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R J Hardy

Publications and source records attributed to R J Hardy.

At least 19 recordsLinked to original sources
PubMed1995

Correlation of retinopathy of prematurity in fellow eyes in the cryotherapy for retinopathy of prematurity study. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: To examine the similarity of extent (sectors) and severity (stage) of acute-phase retinopathy of prematurity (ROP) between fellow eyes and the concordance of cicatricial outcomes at age 1 year of eyes that did not develop threshold disease. METHODS: Four thousand ninety-nine infants with birth weights of less than 1251 g who participated in a natural history segment of the Cryotherapy for Retinopathy study underwent biweekly eye examinations from 4 to 6 weeks after birth until retinal vasculature was complete or until ROP regressed or reached threshold severity. Eyes were categorized as follows: (1) no ROP, (2) less than prethreshold ROP, (3) prethreshold ROP, (4) threshold ROP, and (5) unable to determine. The presence and stage of ROP residua in fellow eyes were evaluated at 12 months. RESULTS: Acute-phase ROP status between 32 and 42 weeks postconceptional age showed a high degree of correspondence between fellow eyes in severity (stage) and location (zone) of ROP, presence of plus disease, and sectors of stage 3 retinopathy. More variability between eyes was seen when cicatricial status at age 1 year was examined. This higher variability was evident even though results from patients with threshold ROP (many of whom underwent cryotherapy) were excluded. CONCLUSION: The usual course of ROP during its acute phase is for fellow eyes to be very similar in ROP status. However, asymmetry between eyes is not unusual in eyes with posterior pole residua of ROP.

Acute Disease↗
PubMed1994

Data monitoring in clinical trials: the case for stochastic curtailment.

Interim analyses have become an essential part of the monitoring process of clinical trials. Stochastic curtailment has been used in such analyses. This procedure allows for calculation of the probability of rejecting the null hypothesis at the end of a trial given the current data and assuming the null or an alternative hypothesis for the remainder of the trial. Such information can be used to decide whether a trial should continue or be stopped early due to either treatment benefit or harm or because of lack of power to show an effect. Using stochastic curtailment, stopping rules for one- or two-sided test trials can be easily visualized by constructing boundaries based on the null and alternative hypotheses. Interim Z test statistics falling above or below these boundaries can aid in interim monitoring decisions. Methods for constructing boundaries, expected trial times and examples of clinical trials in cardiovascular and vision research where stochastic curtailment was used are presented.

Clinical Trials as Topic↗
PubMed1992

The standardized mortality ratio and life expectancy.

This paper develops a theoretical relation between the standardized mortality ratio (SMR) and the expected years of life and establishes a regression equation for easy conversion between these two statistics. The mathematical expression of the derived relation is an approximation, requiring an assumption of constant age-specific mortality ratios. It underestimates the "true" value calculated based on life table technique when the age-specific mortality ratios increase with age. This equation provides a conservative method to estimate the expected years of life for cohort mortality studies and facilitates an assessment of the impact of work-related factors on the length of life of the worker. It also allows one to convert the SMR to life expectancy in smaller studies whose sole objective is to determine the SMR in a working population. A 1% decrease (or increase) in the standardized mortality ratio will result in 0.1373 years increased (or decreased) life expectancy based on white male data for the US population. Furthermore, with data from 14 large oil refinery and chemical worker cohorts of white males, the "derived" expected years of life based on the regression equation closely predicts the corresponding value calculated using a standard life table technique. This statistical equation is expected to have practical applications when used in conjunction with the SMR to provide an approximate measure of life expectancy, a term and statistic familiar to most lay people.

Adult↗
PubMed1992

Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys.

Simian hemorrhagic fever (SHF) virus and a new strain of Ebola virus were isolated concurrently in recently imported cynomolgus monkeys (Macaca fascicularis) being maintained in a quarantine facility. Ebola virus had never been isolated in the U.S. previously and was presumed to be highly pathogenic for humans. A chronology of events including measures taken to address the public health concerns is presented. The clinicopathologic features of the disease were abrupt anorexia, splenomegaly, marked elevations of lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, with less prominent elevations of blood urea nitrogen, creatinine, and other serum chemistry parameters. Histologically, fibrin deposition, hemorrhage, and necrosis of lymphoid cells and reticular mononuclear phagocytes were present in the spleens of SHF and of Ebola virus-infected animals. Intravascular fibrin thrombi and hemorrhage were also present in the renal medulla and multifocally in the gastrointestinal tract. Necrosis of lymphoid and epithelial cells was occasionally noted in the gastrointestinal tract. The histopathologic findings considered specific for Ebola virus infection include hepatocellular necrosis, necrosis of the zona glomerulosa of the adrenal cortex, and interstitial pneumonia, all of which were generally associated with the presence of 1 to 4 mu intracytoplasmic amphophilic inclusion bodies. The disease spread within rooms despite discontinuation of all direct contact with animals, and droplet or aerosol transmission was suspected. Antibody to Ebola virus developed in animal handlers but no clinical disease was noted, suggesting a less virulent strain of virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Genetic epidemiology of childhood brain tumors.

The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome.

Adolescent↗
PubMed1991

Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) is a randomized clinical trial sponsored by the National Eye Institute (NEI) designed to test whether cryotherapy applied to eyes of premature infants with a specified extent of stage 3+ ROP significantly decreases the incidence of an unfavorable outcome. An unfavorable outcome is defined as either retinal detachment or a retinal fold and was determined at 3 months posttreatment by the use of a masked photographic system. Enrollment into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled closing date for enrollment because of demonstrated treatment benefit. The purpose of this article is to discuss the operations involved in the orderly termination of enrollment and dissemination of results from this trial. These activities included preparation of trial participants and staff, release of trial information, continuing patient care, data collection and coding, and publication of trial results.

Blindness↗
PubMed1991

Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was a randomized trial designed to test whether cryotherapy applied to the retina significantly decreased the incidence of retinal detachment, retinal fold, or retrolental "mass." Randomization into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled end of the intake period. At the time of the decision, a favorable outcome at 3 months posttreatment occurred more frequently in eyes treated with cryotherapy (78%) as compared to untreated eyes (57%) (chi 2 = 20.5). The basic statistical method used in monitoring the results was conditional power (or stochastic curtailment). Several other issues were considered in deciding to terminate the trial, including the examination of results across subgroups and clinical centers, the completeness of follow-up, clinical assessment of outcome, and long-term consequences of the treatment.

Bias↗
PubMed1991

Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new insight into the development of ROP.

Cryosurgery↗
PubMed1990

A surveillance system for assessing health effects from hazardous exposures.

A statistical procedure for monitoring the health status of a community potentially exposed to a hazardous environment is presented. It utilizes two levels of investigation. Level I studies monitor routinely collected vital statistics and routes of community exposure whereas level II studies require additional data collection and are further distinguished by their design and duration. In a level I study, routine vital statistics for specified end points over a specified period of time are monitored, and the observed number of events is compared with the expected number of events for a given population. The statistical model used with this procedure employs a two-step decision rule based on the standardized mortality ratio for the study community. An "alert status" is invoked when the number of events exceeds a prescribed excess. An "action status" is indicated if the excess noted in the initial period persists or if the observed number of events in the initial period greatly exceeds expectation. Should an "action status" be justified, level II studies to determine the likely explanation for the significant excess are initiated. This could include the conduct of a "case-control" study using the exposure data available from monitoring the community.

Cluster Analysis↗
PubMed1989

An illness-death process with time-dependent covariates.

A general model for the illness-death stochastic process with covariates has been developed for the analysis of survival data. This model incorporates important baseline and time-dependent covariates in order to make an appropriate adjustment for the transition and survival probabilities. The follow-up period is subdivided into small intervals and a constant hazard is assumed for each interval. An approximation formula is derived to estimate the transition parameters when the exact transition time is unknown. The method developed is illustrated with data from a study on the prevention of the recurrence of a myocardial infarction and subsequent mortality, the Beta-Blocker Heart Attack Trial (BHAT). This method provides an analytical approach with which the effectiveness of the treatment can be compared between the placebo and propranolol treatment groups with respect to fatal and nonfatal events simultaneously.

Biometry↗
PubMed1988

Lung cancer mortality among women employed in high-risk industries and occupations in Harris County, Texas, 1977-1980.

Lung cancer is rapidly becoming the leading cause of cancer mortality among women. Interviews conducted with 259 women with lung cancer and 278 women without lung cancer or with their next-of-kin in Harris County, Texas from July 1, 1977 to June 30, 1980 revealed that 12 (4.6%) of the women with lung cancer had never smoked cigarettes. The odds ratio (OR) for current smoking was 15.7. Odds ratios for smoking for living women (OR = 17.5) were higher than for those who were deceased (OR = 12.6). Lifetime occupational histories were classified a priori into high- and low-risk categories. Data were stratified according to employment in a high-risk industry or occupation, a high-risk industry, a high-risk occupation, or both a high-risk industry and occupation. Although not statistically significant, odds ratios for employment in high-risk categories support earlier estimates that attributed 5% of lung cancer mortality in women to employment in hazardous occupations. Employment of a husband or household member in selected industries and occupations yielded significantly increased odds ratios. More cases (15.9%) than controls (6.9%) reported a family history of lung cancer (OR = 2.4). No significant increase in smoking-adjusted odds ratios was found for the use of hair spray, hand-held dryers, or alcohol, or for having lived with a household member who smoked cigarettes.

Adenocarcinoma↗
PubMed1988

The relation between degree of blood pressure reduction and mortality among hypertensives in the Hypertension Detection and Follow-Up Program.

The relation between degree of diastolic blood pressure reduction and mortality was examined among hypertensive persons in the Hypertension Detection and Follow-up Program. This program, conducted from 1973-1979, was a multicenter community-based trial, which followed 10,940 hypertensive participants for five years. The one-year annual visit was the first occasion on which change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,053 participants, 568 deaths occurred. With time-dependent life tables and time-dependent Cox life table regression analyses, the existence of a quadratic function which modeled the relation between diastolic blood pressure reduction and mortality was supported, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a diastolic blood pressure reduction of 26.2 mmHg (standard error = 13.4) in the whole population and 10.0 mmHg (standard error = 5.3) in the baseline diastolic blood pressure stratum 90-104 mmHg. After this reduction, there was a small increase in the risk of death. There was no evidence of the quadratic function after fitting the same model with systolic blood pressure. Methodological issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide, and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed not only to pharmacologic therapy but also to regression to the mean, and to other factors unrelated to treatment.

Actuarial Analysis↗
PubMed1988

Air pollution and lung cancer mortality in Harris County, Texas, 1979-1981.

Elevated lung cancer mortality rates in Harris County, Texas compared with other US counties and previously published reports that suggested a causal relation between air pollution and lung cancer in Houston prompted this ecologic analysis. A weighted regression analysis was used to examine the air pollution-lung cancer mortality relation for white males in Harris County, Texas, 1979-1981. The regression model included the following census tract-specific characteristics: median age for white males, two social and demographic factors not strongly correlated with pollution (family life cycle and migration), an age-dependent smoking index, and a pollution measure based on total suspended particulates. This model indicated a statistically significant contribution of the pollution measure in explaining the intracounty variation in lung cancer mortality rates. The relation between air pollution and lung cancer mortality, however, appeared to be highly dependent on which social and demographic factors were selected for inclusion in the analysis. Air pollution was not demonstrated to be a strong determinant of lung cancer mortality in this study in that the presence of air pollution accounted for less than 5% of the total variation in intraurban lung cancer mortality. In addition, the interpretation of geographic analysis must be guarded due to the introduction of potential bias due to aggregation. The hypothesis that air pollution is contributory to lung cancer cannot be tested until other, stronger individual risk factors for lung cancer can be better measured and controlled in studies of this association.

Adult↗
PubMed1987

Incidence of pelvic endometriosis in Rochester, Minnesota, 1970-1979.

To the authors' knowledge, the incidence pelvic endometriosis in the general female population has not been previously reported. The purpose of the present study was to determine the incidence rate of diagnosed pelvic endometriosis among white females of reproductive age (15-49 years) in Rochester, Minnesota, during 1970-1979. Incidence rates were prepared first with histologically confirmed cases alone and then with the successive inclusion of progressively less certain cases: surgically visualized, clinically probable, and clinically possible. The overall incidence of pelvic endometriosis more than doubled (from 108.8 to 246.9 cases per 100,000 person-years) as the definition of a case was extended from histologically confirmed cases alone to all cases. Age-specific incidence rates increased in successive age groups through age 44 and then declined for women 45-49 years of age. Methodological problems in the definition and ascertainment of incident cases of pelvic endometriosis are described in detail.

Adolescent↗
PubMed1987

A ten year study of partial mastectomy for carcinoma of the breast.

Since 1970, 334 patients have undergone partial mastectomy, axillary dissection and irradiation for treatment of invasive carcinoma of the breast. The average follow-up period is 59 months. Survival curves were calculated for the entire study group and for patients classified by tumor size, nodal status and stage of disease. The five year over-all survival rate for 334 patients is approximately 87 per cent; the ten year survival rate is approximately 64 per cent. Of the 334 patients, 247 (74 per cent) have been observed for at least two years. Fourteen of these patients (5.7 per cent) have had a recurrence of carcinoma develop within the treated breast.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

A computer program for an illness-death process with time-dependent covariates.

This paper presents a computer program for estimating transition probabilities between states in a stochastic model for an illness-death process which incorporates time-dependent covariates. Parameters are estimated by the method of maximum likelihood using the Newton-Raphson iterative procedure. The program provides the standard normal deviate statistics as well as the value of the maximum of the likelihood function which can be used on repeated applications to test hypotheses concerning coefficients associated with covariates. Although this program is demonstrated by using a model with two 'illness' states and two 'death' states, it is also suitable for analyzing data with models involving fewer states, such as the analysis of survival time with covariates assuming a proportional hazard model.

Computers↗
PubMed1983

Serum cholesterol and cancer in the Hypertension Detection and Follow-up Program.

The relation between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program. During the 5 years of follow-up, 286 new cancer cases were documented among the 10,940 participants. Overall, age-adjusted cancer incidence rates, computed by baseline serum cholesterol quartiles, showed a small, but statistically significant, inverse relation between serum cholesterol and cancer incidence. No evidence suggested that the observed relationship was primarily due to confounding by other cancer risk factors, association of low serum cholesterol with incipient but undiagnosed cancer, or problems of competing risks. However, the relationship is weak and a causal interpretation of these immediate results cannot be argued persuasively. Examinations of specific cancer sites and factors related to serum cholesterol are suggested as important lines of research toward clarification of the complex relationships observed.

Adult↗