public attentionthat is, food additives, occupational exposures, pollution, and industrial products-account for less than 8OJo of cancer deaths. The most intriguing conclusion in terms of cancer prevention was that dietary factors may be implicated in approximately 35% of all cancer deaths. Thus, through dietary manipulation, a large proportion of cancers may be preventable. In general, there are two ways to modify dietary intakes: either by advising people to give up those food items or dietary habits which appear to cause cancer or by adding protective agents to the diet. Since proscription of carcinogens seems less feasible than prescription of cancer inhibitors, dietary supplements may be more effective in reducing cancer risk than would restriction of certain foods and drinks. One of the nutritional factors which appears most promising as an antineoplastic agent is vitamig. A, either as retinol (preformed vitamin A, derived from animal sources) or beta-carotene (provitamin A, derived from vegetable sources). Surplus retinol is stored in the liver until needed, and an excess can produce liver toxicity and other harmful side effects (2). Upon absorption, beta-carotene is converted to retinol only as required by the body. Excess betacarotene circulates in the blood and is

A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women

The association between history of postmenopausal hormone use as of 1976 and breast cancer incidence during 1976-1980 was examined prospectively among 33,335 married, postmenopausal registered nurses aged 30-55 years at entry. Half the women reported postmenopausal hormone use, and one fourth had taken these drugs for over five years. During 1976-1980, 221 new cases of breast cancer were identified. The relative risk (RR) for those who had used postmenopausal hormones when compared with women who had never used them was 1.1 (95% confidence limits (CL) 0.8, 1.4); for current and past users, the relative risks were 1.0 (95% CL 0.7, 1.4) and 1.3 (95% CL 0.9, 1.8), respectively. These ratios were not substantially modified by whether or not a womans ovaries had been removed or by other known breast cancer risk factors. No increase in breast cancer risk was apparent among women who had used postmenopausal hormones for less than five years (RR = 1.0, 95% CL 0.5, 1.6). An apparent effect among the subgroup of women who had used them for five to nine years (RR = 1.5, 95% CL 1.0, 2.2) was not present among the few women with longer-term use (RR = 0.9, 95% CL 0.4, 1.6). These findings are moderately reassuring, but since there are as yet few women in this cohort with long-term durations of use and, particularly, with long intervals since first use, continued follow-up of this and other cohorts will be required before firm conclusions can be drawn, especially among specific subgroups.

Oral contraceptives and breast cancer. A prospective cohort study

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.