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Medical treatment to prevent recurrent calcium urolithiasis. A guide to critical appraisal.

Among patients with urolithiasis, the recurrence rate is 10-23% per year. We have applied guidelines for critical appraisal to 46 publications addressing the efficacy of thiazides, orthophosphates, cellulose phosphate, allopurinol, magnesium and citrate as prophylaxis against recurrent urolithiasis. The 34 studies which do not have a randomly allocated control group are subject to methodologic deficiencies such as co-intervention, variable outcome measures, variable natural history, statistical regression to the mean, selection bias and incomplete follow-up of patients. These deficiencies make conclusions regarding the efficacy of an intervention suspect. Among the 12 randomized clinical trials are 5 thiazide, 2 orthophosphate, 4 allopurinol and 1 magnesium intervention. The methodologic and statistical questions addressed were: adequacy of randomization, clinical relevance of outcomes, description of patients, clinical and statistical significance, and completeness of follow-up. Based on these methodologic considerations, one could not conclude that orthophosphates, cellulose phosphate, magnesium or citrate were efficacious in preventing recurrent urolithiasis. Two of the 5 thiazide and 1 of the 4 allopurinol randomized clinical trials demonstrate convincing evidence for efficacy of these interventions. With the exception of pilot studies of new interventions, conclusions about efficacy of interventions claimed to decrease the urolithiasis recurrence rate should be based on methodologically sound randomized clinical trials.

Allopurinol

Statistical analysis of productivity in one physical therapy department.

The purposes of this retrospective study were to document productivity-relevant measurements, describe the relationships between these measurements, and discuss the implications of the relationships in one physical therapy department. The department's inputs (clinician and staff hours worked), outputs (patient visits, patient procedures, hours charged, and dollars charged), and productivity (staff utilization, financially productive time, and dollars charged per staff hours worked) were monitored. Pearson product-moment correlations, partial correlations, and linear regression statistics were calculated to determine the relationships between the variables measured. During the 30-month period studied, average daily census of the institution decreased, clinician hours worked decreased, patient procedures and dollars charged increased, and the three productivity measures increased. The relationship between output measures and clinician hours worked was apparent only after the effects of increased productivity were controlled. Departmental outputs and productivity were independent of the institution's census. The findings provided no evidence that decisions regarding staffing should be based on institutional census.

Efficiency

Generation 04 sodium slides and generation 04 reference fluid evaluated for use with the Ektachem 400 Analyzer.

Evaluation of a new generation of sodium slides and reference fluid for use with the Kodak Ektachem 400 Analyzer demonstrated improved performance in generation 04 over the previous generation 03 slide for sodium determinations. A decrease in between-replicate imprecision and a correction of the "serum" assigned values of the calibrators used to calibrate the slide used with the reference fluid account for the improvement. When generation 04/Ektachem results (y) were compared with results obtained with a Beckman ion-selective electrode (x), linear regression statistics were: slope = 0.88, y-intercept = 15.4 mmol/L, and Syx = 2.1 mmol/L. The average fixed bias in comparison with the Beckman electrode decreased from +1.9 mmol/L with generation 03 to -0.6 mmol/L with generation 04 materials. Random error is indicated by a decrease in Syx from 2.8 mmol/L for generation 03 to 2.1 mmol/L for generation 04. Application of Deming's regression, a more accurate portrayal of the generation 04 sodium data set, produces a slope of 1.0 and a y-intercept of -0.6 mmol/L.

Humans

Methodology for statistical analysis of SENCAR mouse skin assay data.

Various response measures and statistical methods appropriate for the analysis of data collected in the SENCAR mouse skin assay are examined. The characteristics of the tumor response data do not readily lend themselves to the classical methods for hypothesis testing. The advantages and limitations of conventional methods of analysis and methods recommended in the literature are discussed. Several alternative response measures that were developed specifically to answer the problems inherent in the data collected in the SENCAR bioassay system are described. These measures take into account animal survival, tumor multiplicity, and tumor regression. Statistical methods for the analysis of these measures to test for a positive dose response and a dose-response relationship are discussed. Sample data from representative initiation/promotion studies are used to compare the response measures and methods of analysis.

Animals

Risk factors for cancer of the renal parenchyma.

A case-control study of cancer of the renal parenchyma (360 cases and 985 controls) investigated lifestyle and dietary risk factors by means of a questionnaire survey. A lifetime history concerning urological disease and consumption of analgesics, tobacco, and prescribed medicines, was obtained together with current dietary and demographic information. Estimates of relative risk were calculated using logistic regression. Statistically significant associations were found with phenacetin-containing analgesics, urological disease and increasing consumption of milk. No association was found with consumption of aspirin, paracetamol, prescribed medicines, tea, coffee or animal proteins other than milk, or with the type of fat or oil used for cooking or spreading. The association with tobacco just failed to reach significance.

Australia

Statistical models of the demand for emergency medical services in an urban area.

First- and second-order statistical regression models are presented for the Emergency Medical Services (EMS) demand in an urban area as it relates to various socioeconomic, demographic, and other characteristics of the area. Individual models are formulated for different types of medical emergencies with the city of Atlanta, GA, serving as the data base. These models are generally shown to provide excellent fits to the empirical data.

Emergency Medical Services

Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged.

Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor. Using stepwise regression statistical analysis, the variables age, cholesterol, cholesterol/total phospholipid and phosphatidyl ethanolamine/phosphatidyl choline molar ratios were all shown to have a significant positive influence on membrane microviscosity, whereas total phospholipids had a negative effect. No statistically significant difference was seen in content of any single saturated or unsaturated fatty acid between young and old donors. After pooling, however, the proportion of all unsaturated fatty acids was significantly higher in cells from the elderly as a consequence of an increase of n-6 and n-3 polyunsaturated fatty acids. Changes in lipid composition and physical properties of lymphocyte plasma membranes may, therefore, be responsible (at least partially) for the diminution of immune reactivity in old age.

Adult

Interrelationships among carcinogenicity, mutagenicity, acute toxicity, and chemical structure in a genotoxicity data base.

The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well-known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors. As expected on the basis of the large variety of chemical classes represented in the IPESTTC data base, no simple relationship between mutagenicity or carcinogenicity and chemical descriptors was found. To overcome this problem, a new pattern recognition method (REPAD), developed by us for structure-activity studies of noncongeneric chemicals, has been used. This allowed us to highlight a significant difference between the whole patterns of relationships among chemicophysical variables in the two groups of active (mutagenicity and/or carcinogenic) and inactive chemicals. This approach generated a classification rule able to correctly assign about 80% of carcinogens or mutagens.

Carcinogens

Productivity of the clinical dietitian: measurement by a regression model.

Productivity of 283 clinical dietitians employed in 40-bed to 1,200-bed medical centers and community and general hospitals nationwide was measured from a survey. Stepwise multiple linear regression statistical analyses were used to analyze data. Five measures of productivity were developed; hours in non-patient care divided by total hours worked and the activity level in activities nonproductive in relation to the job description activities produced the better models for measuring productivity of the clinical dietitian. Activity levels measured in the study showed high-level task activities (consuming a large amount of work time) were conducting individual diet instructions, conducting nutrition assessments, reviewing and recording in medical records, and supervising support personnel. Taking anthropometric measurements, participating in medical rounds, attending professional conferences, and purchasing and dispensing specialized products were found to be low-level task activities (consuming little work time). The average amount of time spent on the job per week was 42.7 hours with a mean of 20.4 hours spent in direct patient care, 13.6 hours in indirect patient care, and 7.3 hours in nonpatient care.

Dietary Services

Perinatal factors associated with the respiratory distress syndrome.

Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses.

Adrenal Cortex Hormones

Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems demonstrating the importance of cytokinetic factors in the administration of chemotherapy and suggest that such factors may be of clinical importance in selecting approaches to therapy.

Adult

Ultrasonic measurements of subcutaneous adipose tissue thickness in man.

Subcutaneous adipose tissue thickness (SCATT) has for many years been measured using skinfold calipers, but calipers have several disadvantages, not least that they compress the skinfold. Measuring SCATT using ultrasound was validated by comparing thicknesses at 12 sites with soft-tissue radiographs in 24 adults and with depth gauge measurements on a cadaver. Correlation coefficients ranged from 0.87 to 0.99, and the regression statistics showed no significant difference between ultrasound and the other procedures. The standard errors of estimate of body density from SCATT measured by calipers and ultrasound in 63 young men was +/- 7.8 and 7.3 kg X m-3, respectively. Although problems in the identification of the adipose tissue-muscle interface can arise, ultrasound is a viable alternative to skinfold calipers and is to be preferred when measuring uncompressed SCATT.

Adipose Tissue

Electronic structure--activity relationships of antibacterial acridines.

The antibacterial activity of a series of amino- and fluorinated acridines was studied in the framework of their electronic structures. To calculate the electronic structure, a simple Hückel molecular orbital theory was used. A statistical regression analysis revealed linear correlations between the activity and the electronic indexes, particularly the electron density at the ring nitrogen.

Acridines

Interpretive criteria for CI-960, fleroxacin and temafloxacin susceptibility tests with Haemophilus influenzae.

Haemophilus influenzae strains with varied ampicillin resistance and beta-lactamase production patterns were tested against three investigational fluorinated quinolones (CI-960, fleroxacin, temafloxacin) using Haemophilus Test Medium (HTM) and National Committee for Clinical Laboratory Standards (NCCLS) methods. The disk diffusion zones and MICs were compared and regression statistics and scattergrams generated. The rank order of the agents according to activity against Haemophilus influenzae was CI-960 (MIC50 0.002 microgram/ml) greater than temafloxacin (MIC50 0.015 microgram/ml) greater than fleroxacin (MIC50 0.03 microgram/ml). The recommended susceptibility interpretive criteria for the 5-micrograms disks of each drug were: for CI-960 greater than or equal to 23 mm (MIC correlate less than or equal to 1 microgram/ml); for fleroxacin greater than or equal to 19 mm (MIC correlate less than or equal to 2 micrograms/ml); and for temafloxacin greater than or equal to 16 mm (MIC correlate less than or equal to 2 micrograms/ml). All recent Haemophilus influenzae isolates tested were susceptible to these potent fluoroquinolones and no interpretive errors were observed.

Anti-Infective Agents

Use of contraceptives prior to and after conception and exposure to other fetal hazards.

In a large prospective study, set up to determine whether reproductive outcomes are affected by prior contraceptive use, 34,344 women were recruited at their first antenatal visit and followed until pregnancy termination. This paper summarizes the study methods and describes the demographic differences between subjects who used various contraceptives shortly before conception, and those who experienced contraceptive failures. Thirty percent of the women had used oral contraceptives (OCs) during the 5 months prior to conception and 2.4% had continued using them after their LMP. IUDs had been used by 5.8% of women before conception and 1.1% after. If these rates are also true for the whole population of the U.S., they indicate that approximately 70,000 babies are born each year following pill-failures and 30,000 following failures of IUD's. Exposure to other fetal hazards was common, with 48% of pregnant women drinking alcohol, 28% smoking, and 15% receiving diagnostic X-rays. OC use was more common among smokers and drinkers, and OC failures were significantly associated with the use of anti-epileptics, aspirin, and with exposure to radiation.

Adult

Intra-uterine device failure: relation with drug use.

A case-control study was undertaken in order to test the relationship between commonly used anti-inflammatory agents and the efficacy of intra-uterine devices (IUDs). Women who had become pregnant while wearing an IUD were compared with non-pregnant IUD users. 717 cases and 717 controls were recruited from the same medical practices. The case-women (IUD failure) used anti-inflammatory drugs, particularly aspirin, more frequently than the controls (p less than 0.001). In contrast, oral progestins, taken in the second part of the cycle (16th to 25th day) were more frequently used by the control-women group (p less than 0.001). Although cases and controls differed in age and gravidity (younger and higher, respectively) standardization for these items did not change the findings for drug use.

Age Factors

Classically conditioned heart rate responses in Macaca mulatta after beta-adrenergic, vagal and ganglionic blockade.

Heart rates of 5 rhesus monkeys (Macaca mulatta) were monitored during classical conditioning trials consisting of a visual conditioned stimulus followed after 10 sec by an electric shock to the tail. Heart rates typically increased at the onset of the visual stimulus, and returned to baseline before shock delivery. Autonomic blocking agents were subsequently administered; their effects on resting heart rates, and on acceleratory and deceleratory phases of the biphasic conditioned heart rate responses were examined, both in the raw data, and with a statistical regression technique. Beta-adrenergic blockade by propranolol lowered resting heart rates and was found, after regression analysis, to reduce the heart rate increase phase, and to weakly enhance the subsequent heart rate decrease phase of the conditioned response. Vagal blockade by atropine sulfate elevated resting heart rate, and markedly reduced both acceleratory and deceleratory heart rate phases of the conditioned responses. Ganglionic blockade by chlorisondamine also elevated resting heart rates (less than atropine), and almost completely eliminated conditioned heart rate changes. Several sources of evidence suggest a predominant vagal tone over resting heart rates, as well as mostly vagal mediation (with some sympathetic contribution) of the biphasic conditioned rate response.

Animals