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Biomedical subjects

W O Spitzer

Publications and source records attributed to W O Spitzer.

At least 37 records · Page 2Linked to original sources
PubMed1997

The 1995 pill scare revisited: anatomy of a non-epidemic.

Two years after the October 1995 pill scare that received worldwide attention, this synthesis of evidence goes back to the earliest research on risks of first generation oral contraceptives (OCs). It also covers epidemiological data published since, emphasising the 1995-1996 findings. Late breaking data are also examined. The key issue: are there differences in the risk profiles of second and third generation OCs. The ultimate question is: did any epidemics of venous thromboembolism (VTE) occur? This synthesis of evidence leads to the following conclusions and observations: (i) all OCs on the market are becoming progressively safer; (ii) relative risks of about 2 for VTE, even if real, are clinically unimportant and of no public health significance; (iii) the weak odds ratios contrasting third and second generation OCs, ranging from 1.5 to 2.3 in the 1995-1996 studies are more likely explained by bias than by a causal relationship; (iv) incidences of VTE among users of any OC have been declining over the past three decades; (v) absolute rates of VTE for third generation OC users reported in 1995-1996 are lower than those for users of second generation OCs in 1988 and 1991; (vi) there is no difference in risk of VTE between first starters on second generation OCs versus first starters on third generation OCs; (vii) users of third generation OCs are at much lower risk of acute myocardial infarction than users of second generation OCs; (viii) among users of any OC, the occurrence rates of stroke are low, they are declining, and no differences between second and third generation OCs are apparent; (ix) 2 years after the pill scare there are no epidemics of VTE; (x) there have been excessive rates of therapeutic abortions in some countries; and (xi) the benefit-risk ratio is favourable for users of any OC.

Contraceptives, Oral↗
PubMed1996

Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

OBJECTIVE: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism. DESIGN: Matched case-control study. SETTING: 10 centres in Germany and United Kingdom. SUBJECTS: Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. RESULTS: Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year. CONCLUSIONS: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Adolescent↗
PubMed1996

Third generation oral contraceptives and risk of myocardial infarction: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

OBJECTIVE: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of myocardial infarction. DESIGN: Matched case-control study. SETTING: 16 centres in Austria, France, Germany, Switzerland, and the United Kingdom. SUBJECTS: Cases were 153 women aged 16-44 with a myocardial infarction event. Controls were 498 women (at least 3 controls per case) unaffected by myocardial infarction who were matched with their corresponding case for age and for hospital or community setting within four months of the index infarction. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. RESULTS: The estimated odds ratio for myocardial infarction of third compared with second generation oral contraceptives among all 651 study subjects was 0.36 (95% confidence interval 0.1 to 1.2) (P = 0.11). The odds ratio for the United Kingdom and Germany alone was 0.45 (0.1 to 1.8) (P = 0.26). Other odds ratios for the five countries were 3.1 (1.5 to 6.3) (P = 0.003) for use of second generation products v no current use and 1.1 (0.4 to 3.4) (P = 0.9) for use of third generation products v no current use. Among the confounding variables the independent contribution of smoking (for which adjustment was made in the above estimates) proved to be important (10.1 (5.7 to 17.9), P < 0.001). CONCLUSION: An odds ratio of 0.45 with wide confidence intervals shows that third generation oral contraceptives compared with second generation products are associated with a reduced risk of myocardial infarction or with no difference. This finding from an interim analysis should be interpreted with extreme caution. However, the excess risk of venous thromboembolism associated with the use of third generation products may be balanced by the reduced risk of myocardial infarction associated with the same products.

Adolescent↗
PubMed1996

Interim review of the Transnational Case-control Study of Oral Contraceptives and Health: approved protocol revisions through September 1995.

UNLABELLED: The protocol of the Transnational Study on Oral Contraceptives has been published at the outset of the study in order to ensure the correct performance of the study and to ensure the study's scientific integrity. Potential revisions and additions to this protocol had been announced in the prior publication. This article focuses on those points of protocol which have been resolved as practical experience was gathered as well as additional modifications required by practical and scientific considerations. The major alterations are based on exposure prevalences in controls and on power calculations. The low (1.8%) exposure to gestodene among German controls led to the discontinuation of the German component and to the accelerated accession in additional countries. THE CASE: control ratio was altered to 3:1 for purposes of economy based on power calculations. Numerous minor points, most addressed in the prior protocol, have been resolved. It is found that these modifications of the study protocol do not impair the study's conduct, its scientific integrity, nor its capability of providing answers to the study question.

Journal Article↗
PubMed1996

The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. The Transnational Research Group on Oral Contraceptives and the Health of Young Women.

A matched case-control study was undertaken in 10 centers in Germany and the United Kingdom to explore the association of current use of major combination oral contraceptives with the occurrence of venous thromboembolism. The cases recruited were 505 women aged 16-44 years with venous thromboembolism, controls were 1877 women (at least 3 controls per case) matched for 5-year age group and region without VTE. The main outcome measures were odds ratios derived by comparing current use of a specific oral contraceptive or group of OC against current use of other groups or against no current use of OC. The odds ratios (95% confidence intervals) for venous thromboembolism were: for third generation products (low dose ethinyloestradiol, gestodene and desogestrel) versus second generation products (low dose ethinyloestradiol, no gestodene and desogestrel, 1.5 (1.1 to 2.0), for third versus second generation products with norgestimate included in third generation, 1.6 (1.2 to 2.2). The odds ratios for current use for women aged 16-44 of specific progestagens versus levonorgestrel-containing compounds were 1.7 (1.1 to 2.6) for gestodene, 1.8 (1.2 to 2.6) for desogestrel, 1.9 (1.0 to 3.6) for norgestimate and 1.3 (0.7 to 2.5) for progestagen-only pills. For women aged 25 to 44 likely to be exposed to any of these progestagens, odds ratios for the comparison of progestagens versus levonorgestrel showed a successive increase by market introduction ranging from 1.5 (0.9 to 2.5) for desogestrel with 30 micrograms oestrogen content (introduced 1981) to 2.8 (1.3 to 6.5) for desogestrel with 20 micrograms oestrogen content (introduced 1992) significant in linear trend analysis (p = 0.00012). The influence of norgestimate classification as third or second generation product does not significantly alter the results regarding the association of third generation products and venous thromboembolism. A direct comparison of current use of norgestimate (which is primarily metabolized to levonorgestrel) versus levonorgestrel shows an increased odds ratio. The trend of increasing risk of progestagens by recency of market introduction when compared with levonorgestrel is strongly indicative of the existence of external bias due to attrition of susceptibles.

Adolescent↗
PubMed1996

Rebuilding confidence in oral contraceptives: a new imperative in family planning.

On December 14, 1995, the first public presentation of results of the Transnational Case-Control Study of Oral Contraceptives and the Health of Young Women was made at the winter meeting of the British Pharmacological Society at Brighton. Four weeks later, those results and further analyses were published in the British Medical Journal. There has been much debate about them in Europe and elsewhere. I feel privileged to have been invited to write a Leading Article about the safety of combined oral contraceptives in the British Journal of Clinical Pharmacology. These are personal opinions about the meaning of all the recent pharmacoepidemiological findings. With an historical context as the background I have added my personal reflections as a scientist and a public health doctor. These views do not necessarily reflect the views of my co-investigators.

Cerebrovascular Disorders↗
PubMed1996

Analysis of Centers for Disease Control and Prevention criteria for the eosinophilia-myalgia syndrome in a geographically defined population.

OBJECTIVE: To test whether individuals can be identified in a geographically defined population who would meet criteria for the eosinophilia-myalgia syndrome (EMS) established by the US Centers for Disease Control and Prevention (CDC), i.e, (1) eosinophil count > 1 x 10(9)/l, (2) myalgia severe enough to limit usual activities of daily living, and (3) no evidence of infection or neoplasm that could explain the first 2 findings. METHODS: To discover the number of individuals who would meet CDC criteria, the population was exhaustively searched using methods adapted from active pharmacoepidemiologic surveillance. Medical consultants and primary care practitioners were questioned as many as 5 times in a search for patients with severe myalgia. A predetermined protocol was used to screen those patients who appeared to meet CDC criteria for EMS using active surveillance methods. The study population was limited to Québec and Ontario (combined population 18,980,000) with special attention to the period July 1, 1992, to June 30, 1993. RESULTS: The prevalence of severe incapacitating myalgia was 43 per 100,000 persons, including 19 individuals with eosinophilia > 1 x 10(9)/l, who met CDC criteria for EMS. None of these individuals were reported to have taken L-tryptophan (LT). CONCLUSION: The CDC criteria for EMS are met by individuals in the general population who have never been exposed to LT.

Adult↗
PubMed1995

Continuing occurrence of eosinophilia myalgia syndrome in Canada.

Eosinophilia myalgia syndrome (EMS), was defined by the Centers for Disease Control (CDC) as eosinophilia > 1000 mm3 and incapacitating myalgia without infection or neoplasm. Studies suggested that use of L-tryptophan (L-T), was a risk factor. We conducted a pharmacoepidemiological survey in Canada where access to L-T is limited. Using the active surveillance method, a 100% sample of potentially involved specialists and a 15% sample of family physicians from Ontario and Quebec were surveyed regarding treatment of patients with severe myalgia within the past year. Follow-up amplified clinical and laboratory information. Overall response rates were 61.4%. Thirty-eight per cent of respondents reported at least one patient. Of 6423 patients assessed, 19 'definite' and 25 'possible' EMS cases were identified. Information from physicians did not suggest use of L-T in patients with definite or possible EMS. It was considered that the cases found an underestimate of the incidence of EMS. Its continuing occurrence in Canada brings causal interpretations of earlier studies into question.

Adult↗
PubMed1994

Outmigrant ascertainment for bias assessment in environmental epidemiology.

BACKGROUND: In the summer of 1985, the McGill Epidemiology Rapid Response Unit undertook a study comparing two areas exposed to emissions of 'sour gas' refineries to an unexposed area. One operational objective of the project was the identification and survey of all the people who had lived in the study area but had since moved (outmigrants). METHODS: We estimated the number of outmigrants (people who had ever lived in the area during the period 1957 to 1985) to be 3363 by using information obtained from our cross-sectional survey and from population statistics for the area of interest. Ten different methods combined lead to the identification of approximately 87% of all the outmigrants who left the study area during that period. We used vital statistics to identify the outmigrants who had died and mailed questionnaires to obtain the necessary information from the others. RESULTS: We confirmed the vital status of approximately 46% of them (1532/3363). The results from the outmigrant survey showed that they were younger than area residents, that they experienced lower rates of heart disease and hypertension and that they had moved for health reasons in only 1.3% of the cases. These findings were similar across comparison areas. CONCLUSION: We concluded that there was no effect due to migration bias on the cross-sectional study results. This evidence considerably strengthened the conclusions regarding the effects of exposure, a benefit that largely justified the cost of identifying and surveying the outmigrants.

Adolescent↗
PubMed1994

A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists.

The association between the use of inhaled beta-agonists and the risk of death and near-death from asthma has previously been reported. It was based on a nested case-control study of 129 cases and 655 control subjects selected from a cohort of 12,301 users of asthma drugs followed during the period 1980 through 1987. In this paper we examine the question of asthma and non-asthma mortality using data from the entire cohort of 12,301 asthmatics. There were 46 asthma and 134 non-asthma deaths in this cohort, for which there were 47,842 person-years of follow-up. The overall rate of asthma death was 9.6 per 10,000 asthmatics per year. This rate varied significantly according to the use of fenoterol, albuterol, or oral corticosteroids in the prior 12 months and the number of asthma hospitalizations in the prior 2 years. The rate decreased significantly, by 0.6 asthma deaths per 10,000 asthmatics per year over the study period, after controlling for the effect of the four other risk factors. It also increased significantly with the use of all beta-agonists, and more so for fenoterol than for albuterol, although this difference was partly explained by the dose inequivalence of the two drugs. Change-point dose-response curves showed that the risk of asthma death began to escalate drastically at about 1.4 canisters (of 20,000 micrograms each) per month of inhaled beta-agonist, the recommended limit. For non-asthma death, the overall rate of 28 deaths per 10,000 asthmatics per year was not related to the use of inhaled beta-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗