Biomedical subjects

T R Holford

Publications and source records attributed to T R Holford.

At least 19 recordsLinked to original sources

PubMed1995

Measurement of exposure to environmental tobacco smoke in pregnant women.

The authors compared three methods used to measure exposure to environmental tobacco smoke in pregnant women: personal air monitor, urine cotinine, and questionnaire. Environmental tobacco smoke exposure assessment methods were compared for agreement using Cohen's Kappa and the Spearman rank order correlation coefficient. Women who reported exposure had significantly higher levels of air nicotine concentration compared with women who reported no exposure, but urine cotinine did not differ. Air nicotine was more highly correlated with home exposure (r = 0.34) than work exposure (r = 0.18). Urine cotinine correlated with work exposure (r = 0.14) but neither home nor social exposure. Agreement was "fair" (Kappa = 0.29) when self-reported exposure was compared with air monitor, but agreement was "poor" when urine cotinine was compared with self-report (Kappa = 0.08) and air monitor (Kappa = 0.10). In low environmental tobacco smoke exposure environments, all three methods for measuring exposure may have a role, although modification to monitoring protocols will be needed to improve monitoring sensitivity and exposure classification.

Adult↗

PubMed1995

Time trend in pancreatic cancer incidence in Connecticut, 1935-1990.

A total of 13,246 incident pancreatic cancer cases, reported to the Connecticut Tumor Registry between 1935 and 1990, were included in our study. Results indicate that the overall age-adjusted incidence rate of pancreatic cancer increased between 1935 and 1964 in males, and leveled off thereafter. Since 1975, the incidence rate has in fact been decreasing, from 12.04/100,000 in 1975-79 to 10.44/100,000 in 1985-90. In females, the overall age-adjusted incidence rate also increased between 1935 and 1974. Since then, however, it has remained relatively stable. Age-specific incidence rates also show no signs of an increase in rate from any age group, or from either sex for recent birth cohorts. There is also no clear increase in the incidence of pancreatic cancer in any of the ethnic/gender categories since the early 1970s. Age-period-cohort modeling shows that the increasing birth cohort trend peaked among those born around 1920-1925 and, for recent birth cohort, a slightly decreasing trend was observed in both males and females. Our study reveals no signs of an increase in the immediate future in pancreatic cancer incidence rate in any of the sex, ethnic and age groups in Connecticut.

Adult↗

PubMed1995

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods. We assessed EMF exposure using personal monitors, home measurement, video display terminal use, and wire code. Exposure to EMF during pregnancy, either at conception, at < or = 16 weeks, or in the third trimester, showed no important relation to risk of low birth-weight or fetal growth retardation. This result was the same whether we used subjective measures of exposure or direct measurement. Use of video display terminals at home or work, exposure to > or = 2.0-milligauss fields as measured by home or personal monitors, and home wire code were unrelated to the reproductive outcomes studied. A time-weighted analysis of electric bed use, which accounted for strength of EMF exposure and hours of use, also showed evidence of no meaningful increase in risk. None of the exposure measures showed a dose response relation to risk. We conclude that risk of low birth-weight and intrauterine growth retardation is not increased after electrically heated bed use during pregnancy.

Adult↗

PubMed1995

Change points in the series of T4 counts prior to AIDS.

The absolute number of T4 cells has been established as an important clinical marker of disease progression to acquired immunodeficiency syndrome (AIDS) in persons infected with human immunodeficiency virus (HIV). Series of T4 counts are analyzed from the 131 homosexual men who entered the New York Blood Center Study in 1984, mostly seropositive for HIV, and who developed AIDS as participants by 1990. These series exhibit a gradual decline of the log(T4) count followed by a more rapid decline close to the time of the development of AIDS. Empirical Bayes and hierarchical Bayes change point models are proposed to estimate the distribution of the time before AIDS when this rapid decline begins. Results using the EM Algorithm and Markov chain Monte Carlo indicate that the mean change point occurs approximately 1 year before diagnosis with a standard deviation of 9 months. Detection of a change point may indicate that an AIDS diagnosis is increasingly likely for an individual HIV-positive but AIDS-free.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Time trend and the age-period-cohort effect on the incidence of histologic types of lung cancer in Connecticut, 1960-1989.

BACKGROUND: Recent epidemiologic studies have suggested changing patterns of lung cancer incidence by histologic type. The observed time trends have been attributed to a change in the rate of cigarette smoking, changes in exposure to new environmental carcinogens, and changes in the criteria for the histopathologic diagnosis of lung cancer. The current study was designed to examine the incidence patterns of lung cancer by histologic type in Connecticut and to use this information to project the future trend of the disease in this population. METHODS: This study was based on all the lung cancer cases reported to the Connecticut Tumor Registry between 1960 and 1989. On the basis of this data set, crude and age-adjusted incidence rates of lung cancer were calculated by histologic type for each sex. The age-specific incidence rates are presented by calendar year and cohort year of birth. A regression model was used to identify birth cohort, period, and age as determinants of the observed time trends. RESULTS: For the overall age-adjusted incidence rates, squamous cell carcinoma and small cell carcinoma have stabilized in men, whereas they are still increasing in women. The incidence of adenocarcinoma has been increasing in both men and women, but there has been a much sharper incidence among females since the mid-1970s. An examination of age-specific incidence rates by birth cohort and the results from age-period-cohort modeling indicate that incidences of all three major histologic types of lung cancer in the recent birth cohorts either have started decreasing (squamous cell carcinoma) or shown a clear reduction in the rate of increase (adenocarcinoma and small cell carcinoma). This study, however, did not indicate an increase of bronchoalveolar lung carcinoma, which was reported by other clinically based studies. CONCLUSION: While the overall age-adjusted incidence rates showed different incidence patterns for different histologic types of lung cancer, a decreasing or stabilized rate for all three major histologic types of lung cancer was observed in recent birth cohorts in both males and females. The observed incidence pattern is consistent with smoking trends over time including changes in smoking prevalence and the consumption of low tar and filter cigarettes. It is expected that if the current trend in tobacco smoking continues and if there are no major changes in other risk factors for lung cancer, a forthcoming stabilization or decrease in the rate of lung cancer incidence for all major histologic types (including adenocarcinoma) in both sexes in Connecticut could be anticipated.

Adenocarcinoma↗

PubMed1994

Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Denmark.

In a previous investigation, statistical modelling was used to examine the relationship between large-bowel-cancer incidence and age, time period and birth cohort by anatomic sub-site and sex, using data from the Connecticut Tumor Registry (CTR) for the period 1950 to 1984. This analysis revealed differences in age-period-cohort patterns that suggested etiologic distinctions among sub-site groupings and between the sexes. To test the generalizability of the Connecticut findings, we have conducted a similar age-period-cohort analysis using data from the Danish Cancer Registry (DCR) for the period 1953 to 1987. Cancers of the large bowel were classified into 6 anatomic sub-sites: cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum. Data were fitted to log-linear age-period-cohort models. If we interpret differences in age-period-cohort patterns as reflecting etiologic distinctions, the Denmark analysis, in conjunction with the Connecticut findings, was consistent with there being etiologic distinctions between cancers of the colon vs. the rectum in both males and females, between cancers of the cecum and the ascending colon vs. the remainder of the colon in females and between males vs. females for cancers of the sigmoid colon and rectum. Cancers of the cecum and the ascending colon were the most similar between males and females. Due to the ambiguities of age-period-cohort modelling, these should be considered only tentative conclusions that can be tested by analytical epidemiologic studies.

Adult↗

PubMed1994

Time trends in the incidence of renal carcinoma: analysis of Connecticut Tumor Registry data, 1935-1989.

Recent trends in the incidence of renal cancer, stratified by histology, have not been reported. This study utilized data from the Connecticut Tumor Registry (CTR), the oldest population-based cancer registry in the United States, to establish time trends in the incidence of adenocarcinoma and transitional cell carcinoma of the kidney and urinary tract. All 10,209 incident cases of renal cancer reported to the CTR between 1935 and 1989 were analyzed. Regression modelling was employed to determine the effects of age, period, and birth cohort on incidence rates, and to project future trends. The incidence rate of adenocarcinoma increased in females from 0.7/100,000 in 1935-39, to 4.2/100,000 in 1985-89; and in males, from 1.6/100,000 in 1935-39, to 9.6/100,000 in 1985-89. The reported incidence of transitional cell carcinoma increased in males from 0.5/100,000 in 1950-54 to 2.8/100,000 in 1985-89, and in females from 0.2/100,000 to 1.1/100,000 over the same period. Regression modelling revealed that both net and recent drift, the sum of period and cohort slopes, were positive for adenocarcinoma in both sexes, largely due to a positive cohort effect. While the net drift for transitional cell carcinoma was positive, recent drift was negative in both sexes due primarily to a negative cohort effect. Incidence rates of adenocarcinoma are likely to rise in the immediate future, with the rate of rise in females possibly exceeding that in males. Incidence rates of transitional cell carcinoma will stabilize.

Adult↗

PubMed1994

Malignant melanoma incidence in Connecticut (United States): time trends and age-period-cohort modeling by anatomic site.

This study examined time trends and age-period-cohort patterns in the incidence of cutaneous malignant melanoma (CMM) by gender and anatomic site in Connecticut (United States) between 1950 and 1989, using data from the population-based Connecticut Tumor Registry. A total of 8,249 invasive CMM incident cases were included. Cases were grouped into melanomas of the head and neck, upper limb, lower limb, and trunk. Between 1950 and 1989, rates increased substantially for all sites. The largest relative increases occurred in melanoma of the upper limb for both males and females; the largest absolute increase occurred for melanoma of the trunk in males; and the smallest increase occurred in head and neck melanoma in females. Recent trends for time periods 1970-89 among birth cohorts 1930-69 indicated that the rate of increase of CMM is slowing substantially among males, but not among females. Nevertheless, continued overall increases in CMM incidence are likely in Connecticut in the 1990s in both genders, with a decrease in the male-female ratio. The age-period-cohort patterns were significantly different between the genders and among anatomic sites, suggesting different trends in carcinogenic exposures (mainly ultraviolet radiation from the sun) or etiologic distinctions between males and females and among the sites.

Adult↗

PubMed1993

The time trend and age-period-cohort effects on incidence of adenocarcinoma of the stomach in Connecticut from 1955-1989.

BACKGROUND: Adenocarcinoma of the gastric cardia has been be increasing in Connecticut, and the risk factors responsible for the increasing incidence are unknown. This study examined the incidence pattern of adenocarcinoma of the gastric cardia and distal stomach in Connecticut during the past decades and identified components of birth cohort, period, and age as determinants of the observed time trends by regression modeling. METHODS: This study was based on all histologically confirmed incident cases of gastric adenocarcinoma reported to the Connecticut Tumor Registry between 1955 and 1989. Stomach cancers were grouped into cancers of the gastric cardia, distal stomach, or unknown/unspecified subsite. Age-adjusted incidence rates were calculated by the direct method standardized to the 1970 United States population. A regression model was used to identify birth cohort, period, and age as determinants of the observed time trends. RESULTS: The results indicated that the incidence rate of adenocarcinoma of the cardia is increasing, particularly in white males, whereas adenocarcinoma of the distal stomach is now decreasing in both sexes in Connecticut. Regression modeling suggests that the increase of adenocarcinoma of the cardia may be explained partly by a birth cohort phenomenon. CONCLUSION: There is little information regarding the risk factors that might be responsible for the observed increasing trend for adenocarcinoma of the cardia, although smoking, alcohol intake, retinol intake, and hiatal hernia have been associated with an increased risk of adenocarcinoma of the cardia or gastric cancer. Considering the different epidemiologic features of adenocarcinoma of the cardia and distal stomach, future analytic studies should separate cancer of the gastric cardia and cancer of the distal stomach in searching for etiologic factors.

Adenocarcinoma↗

PubMed1993

Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Connecticut.

In order to investigate etiologic distinctions among the anatomic sub-sites of the large bowel by sex, the relationship between large-bowel-cancer incidence and age at diagnosis, time period at diagnosis, and birth cohort was analyzed by anatomic sub-site and by sex, using data from the Connecticut Tumor Registry. Included in the study were all incident large-bowel-cancer cases occurring between 1950 and 1984 among Connecticut residents aged 40 to 79. Cancers of the large bowel were classified into 5 anatomic sub-sites: ascending colon (including cecum), transverse colon (including flexures), descending colon, sigmoid colon, and rectum (including rectosigmoid junction, anal canal, and anus). The data were fitted to log-linear age-period-cohort models. For each of the sub-sites, the age-period-cohort patterns for males and females differed. Within each sex, sub-site groupings with common patterns were indicated. Among males, the age-period-cohort patterns for the colon sub-sites were fairly similar; but the pattern for the rectum differed markedly from that for the colon sub-sites. There were secondary differences among the colon sub-sites that pointed to a secondary distinction between the right and the left colons. Among females, the age-period-cohort patterns for the left colon sub-sites and the rectum were fairly similar. The pattern for the transverse colon differed moderately from that of the left colon, and differed substantially from that of the rectum and the ascending colon. The ascending colon differed markedly from each of the other sub-sites. It is possible that these differences in age-period-cohort patterns reflect etiologic distinctions among sub-site groupings and between the sexes.

Adult↗

PubMed1993

The risk of determining risk with multivariable models.

PURPOSE: To review the principles of multivariable analysis and to examine the application of multivariable statistical methods in general medical literature. DATA SOURCES: A computer-assisted search of articles in The Lancet and The New England Journal of Medicine identified 451 publications containing multivariable methods from 1985 through 1989. A random sample of 60 articles that used the two most common methods--logistic regression or proportional hazards analysis--was selected for more intensive review. DATA EXTRACTION: During review of the 60 randomly selected articles, the focus was on generally accepted methodologic guidelines that can prevent problems affecting the accuracy and interpretation of multivariable analytic results. RESULTS: From 1985 to 1989, the relative frequency of multivariable statistical methods increased annually from about 10% to 18% among all articles in the two journals. In 44 (73%) of 60 articles using logistic or proportional hazards regression, risk estimates were quantified for individual variables ("risk factors"). Violations and omissions of methodologic guidelines in these 44 articles included overfitting of data; no test of conformity of variables to a linear gradient; no mention of pertinent checks for proportional hazards; no report of testing for interactions between independent variables; and unspecified coding or selection of independent variables. These problems would make the reported results potentially inaccurate, misleading, or difficult to interpret. CONCLUSIONS: The findings suggest a need for improvement in the reporting and perhaps conducting of multivariable analyses in medical research.

Humans↗

PubMed1993

Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2.

Previous analyses of the National Acute Spinal Cord Injury Study (NASCIS) have not distinguished recovery of segmental function at the injury level from recovery of the long spinal tracts. Recovery at the injury level could be of considerable clinical significance, but long-tract recovery is the ultimate therapeutic goal. This analysis demonstrates that the greatest proportion of all neurological recovery and of recovery due to treatment with very high doses of methylprednisolone within 8 hours of injury occurs below the lesion. Methylprednisolone treatment administered early following injury has been found to improve recovery below the lesion in patients initially diagnosed as having complete or incomplete injuries; it also leads to greater (but still relatively small) improvement in the injury level. The analysis indicates that delayed treatment with methylprednisolone is associated with decreased neurological recovery. Naloxone administration also improved neurological function below the lesion in patients with incomplete injuries; these results support further experimental work with this drug. This observation of differential neurological response within a narrow treatment window has important implications for both experimental studies and clinical management. Early clinical management with high-dose methylprednisolone is supported by this analysis.

Drug Administration Schedule↗

PubMed1992

Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer.

This study examined risk factors for development of a contralateral breast cancer among 4,660 US women diagnosed with a first primary breast cancer between 1980 and 1982. The authors believe it to be the first prospective cohort study on this topic that has employed direct patient interviews. All subjects were interviewed within 6 months of the diagnosis of their initial tumor as part of the multi-center, population-based, case-control Cancer and Steroid Hormone Study, and they were followed until the end of 1986 through the Surveillance, Epidemiology, and End Results program. Exclusive of those diagnosed during the initial 6 months after diagnosis of a first primary, 136 second primary breast cancers were identified. Proportional hazards models were used to assess the independent effects of multiple predictors. Specific risk factors evaluated included: age at diagnosis of first primary, exposure to exogenous hormones, menstrual and reproductive histories, tumor characteristics, demographic variables, and treatment modalities. The age-specific incidence rates of second primary breast cancer were higher in all age categories than are the incidence rates of breast cancer in the general population, yet the age at diagnosis of first primary breast cancer was not an important predictor of contralateral breast cancer. The risk of contralateral breast cancer was increased among cohort members who reported a personal history of benign breast biopsy (multivariable-adjusted rate ratio (RR) = 1.69, 95% confidence interval (CI) 1.13-2.53) and in those with an initial tumor that was classified as lobular carcinoma (multivariable-adjusted RR = 1.96, 95% CI 1.17-3.27). Treatment with chemotherapy for the first primary was associated with a lower risk of development of a second breast cancer (multivariable-adjusted RR = 0.56, 95% CI 0.33-0.96), while radiation therapy had little effect on the risk (multivariable-adjusted RR = 1.19, 95% CI 0.78-1.80).

Adult↗

PubMed1992

The genetic epidemiology of second primary breast cancer.

It is well established that women with a family history of breast cancer run a higher risk of breast cancer than do women without a family history. The evidence, however, is less clear regarding a possible association between a family history of breast cancer and risk of second primaries. The purpose of this prospective study was to estimate the risk for second primary breast cancer associated with having a family history of breast, endometrial, and ovarian cancers. A cohort of 4,660 women with a first primary breast cancer diagnosed between 1980 and 1982 were interviewed as part of the Cancer and Steroid Hormone Study, a multi-center population-based case-control study, and followed through eight Surveillance, Epidemiology, and End Results (SEER) program registries for 4 to 6 years. Of these women, 136 developed a second primary breast cancer in the contralateral breast at least 6 months after diagnosis of the first primary. Cox proportional hazards modeling techniques were used to model the time to onset of second primary breast cancer while adjusting for multiple predictors. The risk of contralateral breast cancer was elevated among cohort members who reported a history of breast cancer in a first-degree relative (multivariable-adjusted rate ratio (RR) = 1.91, 95% confidence interval (CI) = 1.22-2.99). Early age at onset (< 46 years) in the relative further increased the risk of developing contralateral breast cancer (sister: multivariable-adjusted RR = 3.36, 95% CI 1.62-6.98; mother: multivariable-adjusted RR = 2.35, 95% CI 1.02-5.43). Bilateral breast cancer in mothers was also associated with more than a two and a half-fold increase in risk (multivariable-adjusted RR = 2.55, 95% CI 1.02-6.35). The association between family history of breast cancer and risk of contralateral breast cancer did not vary substantially according to age at onset of the first primary breast cancer. The age-adjusted rate ratio for development of a second primary breast cancer among women with a first-degree relative with endometrial cancer was 2.13 (95% CI 1.04-4.35), while the corresponding rate ratio among women with a family history of ovarian cancer was 1.69 (95% CI 0.42-6.83). There was little evidence that age at onset among the relatives with endometrial or ovarian cancer affected the risk. Some of these findings have not been previously reported and need replication in future studies.

Adult↗

PubMed1992

Time trends of non-Hodgkin's lymphoma: are they real? What do they mean?

Factors that need to be considered in the analysis of time trends in disease incidence are age, year of diagnosis, and birth cohort. When these are included in a log-linear model, a nonidentifiability problem arises from the linear dependence among these three time factors so that only specified functions of the parameters can be unambiguously determined. One of these invariant functions is the drift or the sum of the period and cohort trend. Non-Hodgkin's lymphoma incidence rates from Connecticut for the period 1935-1989 were analyzed for males and females. In addition to an age effect, both period and cohort significantly improved the fit of the model. The estimated drift shows that there has been a 10.3% increase in risk every 5 years since 1965 for females and 9.2% for males. It is unlikely that a trend of this magnitude can be attributed entirely to data artifact.

Adult↗

PubMed1992

Epidemiology of non-Hodgkin lymphoma in Connecticut. 1935-1988.

BACKGROUND: During the past decades, there have been reports of increases in the incidence and mortality rates due to non-Hodgkin lymphoma (NHL) in many parts of the world. The risk factors responsible for the increasing incidence are largely unknown. This study provided an overview of the incidence pattern of NHL in Connecticut and generated hypotheses for additional investigation. METHODS: This study was based on all the NHL cases reported to the Connecticut Tumor Registry (CTR) between 1935 and 1988. Crude, age-adjusted, and age-specific incidence rates of NHL were calculated for each sex. Age-adjusted incidence rates were calculated by the direct method standardized to the 1970 United States standard million population. The data are presented by calendar year and cohort year of birth to examine the secular trends and birth cohort effects. Racial information was not coded before 1957 and is of uncertain validity until the early 1970s; therefore, racial analysis was restricted to 1970-1988. Analyses by histologic subtypes and by anatomic sites were restricted to the last 3 decades (1960-1988) because more accurate classification systems were used during this time. RESULTS: A total of 11,326 newly diagnosed cases of NHL were included in the study. Of them, 5866 (52%) were diagnosed in men and 5460 (48%) were diagnosed in women. The study results indicated that the incidence rate of NHL has been increasing during the past decades for men and women, whites and blacks, nodular NHL and diffuse NHL, disease originating from lymph nodes and disease originating from other sites, and in all age groups, especially the older age groups. Birth cohort examination did not show any indication of a decline or levelling off in incidence rates among recent birth cohorts. Age-specific incidence rates in both sexes suggested that the rates increase with age, with a sharp increase beginning at 50 years of age and peaking at 80 years of age. Men had a 30% higher incidence rate than women, and whites had approximately 1.5 times the age-adjusted incidence rate of blacks. CONCLUSIONS: The results indicated that the incidence rate of NHL has been increasing in Connecticut during the past decades and is likely to continue to rise in the coming years. Analytical epidemiologic studies are needed to examine the risk factors that might account for the increase in NHL.

Adult↗

PubMed1992

A model for estimating level and net severity of spinal cord injuries.

Objective and detailed neurological assessments are essential in studies of the treatment and the epidemiology of acute spinal cord injuries. In practice, investigators use the expanded score, found by taking the total of the individual determinations, but this summary obscures important detail as to the level and the overall severity of injury. To address this issue, we present a method for estimating level and net severity of injury that makes use of isotonic regression and the Spearman-Kärber estimator. We describe the method for both sensory and motor assessments of neurologic function. In the special case where one gives an identical weight to the response at each level, these estimators algebraically partition the expanded score into separate contributions due to level and net severity. We provide a numerical example using data from the first National Acute Spinal Cord Injury Study, and we present a summary of the distribution of these parameters for this population.

Evaluation Studies as Topic↗

PubMed1992

A reversal in the long-term increase in deaths attributable to malignant melanoma.

For a few years in the 1980s, United States mortality rates suggested a plateau in the long-term increase for malignant melanoma. However, temporary plateaus in the increase of the age-adjusted rate by year of death have occurred in previous decades, only to be followed by a continued upward increase, with a long-term rise of about 2% per year. To determine whether a cessation in the long-term increase might be in progress, death rates were analyzed by year of birth, age at death, and year of death: (1) the long-term patterns of change are best described by birth cohort rather than by time period of death, indicating that analyses by a year of birth are key to a better understanding of the long-term trends; (2) in both men and women, evidence for a change in slope begins among those born in the early 1930s; (3) the decline in the rates begins among women born since the early 1930s and among men born since the early 1950s: the slope for men is -0.2661 (95% confidence limits [CL] = -0.380 to -0.152), and, for women, the slope is -0.02354 (95% CL = -0.041 to -0.005); (4) long-term Connecticut and US mortality trends were similar in pattern and direction, and long-term Connecticut incidence rates showed a persistent increase through the 1955 to 1965 birth cohorts. These analyses suggest a persistent cessation in the long-term increase and a downward trend in death rates from this cancer.

Adolescent↗