An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease.

OBJECTIVE: Although the Global Deterioration Scale has been widely used since its publication in 1982, its stages are based on implicit assumptions about the linearity, temporality, and interdependence of cognitive, functional, and behavioral impairment in Alzheimer's disease. The authors evaluated the validity of these assumptions and tested the hypothesis that psychopathology and functional impairment would occur in earlier stages than the Global Deterioration Scale predicts. METHOD: The analyses were based on data on 324 patients with Alzheimer's disease who were selected from a registry of such patients. Data analyses included 1) descriptive statistics on the frequency of psychiatric symptoms and difficulties with activities of daily living and 2) logistic regression, with symptoms and functional impairment as independent variables, to test for significant changes in patients' status between stages of the Global Deterioration Scale. RESULTS: More than 50% of the patients at stage 2 displayed psychopathology, and 32% had two or more symptoms. The significant increase in psychiatric symptoms occurred between stages 3 and 4, not between stages 5 and 6 as predicted by the Global Deterioration Scale. Impairment in functional status was observed at all stages, and significant increases occurred between stages 3 and 4 as well as between stages 5 and 6. CONCLUSIONS: Psychiatric symptoms and functional impairment occur earlier than predicted by the Global Deterioration Scale, and the rate of change is also different from that specified in the scale. Separate scales to describe cognitive, clinical, and functional status may be the best way to describe the illness until better multidimensional instruments are developed.

Characteristics of surviving and nonsurviving patients with primary pulmonary hypertension.

Primary pulmonary hypertension is considered a fatal illness, with survival typically of less than four years, although survival of more than 10 years has been well documented. To assess the characteristics of patients with primary pulmonary hypertension who survive versus those who do not, 12 patients with primary pulmonary hypertension were followed, and their clinical course was documented with serial catheterization. The survivors, four male and three female, had their illness for a mean of 5.2 +/- 2 years from the time of initial catheterization, with six of the seven alive at the end of the follow-up period. The five nonsurvivors, all female, had a mean survival of 0.3 +/- 0.2 years. The nonsurviving group had significantly higher right atrial pressures (17 +/- 6 versus 6 +/- 2 mm Hg), lower cardiac indexes (1.2 +/- 0.1 versus 2.3 +/- 0.5 liters/minute/m2) and stroke volume indexes (12 +/- 7 versus 30 +/- 5 ml/beat/m2), and higher systemic resistances (64 +/- 13 versus 43 +/- 14 units) and pulmonary resistances (57 +/- 31 versus 20 +/- 4 units). The pulmonary artery pressure did not significantly differ between the groups. Using regression analysis, it was found that stroke volume index and right atrial pressure were the best independent predictors of survival, with a coefficient of determination (r2) of 83 and 72, respectively. When the initial and most recent catheterization data were compared among the survivors, no significant differences were found. Determining the stroke volume index and right atrial pressure of patients with primary pulmonary hypertension at the time of their initial presentation should help in predicting their clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension.

The effects of 3 types of vasoactive agents, hydralazine, nifedipine and amrinone, were evaluated in 7 patients with primary pulmonary hypertension (PPH). Hemodynamic values were measured before and after drug administration in every patient. All drugs increased cardiac output and reduced both systemic and pulmonary resistance in the patients studied. Only nifedipine significantly reduced pulmonary artery (PA) pressure (6 +/- 5 mm Hg). In addition, it decreased pulmonary resistance to a greater degree than systemic resistance in 2 of the 7 patients, suggesting that nifedipine can cause selective pulmonary vasodilation in some patients. Hydralazine appeared to increase cardiac output and stroke volume by reducing systemic resistance. There was no evidence of direct pulmonary vasodilating effects; it decreased systemic resistance more than pulmonary resistance in every case. The increase in cardiac output from amrinone was secondary to a decrease in systemic arterial pressure with reflex tachycardia; stroke volume was unchanged. Amrinone had little pulmonary effect in all but 1 patient, in whom it substantially reduced PA pressure and pulmonary resistance. The mechanism of action of these 3 drugs in PPH differs. Nifedipine holds the most promise as an effective pulmonary vasodilator. A study of the effects of long-term administration of nifedipine in PPH is warranted.

Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension.

The pulmonary artery (PA) pressure and pulmonary resistance at rest have been noted to vary spontaneously in patients with primary pulmonary hypertension. To evaluate this variation, in 12 patients (8 women, 4 men, aged 43 +/- 13 years), hourly measurements were made for 6 consecutive hours of heart rate, systemic and PA pressures, cardiac output, systemic and pulmonary resistance. After these baseline measurements the patients were tested with hydralazine and nifedipine therapy. Spontaneous variability in pulmonary pressures and resistances occurred in each patient, with the amount of variation (coefficient of variation) in PA pressure averaging 8% and in total pulmonary resistance 13% over the 6 hours. The patients with the most variability in mean PA pressure also had the most variability in cardiac output (r = 0.69, p = 0.02). Variability also correlated with the severity of the disease, as the patients with the highest total pulmonary resistances also had the most variation for that factor (r = 0.91, p less than 0.01). The amount of variability did not correlate, however, with the acute response to either hydralazine or nifedipine administration. Based on the average coefficients of variation in these 12 patients, estimates were obtained of the percent change needed for an observed change to be attributed to a drug effect with 95% confidence. From these estimates, it was projected that for a single patient, a mean change in pulmonary resistance of 36% or a mean change in PA pressure of 22% would be required in order to attribute the changes to a drug effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic beverages and breast cancer: some observations on published case-control studies.

We identified 38 case-control studies investigating possible associations between alcoholic beverage consumption and cancer of the female breast. Each study was characterized according to design features such as: control type (hospital or community based), risk factors controlled for, matching strategy, and statistical power. We examined the effect of these design variables on several outcome variables including identification of any significant elevation in odds ratio and characterization of any dose-response effect. The major finding of this study is that of a striking difference between hospital and community based controlled studies with respect to (1) the level of any estimated dose-response effect, and (2) the finding of statistically significant elevations in odds ratios at levels of consumption below 4 drinks per week. In summary, the generally weak associations reported in these case-control studies along with the measurement and/or selection biases implied by our findings would lead one to the conclusion that present evidence does not support a causal association. This conclusion seems to be in accord with results from cohort studies and with similar conclusions from several other reviews.

The prevalence of pulmonary hypertension in the United States. Adult population estimates obtained from measurements of chest roentgenograms from the NHANES II Survey.

Because a definitive diagnosis of pulmonary hypertension requires cardiac catheterization, there have been no data on the prevalence of pulmonary hypertension in the general population. The diameter of the right descending pulmonary artery, as measured from chest roentgenograms, has been used by clinicians as a noninvasive indicator of pulmonary hypertension. Chest roentgenograms from the Second National Health and Nutrition Examination Survey, a sample survey of the US civilian noninstitutional population, were used in conjunction with estimates of sensitivity and specificity of this technique determined from patients who underwent right heart catheterization to estimate the prevalence of pulmonary hypertension (mean pulmonary artery pressure greater than 20 mm Hg at rest) in the US population aged 25 years and older. The prevalence is estimated to be very low in the population at large, primarily because of the low prevalence in women of all ages. The prevalence in men is 13.4 percent above age 34, and increases to 28.2 percent above age 64. Thus, in elderly men, pulmonary hypertension is relatively common and may have an important impact in the management of this age group.

Timing of single lung transplantation for primary pulmonary hypertension.

Single lung transplantation has been advocated as a definitive treatment for primary pulmonary hypertension. Because of reports of improved survival in some patients with vasodilators and anticoagulants, the timing of referral for single lung transplantation needs to be examined. Survival in primary pulmonary hypertension was estimated, with the use of a proportional hazards model, from data obtained from the National Institutes of Health registry on primary pulmonary hypertension. Waiting times for single lung transplantation, obtained from the United Network for Organ Sharing, were found to follow an exponential distribution. Under the assumption that waiting time and survival are independent, a model was developed to estimate the probability of surviving to single lung transplantation, depending on the waiting time for a single lung transplantation, and the delay in transplant referral. Examples were computed with hemodynamic data from the National Institutes of Health registry on primary pulmonary hypertension: waiting times of 6, 12, 18, and 24 months and delays in single lung transplantation referral of 0, 1, 2, and 3 years. For a waiting time of 6 months, the chance of surviving to single lung transplantation with a 3-year delay varies from 19% for a patient with a mean pulmonary artery pressure of 80 mm Hg to 72% for a patient with a mean pulmonary artery pressure of 41 mm Hg. For a waiting time of 24 months and a 3-year delay in single lung transplantation referral, this probability varies from 14% (mean pulmonary artery pressure 80 mm Hg) to 59% (mean pulmonary artery pressure 41 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Measles antibody titers in early infancy.

OBJECTIVE: To determine the prevalence of measles seronegativity among infants younger than 6 months and to ascertain their serologic response to measles vaccine. DESIGN: Cross-sectional measles antibody survey during the 1989 measles epidemic in Chicago, Ill. SETTING: Inner-city perinatal center. PARTICIPANTS: Two hundred three infants younger than 6 months who had been admitted to the neonatal intensive care unit at birth; 130 (64%) of these infants were premature. Transplacental antibody transfer was evaluated in a subset of 89 mother-newborn pairs. INTERVENTION: Administration of measles monovalent vaccine to seronegative infants. MEASUREMENTS/RESULTS: Measles IgG antibody was measured using indirect fluorescent assay. At birth, 19 (38%) of 50 neonates born at less than 37 weeks' gestation had antibody titers that were twofold to fourfold lower than those of their mothers compared with three (8%) of 39 neonates born at more than 37 weeks' gestation (P < .01). Of the 203 study infants, fewer than 4% were seronegative at birth, while 74% of these infants aged 4 to 5 months were seronegative. Univariate logistic regression analysis indicated that the independent variables related to seronegativity were as follows: gestational age at birth (P = .007), chronological age (P < .001), history of having received three or more packed red blood cell transfusions (P < .001), and maternal age at delivery (P = .001). Multiple logistic regression analysis confirmed the association of seronegativity with chronological age (P < .001), gestational age (P < .02) and maternal age at delivery (P < .001). Seroconversion following administration of the measles vaccine was documented in 11 (79%) of 14 infants. CONCLUSION: A significant proportion of 4- to 5-month-old infants who had been admitted to the neonatal intensive care unit at birth lack measurable measles antibody; this population should be taken into account when strategies to control measles are considered.

The estimated survival probability index of trauma severity.

An index of survival rates associated with ICDA injury codes was constructed with data from the 1973 Hospital Discharge Survey (HDS). Discharge records from three regions covered by the HDS allowed estimation of survival rates among patients suffering single injuries coded under 92 ICDA integers. These estimated rates were then applied to records from the fourth HDS region, including those for patients suffering multiple injuries: estimated survival probability index values were generated as the product of the single-condition survival rates for each patient's various injuries. Mortality rates predicted from the index values correlated well with mortality rates estimated for the universe of patients discharged in 1973 from the fourth region. The index is intended for retrospective analysis of discharge records as a possible approach to care evaluation.

Statistical methods in public health and epidemiology: a look at the recent past and projections for the next decade.

This article attempts to prognosticate from past patterns, the type of statistical methods that will be used in published public health and epidemiological studies in the decade that follows the millennium. With this in mind, we conducted a study that would characterize trends in use of statistical methods in two major public health journals: the American Journal of Public Health, and the American Journal of Epidemiology. We took a probability sample of 348 articles published in these journals between 1970 and 1998. For each article sampled, we abstracted information on the design of the study and the types of statistical methods used in the article. Our major findings are that the proportion of articles using statistical methods as well as the mean number of statistical methods used per article has increased dramatically over the three decades surveyed. Also, the proportion of published articles using study designs that we classified as analytic has increased over the years. We also examined patterns of use in these journals of three statistical methodologies: logistic regression, proportional hazards regression, and methods for analysis of data from complex sample surveys. These methods were selected because they had been introduced initially in the late 1960s or early 1970s and had made considerable impact on data analysis in the biomedical sciences in the 1970s-90s. Estimated usage of each of these techniques remained relatively low until user-friendly software became available. Our overall conclusions are that new statistical methods are developed on the basis of need, disseminated to potential users over a course of many years, and often do not reach maximum use until tools for their comfortable use are made readily available to potential users. Based on these conclusions, we identify certain needs that are not now being met and which are likely to generate new statistical methodologies that we will see in the next decade.

Focal segmental glomerulosclerosis in adult African Americans.

We have previously shown that idiopathic focal segmental glomerulosclerosis (FSGS) is the most common non-proliferative primary glomerulopathy in adult African Americans. In this report we present our experience with treated FSGS in 15 such patients followed over five years. They were all treated with prednisone 60 mg daily for three months, followed by a slow tapering. In addition, two patients later had cyclophosphamide, and five had enalapril. At entry hypertension was present in 73% of the patients, nephrotic syndrome in 87%, and elevated serum creatinine (> or = 1.4 mg/dl) in 40%. Five of the 15 patients (33%) developed end-stage renal failure (ESRF), one of them having a "malignant" course after the advent of pregnancy. Two patients (13%) have chronic renal insufficiency (CRI; serum creatinine > 2.5 mg/dl); three (20%) have mild renal insufficiency (serum creatinine 1.4-2.5 mg/dl), and five patients (33%) have normal renal function. The cumulative renal survival was 93% at five years, but only 26% at eight years. At last follow-up all the ten patients who did not develop ESRF were in partial remission (urinary protein of 1.3 g/day +/- 1.21), but 4 of the 5 patients who did not develop ESRF had no prolonged partial remission of nephrotic syndrome. Neither the initial clinical parameters not the use of enalapril correlated with the renal outcome (univariate analysis). However, 4 of the 5 patients who developed ESRF had elevated serum creatinine at entry, versus only 2 of the 10 not developing ESRF (p = 0.09 by two-sided, and 0.045 by one-sided Fisher's exact test). We conclude that the short-term renal outcome in nephrotic adult African Americans with treated FSGS is comparable to that of the non-African Americans, but their long-term prognosis may be poorer. Patients developing ESRF were more likely to present with elevated serum creatinine. Enalapril did not seem to modify the course of renal disease, but its utility and that of other ACE inhibitors in the treatment of FSGS must await prospective randomized studies.

Hyperaluminemia in renal failure: the influence of age and citrate intake.

Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, we studied 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution. We found that the four encephalopathic cases were older than the 34 azotemic patients (68 years +/- 14 SD, vs 50 +/- 13, p less than 0.05), had a higher mean serum aluminum value (727 micrograms/l +/- 320 vs 92 +/- 73, p less than 0.005), had taken more aluminum hydroxide (5 g/day +/- 0.9 vs 1.6 +/- 1.8, p less than 0.01), and more Shohl's solution (64 ml/day +/- 19 vs 20 +/- 29, p less than 0.01). In all 38 patients the serum aluminum values correlated directly with age (p = 0.01), aluminum hydroxide (p = 0.001) and concomitant citrate intake (p = 0.004). In the five healthy volunteers the 24-hour urinary aluminum excretion increased from a baseline of 22 micrograms +/- 19 SD to 167 +/- 109 (p = 0.05) during aluminum hydroxide intake, rising to 580 +/- 267 (p = 0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 micrograms/l +/- 2 SD, 44 +/- 34 (p = 0.1), and 98 +/- 58 (p less than 0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.

The revised estimated survival probability index of trauma severity.

The construction of a revised version of the Estimated Survival Probability Index (or ESP index) is described. The original index had been proposed as a tool that would be useful in grading from hospital medical records the severity of injuries sustained by patients hospitalized with trauma conditions. The revised index (RESP) is based on a data set of 61,419 records. Unlike the ESP, the RESP index is based upon parameters that are age specific and specific to decimal ICDA codes. The RESP is validated by correlating RESP scores with observed mortality by using an independent set of multiple-trauma patients. Overall, a strong monotonic relationship between the RESP index and increasing mortality was demonstrated. Also, the RESP index correlated with mortality in selected subsets of multiple trauma patients with extremely severe injuries. Some uses and limitations of this index are discussed.

Synthetic estimates of work loss disability for each state and the District of Columbia.

A method of synthetic estimation of health characteristics for local areas, devised by the National Center of Health Statistics, was evaluated in a recent study. In the method, local data on population are combined with national data on a given health characteristic to produce an indirect estimate of that characteristic. The health characteristic selected in the study was that of complete and partial work loss disability. Therefore, synthetic estimates of complete and partial work loss disability were calculated for each State by combining the estimated rates of such disability for the United States, specific to a set of demographic domains, with the data relating to the distribution of each State into this set of demographic domains. The synthetic estimates of complete and partial work loss disability for each State were then compared with the direct estimates available from the 1970 decennial census. For partial work loss disability, agreement between the synthetic and the direct estimates, as judged by the median percentage absolute difference, was fairly good; for complete work loss disability, agreement was rather poor. On the other hand, the correlation between the synthetic and the direct estimates was higher for complete work loss disability than for partial, partly because the synthetic estimates had a greater spread for complete work disability than for partial. The skewness of the distributions of the squared differences indicates that the evaluation based on median percentage absolute differences was more descriptive than the one based on mean square errors.

Effects of characteristics of the survey instrument on response rates to a mail survey of community hospitals.

A 4-factor, 16-cell experimental design was used to investigate the relationship between response rates of community hospitals to a survey conducted by the American Hospital Association (AHA) and 4 characteristics of the survey instrument, each varied dichotomously: the perceived length of the questionnaire, the order of questions, the orientation of the appeal made in the cover letter, and the presence or absence of a promise to share the results of the study with respondents. Response rate variations between the various cells were examined and multiple logistic regression was used to analyze the significance of the association between response rates and each of the four survey instrument variables while controlling for the effect of the others. At the same time, control was also maintained for the effects of five institutional characteristics of hospitals which a previous study had shown to have a significant relationship to response: bed size, location within or outside a standard metropolitan statistical area, AHA membership status, type of ownership, and form of control. The perceived length of the questionnaire and the order of questions were found to have a significant effect on response rates, but the orientation of the cover letter and a promise to share the results of the study with the respondents were found to be insignificant.

An investigation of institutional characteristics associated with response rates in mail surveys of community hospitals.

This paper describes the nature and strength of the relationship between six institutional characteristics of U.S. community hospitals and the rates of response of these hospitals to a nationwide survey conducted by the American Hospital Association (AHA). Furthermore, it demonstrates how one can calculate accurately the relative probability of response of hospitals with various combinations of these characteristics. The six characteristics studied were bed size, teaching status, AHA membership status, location within or without a Standard Metropolitan Statistical Area, investor or other form of ownership, and control by State or local government or by another type of organization.The six characteristics were treated as dichotomous variables throughout most of the analysis. Odds ratios were calculated for each variable as a preliminary measure of the strength of its association with response.The effects of confounding on those odds ratios were controlled for by multiple logistic regression, which estimates the probability of response of hospitals with given characteristics. A logistic odds ratio was calculated for each variable to estimate the independent effect that specified values had on the odds of responding. All variables except status as a teaching or nonteaching hospital were shown to have a significant relationship to response.Hospitals were divided into classes according to probability of response, and the probability of response was compared with actual rates of response in the survey. Both increase at equal rates. Similar results were obtained by applying this method to two other, dissimilar, surveys.This method is generalizable to other surveys and should prove useful to researchers wishing to increase response rates in their surveys of hospitals.

Time to nursing home admission for persons with Alzheimer's disease: the effect of health care system characteristics.

OBJECTIVE: To study the influence of state health care system characteristics on time to nursing home admission (NHA) for persons with Alzheimer's disease (AD). METHOD: Up to nine years of Consortium to Establish a Registry for Alzheimer's Disease (CERAD) data on 639 non-Latino White individuals were merged with longitudinal data from the 28 states in which the CERAD participants resided. The state variables reflected characteristics of each state's long-term care (LTC) system, including Medicaid LTC spending practices and the supply of LTC providers. Cox Proportional Hazards Models with time-varying covariates were used to evaluate the risk factors associated with time to NHA. RESULTS: There was differential influence of state variables by marital status. For unmarried non-Latino White persons with AD, a higher percentage of Medicaid LTC spending on home and community-based services (HCBS) was significantly associated with a longer time to NHA. For married persons, a greater number of home health agencies was associated with a longer time to NHA. Other associations also varied by marital status. CONCLUSION: Study findings support the utility of targeted continued expanded provision of HCBS by states and provide a basis for future research regarding the impact of changing state health care systems on LTC utilization for persons with AD.

High barium levels in public drinking water and its association with elevated blood pressure.

A maximum contaminant level for barium in drinking water has been set at 1. mg/L. This study examines for the first time, whether there are significant differences in mean blood pressure levels between a high and a low barium community. A total of approximately 2,400 Illinois residents in West Dundee, with a mean barium drinking water level of 7.3 mmg/L, and in McHenry, with a mean barium level of 0.1 mg/L, were studied. All other drinking water constituents were nearly identical between the two communities, with the major difference being the level of barium ingested. No significant differences (P greater than .05) were found in blood pressures between the high and low barium communities. Adjustment for duration of exposure, home water softeners, and high blood pressure medication did not alter the findings. The data from this study suggest that elevated levels of barium in drinking water do not significantly elevate blood pressure levels in adult males or females. It is recommended that the drinking water standard of 1. mg/L be re-examined for other possible health effects.