Interexaminer reliability of supine leg checks for discriminating leg-length inequality.

OBJECTIVE: The purpose of this study was to quantify interexaminer reliability of a standardized supine leg check procedure used to screen for leg-length inequality. METHODS: Two doctors of chiropractic used a standardized supine leg check procedure to examine 50 volunteers for leg-length inequality. The order of examination was randomized. The side and magnitude of leg-length inequality were determined to the nearest 1/8 in. Subjects and examiners were blinded. Interexaminer reliability was assessed with a Bland-Altman plot, tolerance table of absolute differences, a quadratic weighted κ statistic for quantitative scores, and a Gwet's first-order agreement coefficient for dichotomous ratings. RESULTS: The quadratic weighted κ statistic to quantify the reliability of the rating scale was 0.44 (95% confidence interval, 0.21-0.67), indicating moderate reliability. The 2 examiners agreed exactly 32% of the time, within 1/8 in 58% of the time, within 3/16 in 72% of the time, and within 3/8 in 92% of the time. The Bland-Altman plot revealed possible heterogeneity in reliability that requires additional study. The examiners agreed on the presence of a leg-length inequality of at least 1/8 in in 40 (80%) of 50 subjects (first-order agreement coefficient, 0.76), suggesting good agreement for this diagnostic category. CONCLUSION: The examiners showed moderate reliability in assessing leg-length inequality at 1/8-in increments and good reliability in determining the presence of a leg-length inequality.

Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine.

BACKGROUND: Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. PURPOSE: To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. METHODS: The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. RESULTS: Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8-13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m2, abnormal pretreatment liver function, and reduced creatinine clearance. CONCLUSION: This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates.

Mortality resulting from blood dyscrasias in the United States, 1984.

Blood dyscrasias are rare but serious diseases. We used national death certificate data for the year 1984 to estimate the number and rate of deaths caused by four blood dyscrasias. These diseases contributed to 4,490 deaths, corresponding to a mortality rate of 18.9 per million United States population. Aplastic anemia was the most frequent cause of death, followed by thrombocytopenia, agranulocytosis, and hemolytic anemia. Mortality rates varied by age, with a small peak in young children, lower rates for ages five through 34 years, and exponentially increasing rates beyond 35 years of age. Although drug relatedness could not be reliably ascertained from our data, other surveys have estimated that approximately 30% of fatal blood dyscrasias are caused by therapeutic drugs. Assuming that 30% drug attribution also applies to the U.S. population as a whole, approximately 1,350 blood dyscrasia deaths in the U.S. in 1984 may have been caused by drugs.

The incidence of depression in new users of beta-blockers and selected antihypertensives.

We studied the occurrence of depression in new users of propranolol (n = 704), other beta-blockers (n = 587), angiotensin-converting enzyme inhibitors (n = 976), calcium channel blockers (n = 742), and diuretics (n = 773) in the Harvard Community Health Plan population. The period of the study was from April 1988 to June 1991. All study subjects were followed for new or newly recurrent depression for up to 6 months after receiving their first study prescription. Case status was confirmed by blinded medical record review. We found 10 cases of depression that met DSM-III-R criteria ("major depression") and an additional 18 cases that had one or more symptoms consistent with depression ("minor depression"). Rates of major depression in users of beta-blockers and users of non-beta-blocker study drugs were 5.8 per 1000 person-years of exposure and 9.6 per 1000 person-years, respectively. None of the cases of major depression was propranolol associated. Rates of major or minor depression (combined) in users of beta-blockers and users of non-beta-blockers were 20.2 per 1000 person-years and 25.2 per 1000 person-years, respectively. The age- and sex-adjusted relative risk of major or minor depression associated with the use of beta-blockers compared to non-beta-blockers was 0.8 (95% CI, 0.3-1.9). The relative risk associated with propranolol compared to non-beta-blockers was also 0.8 (95% CI, 0.1-2.7). Therefore, depression occurred no more frequently in beta-blocker users than in other members of the study base.

A method of pharmacoepidemiologic analysis that uses computerized Medicaid.

A method of pharmacoepidemiologic data analysis that utilizes computerized Medicaid data is presented. A cohort design in which Medicaid enrollees receiving drugs that are normally used to treat similar underlying conditions is described. A period of time in which Medicaid service transactions are evident is required before an individual is eligible for selection into a cohort. Selection of study subjects and descriptions of cohorts are based on Medicaid service histories occurring during the preliminary, prerequisite period. Time at risk is considered to begin after a prescription for a study drug is dispensed and continues until either a refill is dispensed, a prescription for an alternative drug within the same therapeutic class is dispensed, or a predetermined number of days has passed. Subjects are followed forward in time and relevant health care transactions that are suggestive of suspected adverse drug reactions are noted. Incidence densities associated with sequentially ranked prescriptions within sequential courses of therapy are compared. Methods to increase the accuracy of case ascertainment are briefly discussed. Separate validation studies may be used to evaluate the validity of computerized case ascertainment methods and to compensate for misclassification of outcome. The proposed method is intended to provide timely estimates of risk for selected outcomes. For outcomes that cannot be accurately ascertained from computerized data, this method may be useful in determining the feasibility of more customized studies.

Variations in the use of medication for the treatment of childhood asthma in the Michigan Medicaid population, 1980 to 1986.

Asthma is a leading cause of morbidity in the United States and is a leading cause of disability in children. Prevalence has been shown to be highest in male children, blacks, and urban residents. Racial and residential differences have been attributed to economics. Medicaid claims data allow for the comparison of asthma morbidity and treatment of patients with different demography but of low socioeconomic status. Michigan Medicaid claims data for recipient children between 5 and 14 years of age were used to ascertain demographic factors associated with asthma treatment from 1980 through 1986. A cross-sectional analysis was used. Black asthmatics were found to receive medical care more frequently, but to obtain asthma drugs less frequently than other groups. The prevalence of different prescription asthma preparations also varied by race and residence. Black, urban residents obtained fixed-combination drugs more frequently and steroids less frequently than other groups. Rural patients, in general, had fewer medical contacts but obtained more prescription products per provider contact, whether black or white. Possible reasons for this variation are discussed.

Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism.

To assess possible differences in the incidence of venous thrombosis and pulmonary embolism associated with oral contraceptives of varying hormonal potencies, the authors conducted a retrospective cohort study in the 15-44 year old Michigan Medicaid population. Cohorts were defined by the progestin- and oestrogen-potencies of oral contraceptives in use at the time of follow-up as classified by an oral contraceptive potency scheme. Using the low-oestrogen-/low-progestin-potency formulations for reference (rate ratio = 1), adjusted rate ratios of 0.8 (95% CI: 0.5 to 1.3, P = 0.41) and 0.6 (95% CI 0.4 to 1.2, P = 0.13) were observed for intermediate-progestin-potency and high-progestin-potency formulations, respectively. Adjusted rate ratios of 1.4 (95% CI: 0.8 to 2.3, P = 0.21) and 2.6 (95% CI: 1.2 to 5.5, P = 0.01) were observed for intermediate- and high-oestrogen-potency formulations. These data suggest a dose-response relationship between oral contraceptive oestrogen potency and venous thromboembolism, whereas no such evidence for a dose-response relationship between oral contraceptive progestin potency and venous thrombo-embolism was found.

Activated rate processes and a specific biochemical mechanism for explaining delayed laser induced thermal damage to the retina.

Laser induced thermal damage to the retina is investigated. The one step Arrhenius type thermal damage integral of Henriques is analyzed for its strengths and weaknesses. The zero-order activated rate process is shown to well represent the data for pulse durations greater than 10 µs. A zero-order biochemical damage mechanism involving free radical formation and thermal disruption of the melanosome's protein coat is proposed as the initial molecular process that leads to cellular damage which appears after a delay. Data are presented that show the photoactivation of melanin granule oxidative reactivity. This in vitro data is evidence for an important step in our hypothesized damage pathway. © 1999 Society of Photo-Optical Instrumentation Engineers.

The reliability of muscle function analysis using different methods of stimulation.

BACKGROUND: The purpose of our study was to determine the reliability of nonvolitional muscle function analysis (MFA) by determining the day-to-day and within-day reliability of conventional electrical stimulation and a newer, magneto-electrical stimulation method, using standard laboratory methodology. METHODS: Ten healthy, human immunodeficiency virus-negative adult men volunteered as subjects. MFA consisted of measuring the maximal relaxation rate, for magneto-electrical stimulation at 1 Hz and conventional electrical stimulation at 20 Hz, and force-frequency ratios using conventional electrical stimulation at 10 Hz:20 Hz and 10 Hz:50 Hz. Within-day and day-to-day reliability were determined by calculating the coefficient of variation (CV) for all subjects. RESULTS: Maximal relaxation rate using magneto-electrical stimulation had a significantly lower CV compared with the other nonvolitional MFA methods (p = .002). CONCLUSIONS: Maximal relaxation rate using magneto-electrical stimulation was more reliable and technically easier than the other muscle function parameters examined. However, the day-to-day CV of muscle function parameters is larger than traditional nutrition assessment techniques. Development within the field should strive to improve testing techniques so that the reliability of MFA will allow definition of a range of normal values against which an individual's value can be compared. Until this is available, the precision and reliability of MFA restrict its use to research and population studies.

Epidemiologic critique of the report on adverse reactions to ionic and nonionic media by the Japanese Committee on the Safety of Contrast Media.

The author takes a critical look at the findings of the Katayama study of adverse reactions to ionic and nonionic contrast media. The author suggests that although the relative risks appear to be large and favor the use of nonionic media, serious adverse reactions were infrequent with both media types and risks were small on an absolute scale. In addition, the study demonstrates the potential for several serious information and selection biases. The accuracy of risk estimates are therefore called into question. Nevertheless, this study is extremely important in clarifying the risks associated with ionic and nonionic media during venography.

Photoacoustic generation for a spherical absorber with impedance mismatch with the surrounding media.

Pressure generation in a spherical absorber due to energy deposition from pulsed lasers is studied. For a variety of conditions, analytical solutions are derived that allow quick computation of exact results. For the special case of identical acoustic impedance, the pressure transient spreads to the surrounding medium by a single compressive pulse followed by a tensile pulse at the end of illumination. For the general case of impedance mismatch, the pressure transient is in the form of a series of dampened compressive and tensile pressure pulses. In this paper both the amplitude ratio and the sign of consecutive pressure pulses are determined analytically, and are shown to be dependent upon the impedance mismatch. For laser pulses of duration much less than the absorber's characteristic oscillation time, a stress confinement limit is reached for most of the absorber, but a sharp tensile stress in the core region of the sphere is predicted. This region of high stress is defined by r < or =r(c), and we show that r(c) is proportional to the laser pulse duration tau(0). Upon further shortening of the laser pulse duration, the strength of this tensile stress continues to increase while its spatial distribution is sharpened. This observation has relevance to a number of experiments where laser-induced pressure transients cause the absorber to fracture.

Trends in the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population, 1980 to 1986.

BACKGROUND: Despite advances in therapy, morbidity and mortality rates as a result of pediatric asthma appear to have increased during the past decade. Epidemiologic evidence suggests that these increases disproportionately affected black children and the urban poor. METHODS: With use of data from the Medicaid Management Information System, we estimated the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population for the period 1980 to 1986. RESULTS: Large increases were seen between 1980 and 1984, with leveling off or a slight decline thereafter. In 5- to 9-year-old children, the prevalence of asthma hospitalization increased from 2.3 per 1000 persons in 1980 to 4.5 per 1000 in 1984. Ten- to 14-year-old children demonstrated an increase of 2.2 per 1000 in 1980 to 3.2 per 1000 in 1984. Comparable trends occurred in all strata defined by age, race, residency, and gender. However, the largest increases were noted in urban black children, in which the rate more than doubled from 3.2 per 1000 in 1980 to 7.1 per 1000 in 1984. The adjusted relative risk for asthma hospitalization associated with being male was 1.6 (95% CI: 1.5, 1.7), with being black was 2.2 (95% CI: 2.1, 2.4), and with living in an urban county was 1.1 (95% CI: 1.04, 1.4). CONCLUSIONS: Within this relatively homogeneous low socioeconomic population, black race remained a strong predictor for asthma hospitalization, whereas urban residence was only minimally associated with this outcome.

Hemoglobin-carbon monoxide binding rate. Low temperature magneto-optical detection of spin-tunneling.

The spin-tunneling model of Hb--CO binding is used to calculate the binding rate at low temperature and high magnetic fields. The rate is calculated in second order perturbation theory assuming that spin-orbit coupling mediates the Hb iron electronic state change. The reaction which occurs at the crossing of the S = 2 and S = 0 energy vs. configuration coordinate curves is nonadiabatic, having a small electronic transition matrix element. Since detection of CO binding by polarized light in the Soret band makes it possible to observe hemes at specific orientation to the field direction, the rate is calculated for arbitrary heme orientation. Comparison with measurements at low temperature in zero field is made for spin quantization along the molecular crystal field direction.

Steroidal contraceptive use update, United States, 1989-1994.

OBJECTIVE: To update United States steroidal contraceptive use data for the period 1989 to 1994. STUDY DESIGN: Pharmaceutical marketing data were used to examine trends in the utilization and distribution of oral contraceptives, Norplant, and Depo-Provera. RESULTS: There were 56.8 million prescriptions for oral contraceptives dispensed through retail pharmacies in 1994. Estrogen and progestin doses remained fairly stable over time. The average ethinyl estradiol dose of formulations was approximately 34 microg per pill. Mentions for oral contraceptives among 35- to 44-year-old women increased. Approximately 169,000 Norplant systems were distributed from 1991 through 1994. More than 1.5 million milliliters of Depo-Provera were distributed from 1993 to 1994. CONCLUSIONS: Oral contraceptives remain a popular form of contraception. Parenteral formulations have been rapidly accepted.

Use of subsequent anticoagulants to increase the predictive value of Medicaid deep venous thromboembolism diagnoses.

Linked data bases that derive their information from health care administrative sources are increasingly being used to conduct pharmacoepidemiologic research. Computerized case ascertainment using these data would be highly advantageous in terms of time and cost considerations. For a study of oral-contraceptive-associated deep venous thromboembolism, we evaluated the utility of using anticoagulant treatment codes to validate diagnostic codes suggestive of deep venous thrombosis and pulmonary embolism. By requiring evidence of outpatient anticoagulant use within six months of hospitalization, the predictive value of case ascertainment increased from 42% to 65% for "probable" deep venous thromboembolism and from 70% to 97% for "possible" deep venous thromboembolism. In addition, use of anticoagulant treatment codes as a second marker of disease resulted in nondifferential outcome misclassification when the study base was restricted to current oral-contraceptive users. Use of confirmatory treatment claims may provide a rapid, cost-effective alternative to medical-record-based case ascertainment for pharmacoepidemiologic studies of selected outcomes conducted in Medicaid and other linked universal health care coverage populations.