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Paediatric and Perinatal Epidemiology. 1998 Apr; 12(2):176-181.In children, the treatment of acute diarrhoea with the World Health Organization (WHO) standard oral rehydration solution (ORS) provides effective rehydration but does not reduce the severity of diarrhoea. In community practice, carob bean has been used to treat diarrhoeal diseases in Anatolia since ancient times. In order to test clinical antidiarrhoeal effects of carob bean juice (CBJ), 80 children, aged 4±48 months, who were admitted to SSK Tepecik Teaching Hospital with acute diarrhoea and mild or moderate dehydration, were randomly assigned to receive treatment with either standard WHO ORS alone or a combination of standard WHO ORS and CBJ. Three patients were excluded from the study because of excessive vomiting. In the children receiving ORS + CBJ the duration of diarrhoea was shortened by 45%, stool output was reduced by 44% and ORS requirement was decreased by 38% compared with children receiving ORS alone. Weight gain was similar in the two groups at 24 h after the initiation of the study. Hypernatraemia was detected in three patients in the ORS group but in none of those in the ORS + CBJ group. The use of CBJ in combination with ORS did not lead to any clinical metabolic problem. We therefore conclude that CBJ may have a role in the treatment of children's diarrhoea after it has been technologically processed, and that further studies would be justified. (author's)
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH. 1998 Dec; 52(12):775-85.The World Health Organization (WHO) Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception has quantified the risks of idiopathic venous thromboembolism (VTE), ischemic and hemorrhagic stroke, and acute myocardial infarction (AMI) associated with use of combined oral contraceptives (OCs). The present case-control study estimated the age-specific incidence and mortality of these four diseases among women with no cardiovascular risk factors and modelled the risks attributable to OC use, smoking, and the interaction of the two. Data sources included relative risk estimates from the WHO study and observed incidence rates obtained from hospitals in UK's Oxford region in 1989-93. The increased risk of VTE associated with OC use among nonsmokers contributed over 90% of all cardiovascular events among women 20-24 years and more than 60% in those 40-44 years. Among OC users who smoked, hemorrhagic stroke and AMI accounted for 80% of cardiovascular deaths in the 20-24 year group and 97% among those 40-44 years. Cardiovascular mortality associated with smoking exceeded that associated with OC use at all ages. Attributable risk associated with OC use was 1 death/year/370,000 users aged 20-24 years, 1/170,000 users aged 30-34 years, and 1/37,000 users aged 40-44 years. Among smokers, annual cardiovascular mortality attributable to OC use was estimated at about 1/100,000 users among women under 35 years old and 1/10,000 users among those 35 years of age and older. Among healthy women 35 years and older, the additional mortality associated with OC use is 1.4/100,000/year compared with 5.4/100,000 among smokers and 14/100,000 women who both use OCs and smoke. Any potential reduction in AMI or stroke risk associated with third-generation OCs would be a more important consideration in older women, especially smokers. However, the mortality associated with smoking is far greater than that associated with use of all types of OCs at all ages.
Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
CONTRACEPTION. 1998 May; 57(5):315-24.As part of a World Health Organization Collaborative Study conducted at 21 centers in Africa, Asia, Europe, and Latin America in 1989-93, the risks of cardiovascular disease associated with use of oral and injectable progestogen-only and combined injectable contraceptives were investigated. 3697 cases of cardiovascular disease (59% stroke, 31% venous thromboembolism, and 10% acute myocardial infarction) were available for analysis and age-matched with up to three controls. 53 cases were current users of oral progestogen-only contraception, 37 were using an injectable progestogen-only method, and 13 were using combined injectable contraception. The adjusted odds ratios for all cardiovascular diseases compared with nonusers of any type of steroid hormone contraceptive were 1.4 (95% confidence interval (CI), 0.79-1.63) for current users of oral progestogen-only methods, 1.02 (95% CI, 0.68-1.54) for users of injectable progestogen-only contraceptives, and 0.95 (95% CI, 0.49-1.86) for use of combined injectable contraceptives. No significant changes in risk for stroke, venous thromboembolism, or acute myocardial infarction or these three conditions combined was apparent in association with any of the contraceptive methods. However, a nonsignificant increase in risk of venous thromboembolism was apparent for both types of progestogen-only contraceptives. Among women with a history of hypertension, the odds ratio for stroke rose from 7.2 (95% CI, 6.1-8.5) among nonusers of any type of steroid hormonal contraceptive method to 12.4 (95% CI, 4.1-37.6) among current users of all oral progestogens.
CONTRACEPTION REPORT. 1996 Nov; 7(4):4-9.Two recent studies provide confirmation of the safety of low-dose oral contraceptives (OCs) with respect to stroke. The first study (Petitti et al.) investigated all strokes that occurred in 1991-94 among women 15-44 years of age who were members of the Kaiser Permanente Medical Care Programs of Northern and Southern California. A total of 408 confirmed strokes occurred among 1.1 million women during 3.6 million women-years of observation. There was no increased risk of ischemic or hemorrhagic stroke among current low-dose OC users. The adjusted odds ratio (OR) for ischemic stroke among current users compared to former users and never users was 1.2 (95% confidence interval (CI), 0.5-2.6). The adjusted OR for hemorrhagic stroke was 1.1 (95% CI, 0.6-2.2). Past users had a significantly decreased ischemic stroke risk compared to never users (OR, 0.5; 95% CI, 0.3-0.98). For subarachnoid hemorrhage, the OR was 1.5 (95% CI, 0.6-3.6) for current users compared to former and never users. The second study (World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception) investigated 3792 cases of stroke, myocardial infarction, and venous thromboembolism and 10,281 hospitalized controls. Current OC use significantly increased the risk of ischemic stroke in both Europe (OR, 3.0; 95% CI, 1.7-5.4.0) and developing countries (OR, 2.9; 95% CI, 2.1-4.0). Current OC use was associated with hemorrhagic stroke in developing countries (OR, 1.8; 95% CI, 1.3-2.3), but not in Europe (OR, 1.4; 95% CI, 0.8-2.3). European users of low-dose OCs showed no excess risk of stroke. Both smoking and hypertension were independent risk factors for stroke.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1992 Oct; 167(4 Pt 2):1171-6.The largest case control study on the association between oral contraceptive (OC) use and cancer is the US Cancer and Steroid Hormone (CASH) study. Since it did not use hospital-based patients as controls, it eliminated some biases. Since OCs suppress ovulation and suppressed ovulation is linked with reduced risk of ovarian cancer, scientists believe OCs may reduce this cancer risk. The CASH study shows that OC use indeed decreases the risk of ovarian cancer 40% (relative risk [RR]=.6 and this protection lasts for more than 10 years after OC discontinuation. Protection increases with duration of OC use (<1 year RR=.6 and >10 years RR=.2). Estrogenic stimulation of the endometrium without ample progestational protection causes endometrial cancer. Thus combined OCs which have estrogen and progestin components should reduce the risk of endometrial cancer. The CASH study reveals OC use for at least 12 months reduces this risk 50%. OCs have a protective effect for at least 15 years after stopping OC use. In addition, UK national mortality data show OC use caused the decline in ovarian cancer mortality and a 40% decrease in endometrial cancer mortality over the last 20 years. A WHO 7-county case control study indicates that OC users in developing countries have the same protective effect against ovarian and endometrial cancer as those in developed countries. Studies of OC use and cervical cancer have had conflicting results due to 3 biases: cervical cancer is associated with sexual behavior and is therefore a sexually transmitted disease; detection bias. A study in Costa Rica conducted by CDC study has addressed the 1st and 3rd biases. It found no increased risk of invasive cervical cancer or carcinoma in situ with OC use. Studies of OC use and breast cancer have also had conflicting results, but the data clearly indicate that OC use does not increase the overall risk of breast cancer. In fact, OC benefits surpass breast cancer risks.
CONTRACEPTION. 1992 Apr; 45(4):363-8.Researchers analyzed interview and physician records' data on 45 women with breast cancer (cases) admitted to the Central Institute of Cancer Research in Berlin, East Germany between November 1982-June 1986 and born in 1983 or later and 194 women (controls) admitted to the Klinikum Berlin-Buch also in East Germany for conditions other than breast cancer to compare recall accuracy in women who had ever used an IUD. These women were drawn from case control study of the relationship between breast cancer and oral contraceptive use was part of the WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Agreement between patient recall and physician records was exceptional for duration of IUD use (p<.001), number of IUD episodes (kappa=0.79), time since 1st IUD and time since last IUD use (p<.001). Agreement rates did not differ between cases and controls. 75% of the women could not name the IUD brand used so the researcher could not examine agreement of brand name. Thus, other than brand name, this study showed that validity of information on IUD use obtained from interviews is significant. In fact, it also pointed out that case control studies probably yield sound relative risk estimates.
CANCER CAUSES AND CONTROL. 1991 Nov; 2(6):389-94.As part of the Who Collaborative Study of Neoplasia and Steroid Contraceptives, physicians gathered data from 2796 cases and 18,900 controls from at least 1 hospital in each country between 1979-1982 and stopped between 1982-1988 to examine the association between breast cancer in women and combined oral contraceptives (COCs), particularly around menopause. The countries included Australia, Democratic Republic of Germany, Israel, Chile, China, Colombia, Kenya, Mexico, the Philippines, and Thailand. The relative risk (RR) was higher in women who had used COCs in the last year, but the increased RR was no greater for women who would be near menopause (45-49 years) than it was for women <40 years old (1.3 vs. 1.4). In fact, the RR was highest in 40-44 year old women (2.1). Further the RRs were greater in women who began using a COC >45 years of age than they were for women who began using it <45 years of age, but the RR did not increase with duration. For example, the RR for women who began to take the COC <45 years for 12-48 months was 0.86 compared to 1.4 for those who began >45 years. The RR for women who began to take the COC at >45 years old remained at 1.4 for the other durations. In addition, the RR in women who ever used COCs was greater in women who underwent an artificially induced menopause than those who underwent a natural menopause (1.7 vs. 1.04). This higher risk in COC users occurred no matter the duration between last use of COCs and induced menopause and the method of artificial menopause. In conclusion, this study did not support the hypothesis that COCs increase the risk of breast cancer in women who use them around the time of menopause.