Using medication history to measure confounding by indication in assessing calcium channel blockers and other antihypertensive therapy.

Reported findings of elevated risk of adverse events associated with calcium channel blocker use in hypertensives may be due partly to unmeasured confounding by indication. To determine if such confounding occurs, we conducted a retrospective cohort analysis of 77 196 Pennsylvania Medicaid recipients aged 18 to 61 who were treated with antihypertensive medication between 1990 and 1992. All diagnoses and dispensed prescriptions during the year prior to study entry were examined. Prior recipients of multitherapy (n = 18 763) were more likely to have had previously diagnosed risk factors (OR = 1.31 [95% CI, 1.30-1.33]) than subjects with prior monotherapy (n = 11141). New initiators (n = 47292) were less likely to have had previously diagnosed risk factors (OR = 0.48 (95% CI, 0.47-0.49)) than previous users (n = 29904). The likelihood of being prescribed calcium channel blocker rather than other monotherapy was significantly higher for subjects diagnosed during the previous week with arteriosclerotic cardiovascular disease OR = 7.78 (95% CI, 2.72-22.28), P < 0.0001; angina OR = 2.92 (95% CI, 1.77-4.83), (P < 0.0001); diabetes OR = 1.49 (95% CI, 1.07-2.06), (P = 0.0004); and hypertension OR = 1.57 (95% CI 1.35-1.82), (P < 0.0001). Calcium channel blockers were selectively prescribed to subjects at elevated risk of adverse events. Confounding by indication was found in this large indigent population. Unmeasured confounding may contribute to overestimated relative risk of adverse events associated with calcium channel blocker therapy vs diuretics or beta-blockers. At least 1 full year of subjects' medical and prescription drug history should be examined prior to study entry; shorter observation periods will miss clinically relevant information about risk.

Multicenter US study of hospital resource utilization associated with cytomegalovirus-related readmission of renal and heart transplant patients.

Incidence of cytomegalovirus (CMV)-related rehospitalization and associated resource use were captured by the Transplant Infection Cost Analysis (TICA) program, which examined patient records and hospital billing data in multiple solid organ transplant centers in the US. The experiences of two adult heart and three adult renal transplant centers were each pooled for analysis. Financial data were standardized to 1998 US dollars using the Medical Care component of the US Consumer Price Index. CMV-related readmissions among renal transplant patients averaged 10.5 days (range 1-56) with average charges of $22,598. Heart transplant patients readmitted for CMV incurred an average charge of $42,111 and average hospital stay of 10.9 days (range 2-95). CMV-related hospital resource use represented a significant portion of the average cost of the original transplant and associated length of stay.

Supplemental calcium for the prevention of hip fracture: potential health-economic benefits.

We assessed the cost-effectiveness of daily calcium supplementation for the prevention of primary osteoporotic hip fractures. The assessment was based on our meta-analysis of the published relative-risk estimates from 3 double-masked, placebo-controlled, clinical trials and our analysis of raw data from the National Health and Nutrition Examination Survey 1988-1994 on the daily intake of calcium supplements by adults in the United States. These data were then used to estimate the preventable proportion of hip fractures. The 1995 National Hospital Discharge Survey database provided the number and demographic characteristics of patients discharged with a primary diagnosis of hip fracture, as well as their discharge destination. The 1990 itemized costs of hip fractures, as estimated by the US Congress Office of Technology Assessment, were inflated to 1995 dollars using the medical care component of the Consumer Price Index. Using these inflated itemized costs, we then estimated the weighted average expenditures, reflecting both the types of services associated with specific hospital-discharge destinations and the demographic characteristics of discharged patients. The cost of supplements containing 1200 mg/d of elemental calcium for the mean duration (34 months) of the 3 clinical trials was calculated on the basis of 1998 unit-price and market-share data for 6 representative products. For 1995, the data indicate that 290,327 patients aged > or =50 years were discharged from US hospitals with a primary diagnosis of hip fracture, at our estimated direct cost of $5.6 billion. Based on the risk reductions seen in the 3 trials, we estimated that 134,764 hip fractures and $2.6 billion in direct medical costs could have been avoided if individuals aged > or =50 years consumed approximately 1200 mg/d of supplemental calcium. Additional savings could be expected, because this intervention is also associated with significant reductions in the risk for all nonvertebral fractures. Comparing the cost of calcium with the expected medical savings from hip fractures avoided, it is cost-effective to give 34 months of calcium supplementation to women aged > or =75 years in the United States. If, as the published studies suggest, shorter periods of supplementation result in an equivalent reduction in the risk of hip fractures, calcium supplementation becomes cost-effective for all adults aged > or =65 years in the United States. The data support encouraging older adults to increase their intake of dietary calcium and to consider taking a daily calcium supplement. Even small increases in the usage rate of supplementation are predicted to yield significant savings and to reduce the morbidity and mortality associated with hip fracture at an advanced age.

Economic impact of automated primary screening for cervical cancer.

OBJECTIVE: To construct a markovian model to project the marginal cost of the AutoPap System as compared to manual cervical cytologic screening. STUDY DESIGN: Data from a clinical trial and published literature were entered into a seven-state markovian decision-analytic model to estimate the marginal cost per year of life saved that could be attributed to changes in primary screening technology. RESULTS: Annual screening with AutoPap produced a meaningful increase in life expectancy of 32.1 days relative to manual screening at a marginal savings of $628 per person (or a marginal savings of $7,144 per life-year saved). Less frequent screening yielded lower positive savings. CONCLUSION: Automated screening for cervical cancer has the potential to significantly improve health care outcomes and reduce cost.

Tapping the savings from vitamin-based prevention.

Published scientific studies show that perinatal consumption of multivitamins containing folic acid and zinc can significantly reduce the risks of low birthweight, premature births, spina bifida, and cardiovascular birth defects. Daily intake of vitamin E supplements reduces the risk of coronary heart disease in older Americans. The authors believe that if all at-risk Americans took the recommended amounts of vitamin supplements, significant numbers of hospitalizations for these conditions could be avoided, and the managed care industry could save approximately $5.5 billion, using 1995 figures.

Potential biases in assessing the risks of pharmacotherapy due to mismeasurement of drug exposure.

We undertook this review to propose a minimum set of standards with which any evaluation of pharmacotherapy should comply, to review the evidence on which the relative risks of calcium channel blocker therapy for hypertension are based, and to evaluate published studies against these proposed standards. We selected English-language primary study reports published in peer-reviewed biomedical journals between 1995 and 1997. All the reviewed studies suffer from either possible misclassification of antihypertensive drug therapy, mismeasurement of drug exposure, or both. Given the inadequate documentation of subjects' drug therapy, resulting relative risk estimates cannot be substantiated.

Hiring by radiology groups in 1996.

PURPOSE: To determine the hiring activity of radiology groups in 1996. MATERIALS AND METHODS: A survey was mailed to a stratified, random sample of 794 radiology groups in autumn 1996. The response rate was 78%. Responses were weighted to be representative of all of the approximately 3,300 groups in the United States. Findings were compared with those of previous, similar surveys. RESULTS: In the 12 months before the survey, groups sought to hire 1,732 +/- 155 (+/- 1 standard error) diagnostic radiologists and radiation oncologists; 788 +/- 105 of these positions were to fill expansion positions, 562 +/- 86 were replacements for persons who had left the profession, and 382 +/- 78 were replacements for persons who moved to other radiology positions. During the year, an additional 500 +/- 119 positions were vacated that groups did not seek to refill. Groups succeeded in hiring 1,438 +/- 143 radiologists. The percentage of available positions that were filled did not differ across fields. Managed health care reduced the probability a group was expanding but did not otherwise affect hiring activity. CONCLUSION: The 1991-1995 decline in hiring has ceased and perhaps even reversed. There were approximately as many positions available in 1996 as were needed by graduates, although there may have been a small shortfall.

Potential health economic benefits of vitamin supplementation.

This study used published relative risk estimates for birth defects, premature birth, and coronary heart disease associated with vitamin intake to project potential annual cost reductions in U.S. hospitalization charges. Epidemiological and intervention studies with relative risk estimates were identified via MEDLINE. Preventable fraction estimates were derived from data on the percentage of at-risk Americans with daily vitamin intake levels lower than those associated with disease risk reduction. Hospitalization rates were obtained from the 1992 National Hospital Discharge Survey. Charge data from the 1993 California Hospital Discharge Survey were adjusted to 1995 national charges using the medical component of the Consumer Price Index. Based on published risk reductions, annual hospital charges for birth defects, low-birth-weight premature births, and coronary heart disease could be reduced by about 40, 60, and 38%, respectively. For the conditions studied, nearly $20 billion in hospital charges were potentially avoidable with daily use of folic acid and zinc-containing multivitamins by all women of childbearing age and daily vitamin E supplementation by those over 50.

Myocardial infarction in newly diagnosed hypertensive Medicaid patients free of coronary heart disease and treated with calcium channel blockers.

PURPOSE: A retrospective cohort analysis of 1,406 newly diagnosed hypertensive patients, aged 18 to 59, without prior coronary heart disease and initially treated with calcium channel blockers (CCBs) or eight other drug regimens was conducted to evaluate the relative risk of acute myocardial infarction (AMI) among patients on CCBs alone or with a diuretic. MATERIALS AND METHODS: Administrative claims data from Pennsylvania's Medicaid program were the data source. Patients were followed up from 1987 to 1994. RESULTS: There was a highly significant trend towards prescribing CCBs between 1988 and 1991 (P = 0.0001). A total of 67 AMIs occurred, 33 of which were during original drug therapy. Compared with those treated with beta blockers, the relative risk of AMI among patients treated only with CCBs was 0.49 (95%) confidence interval [CI] 0.11 to 2.20). Compared with diuretic therapy, the AMI relative risk associated with CCB therapy was 0.60 (95% CI 0.16 to 2.32) when patient drug regimen was classified based on the first six prescriptions. Several alternative drug regimen classification schemes were tested to evaluate the sensitivity of relative risk of AMI to classification of drug therapy. CONCLUSIONS: The measurement of relative risk of AMI was highly dependent on the study design, including patient selection criteria and classification of patient drug therapy. Previous findings of elevated risk of AMI from CCB antihypertensive therapy could not be confirmed.

Provision of primary-preventive health care services by obstetrician-gynecologists.

OBJECTIVE: To determine the extent to which obstetrician-gynecologists serve as primary care providers for women 15 years and older. METHODS: Three national data bases were analyzed to determine if differences exist in the content of care provided to women during a general medical examination by three medical specialties. Reasons for medical visits by women to obstetrician-gynecologists were compared with other medical specialties, and women who rely on obstetrician-gynecologists for their care were characterized demographically. Survey data on the self-perceived role of obstetrician-gynecologists as primary care providers were also examined. RESULTS: Obstetrician-gynecologists provided more office-based, general medical examinations to women 15 years and older than either general-family practitioners or internists. This finding was also true for women of reproductive age, defined as those 15-44 years old. When asked if they considered themselves primary care providers or specialists, 48.3% of ACOG fellows designated the former. CONCLUSION: Obstetrician-gynecologists are important providers of primary and preventive care for women, and nearly half of all obstetrician-gynecologists consider themselves to be primary care providers.

Reversible jaundice in primary biliary cirrhosis due to hyperthyroidism.

A patient with primary biliary cirrhosis had a dramatic deterioration in liver function with jaundice over 2 months as a result of development of Graves' disease. Clinical examination and radiological and cardiovascular investigations excluded heart failure and biliary obstruction as the cause of this deterioration. The patient's jaundice entirely reversed with treatment of hyperthyroidism, with bilirubin levels decreasing from 244 to 16 mumol/L (14.35 to 0.94 mg/dL). Deterioration in liver function in a patient with primary biliary cirrhosis as a result of hyperthyroidism has not previously been described.

Limitation of exercise-induced R wave amplitude changes in detecting coronary artery disease in asymptomatic men.

The exercise electrocardiograms of 255 asymptomatic men were analyzed for changes in R wave amplitude and ST segments. The results were correlated with findings at cardiac catheterization. There were 65 men with coronary artery disease and 190 normal subjects. R wave amplitude changes were evaluated in bipolar leads X, Y and Z. The predictive value of an abnormal ST segment response for detecting disease was only 29%. This value was improved to 42% using R wave amplitude changes with a sensitivity of 28% and specificity of 87%. Exercise-induced R wave amplitude changes enhance the specificity of detecting coronary disease in asymptomatic men over ST segment criteria alone but the sensitivity is poor and the predictive value is not enhanced. Thus, these criteria are limited in adding to the diagnostic accuracy of stress testing.