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Objective: To assess the reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility when compared to infertile couples with a normal cavity at hysteroscopy.Material and Methods: All patients with a diagnosis of infertility who underwent hysteroscopic evaluation by a single surgeon between 1975 and 1996 were sent a questionnaire as routine follow-up regarding their reproductive history. All 100 subjects who were located responded to the questionnaire, and 78 subjects met the inclusion criteria; age45 years, 12 months of infertility, and 18 months of follow-up with attempts to conceive including in vitro fertilization in patients with bilateral tubal occlusion.Results: Of the 78 subjects, 36 had undergone a myomectomy, 23 a polypectomy, and 19 had a normal cavity. Among the three groups there was no significant difference in their ages, types of infertility, length of infertility, or follow-up after the procedure. Using the Cox proportional hazard model, and adjusting for age, polypectomy patients had a significantly higher pregnancy rate (RR 3.89, P.01) and a higher live birth rate (RR 2.42, P =.06) than patients with a normal cavity. Patients who had undergone a myomectomy also had a higher pregnancy rate (RR 2.02, P =.11) and live birth rate, but this did not achieve statistical significance. Pregnancy following a hysteroscopic myomectomy was associated with a larger fibroid resection (3.15 cm vs 2.5 cm P =.05). The spontaneous abortion rate following the myomectomy, polypectomy, or a normal study was equivalent, 28.1%, 23.1%, and 29.2%, respectively.Conclusions: Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to enhance fertility when compared to infertile patients with a normal cavity. Despite concern that hysteroscopic resection of a large myoma may ablate a large surface area of the endometrial cavity, patients with larger myomas were more likely to conceive following resection.

We tested whether familial aggregation of Down syndrome and Alzheimer's disease (AD) is present for trisomies of other autosomes. We compared rates of Alzheimer-like dementia in the parents of women with trisomic pregnancy losses (n = 109) with those in parents of women with chromosomally normal losses (n = 151) and births (n = 216). Relative risks of Alzheimer-like dementia in parents of women with trisomic losses were 1.2 (95% CI 0.6, 2.2) and 0.9 (95% CI 0.5, 1.5) in comparison to parents of women with chromosomally normal losses and births, respectively. Associations were similar among women whose index pregnancy occurred before age 35 or later. Our data do not support an association between the occurrence of AD and trisomy of all autosomal chromosomes. They raise the possibility that familial aggregation with AD is specific to trisomy 21.

SUMMARY Bartlett's bias correction to the profile score function is proved equal, to first order, to the leading correction term of the double saddlepoint approximation to the conditional score function in canonical exponential families. Gart (1985, 1987) has pointed out the effectiveness of Bartlett's bias correction to the profile score function in approximate conditional binomial likelihood analysis. While the leading term in Bartlett's (1953, 1955) expansion of the bias function ignores terms of order O(n-2), the first-term correction works well for conditional analysis because, as shown in this note, in canonical exponential families it agrees with the first correction term of the double saddlepoint approximation to the conditional score function, and that approximation is accurate up to terms of order O(n')

OBJECTIVES: This study investigated whether, in a general obstetric population, exercise in pregnancy affects the timeliness of delivery. The hypothesis was that maternal exercise would not raise the risk of preterm birth. METHODS: A community cohort of 557 prenatal patients was followed up until the time of delivery. Data were collected on exercise in each trimester: none, low-moderate (< 1000 kcal [4184 kJ]/wk in energy expenditure), or heavy (> or = 1000 kcal/wk). Timely delivery was adopted as an outcome criterion. Thus, in the analysis, a term birth was treated as optimal and survival techniques were used to estimate risks for both preterm and postdates delivery. RESULTS: No association was found between low-moderate exercise and gestational length. Heavier exercise appeared to reduce, rather than raise, the risk of preterm birth. The adjusted relative risk among conditioned heavy exercisers was 0.11 (95% confidence interval = 0.02, 0.81). After term, conditioned heavy exercisers delivered faster than nonexercisers. CONCLUSIONS: The most important finding was the lack of evidence that vigorous maternal exercise is a risk factor for preterm delivery. A promising finding was that conditioned heavy exercisers have timely deliveries.

Objective. Recent studies have shown that lack of continuing primary care for asthma is associated with increased levels of morbidity in low-income minority children. Although effective preventive therapy is available, many African-American and Latino children receive episodic treatment for asthma that does not follow current guidelines for care. To see if access, continuity, and quality of care could be improved in pediatric clinics serving low-income children in New York City, we trained staff in New York City Bureau of Child Health clinics to provide continuing, preventive care for asthma. Methods. We evaluated the impact of the intervention over a 2-year period in a controlled study of 22 clinics. Training for intervention clinic staff was based on National Asthma Education and Prevention Program guidelines for the diagnosis and management of asthma, and included screening to identify new cases and health education to improve family management. The intervention included strong administrative support by the Bureau of Child Health to promote staff behavior change. We hypothesized that after the intervention, clinics that received the intervention would, compared with control clinics, have increased numbers of children with asthma receiving continuing care in the clinics and increased staff use of new pharmacologic and educational treatment methods. Results. In both the first and second follow-up years, the intervention clinics had greater positive changes than control clinics on measures of access, continuity, and quality of care. For second year follow-up data these include: for access, greater rate of new asthma patients (40/1000 vs 16/1000; P < .01); for continuity, greater percentage of asthma patients returning for treatment 2 years in a row (42% vs 12%; P < .001) and greater annual frequency of scheduled visits for asthma per patient (1.85 vs .88; P < .001); and for quality, greater percentage of patients receiving inhaled β agonists (52% vs 15%;P < .001) and inhaled antiinflammatory drugs (25% vs 2%; P < .001), and greater percentages of parents who reported receiving patient education on 12 topics from Bureau of Child Health physicians (71% vs 58%; P < .01) and nurses (61% vs 44%; P < .05). Conclusion. We conclude that the intervention substantially increased the Bureau of Child Health staff's ability to identify children with asthma, involve them in continuing care, and provide them with state-of-the-art care for asthma.

See related article, pages 2410–2414. In this issue, Palesch et al1 discuss the single-arm, phase II futility study design and illustrate how its use might have avoided 3 large (and costly) but negative phase III therapeutic trials for ischemic stroke patients. The authors offer strong arguments to support their conclusion that use of this design as a strategy in phase II development “could permit the testing of a wider array of promising treatments at a fraction of the cost of taking all treatments directly to phase III trials.” In a nutshell, they argue that there is utility in futility testing. Although common in early-phase oncology trials, the futility study (single- or double-armed) may be less familiar to readers of this journal, and careful scrutiny of the design, especially of the formulation of null and alternative hypotheses, is worthwhile. Briefly, in a futility study, the null hypothesis states that the experimental therapy is sufficiently promising to warrant definitive, phase III testing, whereas the alternative hypothesis states that the experimental therapy lacks the prespecified superiority. Thus, the futility design reverses the logical status of null and alternative hypotheses as most often formulated in the traditional efficacy design. Whereas in the latter design, sufficient evidence is required to declare a therapeutic effect statistically significant, in the futility design, there is a presumption of benefit, and sufficient evidence is required to declare a significant shortfall from that benefit, such that it would be futile to proceed to large-scale testing with the given therapy. The authors argue that this formulation, with its null presumption of benefit, is appropriate in phase II research on the grounds that of the 2 types of error that can be committed—declaring a truly superior therapy futile or declaring a truly nonsuperior therapy worthy of continued testing—the former is …

Objective. —To determine the long-term effectiveness of comprehensive support and counseling for spouse-caregivers and families in postponing or preventing nursing home placement of patients with Alzheimer disease (AD). Design. —Randomized controlled intervention study. Setting. —Outpatient research clinic in the New York City metropolitan area. Participants. —Referred, volunteer sample of 206 spouse-caregivers of AD patients who enrolled in the study during a 31/2-year period. All patients were living at home at baseline and had at least 1 relative living in the area. Intervention. —Caregivers in the treatment group were provided with 6 sessions of individual and family counseling within 4 months of enrollment in the study and were required to join support groups. In addition, counselors were available for further counseling at any time. Main Outcome Measure. —Time from enrollment of caregivers in the study to placement of the AD patients in a nursing home. Results. —Using Kaplan-Meier survival analysis, we estimated that the median time (weighted average of estimates for male and female caregivers) from baseline to nursing home placement of AD patients was 329 days longer in the treatment group than in the control group ( z =2.29; P =.02). The relative risk (RR) from a Cox proportional hazard model of nursing home placement (intent-to-treat estimate) after adjusting for caregiver sex, patient age, and patient income was 0.65 (95% confidence interval [CI], 0.45 to 0.94; P =.02), indicating that caregivers were approximately two thirds as likely to place their spouses in nursing homes at any point in time if they were in the treatment group than if they were in the control group. Treatment had the greatest effect on risk of placement for patients who were mildly demented (RR, 0.18; 95% CI, 0.04 to 0.77) or moderately demented (RR, 0.38; 95% CI, 0.17 to 0.82). Conclusions. —A program of counseling and support can substantially increase the time spouse-caregivers are able to care for AD patients at home, particularly during the early to middle stages of dementia when nursing home placement is generally least appropriate.

We tested whether transvaginal ultrasonography could detect the age-related decrease in follicle counts that has been observed in autopsy studies.Thirty-one healthy volunteers in three age groups (22 to 25, 30 to 33, and 39 to 42 years) underwent ultrasonography in the follicular and luteal phases of the menstrual cycle. At the conclusion of the study the 124 ovarian scans were randomly ordered and antral folliclesor = 2 mm were counted by an evaluator unaware of age. Ordinary least-squares linear regression was used to estimate the associations of age with the total antral follicle count and with ln (1 + follicle count).The numbers of antral folliclesor = 2 mm decreased by about 60% between 22 and 42 years. Age-related decreases were similar for both phases of the cycle and held for both smaller (2 to 3.5 mm) and larger (3.5 mm) follicles.We hypothesize that ultrasonographically derived counts of follicles provide a measure of reproductive age that may help to predict age-related phenomena.

OBJECTIVES: This study investigated the relationship between psychosocial and behavioral factors and the frequency of emergency department visits for childhood asthma. METHODS: Data obtained from a survey of parents of 445 children who were being treated for asthma in the emergency room of a large urban hospital were examined. RESULTS: Factors associated with high emergency department use included the child's being of younger age, a greater number of days with symptoms of asthma, a higher number of asthma medicines prescribed, a prior hospitalization for asthma, a lower level of parental confidence in the efficacy of medicines, and a failure to use a criterion for deciding to seek emergency care. CONCLUSIONS: Younger children with asthma and children with previous hospitalization for asthma are at high risk for using emergency care. Families who use the emergency department frequently need to be further educated in the inflammatory nature of the disease, in the efficacy of proper use of medicine, in the need for ongoing care, and in criteria to distinguish those symptoms that can be handled at home from those requiring emergency care.

Data from the first phase (1974-1979) of this New York City case-control study showed that 1) cigarette smoking during pregnancy was associated positively with chromosomally normal spontaneous abortion and 2) both past and current smoking were associated inversely with trisomic loss in women under age 30 years and positively in older women. The authors used data from two subsequent study phases (1979-1982 and 1982-1986) to test the stability of these associations over time and the homogeneity between payment groups (private vs. public). Spontaneous abortions (cases) were classified as chromosomally normal (n = 1,388), trisomic (n = 557), or other chromosomally aberrant (n = 409). Controls (n = 4,165) were women who had registered for prenatal care before 22 weeks' gestation and delivered at 28 weeks or later. For chromosomally normal loss, later data gave modest support to prior observations. In the total sample, current smoking (defined as smoking during the month of the last menstrual period) of 14 or more cigarettes per day was increased among chromosomally normal cases in comparison with controls (adjusted odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1-1.7) and in comparison with other aberrant cases (adjusted OR = 1.2, 95% CI 0.8-1.8). Stronger associations in public patients than in private patients (adjusted odds ratios of 1.4-1.5 versus 0.8-0.9, respectively) might indicate either a mediating effect of social disadvantage or a chance fluctuation. For trisomic loss, later data did not support prior observations. Associations between trisomy and past or current smoking did not vary significantly with age in either payment group; assuming no effect modification of age, adjusted odds ratios for smoking in relation to trisomy were 0.9-1.0.

In case-control studies in which cases are ascertained from hospitals, controls are frequently chosen from among patients with other diseases at the same hospitals. This study was undertaken to examine the extent to which a hospital control group is representative of the population to which inferences are made. A hypothetical hospital control group was assembled consisting of 233 men and women aged 40-74 years who were surgical inpatients at the two hospitals in Otsego County, New York, in 1990. The characteristics of this group were compared with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted health census in the same county in 1989 with the use of health-related data collected in the census. In this rural setting, only small differences were found between the hospital control group and the census population on most of the measures considered, including demographic characteristics, certain health behaviors, and the prevalence of common conditions. However, the female hospital controls were more likely to be overweight than the females enumerated in the census, and the men were more likely to have ever smoked cigarettes. These differences were large enough to lead to different interpretations about the strength of the associations between these variables and case-control status.

The value of exercise during pregnancy is controversial; both benefits and risks have been hypothesized. As empiric evidence is scant, the issue was investigated in a prospective study that assessed the impact on fetal growth of maternal exercise in each trimester of pregnancy. A cohort of over 800 prenatal patients was recruited from obstetric practices in Pennsylvania and New York between January 1987 and June 1989. Subjects were interviewed at entry into care and recontacted at 28 and 36 weeks of gestation. In women with prior adverse outcomes or a lack of conditioning, the associations between maternal exercise and fetal growth were equivocal. In fit, low-risk, prenatal patients, exercise was positively associated with fetal growth. With low-moderate exercise levels, the adjusted mean birth weights were about 100 g higher than in nonexercisers (117 g; 95% confidence interval 17 to 217 g). With heavier exercise, larger birth weight increments were seen, close to 300 g in those who exercised throughout pregnancy at levels of about 2,000 kcal/week in energy expenditure (276 g; 95% confidence interval 54 to 497 g). These results suggest that the guidelines issued by the American College of Obstetricians and Gynecologists may be too stringent for well-conditioned, low-risk, prenatal patients. Additional research to define safe limits more precisely seems warranted.

Summary. The association of trisomy with advancing maternal chronological age suggests that some aspect of physiological ageing is accelerated in women with trisomic pregnancies. This paper develops a quantitative theoretical model based on the hypothesis that trisomy risk is primarily a function of the size of the oocyte pool and, in particular, that risk is increased in women with accelerated rates of oocyte atresia and hence smaller pools at given chronological ages. Since the rate of oocyte atresia is a determinant of age at menopause, this hypothesis leads to the prediction that women who have had trisomic pregnancies reach menopause earlier than women who have not. We used data relating chronological age to oocyte number, trisomy and menopause to deduce the distribution of oocyte atresia rates in all women and in women with trisomic pregnancies. Given certain simplifying assumptions, we predict that associations between trisomy and age at menopause will vary with a woman's age at the time of trisomy such that trisomies at 34–43 years will be associated with a 1–3.4 year earlier onset of menopause, while trisomies at younger or older ages will have no or little association with age at menopause. This model, while vulnerable to the uncertainties that attend its assumptions, provides a testable prediction that permits separation of one aspect of physiological age from chronological age.

Control groups selected by random digit dialing are frequently used in case-control studies. Concern about the potential for bias in these control groups has been expressed, primarily because of low response rates. This study compares the characteristics of a hypothetical control group consisting of 341 men and women aged 40-74 years, selected by random digit dialing and participating in an interview in 1990, with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted census in the same upstate New York county in 1989. For most measures, no differences were seen between the random digit dialing sample and the census population. However, the hypothetical control group was more likely to have had their cholesterol checked in the past 2 years and was somewhat more likely to have had other screening tests as well. In addition, the hypothetical control group was somewhat better educated. The results suggest that, at least in this setting, control groups selected by random digit dialing are representative of the general population in most respects; however, caution should be used when studying the relation between screening tests and disease occurrence by means of case-control studies using controls selected by random digit dialing.

The antihypertensive and metabolic effects of placebo (PL), a fixed combination of hydrochlorothiazide (25 mg) and triamterene (50 mg) (HCTZ/TRI), atenolol (25 mg) (Ate-25), atenolol (50 mg) (Ate-50) and their combination with HCTZ/TRI given once daily, were tested on 256 patients with mild-to-moderate essential hypertension. After 3 weeks of PL monotherapy, 43 patients were randomized to PL (group 1), 41 patients to HCTZ/TRI (group 2), 44 patients to Ate-25 (group 3), 42 patients to Ate-50 (group 4), 43 patients to Ate-25/HCTZ/TRI (group 5), and 43 patients to Ate-50/HCTZ/TRI (group 6) in a double-blind parallel design study and were followed for 4 weeks. At the end of week 7, those patients who were randomized to groups 5 and 6 were allowed to continue for an additional 12 weeks, if their arterial pressure was satisfactorily controlled. Complete blood counts, blood chemistries, urinalyses, and electrocardiograms were done initially and during the study. Monotherapy with HCTZ/TRI, Ate-25, and Ate-50 had significant and equal antihypertensive effects compared with placebo. (P

We tested associations of caffeine from beverages with spontaneous abortions of known karyotype. Spontaneous abortions (cases) were classified as chromosomally normal (n = 510) or chromosomally aberrant (n = 389) and, within the latter category, by type of aberration (237 trisomies, 54 monosomies X, 49 triploidies, 49 others). Controls registered for prenatal care before 22 weeks gestation and delivered at 28 weeks or later (n = 1,423). Caffeine intake in the perifertilization period did not differ among case groups and controls. For the highest category, 225+ mg/day, odds ratios (OR), adjusted for payment group and maternal age, were 1.0 for chromosomally normal cases, 0.9 for trisomies, 1.6 for monosomies X, and 0.8 for triploidies. Caffeine intake during pregnancy was tested for associations with chromosomally normal loss using the chromosomally aberrant cases to provide a robust comparison group. Although the proportion of subjects with intake of 225+ mg/day of caffeine intake in the perifertilization period does not influence the risk of chromosomally normal loss or trisomy. For monosomy X and triploidy, no strong associations were observed, but numbers were insufficient to rule out moderate effects. For caffeine intake during pregnancy, we found little evidence to support an influence on chromosomally normal loss.

Papers p 897 That antenatal experience could have dire consequences is ancient folklore. In 1921 Stockard gave scientific form to the idea in the “critical period” hypothesis: failure of a developing organism to progress from one stage of development to the next within preset time limits could lead to a permanent deficit. Since then several studies have addressed related hypotheses, though mostly in animals. From the 1950s human observational studies reported effects in later life of various exposures—for example, to radiation,1–3 famine,4 and viruses.5 In a large number of more recent publications, Barker has elaborated the idea that fetal experience might “programme” cardiovascular health states in adult life. He has been ingenious in seeking out birth records of cohorts of a half century ago and more. Studies using such sources face some irreparable difficulties—for instance, incomplete samples and attrition on follow up with selective bias, inadequate as well as missing records, and the absence of data crucial for controlled analysis. Some of these problems are being better resolved in later datasets assembled for long continued longitudinal studies. An analysis from one such birth cohort study in New Zealand appears in this week's issue.6 This analysis also addresses a second—entirely reparable—problem previously discussed by one of us.7 This is the observation that Barker's studies, fertile as they have been in stimulating life course studies, do not …

The relationship of paternal age to specific types of trisomy and to chromosomally normal loss was investigated in data drawn from a case-control study of spontaneous abortions. Differences in paternal age between karyotype groups and controls delivering after 28 weeks gestation were tested using an urn model analysis which adjusted, by regression, for maternal age and, by stratification, for the effects of design variables (payment status, phase of study) and demographic factors (language, ethnicity). The magnitude of paternal age differences was estimated using least squares regression analysis. For chromosomally normal cases there was no association with paternal age. Among the fourteen trisomy categories examined, four (7, 9, 18, 21) showed increased paternal age (greater than or equal to 1 year above expectation), three (13, 20, 22) showed decreased paternal age and the rest, including the most common, trisomy 16, showed negligible differences. Only the association with trisomy 22 was statistically significant (P = 0.012), with a predicted reduction in paternal age of 2.1 years (95% CI -4.9, -0.5 years). This association did not vary with maternal age, payment status, phase of study, language or ethnicity. Because previous observations are extensive, the relation of paternal age to trisomy 21 was examined further. The overall association was not significant (beta = 0.8 years; 95% CI -0.8, 2.4 years). Moreover, there was evidence that the magnitude and direction of paternal age associations vary significantly within the sample, although not between subgroups defined on the basis of payment, phase of study, language or ethnicity. With respect to maternal age, the trend is towards a greater paternal age difference for trisomy 21 losses in younger women (P = 0.058). Given the number of tests performed, the finding for trisomy 22 and reduced paternal age could be due to chance. Among trisomy types, the direction of paternal age associations was not consistent for chromosomes grouped according to characteristics that might relate to the probability of nondisjunction, such as size, arm ratio, or nucleolar organizer region content, or to the potential viability of the trisomy. Thus, neither on statistical nor biological grounds do the data provide compelling evidence of paternal age effects on the trisomies found among spontaneous abortions, or on chromosomally normal losses.

The key to elementary probability calculations is an ability to count outcomes of interest among a given set of possibilities called the sample space. For small sample spaces, exhaustive enumeration is possible, although sometimes tricky. Consider the following chestnut

When comparing two proportions, it is common practice simply to quote a figure representing the contrast between them, such as their difference or ratio. Several such measures of association have already been introduced in Section 1.5, and we discuss others in Section 6.3. The properties of these measures and the choice of a “best” one are topics in descriptive statistics and the theory of measurement. There are interesting questions here, but what gives the subject its depth is the fact that the data summarized in the description may often be regarded as informative about some underlying population that is the real subject of interest. In such contexts, the data are used to test some hypothesis or to estimate some characteristic of that population. In testing hypotheses, a statistician computes the statistical significance of, say, the ratio of proportions observed in a sample to test the null hypothesis H0 that their ratio is 1 in the population. In making estimates, the statistician computes a confidence interval around the sample ratio to indicate the range of possibilities for the underlying population parameter that is consistent with the data. Methods for constructing confidence intervals are discussed in Section 5.3. We turn now to testing hypotheses.

Many probability puzzles can be made transparent with knowledge of a few basic rules and methods of calculation. We summarize some of the most useful ideas in this section.

Occasionally data from a matched-sample case-control study with 1:m matching are summarized in a pooled format only rather than in a manner sufficient to conduct an appropriate matched sample analysis. In the case of a single binary risk factor of interest, we show that the Mantel-Haenszel chi-squared statistic that would be calculated from a sufficient summarization is at least m/(m + 1) times the ordinary chi-squared statistic one can obtain from the pooled fourfold table. Thus if the pooled test statistic is at least (m + 1)/m times the chosen critical value, one may deduce that the matched-sample statistic would also reject the hypothesis of no association. The result follows from a simple application of Jensen's inequality.

A general class of multiple logistic regression models is reviewed and an extension is proposed which leads to restricted maximum likelihood estimates of model parameters. Examples of thegeneral model are given, with an emphasis placed on the interpretation of the parameters in each case.

Evaluations of the health effects of exposures in the workplace and environment have broadened to include effects on reproduction, as well as on the development of cancer. Models to assess risks associated with varying doses of exposure rest almost entirely on data about cancer. In this paper we discuss some distinctive features of reproduction which bear on the interpretation of such models, when applied to reproduction, rather than carcinogenesis. Dose-response curves describe the relationship between two exposures (smoking and alcohol drinking) and two outcomes (spontaneous abortion and birthweight) are used to illustrate some of the questions which arise in attempting to determine a "safe" level of exposure.This paper examines the ways in which evaluation of risks of exposure to noxious substances differ in the field of reproduction from the risks of carcinogenesis, and presents models of the effects of varying doses of exposures to smoking and alcohol drinking on spontaneous abortion and birthweight. Models to assess risks associated with varying doses of exposure are almost all based on data about cancer, but the models for risk assessment in reproduction and in oncogenesis differ in at least 3 fundamental ways: 1) the range of relevant adverse reproductive outcomes is more varied and may involve different underlying mechanisms; 2) the relation of timing and duration of exposure to outcome may be different in reproductive endocrinology and in oncogenesis, with many morphological effects depending on exposure at a precise and relatively short period of development; and 3) in reproduction, the exposure can effect 2-3 individuals, although the outcome is usually described in terms of the fetus or infant only. 1 advantageous aspect of the biology of reproduction that has no parallel in carcinogenesis for the study of modest effects is that, for anomalies that are lethal in utero, the search for etiologic factors among aborted fetuses is considerably more parsimonious in terms of the numbers of pregnancies which need to be studied than a similar search among births would be. For example, the sample sizes for exposed and unexposed populations which would be needed to detect, with 80% statistical power, a doubling of the rate of trisomy 21 at conception would be 15,217 births or 1117 abortions. A study of dose-response relations of exposure to smoking and alcohol drinking on spontaneous abortion and birthweight was based on data drawn from an ongoing epidemiological study in 3 New York City hospitals which compares women admitted with spontaneous abortion to a comparison group matched for maternal age and payment status whose pregnancies continued longer than 28 weeks. The data indicate a dose-response relationship between the number of cigarettes smoked each day and both spontaneous abortion and lowered birthweight. In both instances, a logarithmic curve best described the data. A dose-response relationship was also found between alcohol drinking and spontaneous abortion; the odds of abortion increase linearly with increases in the number of days each month on which alcohol is consumed. No relation was found between smoking and alcohol drinking in their effects on spontaneous abortion. The relationship between the exposures of alcohol drinking and smoking and the outcomes of spontaneous abortion and birthweight are used to illustrate some of the problems in attempting to determine a safe level of exposure.

It was hypothesized that a health education program for children with asthma aged 8-11 years that was delivered in elementary schools, would increase children's asthma management skills, self-efficacy and influence on parents' management decisions; reduce school absences and improve school performance. The study population consisted of 239 low-income, predominantly Hispanic and black children from 12 elementary schools (six experimental and six control) in New York City. Parents did not attend educational sessions but received written materials. The program emphasized the child's responsibility for recognizing symptoms and taking appropriate management steps. Follow-up data obtained one year after the program showed that compared to controls experimental group children had higher scores on an index of asthma management (p less than 0.05), greater self-efficacy with respect to asthma management skills (p less than 0.05), more influence on parents' asthma management decisions (p less than 0.05), better grades in school (p = 0.05), and fewer episodes of asthma (p less than 0.01) of shorter average duration (p less than 0.01). No differences were observed for changes in number of school absences. These findings show that asthma health education designed for delivery to children can significantly increase management skills, reduce symptoms of asthma, and improve school performance.

Randomized studies involving long-term follow-up are vulnerable to the effects of unplanned crossover. In surgical studies, such crossover usually occurs when control patients become more symptomatic and undergo operation. In several large studies of coronary bypass grafting, crossover ranged from 25% to 38%. The most common way of dealing with this problem is to apply the "intention-to-treat" principle, which analyzes such crossovers with their originally assigned groups. Besides the logical problem of counting a control patient who actually undergoes operation as "nonsurgical," a more subtle problem arises in terms of statistical power. When statistical power is low, a truly effective treatment may be mistakenly labeled as no better than control, causing a potentially valuable form of therapy to be ignored or discarded. This analysis demonstrates that crossover may have a profound effect on the statistical power of randomized studies and presents a method for predicting the effect of such crossover on statistical power.

We describe an extension of the recursive algorithm of Howard (1972) and Krailo and Pike (1984) for computation of conditional maximum likelihood estimates in multiple logistic regression models for stratum-matched retrospective studies to the multivariate case involving polytomous disease states. APL procedures, suitable for a desktop computing environment, are provided and analyzed.

The applicability of the Coronary Artery Surgery Study (CASS) to clinical practice is seriously hampered by the following findings. (1) The CASS randomized study applies to only a small minority of patients with coronary artery disease. Attempts to extend the conclusions of CASS to the vast majority of patients with coronary artery disease are unjustified. (2) The high percentage of crossover of the medical group made it impossible for CASS to accomplish its primary goal of contrasting medical and surgical treatment. (3) Despite the fact that crossover of medically assigned patients created a bias against surgical treatment, the observed mortality in the surgical group was still 31 % lower than that in the medical group. (4) The failure of CASS to find this difference to be statistically significant must take into account the fact that the statistical power of CASS was so low that a real difference was likely to be overlooked. (5) The conclusion that patients similar to those in the study may safely defer operation is unwarranted and violates the principles of prospective study design. In addition, CASS failed to address the possibility that deferring operation may compromise long-term survival.