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Biomedical subjects

M H Gail

Publications and source records attributed to M H Gail.

At least 19 recordsLinked to original sources
PubMed1992

Projections of the number of persons diagnosed with AIDS and the number of immunosuppressed HIV-infected persons--United States, 1992-1994.

This report presents projections of the number of persons who will initially be diagnosed with a condition included in the 1987 surveillance definition for acquired immunodeficiency syndrome (AIDS) in the United States during the period 1992-1994. The report also presents estimates and projections of the prevalence of persons infected with the human immunodeficiency virus (HIV) who have CD4+ T-lymphocyte (T-cell) counts < 200/microL and who have not been diagnosed with a condition listed in the 1987 AIDS surveillance definition. These estimates and projections are used to predict the effect of expanding the AIDS surveillance definition to include all HIV-infected persons with a CD4+ T-cell count < 200/microL. Approximately 58,000 persons were diagnosed with AIDS in the United States during 1991. During the period 1992-1994, the number of persons newly diagnosed with AIDS is expected to increase by at most a few percent annually, with approximately 60,000-70,000 persons diagnosed per year. Although AIDS diagnoses among homosexual and bisexual men and among injecting drug users are projected to reach a plateau during this period, the number of AIDS diagnoses among persons whose HIV infection is attributed to heterosexual transmission of HIV is likely to continue to increase through 1994. The number of living persons who have been diagnosed with AIDS is expected to increase from approximately 90,000 in January 1992 to approximately 120,000 in January 1995. There is, however, considerable uncertainty in these projections. For example, the plausible range for the number of persons initially diagnosed with AIDS in 1994 is 43,000-93,000. CDC estimates that, as of January 1992, 115,000-170,000 U.S. residents had severe immunosuppression (a CD4+ T-cell count < 200 cells/microL without a diagnosis of AIDS in an HIV-infected person). Only about 50,000 of these persons were receiving medical care for HIV-related conditions and were known to have a CD4+ T-cell count < 200 cells/microL. The number of persons with severe immunosuppression is expected to increase to 130,000-205,000 by January 1995, with the actual number more likely to be in the lower half of this range than the upper half. The expanded AIDS surveillance definition, which includes severe immunosuppression, is predicted to result in an increase of approximately 75% in the number of persons reported during 1993, but an increase of < 20% in 1994 compared with the number of persons who would have been reported had the definition not been changed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Estimating HIV prevalence and projecting AIDS incidence in the United States: a model that accounts for therapy and changes in the surveillance definition of AIDS.

The AIDS incubation distribution is changing in calendar time because of treatment and changes in the surveillance definition of AIDS. To obtain reliable estimates of HIV prevalence and projections of AIDS incidence in the 1990s using the method of backcalculation, we constructed an appropriate incubation distribution for each calendar date of infection. We parameterized the impact of treatment on the incubation distribution by specifying the relative hazard for AIDS in treated versus untreated people as a function of duration of HIV infection. To account for trends in the incubation distribution, we modelled the prevalence of treatment, the distribution of treatment onset times, and the impact of the revision of the AIDS surveillance definition in 1987. We selected and evaluated backcalculation models based on consistency with external information. We defined a 'plausible range' of estimates that took into account uncertainty about the natural incubation distribution and treatment efficacy, as well as bootstrap assessment of stochastic error. Using these methods, we projected that national United States AIDS incidence will plateau during 1991-1994 at over 50,000 cases per year. Projections exhibited substantial systematic uncertainty, and we calculated a plausible range for AIDS incidence in 1994 of 42,300 to 70,700 cases. An estimated 628,000 to 988,000 cumulative HIV infections occurred as of 1 January 1991. After accounting for AIDS mortality, we estimated that 484,000 to 844,000 people were living with HIV infection on 1 January 1991. Favourable trends in HIV incidence appeared in gay men and intravenous drug users. Plausible ranges for our estimates overlapped with those from a 'stage model' approach to incorporating treatment effects in backcalculations. Our approach, however, tended to yield smaller estimates of epidemic size, mainly because the parameters used with the stage model implied that more treatment was in use and that treatment was more effective than in our model.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Early menopause in long-term survivors of cancer during adolescence.

OBJECTIVE: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. STUDY DESIGN: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. RESULTS: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. CONCLUSION: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Adult↗
PubMed1992

Aspects of statistical design for the Community Intervention Trial for Smoking Cessation (COMMIT).

We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation (COMMIT). One outcome measurement, the quit rate in randomly selected cohorts of smokers, is compared with another outcome measurement, the decrease in smoking prevalence, in terms of statistical efficiency and interpretability. The COMMIT study uses both types of outcome measurements. The merits of pair-matching the communities are considered, and sample size calculations take into account heterogeneity among pair-matched communities. In addition to significance tests based on the permutational (randomization) distribution, we also describe approaches for covariate adjustment. The COMMIT design includes 11 pair-matched communities, which should provide good power to detect a 10% or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers. The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking.

Bias↗
PubMed1991

Projections of the incidence of non-Hodgkin's lymphoma related to acquired immunodeficiency syndrome.

Advances in antiretroviral therapy and treatment or prophylaxis against opportunistic infection have resulted in prolongation of the survival of patients with acquired immunodeficiency syndrome (AIDS). Previous research has demonstrated an association between AIDS and risk of non-Hodgkin's lymphoma (NHL). In addition to the approximately 3% of individuals found to have NHL at the time of AIDS onset, others continue to develop NHL following AIDS diagnosis. Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute demonstrated a sharply increasing incidence of NHL among men in the age range 20-49 years since 1983 in the United States. Based on new data on the risk of NHL following AIDS diagnosis, on estimates of improved survival following AIDS diagnosis, and on projections of future AIDS incidence, we considered four sets of assumptions and estimated the number of AIDS-related NHL cases in 1992 to be between 2900 and 9800. Three of these projections were higher than the estimate of 4700 cases obtained by linear extrapolation of SEER incidence trends. These projections of AIDS-related NHL incidence suggest that between 8% and 27% of all NHL cases that occur in the United States in 1992 will arise as a consequence of infection with the human immunodeficiency virus (HIV), imposing a substantial health care burden. More research into the pathogenesis of lymphoma and new approaches to antiretroviral and antilymphoma therapy will be necessary to prevent and treat this formidable complication of infection with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Backcalculation of the number with human immunodeficiency virus infection in the United States.

The method of backcalculation was applied to national surveillance data on the acquired immunodeficiency syndrome (AIDS) in order to estimate the cumulative number of adults with human immunodeficiency virus type 1 (HIV-1) infection as of January 1, 1985 and July 1, 1987. A "plausible range" of estimates was constructed which reflected both uncertainty about the AIDS incubation distribution and random variation from selection and fitting of flexible models of the HIV-1 infection curve. The authors estimated that, as of 1985, 411,000 to 756,000 persons were infected. The infected population included 266,000 to 492,000 homosexual men, 69,000 to 136,000 intravenous drug users, 24,000 to 49,000 homosexual intravenous drug users, and 11,000 to 26,000 persons infected through heterosexual contact. The estimated prevalence of infection among persons aged 15-55 years was 0.31% in whites, 0.78% in Hispanics, and 0.81% in blacks. An estimated 32,000 to 66,000 women were infected. Compared with white women aged 15-55 years, the prevalence of infection was 5.3-fold higher in Hispanic women and 10.2-fold higher in black women. Plausible estimates for the total number infected by July 1987 ranged from 707,000 to 1,376,000, with the most likely estimate equal to 992,000. Backcalculation provides an assessment of the magnitude of the HIV-1 epidemic that is independent of estimates based on prevalence surveys in special populations. The estimates obtained from both methods are consistent and emphasize the need for vigorous programs to prevent the spread of HIV-1, especially in minority communities.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Mean square error of estimates of HIV prevalence and short-term AIDS projections derived by backcalculation.

We simulated multinomial AIDS incidence counts from 27 'representative' AIDS epidemics that spanned a period corresponding to previous applications of backcalculation (1 January 1977 to 1 July 1987) and assessed mean square error for several back-calculated estimators of HIV prevalence and short-term AIDS projections. Estimators were based on flexible model selection procedures that chose the best-fitting non-negatively constrained model of the infection curve from a family of possible step-function models. Selection of the best-fitting model from a family of four-step models each with a long last step of width of 4 or 4.5 years offered a favourable tradeoff between bias and variance when compared with selection from families of models with three steps or from families with a short last step. Five-step models performed as well as four-step models. Three-step models had substantially larger mean square error in some epidemic situations. Percentage root mean square error (PRMSE) for estimates of cumulative HIV prevalence as of 1 January 1985 was less than 14 per cent over a range of hypothetical epidemics of N = 50,000 infected individuals. PRMSE for short-term projections was less than 18 per cent. Estimates of cumulative HIV prevalence as of 1 July 1987 were substantially more uncertain and had a PRMSE of 33 per cent in the unfavourable case of a rapidly rising HIV epidemic. Estimates of cumulative HIV prevalence as of 1 July 1987 were positively biased in HIV epidemics with a rapidly decreasing recent HIV incidence rate and negatively biased in rapidly increasing HIV epidemics. Despite these uncertainties, we obtained useful estimates even for HIV epidemics with as few as 5000 infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A bibliography and comments on the use of statistical models in epidemiology in the 1980s.

This paper reviews developments in statistical modelling in epidemiology in the 1980's, with emphasis on cohort and case-control studies. The central roles of the logistic and proportional hazard models are highlighted, and it is shown how these models lead to a deeper understanding of classical designs and methods of analysis as well as to efficient new designs and analytical procedures. The important area of model misspecification is discussed, including the problems of omitted latent structure, mis-modelling of available measurements, missing data and errors in measurements. Various designs motivated by the logistic model are illustrated numerically, and designs based on the proportional hazards model are discussed, as are papers on sample size determination. There are brief introductions to the literature on other topics, including attributable risk, disease clustering, family studies and genetics, analysis of disease incidence data, infectious disease, longitudinal data, screening and miscellaneous related topics in statistics. An extensive bibliography is indexed according to the outline of the paper.

Data Interpretation, Statistical↗
PubMed1991

Bias despite masked assessment of clinical outcomes when an outcome is defined as one of several component events.

Hypothetical examples are presented that show that bias can result from misclassification of clinical outcomes defined as one of several events, even though the assessment of each component event was masked. In one example, the effect of the overall misclassification is to make a treatment that reduces the risk appear to increase it; in another example, misclassification causes the overall treatment effect to appear stronger than it actually is. These anomalies are due to the fact that the misclassification of the overall outcome can be differential, even though the misclassification of the individual components is nondifferential.

Acquired Immunodeficiency Syndrome↗
PubMed1991

National AIDS incidence trends and the extent of zidovudine therapy in selected demographic and transmission groups.

After mid-1987 fewer than the expected number of cases of AIDS were reported in the United States in some demographic and transmission groups but not in others. Gay men (regardless of intravenous drug use), adults with hemophilia, and transfusion recipients exhibited fewer cases than expected based on previously reliable models. These favorable trends could not be explained by assuming earlier cessation of human immunodeficiency virus (HIV) infection. Favorable AIDS incidence trends were not found in heterosexual intravenous drug users or in persons infected through heterosexual contact. White gay men from New York City, Los Angeles, and San Francisco experienced markedly favorable trends, whereas little changes was observed for nonwhite gay men from nonurban areas. AIDS incidence trends were quantitatively consistent with the fraction of AIDS-free persons with severe immunodeficiency who received zidovudine in three cohorts. Gay men in San Francisco used zidovudine more frequently than did adults with hemophilia, while little was used by intravenous drug users in New York City. Data describing the initial national distribution of zidovudine (March 31-September 18, 1987) indicated relatively high use by patients with severe immunodeficiency in those groups, such as urban white gay men, that subsequently experienced fewer cases of AIDS than expected. Available data suggest that zidovudine, perhaps in combination with other therapies, has been one factor contributing to favorable AIDS incidence trends in some groups. Broader application of therapy might further retard the incidence of AIDS, especially in intravenous drug users, persons infected through heterosexual contact, minorities, women, and persons diagnosed outside major metropolitan areas.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Uncertainty in estimates of HIV prevalence derived by backcalculation.

The incidence of consistently defined acquired immunodeficiency syndrome (AIDS) among adults in the United States was used to "backcalculate" the prevalence of human immunodeficiency virus (HIV) as of January 1, 1985, and July 1, 1987. The sensitivity of estimates to random and systematic sources of uncertainty was assessed. Using a "standard" incubation distribution with a 10-year median time-to-AIDS, we estimated that 544,000 persons were infected as of January 1, 1985, and that 992,000 persons were infected as of July 1, 1987. Variation from model selection and fitting was only 2% and 5%, respectively. Perturbations of the AIDS incidence counts to reflect plausible reporting biases reduced prevalence estimates by as much as 9.6% and 16.0%, respectively. Uncertainty about the incubation distribution had an even greater impact. A "plausible range" of prevalence estimates was calculated using alternative "Fast" and "Slow" incubation distributions. The plausible range varied from 415,000 to 760,000 persons in 1985 and from 737,000 to 1.4 million persons in July 1987. Inclusion of AIDS incidence counts beyond mid-1987 can lead to serious underestimates of prevalence, because use of zidovudine and other therapies beginning in mid-1987 has lengthened the incubation distribution in many severely immunodepressed persons without AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

On power and sample size for studying features of the relative odds of disease.

Estimates of sample size and statistical power are essential ingredients in the design of epidemiologic studies. Once an association between disease and exposure has been demonstrated, additional studies are often needed to investigate special features of the relation between exposure, other covariates, and risk of disease. The authors present a general formulation to compute sample size and power for case-control and cohort studies to investigate more complex patterns in the odds ratios, such as to distinguish between two different slopes of linear trend, to distinguish between two possible dose-response relations, or to distinguish different models for the joint effects of two important exposures or of one exposure factor adjusting for another. Such special studies of exposure-response relations may help investigators to distinguish between plausible biologic models and may lead to more realistic models for calculating attributable risk and lifetime disease risk. The sample size formulae are applied to studies of indoor radon exposure and lung cancer and suggest that epidemiologic studies may not be feasible for addressing some issues. For example, if the risk estimates from underground miners' studies are, in truth, not applicable to home exposures and overestimate the gradient of risk from home exposure to radon by, for example, a factor of 2, then enormously large numbers of subjects would be required to detect the difference. Furthermore, if the true interaction between smoking and radon exposure is less than multiplicative, only the largest investigations will have sufficient power to reject additivity. For the simple case of testing for no exposure effect, when exposure is either dichotomous or continuous, these methods yield well-known formulae.

Aged↗
PubMed1990

Application of DNA fingerprints for cell-line individualization.

DNA fingerprints of 46 human cell lines were derived using minisatellite probes for hypervariable genetic loci. The incidence of 121 HaeIII DNA fragments among 33 cell lines derived from unrelated individuals was used to estimate allelic and genotypic frequencies for each fragment and for composite individual DNA fingerprints. We present a quantitative estimate of the extent of genetic difference between individuals, an estimate based on the percentage of restriction fragments at which they differ. The average percent difference (APD) among pairwise combinations from the population of 33 unrelated cell lines was 76.9%, compared with the APD in band sharing among cell lines derived from the same individual (less than or equal to 1.2%). Included in this survey were nine additional cell lines previously implicated as HeLa cell derivatives, and these lines were clearly confirmed as such by DNA fingerprints (APD less than or equal to 0.6%). On the basis of fragment frequencies in the tested cell line population, a simple genetic model was developed to estimate the frequencies of each DNA fingerprint in the population. The median incidence was 2.9 X 10(-17), and the range was 2.4 X 10(-21) to 6.6 X 10(-15). This value approximates the probability that a second cell line selected at random from unrelated individuals will match a given DNA fingerprint. Related calculations address the chance that any two DNA fingerprints would be identical among a large group of cell lines. This estimate is still very slight; for example, the chance of two or more common DNA fingerprints among 1 million distinct individuals is less than .001. The procedure provides a straightforward, easily interpreted, and statistically robust method for identification and individualization of human cells.

Alleles↗
PubMed1990

On the use of laboratory markers as surrogates for clinical endpoints in the evaluation of treatment for HIV infection.

There are strong ethical and practical reasons for hastening decision-making about the efficacy of new treatments for human immunodeficiency virus (HIV) infection. One strategy is to use early markers of disease progression, such as CD4+ lymphocyte levels, as surrogates for ultimate clinical endpoints, such as the development of acquired immune deficiency syndrome (AIDS) or death, in the evaluation of new therapies. We used a simple model of transitions among three health states (well; alive but with an adverse marker; and having experienced a definitive clinical endpoint) to examine the extent to which treatment comparisons based on the surrogate endpoint predict ultimate clinical benefits. With parameters chosen to model the treatment of HIV infection, computer simulations of clinical trials demonstrated substantial time savings by use of the surrogate endpoint. However, reliance on the surrogate led to serious overestimates of ultimate clinical benefit if treatment entailed delayed toxicity or had only transient beneficial effects. Likewise, reliance on the surrogate led to serious underestimates of ultimate clinical benefit when the treatment had no effect on the transition from well to the marker state but did reduce the rates of transition from the marker state to the ultimate clinical endpoint and directly from the well state to the ultimate clinical endpoint.

Antiviral Agents↗