Prevention Studies

The TCP approach is relatively simple and can be easily applied to studies involving comparisons of different equipments, different processes, or even parts of processes. CCP has now emerged as the most realistic approach that can be employed in economic project analyses. It is the recommended procedure for pollution-prevention studies. The LCC approach is usually applied to the life-cycle analysis (LCA) of a product or seiwice. It has found occasional application in projec t analysis. 

Dipyridamole is a PDE5/PDE6 selective inhibitor that is used widely in conjunction with aspirin to reduce clotting and prevent stroke. More recent studies with a fixed combination of these two drugs (Aggrenox) has been shown in the recent European Stroke Prevention Study 2 to be of greatly added benefit over aspirin alone for prevention of recurrent stroke. 

The European Stroke Prevention Study 2 (ESPS-2) trial examined four treatment arms—extended-release dipyridamole (ER-DP) 200 mg twice daily alone, aspirin 25 mg twice daily alone, ER-DP 200 mg twice daily + aspirin 25 mg twice daily, or placebo. In comparison with placebo the overall reduction in stroke risk was 16% with ER-DP alone and 18% with aspirin alone. The combination of ER-DP and aspirin led to a 37% reduction in stroke risk compared to placebo. Compared with aspirin alone, the combination of ER-DP with aspirin reduced the risk of stroke by 23%. 

Diener HC, Cunha L, Forhes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and asetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 143 1-13. 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

One other study deserves a mention. The Cancer Prevention Study 11 was a prospective investigation using a very large cohort of over one million adult Americans, in which the effects of commercial multivitamin supplements and vitamins A, C or E on mortality were studied, during a follow-up period of seven years. The results were complex in that the use of multivitamins plus vitamins A, C and/or E significantly reduced the risk of lung cancer in both former smokers and life-long non-smokers, but vitamins A, C and E apparently increased the risk in current smokers. 

ALBANES D, HEINONEN O P, HUTTUNEN J K, TAYLOR P R, VIRTAMA J, EDWARDS B K, HAAPAKDSKI J, RAUTALATHI M, HARTMAN A M and PALMGREN J (1995) Effects of alpha-tocopherol and beta carotene supplements on cancer incidence in the alpha-tocopherol beta-carotene cancer prevention study , Am J Clin Nutr, 62, 1427S-30S. 

ALPHA-TOCOPHEROL BETA-CAROTENE (ATBC) CANCER PREVENTION STUDY GROUP (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers , New Engl J Med, 330, 1029. 

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

ATBC = Alpha Tocopherol Beta Carotene Prevention Study CARET = The Beta Carotene and Retinol Efficacy Trial PHYS = Physicians Health Study. 

ALBANES D, HEiNONEN o p, TAYLOR p R, et uL, (1996) a-tocopherol and P-carotene supplementation and Irmg cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study effect of base-line chacteristics and study compliance. J Natl Cancer Inst. 88 1560-70. 

Beta-Carotene Cancer Prevention Study) Gastric cancer 0 45... 

No association. - = Inverse association. + = Positive association. ATBC = a-Tocopherol, p-Carotene Cancer Prevention Study. PSA = Prostate-specific antigen. 

Supplementation study (Multicenter Skin Cancer Prevention Study)... 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, New Engl. J. Med., 330, 1029, 1994. 

Albanes, D. et al., Effect of supplemental P-carotene, cigarette smoking and alcohol consumption on serum carotenoids in alpha-tocopherol, P-carotene cancer prevention study, Am. J. Clin. Nutn, 66, 366, 1976. 

The insolubility of 1 has the major inconvenience that it prevents studying in detail the mechanistic factors which would operate during this hydrometalation process, as in general only the organic substrate and final zirconocene product are observed by NM R spectroscopy. 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Now there are a number of problems with relapse-prevention studies. One is the fact that many people who are taken off antidepressants experience withdrawal symptoms, which in severe cases can last for months. Some of these withdrawal symptoms - sadness, suicidal thoughts, crying spells, trouble concentrating, irritability, anxiety, agitation and insomnia, for example - are also symptoms of depression.12 These withdrawal symptoms could lead both patients and researchers to think that the patient has relapsed. 

The interaction of carotenoids with cigarette smoke has become a subject of interest since the results of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group 1994 (ATBC) and CARET (Omenn et al. 1996) studies were released. P-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. Thus, the autoxidation of P-carotene in the presence of cigarette smoke was studied in model systems (toluene) (Baker et al. 1999). The major product was identified as 4-nitro-P-carotene, but apocarotenals and P-carotene epoxides were also encountered. 

Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, Hartman AM, Palmgren J, Freedman LS, Haapakoski, J, Barrett MJ, Pietinen P, Malila N, Tala E, Liippo K, Salomaa ER, Tangrea JA, Teppo L, Askin FB, Taskinen E, Erozan Y, Greenwald P and Huttunen JK. 1996. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study effects of base-line characteristics and study compliance. J Natl Cancer Inst 88 1560-1570. 

Albanes D, Virtamo J, Taylor PR, Rautalahti M, Pietinen P and Heinonen OP. 1997. Effects of supplemental 3-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 66 366—372. 

Veronesi U, Maisonneuve P, Costa A (1998) Prevention of breast cancer with tamoxifen preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 352 93-97... 

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