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Biomedical subjects

Richard B Singer

Publications and source records attributed to Richard B Singer.

15 recordsLinked to original sources
PubMed2006

Mortality in a complete 4-year follow up of 85-year-old residents of Leiden, classified by serum level of thyrotropin and thyroxine.

BACKGROUND: The authors of the source article emphasize the clinical tendency to screen for, detect and treat for thyroid dysfunction in very elderly patients, in which it is a fairly common disorder, often with occult or no symptoms. Published evidence is conflicting on the benefit, if any, of such a program. Accordingly, they devised a prospective, population-based study to determine outcomes, including survival outcome, based on serum levels of thyroid-stimulating hormone (TSH) and thyroxine. METHODS: A cohort of 558 subjects who had their 85th birthday between September 1997 and September 1999 was enrolled after consent of the subject and screening examination that included serum TSH and thyroxine levels. This represented a 79% sample of all 85-year-old residents of Leiden, the Netherlands. Follow up was complete for survival 4 years to the subject's 89th birthday or prior death, although 70 subjects refused the annual re-examination. Thyroid function, disability, cognitive function and number of chronic diseases were analyzed, in addition to mortality, through Cox regression and other statistical methods. RESULTS: In 67 subjects with abnormally high TSH (>4.8 mIU/ L), the mean annual mortality rate was derived as 64 deaths per 1000 per year. In the 491 subjects with normal TSH or low TSH (<0.3 mIU/L), the mean annual mortality rate was derived at 114 per 1000 per year. Laboratory evidence of hypothyroidism (initially low serum thyroxine) was found in only 37 of the 67 subjects. CONCLUSION: In the 13% of elderly subjects in Leiden with abnormally high serum TSH levels, the mean annual mortality rate was significantly lower than the mortality rate in the 87% of the elderly patients with normal or low serum TSH. The significance is based on 95% confidence levels of the Poisson distribution. The rate in the group with high TSH levels had 16 deaths in 264 person-years of follow up (FU). The majority with normal or low TSH levels had 193 deaths in 1698 person-years of FU.

Actuarial Analysis↗
PubMed2006

Use of a mean entry age underestimates expected mean mortality rate.

OBJECTIVE: To explain the impact of the 10% annual increase in mortality rate in the life tables from about age 45 to 90 years on mean expected mortality rate in any follow-up (FU) group with a wide age range. Use of the mean age to enter a life table invariably underestimates the true mean expected mortality rate in small age groups with an age range of 5 to 10 years. As a result, when mean age and standard deviation (SD) are the only age characteristic given for the cohort reported in a FU study, the mean age must be adjusted upward to enter the life table to obtain a valid mean expected mortality rate of the entire cohort. METHOD: The 1989-91 Decennial US Life Table is used to illustrate the variation of expected annual rate, q', with age, x. The magnitude of the error in mean q' introduced by failure to adjust mean age to obtain mean q' is illustrated in examples of both cardiovascular and cancer FU studies. Other tabular analytical data are also presented. RESULTS: From the 1989-91 US Life Tables for the white population, it is shown that the mean increase in annual mortality rate between ages 45 and 90 years has been found to be 9.36 +/- 0.79% per year for males and 9.94 +/- 1.13 for females. For age groups with a narrow range (10 years or less), a mean age can be used to estimate an accurate mean q'. But if the range exceeds about 15 years, as it does in most groups of patients in a FU study, a tabular q; obtained by entering the life table with the mean age is underestimated and is lower than the actual mean q'. The magnitude of the error increases with the magnitude of the range or SD. Examples are given of the magnitude of the error in one group as patients with coronary heart disease and in another group with cancer. Summary data on the magnitude of the error are also given for multiple groups in each category. CONCLUSION: Recommendations are made on how to adjust the mean age, when possible, to provide a more accurate q', when data by separate age groups are not available.

Adolescent↗
PubMed2006

Progression of mean age and mean expected mortality rate by duration of follow up in cohorts with a wide range of age.

BACKGROUND: [corrected] In a previous article, it was demonstrated that use of mean age to enter a life table to obtain a mean expected mortality rate of a cohort with a wide age range invariably underestimates the true mean expected mortality rate, q'. This is due to the bias introduced by the average 10% annual increase in q' in the approximate age range of 45 to 90 years (rates in the population life table, ages 0-109 years were analyzed to illustrate this). The magnitude of the error was demonstrated in various examples. All of these data were limited to the first year of FU (follow-up) duration. In this article, we analyze progression of mean age, x, and mean expected mortality rate, q', with FU duration in cohorts with all ages combined. When the age range is only 5 or 10 years, the mean age of the survivors does increase very nearly a full year with each year of FU duration. RESULTS: We utilized a 1973-1987 cohort in the SEER database for prostate cancer, all ages and all stages combined, and from this derived a comparative mortality table. We first demonstrated the difference between cumulative expected survival rate, P', as calculated in the SEER database, and the actuarial calculation of P'. The SEER method results in a 5% underestimate of P' vs the actual P' at a duration 14-15 years, and a corresponding overestimate of Q' and q'. Second, we found that the annual mean age of the survivors in the prostate cancer cohort increased from 72.4 years at entry to 80.2 years in a FU of 15 years. Mean expected q' increased from 66.7 per 1000 in the first year to 93.1 per 1000 in the 15th year. The geometric mean annual increase in mean q' was only 2.4% per year, instead of the approximate 10% seen in the life table from about age 45 to 90. Progression patterns by duration for mean age and mean q' are very different in female thyroid cancer, all ages and all stages combined, again for a 1973-1987 cohort. In thyroid cancer, females outnumber males; in both sexes, the proportion of younger patients, under age 45, is much greater than in typical cancer sites, such as prostate cancer. In female thyroid cancer, both mean age and mean q' actually decreased from the mean values at entry for 5 years or more. At entry, mean age was 43.9 years, and mean q' was 8.2 per 1000. These values decreased to 43.5 years and 6.8 per 1000, respectively, at duration 1-2 years, then leveled off and began a gradual increase. At duration 14-15 years, mean age was 53.7 years, and mean q' was 11.4 deaths per 1000 per year. CONCLUSION: Progression of mean q' is erratic and unpredictable, because annual mean age of survivors is highly dependent on the proportion of younger patients in the cohort being followed. If the proportion of patients under age 45 years is high enough, both mean age and mean q' may show an initial decrease from the values found in the year of entry, because, even though each survivor is a year older, the progression of mean age is so heavily biased by the slower progression of q' at the younger than at the older ages. However, with the SEER database, if annual expected survival rates are converted to annual expected mortality rates, the derivation of mean expected mortality rate, q' is accurate, regardless of the width of the age range in the cohort selected and being analyzed. The user of the SEER database is warned that the expected cumulative survival rate, P', is derived in the SEER survival tables on the basis of the first-year age distribution, not on the basis of the changing age distribution that is actuarially observed.

Adolescent↗
PubMed2005

How to prepare a life expectancy report for an attorney in a tort case.

The purpose of this methodology article is to describe a suitable format for a legally acceptable report on the life expectancy of the principal in a tort case that is being advocated or defended by an attorney. Life insurance medical directors and underwriters are clearly skilled and experienced in mortality risk classification for life insurance. However, the judicial system is accustomed to measuring excess mortality only in terms of reduced life expectancy. The analyst preparing the report must convert the excess mortality into a figure for reduced life expectancy and compare this with the life expectancy of persons matched by age, sex and race in the latest Decennial US Life Tables. This process is different from the life insurance underwriting process. A life table projected to age 109 must be constructed as an essential part of the report, and the entire process must be presented clearly and convincingly. There are good reasons why the excess death rate (EDR) should be used as the index of excess mortality in constructing the life table, in preference to the mortality ratio (MR), which is used most of the time in life insurance risk classification. All of these considerations are discussed in this article, which is based on a sample of 40 cases handled by the author, a retired life insurance medical director.

Adolescent↗
PubMed2005

Life expectancy--a commentary on this life table variable.

In 1992, I wrote an article on a method of modifying the Decennial US Life Table to accommodate any pattern of excess mortality expressed in terms of excess death rate (EDR), for the specific purpose of calculating the reduced life expectancy, e. I believe this was the first article published in the Journal of Insurance Medicine (JIM) that dealt specifically with life expectancy as an index of survival and risk appraisal, never used in the classification of extra mortality risk in applicants for life insurance. In this commentary, I discuss the 1989-91 US Decennial Life Table in detail. I link the subject matter of the 1992 article with several more recent articles that also focus on the utility of life expectancy in underwriting structured settlement annuities and preparing reports on life expectancy for an attorney in a tort case. A few references are given for further reading on life table methodology and its use in the most accurate estimate of life expectancy, given the inherent limitations of the life table and the limited duration of follow-up studies.

Adolescent↗
PubMed2005

Mortality in a recent study of 625 patients with chronic obstructive pulmonary disease compared with results of 3 older studies.

OBJECTIVE: To assess comparative mortality in COPD patients by severity in a recent study with results in 3 older studies. METHOD: Analysis is made of a recent multicenter study (7 clinics in the United States, Spain, and Venezuela) of COPD patients. An evaluation cohort of 207 patients was utilized to establish a scoring system based on body mass index (B), airflow obstruction (O--measured by FEV1, forced expiratory volume at 1 second), dyspnea (D), and exercise capacity (E). A scoring system for each of these 4 severity factors led to the development of the BODE Index, with a range of 0-10. This index was shown to produce a wider range of mortality than staging (1 to 3) by the FEV1 alone. RESULTS: From the FEV1 Stage and the BODE Index data, a validation cohort of 625 COPD patients was observed for 52 months. This follow-up showed a wider range of mortality by the BODE Index than that obtained by use of FEV1 staging alone. This recent experience (1997-2002) is compared with results of 3 previously published mortality studies of COPD. CONCLUSION: Incorporation of additional severity factors such as dyspnea and exercise capacity improves the prediction of mortality by severity of the COPD, as compared with the use of FEV1 staging alone. Mortality remains at a very high level in all cases, except for those with the mildest form of COPD.

Aged↗
PubMed2005

Mortality derived from 5-year survival in patients with Alzheimer disease.

OBJECTIVE: The objective of the authors of the source article was to investigate survival and course of the disease in a registry of patients with Alzheimer disease diagnosed from 1987-1996. The objective of this article is to derive expected mortality, age/sex-matched as closely as possible to data available in the article, and to derive comparative mortality from the survival results at 5 years. METHODS: The cohort of 521 patients with newly recognized senile dementia (Alzheimer disease) was drawn from a health organization in western Washington with an enrollment of 23,000 members age 60 years and older. After initial selection, a careful evaluation was made to confirm the diagnosis. The cohort was followed to death or 2001, with follow-up (FU) ranging from 0.2 to 14 years (mean 5.2 years). The authors used elaborate statistical methods in their analysis of results. A detailed description is given in the text of this article on the derivation of both observed and expected mean annual mortality rates to obtain excess death rates (EDR) and mortality ratios (MR) as indices of excess mortality averaged over 5 years of FU. RESULTS: All patients were age 60 or older, mean age was 80.2 years, and females outnumbered males, 66% to 34%. The overall EDR, all patients combined, was 37 extra deaths per 1000 per year. For all males EDR was 52; and for all females, EDR was 33 per 1000 per year. The corresponding MR values were 142%, 149% and 141%. EDR and MR increased with test scores measuring severity of cognitive impairment, with physical features of the severity of the dementia, and especially with the presence of comorbid diseases such as stroke, coronary heart disease (CHD) and congestive heart failure (CHF). With a mean age of 80 years, MR values are relatively low in comparison with EDR, owing to the high mean expected mortality. CONCLUSION: An approximate pattern of increased mortality has been found in a cohort of senile dementia patients in the Group Health Cooperative, in the area of Seattle, Washington, despite some uncertainty attributable to absence of sex and race distribution data within each of the 4 individual age groups.

Aged↗
PubMed2004

Comparative mortality in medically treated aortic regurgitation.

OBJECTIVE: To present and discuss in this article a table of comparative mortality of medically treated patients with aortic regurgitation, derived from data presented in the source article. BACKGROUND: Although there is abundant information on the follow-up (FU) of patients after surgical replacement of a leaking aortic valve, FU studies of patients with aortic regurgitation prior to valve replacement give discordant and confusing results for a number of reasons. The aim of the source study was to confine the results to patients who had been and continued to be on medical treatment only. METHODS: In this article, the triple decrement approach to life table analysis has been emphasized (death, withdrawal due to surgery, and withdrawal due to end of FU). Data in the source article were used to calculate exposures and to prepare a life table incorporating exposures, observed and expected deaths, to derive observed, expected, and excess death rates and mortality ratios. RESULTS: There was no significant excess mortality above that in the age/sex-matched US population in the NYHA class I group. In NYHA class II group, the excess death rate (EDR) averaged 28 per 1000 per year over 0-10 years. In NYHA class III and IV groups, the EDR was very high, averaging 205 per 1000 per year over 0-5 years, with a mortality ratio (MR) of 1100%. CONCLUSION: Based on data presented in the source article, there was no excess mortality in medically treated aortic regurgitation patients with no functional impairment (NYHA class I), compared to the control population. However, the long-term outlook for the AR patients with good NYHA functional classification includes a high incidence of heart failure and valve surgery. Excess mortality was significant in NYHA class II patients, and was very high in patients with NYHA class III and IV impairments. In the source study, exposure to risk of medically managed aortic regurgitation was greatly curtailed by the performance of aortic valve surgery soon after initial diagnosis, most within the first year of FU.

Age Distribution↗
PubMed2004

Conversion of mortality ratios to a numerical rating classification for life insurance underwriting-revisited.

This is a commentary requested by the J Insur Med Editor to accompany a reprinting in this 2004 issue of my 1988 article on "Conversion of Mortality Ratios to a Numerical Rating Classification for Life Underwriting" (J Insur Med 1988;20:54-61). Topics discussed in this commentary include the distinction between short-term and long-term mortality follow-up in certain conditions, the format and the introductory text of the US Decennial Life Tables, the distinction between mortality rate and mortality probability, averaging mortality rates over a period of years, and the great value of the exemplary follow-up study used in the 1988 article.

Actuarial Analysis↗
PubMed2003

Mortality in rheumatoid arthritis patients treated with or without methotrexate.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease associated with excess mortality. In 1974 a registry of RA patients was established at the Wichita Arthritis Center. It has been directed by its founder, Dr. Frederick Wolfe, ever since. The database for RA patients provided results for the present study and 1 of the 4 series reported previously. RESULTS: These are based on a consecutive series (after specific exclusions) of RA patients, 18 years of age and older, treated at the Wichita Arthritis Center, 1981 through 1999. During this period, 588 of the total 1240 RA patients were treated with methotrexate, and 652 patients did not receive any methotrexate. Total exposure amounted to 7584 patient-years, and total deaths numbered 191. An elaborate statistical method was developed by Wolfe and a team of Harvard epidemiologists to adjust for prognostic risk factors, which were higher in the methotrexate than in the non-methotrexate group. Detailed descriptive data were included in the database. Overall excess mortality in comparison with population rates was higher in the methotrexate than in the non-methotrexate group, but the unadjusted difference was not significant. Results for the 1981-1999 total Wichita cohort were compared with those of the 1974-1990 cohort and the 1983 Impairment Study (both before and after adjustment to the older age distribution of the Wichita patients). CONCLUSION: Mortality improved somewhat in the RA patients at the Wichita Center from 1974-1990 to 1980-1999. In the later period, mortality was lower in patients treated with methotrexate than in those not so treated. After the authors of the source article made adjustments for the increased RA severity in the patients treated with methotrexate, mortality was significantly lower in the methotrexate-treated group, with a mortality hazard ratio of 0.4 (95% confidence interval 0.2-0.8).

Actuarial Analysis↗
PubMed2002

Abnormal delay in recovery of pulse rate in 9454 patients referred for treadmill exercise test to Cleveland Clinic, 1990-1997--an independent predictor of excess mortality.

OBJECTIVE: The objective of this article is to present results from the latest of 3 recent reports from the Cleveland Clinic on excess mortality associated with abnormal delay in the recovery of an elevated pulse rate produced in a treadmill exercise test. This is done in the context of a long-standing medical interest in this phenomenon and its prognostic significance (see Comment section). BACKGROUND: Delay in return of the pulse rate after exercise has long attracted medical interest as a potentially unfavorable prognostic factor. However, this has not become a factor in the interpretation of the treadmill exercise test. Cardiologist staff members of the Cleveland Clinic have recently studied the mortality predictive effect of delay in pulse recovery in 3 different cohorts of patients given a treadmill exercise test (modified Bruce protocol). The newest, largest and most complete of these studies is the source article for this report. STUDY DESIGN: This was an observational follow-up (FU) study with a median of 5.2 years (range 1.4-8.7 years). The patients were categorized as abnormal pulse recovery at 1 minute after peak exercise with decrease of only 12 beats per minute or less, and normal if >12 beats per minute. These classes were combined with dichotomous classes according to the exercise test result and with other associated risk factors. RESULTS: A good approximation of exposure was achieved for each of the 4 pulse recovery/exercise test groups. From numerical data in the article, it was possible to derive aggregate mean annual mortality rates for these groups and selected combinations of pulse recovery with other risk factors. Mortality was lowest (2.8 per 1000) in the group with pulse recovery and exercise test both normal (66% of the total patients screened), and this was used as the "expected" rate, without adjustment for any differences in age. On this basis the excess death rate (EDR) was about 7 per 1000 per year when either pulse recovery or exercise test was abnormal, and 28 per 1000 when both were abnormal. Similar levels of EDR were found in the combinations of pulse recovery with other risk factors. CONCLUSION: Abnormal pulse recovery after the treadmill exercise test is a powerful and independent predictor of significant excess mortality.

Exercise Test↗
PubMed2002

Fecal occult blood testing and the incidence of colorectal cancer.

OBJECTIVE: The objective of this abstract is to demonstrate by life table methodology a significant reduction in the mean annual incidence rate of colorectal cancer in randomized groups with annual or biennial screening for fecal occult blood, as compared with the annual incidence rate in the control group. BACKGROUND: Testing for the presence of fecal occult blood has long been used for the early detection of colorectal polyps and potential cancers. The Minnesota Colon Cancer Study, in an earlier report, has shown that colorectal cancer mortality was significantly reduced, but a 12% reduction in incidence of colorectal cancer was not statistically significant. Follow-up in the Minnesota Study has now been extended to 18 years for augmented incidence results, which have now been reported in the source article and in this morbidity abstract. RESULTS: Subjects in Minnesota were recruited in 1975-1978 and randomized into annual or biennial screening for fecal occult blood, and a control group receiving "usual care." Screening was continued 1976-1982, discontinued, then resumed 1986-1992. During 18 years of follow-up, about 235,000 person-years of exposure were accumulated in each randomized group, with 417 and 435 cases of colorectal cancer in each of the screening groups and 507 cases in the control group. CONCLUSION: Aggregate mean annual incidence rates of colorectal cancer were significantly lower in both screening groups than in the control group, as shown in Table 1. In the source article the same was true for the 18-year cumulative incidence rates, which were also significantly reduced (p < 0.001 for the annual screening group and p = 0.002 for the biennial screening group).

Aged↗