Search

Objectives: This study sought to correlate angiographically detected complex lesions and intracoronary thrombus with the severity of clinical presentation in unstable angina (UA)., Background: Unstable angina is usually related to acute thrombosis superimposed on a disrupted plaque. Complex and thrombotic lesions are more prevalent in UA and have been associated with a worse prognosis. The highest levels of the Braunwald classification of UA (III = rest angina within 48 h of presentation; C = postinfarction angina; and c = angina refractory to maximal medical therapy) can be used to assess the severity of clinical presentation, but they have not been directly correlated with thrombotic and complex lesions., Methods: We conducted a prospective study of 284 patients with UA who underwent cardiac catheterization. A single angiographer with no knowledge of the clinical classifications interpreted all angiograms. Culprit lesions identified in 200 patients were classified as simple or complex. Complex lesions included the categories complex morphology, intracoronary thrombus (ICT) or total occlusion. Lesions were also quantitatively analyzed, and Thrombolysis in Myocardial Infarction (TIMI) flow was assessed. Univariate and multivariate logistic regression analyses of the angiographic findings were performed controlling for all cardiac risk factors, previous angioplasty or bypass surgery and multivessel disease, and we sequentially compared Braunwald classes III, C and c with classes < III, < C and < c, respectively., Results: Class III was associated with complex lesions (p = 0.04) and decreased TIMI flow (p = 0.03). Class C angina correlated with complex lesions (p = 0.04), ICT (p = 0.005) and decreased TIMI flow (p = 0.03). Class c angina was associated with ICT (p = 0.02). The degree of stenosis by quantitative angiography was not associated with any particular Braunwald class., Conclusions: Recent rest pain and refractory or postinfarction UA, or both, are strongly associated with the general category of complex lesions and specifically with angiographically detected ICT and decreased TIMI flow.

The purpose of this study was to assess several indexes of cardiovascular risk in men and women with moderate to severe hypertension. We found that women with moderate and severe hypertension have lower ambulatory blood pressure and less cardiac hypertrophy than men with similar clinic blood pressure.

Inheritance of certain germ line haplotypes consisting of three biallelic polymorphisms of p53 has been proposed as a risk factor for breast cancer and colorectal cancer [A. Själander et al., Carcinogenesis (Lond.), 17: 1313-1316, 1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies, pairwise haplotypes of these three polymorphisms were estimated. Extended haplotypes were further projected from the pairwise combinations. To overcome the necessity to estimate pairwise and extended haplotype frequencies, a PCR method has been developed to determine the absolute extended p53 haplotypes in diploid genomes. The method requires allele-specific PCR, confirmed by restriction analysis, and successive amplicon analysis. It has been applied to a nested case-control study of breast cancer (284 subjects; 99 cases and 185 controls; 182 Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that minor variants of the intron 3, codon 72, and intron 6 polymorphisms were moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02 for allele frequency). Accordingly, analysis of haplotype distributions suggested an association of minor p53 haplotypes with breast cancer risk in Caucasians (P = 0.07). The relative allelic frequencies in breast cancer cases compared with controls also differed by age and menopausal status; the 1-2-1 haplotype was overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and younger (P = 0.02). Genotype distributions at each locus and for all control groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype distribution were associated with ethnicity (Caucasians versus African-Americans and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be useful in the study of gene-environment interactions.

Skeletal involvement is a major source of complications in patients with Type 1 Gaucher disease. To investigate the bone density and potential usefulness of bone densitometry in Gaucher disease, dual-energy X-ray absorptiometry was used to measure the density of the lumbar spine, femoral neck, trochanter, and distal radius in 61 adult patients ranging in age from 22 to 77 years. The mean bone density at each site was significantly lower than expected for age and sex. The severity of the osteopenia correlated significantly with other clinical indicators of disease severity, including the N370S/84GG genotype, prior splenectomy, and hepatomegaly. The bone density measurements also correlated significantly with the severity of skeletal disease as assessed by skeletal radiography. Vertebral density remained an independent predictor of the severity of bone involvement even after controlling for age, sex, weight, genotype, splenectomy, and hepatomegaly. These findings suggest that bone density measurements provide a quantitative assessment of bone involvement in Type 1 Gaucher disease, which may permit serial, noninvasive monitoring of bone changes in this progressive disorder.

Objective: To determine the effect of repeated annual influenza immunization on the host's serum antibody., Design: Ten year observational study with cohort design., Setting: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY., Patients: Thirty-eight children and young adults with cystic fibrosis (CF)., Measurements: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year., Results: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer > or = 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different., Conclusions: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period.

Weight loss in Alzheimer's patients has been observed by many clinicians and reported in the international geriatric literature. It represents a puzzling challenge for clinicians and researchers, and it is an important issue for caregivers and nursing home staff concerned with state and federal requirements for nutrition and weight monitoring. Using indirect calorimetry, we studied the resting energy expenditure of 21 elderly patients; 12 were residing in a community setting, and 9 were institutionalized. Of the 12 community-living patients studied, 5 had early to moderate Alzheimer's disease, and 7 were nondemented control subjects. Of the 9 institutionalized patients, all were severely demented, bedridden, and fed exclusively by gastric tube in a closely monitored clinical environment with daily bedside weighing. Four had Alzheimer's disease, and 5 had multi-infarct dementia (MID). Among the outpatients, the Alzheimer's group showed increased energy requirements (p = 0.028) and a significantly different pattern of fat-free mass compared with control subjects (p = 0.031). These observations on community-residing elderly were consistent with, and extended by our findings on energy requirements of, the demented institutionalized patients. The calorie intake necessary for weight maintenance of the bedridden institutionalized patients was determined during their prolonged institutionalization. The presumed maintenance level of calorie intake was then verified during a 10 wk study. During the 10 wk, we documented no significant change in weight with constant energy intake. Compared with MID patients, Alzheimer's patients tended to weigh less (52.84 vs 56.4 kg; p = 0.20) but actually required more calories (1626 vs 1341 kcal, p < 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

We and others have reported an increased incidence of chronic lymphocytic leukemia (CLL) among Ashkenazi (ASH) Jews of European origin. We performed HLA Class I typing on all 50 CLL patients seen by us and compared them with 3886 controls consisting of healthy blood donors from the New York Blood Center. Thirty of our CLL patients were ASH Jews, 17 of whom (57%) expressed the B35 antigen compared with 462 ASH controls (26%). Seven (39%) of the CLL Caucasian patients expressed the B35 antigen compared with 305 (14.5%) of the Caucasian controls. Combining the information from the ASH Jews and the Caucasians the difference is highly significant, (p = 0.0001). The summary odds ratio was 3.7. These results indicate an increased incidence of the antigen B35 amongst ASH and Caucasian patients with CLL.

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

The Mantel-Haenszel test for grouped failure time data (MHF test) compares the distribution of failure times in two cohorts followed for an interval of time when the data are collected in discrete subintervals. This paper derives approximations to the power of the Mantel-Haenszel test for arbitrary failure time distributions in the presence of censoring. The approximations are appropriate for both equal and nonequal odds ratios in the constituent tables, and can be used for arbitrary subdivisions of time. Four approximations are proposed. They differ from each other according to whether the parameter measuring treatment effect is an odds ratio or a difference in proportions, and whether the survival distributions are calculated under the null or alternative hypothesis. In addition, we demonstrate that when the hazards are constant, increasing the number of subintervals often produces only a negligible increase in the power of the MHF test. On the other hand, for arbitrary hazards and nonconstant hazard ratios, the choice of frequency and actual times of measurement can have important effects on power. Finally, the paper presents simple expressions for power under exponential failure and censoring models.

The scan statistic is the maximum number of events in an interval of fixed length w as the subinterval moves over the entire time frame. Previous research derived the null distribution of the scan statistic under the conditional model which assumed that the total number of events was fixed, and under the unconditional model which let the total number of events be a random variable. This paper derives approximations for the power of the scan test for a pulse alternative. Under this alternative, the relative risk of disease on a subinterval (tau, tau + w), tau unknown, is theta-fold as high as it is for other subintervals of length w. Two sets of approximations are given for each model. The first approximation gives highly accurate results, but requires use of a personal computer. The second procedure can be performed on a hand-held calculator and appears very accurate for the cases examined.

Objective: To compare inpatient length of stay among physicians by testing a new method for severity adjusting length of stay., Design: A retrospective validation study with prospective follow-up after an intervention., Setting: A 531-bed community teaching hospital., Patients: Three hundred randomly selected patients from the 30,861 patients discharged in 1990., Intervention: A physician with a significantly prolonged severity-adjusted length of stay was counseled and then monitored for three months., Results: The correlation between the number of comorbidities, complications, and manifestations of disease processes (CCMDPs) was R2 = 0.658, t = 23.96 (p = .001). One physician had an unusually high severity-adjusted length of stay, but lowered it after he was counseled and monitored for three months., Conclusions: The number of CCMDPs recorded on the hospital discharge abstract can be used as a severity index to adjust a patient's length of stay for illness severity. Using linear regression analysis, a picture of the severity-adjusted length of stay can be derived for physicians. Through counseling and monitoring, individual physicians' lengths of stay patterns may be reduced.

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Meaningful comparison of patient outcomes requires an assessment of the severity of illness for the patients being compared. The more severe the underlying illness, the worse the expected outcome. We studied several severity of illness indicators derived from different methodologies in a medical intensive care unit. We compared the Acute Physiologic and Chronic Health Evaluation II, the accepted benchmark indicator for intensive care units, with one complex indicator, Computerized Severity Score, and three simpler indicators, Comorbidity, McCabe-Jackson, and American Society of Anesthesiologists. We found that all correlated well with a comorbidity index. We conclude that the Acute Physiologic and Chronic Health Evaluation II, the Computerized Severity Score, and the McCabe-Jackson scoring systems appear to be comparable predictors of comorbidity in a medical intensive care unit. Selection of a severity indicator will depend on the resources available and the intended uses.

The etiology of the racial disparity in bone mass and fracture rate is unknown. Since the PTH-vitamin D endocrine system is a major regulator of calcium metabolism and bone turnover, this cross-sectional study examined the relationship of radial and lumbar bone density to vitamin D metabolite and PTH concentrations and to calcium intake and excretion in 67 white and 70 black highly comparable, healthy, premenopausal women. Bone density at both radial and lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was slightly but not statistically significantly (P = 0.08), lower in blacks than in whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D concentration in blacks was well within the normal range and was not associated with evidence of secondary hyperparathyroidism. There were no correlations of bone density to vitamin D or PTH concentrations. Although there were no racial differences in dietary intake of calcium and vitamin D or in sodium excretion, 24-h urinary calcium excretion was significantly lower in blacks than in whites, and calcium excretion was inversely associated with radial bone density. In contrast to previous reports, in healthy, normal weight, premenopausal black women there is no evidence of vitamin D deficiency or secondary hyperparathyroidism, suggesting that factors other than the vitamin D-PTH axis are responsible for racial differences in bone mass.

Nonparametric tests of group differences and interaction across strata are developed in which the null hypotheses for these tests are expressed as functions of rho i = P(X > Y) + 1/2P(X = Y), where X refers to a random observation from one group and Y refers to a random observation from the other group within stratum i. The estimator r of the parameter rho is shown to be a useful way to summarize and examine data for ordinal and continuous data.

We designed a study to determine the relative analgesic potency of intramuscular heroin and morphine and to compare mood and side effects in 166 cancer patients with postoperative pain. Heroin was about twice as potent as morphine (95 per cent confidence limits, 1.6 to 2.6 times) in graded-dose, twin-crossover assays. Heroin provided an analgesic peak effect earlier than morphine (1.2 plus or minus 0.08 and 1.5 plus or minus 0.10 hours, respectively [mean plus or minus S.E.M.]). Doses with equal analgesic effects provided comparable improvements in various elements of mood, particularly feelings of peacefulness. Peak mood improvement occurred earlier after heroin than after morphine (1.2 plus or minus 0.10 and 1.8 plus or minus 0.13 hours, respectively). Both analgesia and mood improvement were less sustained after heroin at doses providing equal peak analgesic effects. The drugs shared the most common side effects, with no marked differences in their occurrence; sleepiness was the most frequent side effect after both drugs (46 per cent with each). Heroin has no apparent unique advantages or disadvantages for the relief pain in patients with cancer.

Analgesic studies of buprenorphine, a thebaine derivative and potent partial narcotic agonist, were carried out in patients with cancer who had postoperative or chronic pain. Intramuscular buprenorphine was compared with intramuscular morphine in a series of sequentially related, twin crossover assays and was found to be about 25 times as potent as morphine. Side effects were essentially morphine-like. In a second assay, the acceptability and analgesic activity of sublingual buprenorphine was studied in a 6-dose, balanced, incomplete block assay, a modification of the twin crossover design employed in the all-intramuscular trial. Sublingual buprenorphine was found to be about 15 times as potent as intramuscular morphine and was well accepted by our patients. The 4-dose twin crossover trial in which doses are adjusted sequentially is more flexible in that a wide range of doses may be studied, but it lacks the ability of the 6-dose design to provide estimates of the curvature of the dose-response slopes of the study drugs. When first-dose-only data were analyzed as parallel group assays, the main difference in results compared with the crossover studies was a decrease in efficiency and sensitivity.

The results of this study in postoperative patients have, thus far, revealed little that was not expected from a review of the literature. Heroin hydrochloride appears to be about two to three times more potent than morphine sulfate as an analgesic, to act more promptly and to have a slightly shorter duration of action. There is a suggestion that heroin may have a somewhat different spectrum of side effects and mood effects compared to morphine, but the effects of both drugs on mood were inversely correlated with the patients' feelings at the time of drug administration. Regardless, as a group, patients responded to both drugs with significantly improved moods. A lag time between the peak intensity of analgesic and mood effects of both heroin and morphine suggest a dissociation between these effects. Whether or not these early impressions will be reinforced as this study proceeds, and whether or not the effects of the drugs in patients with chronic pain due to advanced cancer will be any different than in these patients with postoperative pain, remains to be seen.

Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone. Tetrahydrodeoxycorticosterone, in contrast to pregnanolone, is carcinogenic for hamster embryonic cells (HECT test). In patients with recently diagnosed, untreated sigmoidal or rectal cancer the fecal concentration of 21-dehydroxylating organisms is reduced by more than 99% as compared with age-matched controls. The lack of fecal 21-dehydroxylating organisms, therefore, is a potential marker for the disorder. The role of steroid 21-dehydroxylase in the pathogenesis of colorectal cancer is unknown.

Preterm infants of normal birth weight (born before 37 completed weeks of gestation and weighing more than 2,250 g) experience a neonatal mortality risk almost four times higher than do term infants in the same weight range. In an analysis of the effect of hospital level of birth on neonatal mortality, such preterm normal weight infants were found to experience higher mortality if born outside of a Level 3 (tertiary care) center. For all singleton infants in this weight-gestation category born in New York City maternity services during a 3-year period (N = 23,257), the relative mortality risk for Level 1 births (compared with Level 3) was 1.72 (P less than .01) and for Level 2 births 1.47 (P less than .05). The excess mortality at Level 1 and Level 2 units was almost entirely due to a more than twofold higher death rate in black infants born in these units. Several potentially confounding socioeconomic, demographic, and biologic variables entered into a logistic regression model could not account for the higher mortality rates for black infants born in Level 1 and Level 2 units. Among black infants born at Level 1 units, deaths in preterm normal birth weight infants were less likely to occur in a receiving tertiary care center than were either deaths in low birth weight infants or deaths in term normal weight infants, suggesting that the need for special care of preterm normal birth weight infants is underestimated in some hospitals without newborn intensive care units.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

In an analysis of all singleton births and neonatal deaths with known birth weights and gestational ages in New York City maternity services during a three-year period (1976 to 1978), intensive care services at the hospital of birth were found to influence mortality only in preterm (less than 37 weeks' gestation) or low-birth-weight infants (less than 2251 g). By contrast, for infants who were born at term and of normal birth weight, mortality rates did not differ by level of perinatal care available at the hospital of birth. On the average, preterm and low-birth-weight infants were at a 24% higher risk of death if birth occurred outside of a level 3 center, regardless of whether birth occurred at a level 1 or level 2 hospital. Preterm and low-birth-weight infants, though constituting only 12% of births, accounted for 70% of neonatal deaths in New York City. The remaining infants, ie, those born at term and of normal birth weight, who experienced no measurable mortality advantage when born in a level 3 hospital, accounted for 88% of all births.

We examined the neonatal mortality rates of low-birth-weight infants (501 to 2250 g) born between 1976 and 1978 in three kinds of hospitals in New York City: those with newborn-intensive-care units (Level 3), those with capabilities for the care of most premature infants (Level 2), and those without any special facilities for premature newborns (Level 1). Among 13,560 singleton low-birth-weight infants, the adjusted neonatal mortality rate for Level 3 hospitals was 128.5 per thousand live births - significantly lower (P less than 0.001) than the rates for both level 2 (168.1) and Level 1 units (163.0). The association of level of care with mortality could not be accounted for by differences between groups in social or demographic status, in prenatal care, or in medical complication of pregnancy. We infer that birth at a Level 3 center lowers neonatal mortality in low-birth-weight infants. However, only 34 per cent of the patients in this study were born in such units.

Ridit analysis is presented as an appropriate method of analyzing dental clinical data which fall somewhere between the purely categorical (e.g., improved vs. not improved) and the bona fide quantitative (e.g., mg % salivary calcium) scales of measurement. The key feature of the method is the estimation of the probability that a randomly-selected patient from one treatment group is "better-off" than a randomly-selected patient from another. Methods are presented for testing statistical significance and constructing confidence intervals. The method is illustrated on data from a comparative clinical trial of ibuprofen, aspirin and placebo in the relief of post-extraction pain. There were no significant differences in efficacy among the active treatments, but each was significantly superior to placebo.

Zomepirac appears to be an unexpectedly effective oral, non-opioid analgesic. The relative potency of oral zomepirac is roughly 1/5 to 1/8 that of intramuscular morphine. Visual analogues of pain relief offer a reliable alternative to verbal categorical scales, and may provide some advantages in assays of peak drug effect, and in relatively small patient populations.

Infection control programs are primarily oriented toward chronicling the incidence of nosocomial infections (NI). Intervention programs oriented toward preventing infection would be facilitated by identifying patients at greatest risk of NI acquisition. We studied the number of comorbidities as a risk predictor for NIs in patients admitted to the medical intensive care unit (ICU) for three or more days. In 148 patients, we found by regression analysis that the number of comorbidities varied directly with the development of nosocomial infections, as well as with the appearance of new complications and length of ICU stay. Diagnosis-related groups did not adequately account for the variance in comorbidities observed.

The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral oxymorphone was 1/6 as potent as the intramuscular form. In terms of peak effect, however, oral oxymorphone was only 1/14 as potent. These values are almost identical to those obtained in a previous study comparing oral with intramuscular morphine. The analgesic effect of oral oxymorphone rose to a peak later and had a longer duration than the effect of intramuscular oxymorphone. Intramuscular oxymorphone and morphine were also compared in a similar patient group. Intramuscular oxymorphone proved to be 8.7 times as potent as morphine in terms of total analgesic effect and 13 times as potent in terms of peak effect. In roughly equinalgesic doses, the occurrence of side effects was qualitatively and quantitatively similar for oral and intramuscular oxymorphone and for intramuscular oxymorphone and morphine.

It is intuitively appealing in planning a two-period crossover study to have each patient measured on the response variable at the beginning as well as at the end of both periods, and to take the change from the value at the start of the period to the value at the end as the measure of the patient's response to the treatment given during that period. This apparently innocuous procedure may, contrary to one's intuition, produce bias in the analysis of the data for a difference between the residual effects and a difference between the direct treatment effects.

A twin crossover assay of oral zomepirac and intramuscular morphine was completed in 159 cancer patients with postoperative pain. Zomepirac was a surprisingly effective oral analgesic in these patients, 100 mg orally being roughly equivalent to 16 mg intramuscular morphine. Time-effect data indicate that the peak effect for oral zomepirac may occur slightly later than that for morphine but that zomepirac is relatively rapidly effective after oral administration. Side effect occurrence was roughly in the same range for both drugs, with drowsiness, nausea, dry mouth, and feelings of weakness being observed after both drugs while sweating was observed more frequently after zomepirac. The assay further provided a demonstration of the effectiveness of the twin crossover design as a clinical assay method, providing increased sensitivity of crossover data in a patient population available for only a limited number of study treatments.

The two-period repeated measurements crossover design is often employed in clinical trials. This paper presents a unified approach for the statistical analysis of such a design that clarifies the testing procedures and assumptions employed under different conditions. It is shown how the data may be transformed so that it could be analyzed under the framework of a completely randomized repeated measurements design. Applications are given to a comparative bioavailability trial for attainment of steady state levels and to a clinical trial to compare the effects of two hypolipidemics.

The scan statistic evaluates whether an apparent cluster of disease in time is due to chance. The statistic employs a 'moving window' of length w and finds the maximum number of cases revealed through the window as it scans or slides over the entire time period T. Computation of the probability of observing a certain size cluster, under the hypothesis of a uniform distribution, is infeasible when N, the total number of events, is large, and w is of moderate or small size relative to T. We give an approximation that is an asymptotic upper bound, easy to compute, and, for the purposes of hypothesis testing, more accurate than other approximations presented in the literature. The approximation applies both when N is fixed, and when N has a Poisson distribution. We illustrate the procedure on a data set of trisomic spontaneous abortions observed in a two year period in New York City.

Logistic analysis methodology is being increasingly used in the analysis of categorical data from the biomedical sciences. We describe how the relationships between a dichotomous outcome variable and several qualitative classificatory or experimental variables can be modeled in a format similar to that used for quantitative data. The technique of weighted least squares is used to estimate the underlying parameters in the model and to perform various tests of statistical significance. The methodology is illustrated using data from a randomized dental anaesthetic study comparing three local anaesthetic solutions under two operative procedures. The similarities between the logistic analysis of dichotomous data and the analysis of variance applied to quantitative data are stressed.

A statistical method is presented for detecting random variation in the transition probabilities of certain simple, discrete-time Markov chains that have been found useful for modelling follow-up studies.

We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.

Heroin hydrochloride is approximately twice as potent as morphine sulfate, and acts slightly faster but for a shorter duration than morphine. Although patients with chronic pain due to advanced cancer differ from cancer patients with postoperative pain in terms of their degree of tolerance to the analgesic effects of morphine and heroin and their reports of various elements of mood, there is, thus far, no indication that heroin has any unique advantage over morphine in terms of side effect occurrence or effects on mood at equianalgesic doses. Both drugs improve mood provided they are administered in doses which result in analgesia. While there appears to be some slight difference in the spectrum of side effects observed after heroin as compared to morphine, heroin and morphine share the most common side effects. The incidence of side effects following both drugs appear to be highest among those effects which are primarily somatic and undesirable. The use of visual analog scales concurrent with categorical pain and pain relief scores provides a means for the finer estimation of relative analgesic potency and time action. The results of these studies are in general agreement with those of other investigators. Where apparent differences exist they can usually be explained on the bases of differences in methods and subject populations.

Most tests for seasonal clustering are sensitive to the peak in incidence in some season (90-day interval) followed by a trough 6 months later. We present two statistics sensitive to a relatively sharp increase in disease incidence for a season superimposed on a constant incidence over the entire year: the ratchet scan, based on the maximum number of events in k consecutive months, and the continuous circular scan, the maximum number of events in d consecutive days. We tabulate the tail distribution of the ratchet scan for N less than or equal to 35 and k = 2 and 3, and find the asymptotic distribution which is applicable for N greater than or equal to 50 when k = 2 or 3. We evaluate an approximation for the distribution of the continuous scan. The statistics are applied to investigate seasonal clustering of adolescent suicide in the United States. An illustration is given of the application of the circular scan, and a small simulation study and the example are used to compare the statistics with others proposed in the literature.

The 'immunological profile' of amyotrophic lateral sclerosis (ALS) patients was established from standard tests for B- and T-cell function. This showed no significant difference from age and sex-matched other neurological (CNS) disease controls and normal subjects. Immune complex (IC) levels in ALS serum differed significantly from normal controls but not from CNS controls. There was no relation between the various indices of immune activity of IC levels and the clinical disability of the ALS patient or progression of the disease. Distribution of complement-fixing antibodies to poliovirus was similar to sera of ALS and control groups. The in vitro cell-mediated immune responses to poliovirus, however, were significantly greater in ALS patients than in CNS controls and were inversely related to the ALS disability score. Poliovirus has not been demonstrated in the CNS or extra-CNS tissues of ALS patients by conventional means but, if latent or defective poliovirus or related virus were present, this could account for sensitization and a possible autoimmune mechanism. ALS patients exhibited in vitro cellular immunity to ALS and normal CNS subfractions. These responses were not related to the ALS disability score or progression of the disease and probably represent epiphenomena.

Using a data set from the Forsyth Dental Center consisting of repeated measurements of periodontal attachment level on 22 patients over 1 year, we performed correlation analyses at 4 time points (baseline, 1 month, 6 months and 9 months) for 3 units of measurement (sites, teeth and quadrants). Values of the intraclass correlation coefficient were obtained for the cross-sectional measurements and for changes from baseline. The values were positive and often of appreciable magnitude, indicating that measurements of attachment level and of change in attachment level within the same mouth are positively correlated. Taking sites rather than patients as the units of statistical analysis in comparative clinical trials in periodontology will therefore tend to produce underestimated standard errors and overstated statistical significance.

We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.

Meptazinol is an agonist-antagonist opioid analgesic believed to be unique in its selectivity for mu1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double-blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (+/- SE) times to peak effect and to remedication were 0.9 +/- 0.1 and 3.6 +/- 0.2 hours for meptazinol and 1.4 +/- 0.1 and 4.8 +/- 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32, 49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.

A six-point, incomplete block assay of sublingual buprenorphine and intramuscular morphine has been carried out, providing valid relative potency estimates of the two drugs in terms of total relief on both categorical and visual analog scales. Sublingual buprenorphine was about 15.5 times as potent as intramuscular morphine in terms of these total relief estimates. Similar relative potency estimates were obtained using first-dose-only data. There was no evidence of interaction by day in the crossover data, and the crossover study proved more efficient and provided tighter confidence limits. Sublingual buprenorphine produced a lower peak effect than intramuscular morphine. At equivalent peak effects, it produced longer-lasting analgesia. Side effect occurrence was roughly comparable for the two drugs, and no evidence of narcotic antagonist activity was seen after buprenorphine. The six-point assay proved to be effective in defining the dose-effect curves and relative potencies of the two drugs.

Measurement of pain in cancer patients requires all the procedural safeguards essential for the measurement of subjective responses, including the employment of active and inactive controls, double-blind techniques, randomization, and statistical verification of results. Pain is traditionally measured in analgesic studies by employing verbal descriptors of intensity, but more recently visual analogues of pain intensity have been used and generally provide more sensitive measures of pain intensity. Patients with chronic pain tend to rate the categories representing more intense pain as lower in the visual analogue scale than do patients with postoperative pain. This may well reflect differences in the prior pain experiences of the two groups. Patients with chronic cancer pain have greater positive mood effects after the narcotic, morphine, than after the non-steroidal antiinflammatory analgesic, zomepirac, and this appears to be independent of analgesic activity. It is possible to design crossover analgesic studies in cancer patients so as to minimize carry-over effects, and such studies are more efficient than parallel group assays. Crossover studies also provide the ability to measure carry-over when it occurs.