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British medical journal

Hall NF, Gale CR, Syddall H, Phillips DI, Martyn CN. Risk of macular international classification and grading system for age-related maculo- McCarty CA, Mukesh BN, Guymer RH, Baird PN, Taylor HR.
In t’ Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen Cholesterol-lowering medications reduce the risk of age-related T, et al. Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer’s maculopathy progression. Med J Aust 2001;175:340.
disease. N Engl J Med 2001;345:1515-21.
Arnold JJ, Sarks SH. Extracts from “clinical evidence”: age related macu-lar degeneration. BMJ 2000;321:741-4.
Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, etal, for the International ARM Epidemiological Study Group. An Mortality from cardiovascular disease more than 10 years
after radiotherapy for breast cancer: nationwide cohort
study of 90 000 Swedish women

During radiotherapy for breast cancer there is often with previously registered cancers (except squamous cardiovascular
some irradiation of the heart and major blood vessels, cell skin cancer), 89 407 women aged 18-79 with mortality
which could increase cardiovascular mortality many unilateral breast cancer remained. We stratified more than
years later.1–3 The dose of radiation to the heart is analyses of subsequent mortality in groups of five 10 years after
generally higher when the left rather than the right years by calendar year of diagnosis, time since breast is affected. Therefore, indirect evidence on the diagnosis, and age at diagnosis. Stratification by age diagnosis of
magnitude of any risk is available where the tumour was necessary because the proportion of left sided breast cancer
laterality (left or right breast) can be linked to tumours increases with age.5 Each woman’s is compatible
subsequent cardiovascular mortality.1 2 Studies of the contribution to the person years at risk ran from the survivors of the atomic bombing of Japan who date of diagnosis until her date of death, date of radiotherapy
received single doses to the whole body of 0-4 Gy emigration, 100th birthday, or 1 January 1997, causing a
show that the cardiovascular disease risk is dose whichever was earliest. We used Poisson regression to substantial
related and increases by about 14% per gray.4 calculate mortality ratios, left versus right, from the numbers of deaths and person years. Ratios greater Participants, methods, and results
than one indicate greater mortality in women with left sided tumours than in women with right sided Since 1970, the nationwide Swedish cancer registry has recorded the laterality of breast cancers but not Mortality from breast cancer was identical in the use of radiotherapy. Unpublished data from women with left sided or right sided tumours (table).
regional Swedish registries suggest that about 30% of Mortality from cardiovascular diseases was higher in women with early breast cancer during the 1970s and women with left sided tumours. Little excess occurred early ’80s received radiotherapy. We linked registry in the first 10 years after diagnosis (mortality ratio records (1970-96) with national mortality records. The 1.01; 95% confidence interval 0.96 to 1.07), but later study was approved by the ethics committee of the the ratio was 1.10 (1.03 to 1.18; P=0.004), 1.13 (1.03 to 1.25; P=0.01) for ischaemic heart disease (half of all cardiovascular mortality), and 1.08 (0.98 to 1.18) for diagnosed at autopsy or outside Sweden and those other cardiovascular deaths (about 30% of which Karolinska Institute,171 77 Stockholm,Sweden Mortality ratio for women with left sided breast cancer versus women with right sided breast cancer during and after the first 10 years from diagnosis of breast cancer among 89 407 women registered during 1970-96 at the Swedish cancer registry All years
<10 years
>10 years
Mortality ratio, left
Mortality ratio, left
Mortality ratio, left
Cause of death (ICD-9 code)
versus right (95% CI)
versus right (95% CI)
versus right (95% CI)
ICD-9=International classification of diseases, ninth revision.
*P=0.04†P BMJ VOLUME 326 1 FEBRUARY 2003
probably involved heart disease). For the remaining ratio of 1.10 is, however, wide, so the true causes, mortality in women with left sided tumours cardiovascular hazard from radiotherapy in the 1970s did not differ significantly from that in women with Contributors: The study was conceived and designed by PH, SD, Most of the late cardiovascular deaths involved AE, and FG. The statistical analysis was designed by SD and women treated for breast cancer in the 1970s, and PMcG and done by PMcG. All authors contributed to the improvements in radiotherapy techniques since then interpretation of the results and the preparation of the have tended to reduce radiation dose to the heart. For manuscript. PH is guarantor for the data; SD and PMcG are guarantors for the statistical analysis.
cardiovascular ratio, left versus right, was still 1.11 but Funding: Clinical Trial Service Unit (SD, PMcG, and RP)supported by Cancer Research UK, the Medical Research with a wide 95% confidence interval (0.95 to 1.29).
Council, and the British Heart Foundation. Karolinska Institute(FG, AE, and PH) supported by independent Swedish research foundations, government sources, and the European Union.
Competing interests: None declared.
A mortality ratio, left versus right, of 1.10 forcardiovascular disease more than 10 years after Paszat L, Mackillop WJ, Groome PA, Boyd C, Schulze K, Holowaty E.
Mortality from myocardial infarction after adjuvant radiotherapy for diagnosis of breast cancer is compatible with a breast cancer in the surveillance, epidemiology and end-results cancer substantial hazard among some of those actually registries. J Clin Oncol 1998;16:2625-31.
Rutqvist LE, Johansson H. Mortality by laterality of the primary tumour irradiated. For example, if about 30% of women among 55 000 breast cancer patients from the Swedish Cancer Registry.
surviving 10 years after breast cancer had been irradiated then a cardiovascular mortality ratio of 1.10 Early breast cancer trialists’ collaborative group (EBCTCG). Favourableand unfavourable effects on long-term survival of radiotherapy for early in all women and 1.00 in unirradiated women would suggest a ratio of 1.33 in those irradiated. This could Shimizu Y, Pierce DA, Preston DL, Mabuchi K. Studies of the mortality of be produced by a 60% increase in late cardiovascular atomic bomb survivors: non-cancer mortality 1950-1990. Radiat Res mortality after irradiation for a left sided tumour and Weiss HA, Devesa SS, Brinton LA. Laterality of breast cancer in the a 20% increase after irradiation for a right sided United States. Cancer Causes Control 1996;7:539-43.
tumour. The confidence interval for the observed Thromboembolism associated with the new
A 35 year old woman had pulmonary thrombosis contraceptive Yasmin
17 days after she started taking the contraceptive.
She had given birth four months earlier.
Ethinylestradiol with drospirenone has been Our centre, the Dutch spontaneous reporting system for approved as an oral contraceptive in all European Union adverse drug reactions, recently received five reports of countries since 2000 and has recently been launched in thromboembolism as a suspected adverse drug reaction the United Kingdom.2 The public assessment report of to the new oral contraceptive Yasmin (ethinylestradiol the contraceptive gives only one suspected case of pulmonary embolism but also says that the number of A 17 year old woman suddenly collapsed and died cases in the preregistration studies are too low for a after taking the contraceptive for six months. Autopsy showed that she had had a massive pulmonary embolism.
No obvious risk factors for thromboembolism, such as The risk of thromboembolism for women using the smoking, a period of long immobilisation, air flights, or third generation (combined) pill has long been debated.
concomitant medication, were evident.1 Because she died Physicians therefore may prefer a new type of combined suddenly no blood sample was taken. Blood taken from pill, like ethinylestradiol with drospirenone, assuming her parents did not test positive for any of the known risk that these are safer. However, an association of these factors: concentrations of protein C and antithrombin III drugs with a lower risk of thromboembolism has not were normal. The activated partial thromboplastin time been proved by research, and our cases show that newer and partial thromboplastin time were normal, and the contraceptive pills may have a risk of thromboembolism.
existence of factor V Leiden mutation was excluded.
At present, insufficient data on the superiority of A 28 year old woman changed her oral contraceptive ethinylestradiol with drospirenone are available.
from ethinylestradiol with desogestrel (Marvelon) to ethinylestradiol with drospirenone. Four months later shehad thrombosis in one leg and was treated with acenocoumarol. Risk factors or concomitant drugs wereunknown.
Winkler UH. Oral contraception in women at risk of venous disease.
Another patient, a 45 year old woman, had deep vein thrombosis in one leg after taking ethinylestradiol with Sheldon T. Dutch GPs warned against new contraceptive pill. BMJ2002;324:869.
drospirenone for two months, as did a 50 year old Official site of Dutch medicines evaluation board. woman who took the contraceptive for three months.
gnsmiddl/par-yasmin.pdf (accessed 21 October 2002).


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