- Email: [email protected]
Finnish trial of cardiovascular disease prevention
628
retrospective studies and case-reports. However, we think that health educators, instead of recommending oral sex as a definite low or medium risk activity, should emphasise the uncertainty of HIV transmission through oral sex-that there may be differential risks under different circumstances. Health educators should strongly recommend the use of condoms in oral sex. Individuals unwilling to follow that advice should be warned against swallowing semen, especially when there is a history of concurrent or recurrent throat infections or of atopy, hayfever, or allergic pharnygitis. Infection and inflammation in the oropharynx can often be symptomless, so avoiding oral sex only in the presence of throat symptoms is by no means safe. Department of Genitourinary Medicine, Westminster Hospital,
W. CHEN P. L. SAMARASINGHE
London SW1 P 2AP, UK
Murray AB, Greenhouse PRDH, Nelson WLC, et al. Coincident acquisition of Neisseria gonorrhoeae and HIV from fellatio. Lancet 1991; 338: 830. 2. Rozenbaum W, Gharakhanian S, Cardon B, et al. HIV infection by oral sex. Lancet 1988; i: 1395. 3. Goldberg DJ, Green ST, Kennedy DH, et al. HIV and orogenital transmission. Lancet 1988; ii: 1363. 4. Quatro M, Germinario C, Troiano T, et al. HIV transmission by fellatio. Eur J Epidemiol 1990; 6: 339-40. 5. Dossey DE. HIV and orogenital transmission. Lancet 1988; ii: 1023. 6. Detels R, Visschers B. HIV and orogenital transmission. Lancet 1988; ii: 1023.
high neonatal mortality among twins. In these 35 sets, deaths were reported in 4 first-born twins (all by age 4 months) and 6 second-born twins (4 before age 1 month, 2 later), with corresponding estimates of survival to age 1 year of 86% (14) vs 77% (15) (p=082). In data contributed to the registry from the Congo,1 set was concordant uninfected, but all 6 infants in the other 3 sets died before HIV could be assessed. We hope that prospectively collected data on twins and triplets born to HIVinfected women in Rwanda and other developing countries will be contributed to the registry to permit geographical comparisons of the risk factors, morbidity, and mortality of perinatal HIV infection. Viral Epidemiology Section, National Cancer Institute,
Bethesda, Maryland 20892, USA
Finnish trial of cardiovascular disease
1.
HIV-exposed twins SIR,-Dr Goedert and colleagues (Dec 14, p 1471) suggest that infected women intrapartum
among twins born to HIV-1
transmission of the virus often occurs as the first twin encounters the cervix and birth canal. The much higher risk of HIV-1infection among first-born twins, however, was apparent only among twins identified because of an HIV-related illness in at least one twin and not among twins identified because the mother was known to be infected (table, p 1472). Selection bias would occur if second-born twins who were HIV-1 infected were more likely to die early and thus would have been excluded from the analysis. In Rwanda, as in most parts of the world, second-born twins are usally lighter than first-born twins and their perinatal mortality is much higher.1.2 Moreover, among 6 sets of twins born vaginally to HIV-1-infected women and followed up prospectively since the third trimester of pregnancy, we found that only 3 of the first-born twins and 1 of the second-born twins survived beyond the neonatal period. Prospective data collection is necessary to establish beyond doubt the higher risk of HIV-1 infection among first-born twins. MARC BULTERYS
ANN CHAO ABEL DUSHIMIMANA MARTIN KAGERUKA
National University of Rwanda Johns Hopkins University (UNR-JHU) Perinatal AIDS Research Project, BP 399, Butare, Rwanda
PAULA NAWROCKI ALFRED J. SAAH
1.
Kageruka M. Analyse des accouchements de grossesse gémellaire comme indicateur de mortalité périnatle. Rev Méd Rwand 1987; 19: 17-24 2. Golding J. The epidemiology of perinatal death. In: Kiely M, ed. Reproductive and perinatal epidemiology. Boston: CRC Press, 1991: 401-36.
*** This letter has been shown follows.-ED. L.
to
Dr
Goedert, whose reply
SiR,—Thanks to the further efforts of our collaborators we now are missing method of ascertainment for only 6 of the 66 twin and triplet sets that we analysed. 42 (64%) of the sets provided prospective data as they were ascertained because of the mother’s HIV infection. In 8 (19%) of these 42 sets, only twin A was infected, compared with 1 set with only twin B infected and 2 sets with both twins infected. Thus, the excess risk for first-born twins was apparent with ascertainment by way of the mother. 8 first-born twins and 1 second-bom twin in the 66 sets have died, an actuarial estimate of survival to age 3 years being 90% (SEM 6%) for first-born and (6%) 98% for second-born twins (p = 0-08). HIV could not be assessed in 35 additional sets, in part because of
JAMES J. GOEDERT
prevention SiR,—The letter by Dr Durrington and Dr Bhatnagar (Feb 22, p 488) deserves comment. The significant excess of total and cardiac deaths over 15 years in high risk men randomly allocated to
multifactorial intervention to prevent cardiovascular disease in the Finnish trial1 could be due to chance, inadvertent bias in follow-up, or to some component of the initial intervention Durrington and Bhatnagar focus on the last possibility, and conclude that antihypertensive therapy with beta-blockers and thiazides is more likely to have caused the excess mortality than the lipid-lowering drugs used initially. The results of any single trial ought to be considered in the light of all available data.2 An overview of fourteen unconfounded randomised trials of antihypertensive therapy based on thiazide and/or beta-blocker therapy3 concluded that such treatment reduced coronary events significantly, by 14%. Since then further trials based on these drugs have reported reduction in coronary events of 27%4 and 19%,5 and a reduction in total mortality of 43%.6 It seems perverse in the face of this evidence to incriminate antihypertensive therapy when one of the lipidlowering agents used initially, clofibrate, is known to increase total mortality’ and when failure of lipid-lowering drugs to reduce mortality in all prospective trials is causing concern.8 We have commented elsewhere9 that the lay press is likely to take an interest in these matters-and indeed should do so-as long as the experts decline to take a balanced view of the evidence available. It is unfortunate, but understandable, that the Sunday Times could not distinguish drug therapy that actually lowers cholesterol from drug therapy prescribed for that purpose that failed to do so. Nevertheless, the interpretation of the Sunday Times is more plausible than that of Durrington and Bhatnagar, if the excess mortality in the Finnish trial is to be attributed to drugs rather than chance or inadvertent bias. Sheffield Hypertension Clinic, University Department of Medicine and
Pharmacology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
L. E. RAMSAY W. W. YEO P. R. JACKSON
Strandberg TE, Salomaa W, Maukkarinen VA, Vanhanen HT, Sarna HJ, Miettinen TA. Long-term mortality after 5 years multifactorial primary prevention of cardiovascular disease in middle-aged men. JAMA 1991; 266: 1225-29 2. Oglesby P, Hennekens CH. The latest report from Finland: a lesson in expectations JAMA 1991; 266: 1267-68. 3. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart 1.
disease II: short-term reduction in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827-38. 4. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255-64. 5. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. Br Med J 1992; 304: 405-12. 6. Dahlof B, Lindholm LH, Hansson L, Shersten B, Ekbom T, Wester P. Morbidity and mortality in the Swedish trial in old patients with hypertension (STOPHypertension). Lancet 1991; 338: 1281-85. 7. Editorial. Clofibrate. a final verdict? Lancet 1978; ii: 1131-32. 8. Oliver MF. Doubt about preventing coronary heart disease. Br Med J 1992; 304: 393-94. 9.
Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol. Br Med J 1991; 303: 1332-33.
retrospective studies and case-reports. However, we think that health educators, instead of recommending oral sex as a definite low or medium risk activity, should emphasise the uncertainty of HIV transmission through oral sex-that there may be differential risks under different circumstances. Health educators should strongly recommend the use of condoms in oral sex. Individuals unwilling to follow that advice should be warned against swallowing semen, especially when there is a history of concurrent or recurrent throat infections or of atopy, hayfever, or allergic pharnygitis. Infection and inflammation in the oropharynx can often be symptomless, so avoiding oral sex only in the presence of throat symptoms is by no means safe. Department of Genitourinary Medicine, Westminster Hospital,
W. CHEN P. L. SAMARASINGHE
London SW1 P 2AP, UK
Murray AB, Greenhouse PRDH, Nelson WLC, et al. Coincident acquisition of Neisseria gonorrhoeae and HIV from fellatio. Lancet 1991; 338: 830. 2. Rozenbaum W, Gharakhanian S, Cardon B, et al. HIV infection by oral sex. Lancet 1988; i: 1395. 3. Goldberg DJ, Green ST, Kennedy DH, et al. HIV and orogenital transmission. Lancet 1988; ii: 1363. 4. Quatro M, Germinario C, Troiano T, et al. HIV transmission by fellatio. Eur J Epidemiol 1990; 6: 339-40. 5. Dossey DE. HIV and orogenital transmission. Lancet 1988; ii: 1023. 6. Detels R, Visschers B. HIV and orogenital transmission. Lancet 1988; ii: 1023.
high neonatal mortality among twins. In these 35 sets, deaths were reported in 4 first-born twins (all by age 4 months) and 6 second-born twins (4 before age 1 month, 2 later), with corresponding estimates of survival to age 1 year of 86% (14) vs 77% (15) (p=082). In data contributed to the registry from the Congo,1 set was concordant uninfected, but all 6 infants in the other 3 sets died before HIV could be assessed. We hope that prospectively collected data on twins and triplets born to HIVinfected women in Rwanda and other developing countries will be contributed to the registry to permit geographical comparisons of the risk factors, morbidity, and mortality of perinatal HIV infection. Viral Epidemiology Section, National Cancer Institute,
Bethesda, Maryland 20892, USA
Finnish trial of cardiovascular disease
1.
HIV-exposed twins SIR,-Dr Goedert and colleagues (Dec 14, p 1471) suggest that infected women intrapartum
among twins born to HIV-1
transmission of the virus often occurs as the first twin encounters the cervix and birth canal. The much higher risk of HIV-1infection among first-born twins, however, was apparent only among twins identified because of an HIV-related illness in at least one twin and not among twins identified because the mother was known to be infected (table, p 1472). Selection bias would occur if second-born twins who were HIV-1 infected were more likely to die early and thus would have been excluded from the analysis. In Rwanda, as in most parts of the world, second-born twins are usally lighter than first-born twins and their perinatal mortality is much higher.1.2 Moreover, among 6 sets of twins born vaginally to HIV-1-infected women and followed up prospectively since the third trimester of pregnancy, we found that only 3 of the first-born twins and 1 of the second-born twins survived beyond the neonatal period. Prospective data collection is necessary to establish beyond doubt the higher risk of HIV-1 infection among first-born twins. MARC BULTERYS
ANN CHAO ABEL DUSHIMIMANA MARTIN KAGERUKA
National University of Rwanda Johns Hopkins University (UNR-JHU) Perinatal AIDS Research Project, BP 399, Butare, Rwanda
PAULA NAWROCKI ALFRED J. SAAH
1.
Kageruka M. Analyse des accouchements de grossesse gémellaire comme indicateur de mortalité périnatle. Rev Méd Rwand 1987; 19: 17-24 2. Golding J. The epidemiology of perinatal death. In: Kiely M, ed. Reproductive and perinatal epidemiology. Boston: CRC Press, 1991: 401-36.
*** This letter has been shown follows.-ED. L.
to
Dr
Goedert, whose reply
SiR,—Thanks to the further efforts of our collaborators we now are missing method of ascertainment for only 6 of the 66 twin and triplet sets that we analysed. 42 (64%) of the sets provided prospective data as they were ascertained because of the mother’s HIV infection. In 8 (19%) of these 42 sets, only twin A was infected, compared with 1 set with only twin B infected and 2 sets with both twins infected. Thus, the excess risk for first-born twins was apparent with ascertainment by way of the mother. 8 first-born twins and 1 second-bom twin in the 66 sets have died, an actuarial estimate of survival to age 3 years being 90% (SEM 6%) for first-born and (6%) 98% for second-born twins (p = 0-08). HIV could not be assessed in 35 additional sets, in part because of
JAMES J. GOEDERT
prevention SiR,—The letter by Dr Durrington and Dr Bhatnagar (Feb 22, p 488) deserves comment. The significant excess of total and cardiac deaths over 15 years in high risk men randomly allocated to
multifactorial intervention to prevent cardiovascular disease in the Finnish trial1 could be due to chance, inadvertent bias in follow-up, or to some component of the initial intervention Durrington and Bhatnagar focus on the last possibility, and conclude that antihypertensive therapy with beta-blockers and thiazides is more likely to have caused the excess mortality than the lipid-lowering drugs used initially. The results of any single trial ought to be considered in the light of all available data.2 An overview of fourteen unconfounded randomised trials of antihypertensive therapy based on thiazide and/or beta-blocker therapy3 concluded that such treatment reduced coronary events significantly, by 14%. Since then further trials based on these drugs have reported reduction in coronary events of 27%4 and 19%,5 and a reduction in total mortality of 43%.6 It seems perverse in the face of this evidence to incriminate antihypertensive therapy when one of the lipidlowering agents used initially, clofibrate, is known to increase total mortality’ and when failure of lipid-lowering drugs to reduce mortality in all prospective trials is causing concern.8 We have commented elsewhere9 that the lay press is likely to take an interest in these matters-and indeed should do so-as long as the experts decline to take a balanced view of the evidence available. It is unfortunate, but understandable, that the Sunday Times could not distinguish drug therapy that actually lowers cholesterol from drug therapy prescribed for that purpose that failed to do so. Nevertheless, the interpretation of the Sunday Times is more plausible than that of Durrington and Bhatnagar, if the excess mortality in the Finnish trial is to be attributed to drugs rather than chance or inadvertent bias. Sheffield Hypertension Clinic, University Department of Medicine and
Pharmacology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
L. E. RAMSAY W. W. YEO P. R. JACKSON
Strandberg TE, Salomaa W, Maukkarinen VA, Vanhanen HT, Sarna HJ, Miettinen TA. Long-term mortality after 5 years multifactorial primary prevention of cardiovascular disease in middle-aged men. JAMA 1991; 266: 1225-29 2. Oglesby P, Hennekens CH. The latest report from Finland: a lesson in expectations JAMA 1991; 266: 1267-68. 3. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart 1.
disease II: short-term reduction in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827-38. 4. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255-64. 5. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. Br Med J 1992; 304: 405-12. 6. Dahlof B, Lindholm LH, Hansson L, Shersten B, Ekbom T, Wester P. Morbidity and mortality in the Swedish trial in old patients with hypertension (STOPHypertension). Lancet 1991; 338: 1281-85. 7. Editorial. Clofibrate. a final verdict? Lancet 1978; ii: 1131-32. 8. Oliver MF. Doubt about preventing coronary heart disease. Br Med J 1992; 304: 393-94. 9.
Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol. Br Med J 1991; 303: 1332-33.