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The occurrence of time-space clusters was examined in national mortality data on suicide among adolescents aged 15-19 years obtained from the National Center for Health Statistics Mortality Detail Files for 1978-1984. The analyses indicated that overall significant time-space clustering occurred among 15-19 year olds. The authors thus believe that they have documented for the first time that outbreaks of suicide occur more frequently than expected by chance alone. The occurrence of suicide clusters among teenagers appeared to vary considerably by state and year of investigation. There is some indication that there has been an increase in teenage clusters in more recent years.

The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.

The relative analgesic potency of oral and intramuscular codeine 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 codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.

A test for time-space clustering is proposed based on the scan statistic, the maximum number of events in a 365-day period in each of several geographic units. The data under consideration should consist of the exact date and geographic unit for each event, and data should be available for several years for which the risk of disease can be assumed constant. The statistic is the ratio of the excess number of events summed over all the geographic regions, to the square root of the sum of the variances. This statistic is similar in construction to the Ederer-Myers-Mantel statistic (Biometrics 1964;20:626-38), but does not require that attention be limited to calendar years (January 1-December 31). Unlike other tests for time-space clustering, the scan statistic allows one to calculate measures of attributable risk and effect size. Data concerning adolescent suicide are used to illustrate the procedure. The tables and asymptotic formulas given for the mean and variance of the proposed statistic should be useful in the evaluation of both clustering in time and in time-space.

This study examines the utility of birth weight-specific neonatal mortality rates in removing the confounding effects, in comparisons of mortality in low birth weight infants, of several factors that influence crude neonatal mortality. For this purpose, the effects of social, demographic, and biological attributes of mothers on the mortality of their low birth weight babies were examined in the total population of infants weighing 501-2000 gm born in New York City in 1976, 1977, and the first 11 months of 1978 (N = 10,187). The results confirm previous observations that race, sex, and gestational age-for-weight all exert significant influences on mortality even within narrow (250 gm) birth weight bands. However, mothers' education, number of prenatal visits and whether delivery was on private or ward service, all variables which substantially affect crude neonatal mortality, had no overall effect on weight-specific mortality in the weight range under consideration. Two other socioeconomic indicators, whether delivery was financed by Medicaid, and the marital status of the mother, did significantly affect weight-specific mortality, but their effects were abolished when gestation, race, and sex were entered into the analysis. Although neither maternal age nor parity had any significant individual effects on low birth weight mortality, a linear trend towards lower mortality in older mothers was discovered, and certain age-parity combinations experienced significantly elevated or reduced mortality. In general, weight-specific mortality in low birth weight infants is little influenced by the socioeconomic circumstances of their mothers, particularly when race, sex, and gestation are taken into account. Weight-specific neonatal mortality can therefore be a useful tool in the analysis of the effectiveness of perinatal medical care given to low birth weight infants.

Incidence and time of onset of germinal matrix/intraventricular hemorrhage (GM/IVH) were prospectively ascertained in 1,105 infants weighing < or = 2,000 g at birth, a cohort comprising about 85% of all births of that weight born from September 1984 to June 1987 in the central New Jersey counties of Ocean, Monmouth, and Middlesex. Cranial ultrasonography was performed as nearly as possible to age 4 hours, 24 hours, and 7 days. Each scan was reviewed by two independent readers and, if necessary, a third; consensus was achieved on scan of first diagnosis of GM/IVH in 965 of the 1,079 infants with assessable scans. The cumulative incidence of GM/IVH in the first week of life was 24.6% (265/1,079). In the 965 infants with consensus diagnoses, the first scan, at 4.9 +/- 2.2 hours, yielded the highest incidence--10.6% (95/899). Incidence by the second scan (25.1 +/- 4.9 hours) was 6.0% (49/813), and by the third scan (7.2 +/- 0.8 days), 9.0% (64/715). The iterative algorithm for interval-censored data developed by Turnbull (J R Stat Soc [B] 1976;8:290-5) was used to estimate the most likely time of onset based on time of first diagnosis. From 34% to 44% of hemorrhages were present at the first opportunity to scan, which in these data was at age 1 hour. At least a third of GM/IVH in infants < or = 2,000 g appears to be of congenital or immediate postnatal onset.

Statistical analyses of the joint effects of several factors (covariates) on the risk of disease, death, or other dichotomous outcomes, are frequently based on a model that relates the effect of the covariates to some function of the probability of the outcome. The odds ratio, relative risk, and the difference in risks are among the simplest candidates for the outcome function. Each can be specified as a special case of the generalized linear model, but their use has been limited to researchers with access to specialized computer programs that are not yet generally available in standard computer packages. The purpose of this communication is to describe how to implement the maximum likelihood estimation procedures and hypothesis testing associated with the generalized linear model using any computer program that can perform weighted least squares analyses. The procedure is applied specifically to models for relative risks, risk differences, and odds ratios. The techniques are illustrated with SAS and SPSSx programs for data sets previously presented.

The use of the scan statistic in testing for clustering in time is discussed with particular reference to a reported clustering of trisomies in spontaneous abortions in New York City. The scan statistic is the maximum number of observed cases in an interval of preselected length, as the interval is allowed to scan, or slide along, the time frame of interest. A table of the lower tail of the distribution of this statistic is given.