Genitourinary injuries in the newborn.

BACKGROUND: Circumcisions and cesarian sections are common procedures. Although complications to the newborn child fortunately are rare, it is important to emphasize the potential significance of this problem and its frequent iatrogenic etiology. The authors present 7 cases of genitourinary trauma in newborns, including surgical management and follow-up. METHODS: The authors relate 7 recent cases of genitourinary trauma in newborns from a children's hospital in a major metropolitan area. RESULTS: Case 1 and 2: Two infants suffered degloving injuries to both the prepuce and penile shaft from a Gomco clamp. Successful full-thickness skin grafting using the previously excised foreskin was used in 1 child. Case 3, 4, and 5: A Mogen clamp caused glans injuries in 3 infants. In 2, hemorrhage from the severed glans was controlled with topical epinephrine; the glans healed with a flattened appearance. Another infant sustained a laceration ventrally, requiring a delayed modified meatal advancement glanoplasty to correct the injury. Case 6: A male infant suffered a ventral slit and division of the ventral urethra before placement of a Gomco clamp. Formal hypospadias repair was required. Case 7: An emergent cesarean section resulted in a grade 4-perineal laceration in a female infant. The vaginal tear caused by the surgeon's finger, extended up to the posterior insertion of the cervix and into the rectum. The infant successfully underwent an emergent multilayered repair. CONCLUSIONS: Genitourinary trauma in the newborn is rare but often necessitates significant surgical intervention. Circumcision often is the causative event. There has been only 1 prior report of a perineal injury similar to case 7, with a fatal outcome.

Sample size for comparing linear growth curves.

Assuming a linear growth curve model under a suitable link function, we compute the sample size for comparing two treatment groups when the repeated measurements marginally follow exponential family distributions. From the treatment profiles of the chosen link function, we compute the common intercept beta0 and the regression slopes beta1 and beta2 to define delta = beta1 - beta2, the difference to be detected, under a specified alternative hypothesis. The dispersion matrices of the generalized estimating equations estimators are obtained under the null and alternative hypotheses using a suitable working correlation matrix. We compute the sample size assuming that delta is asymptotically normal. Details are worked out for repeated measures designs with binary and count data along with numerical examples.

Surgery for Crohn's disease in infants and children.

The course of Crohn's disease is quite variable in children. To assess the frequency and indications for surgery with current medical therapy, the authors reviewed the cases of 204 children (ages, 0.2 to 18.8 years at diagnosis, median, 12.8 years) who had Crohn's disease treated at a single institution from December 1968 to January 1994, with a median of 3.8 years of follow-up (range, 0.0 to 22.2 years). Ninety-four children (46%) required surgical resection for the following indications: (1) failure of medical therapy with persistent symptoms or growth retardation (n = 44, 47%), (2) intraabdominal abscess or perforation (n = 15, 16%), (3) fistula formation (n = 13, 14%), (4) obstruction (n = 15, 16%), (5) hemorrhage (n = 4, 4%), and (6) appendectomy at exploration for diagnosis (n = 3, 3%). The probability for surgery 3 years after diagnosis is 28.8% and by 5 years is 47.2%. Resections included ileocolectomy (71 children), colectomy (n = 16), small bowel resection (n = 4), and appendectomy (n = 3). Fourteen fistulas in 13 children required surgical intervention (7 enteroenteral, 3 enterovesical, 2 enterovaginal, and 2 enterocutaneous). The median duration from diagnosis to surgery for the fistulas was 2.6 years (range 0.1 to 9.8 years). Forty patients experienced recurring disease after resection during follow-up with a median of 1.8 years (range 0.4 to 18.1 years). The authors found that the course of the disease was unpredictable, with some children requiring early surgical intervention and others continuing with medical therapy for years.

Analysis of a within-subject design with covariates.

This paper deals with a method of analyzing incomplete data, forming a monotone pattern, from a within-subject design with baseline measurements. An assumption of multivariate normality with antedependence structure is made for both the baseline measurements and the response measurements. Adjusted means for the period-by-sequence cells and their dispersion matrix are obtained. Large sample tests are proposed for testing various hypotheses. A numerical example is given to illustrate the methodology.

Some optimal and non-optimal two-stage designs using an alpha-spending function.

While designing a group sequential clinical trial in the pharmaceutical industry setting, we often face a problem of determining the time for an interim analysis. For a two-stage trial we compute the sample sizes n and N per treatment group for the interim and final analyses, respectively, that minimize the average trial size for a specified overall power. We consider this optimization when we monitor the trial using a Lan-DeMets alpha-spending function. Two additional problems considered in this context are (i) finding the sample sizes that maximize the overall power for a specified average trial size, and (ii) finding the sample sizes that achieve specified powers at the interim and final analyses.

Analysis of paired ordered categorical data in a factorial design.

In clinical trials and behavioral sciences, there exist situations where paired responses are obtained from each subject on an ordinal scale. Existing methods for analyzing such data in a factorial design are reviewed and new methods are developed with a special emphasis on pre- and post-treatment responses. The distribution of a square table is decomposed into successively independent pairs of discordant vectors, and assuming a logistic model, a statistics is computed to measure the shift in the marginal distributions. The approach is similar to McCullagh's approach (1). Two other criteria are proposed, one based on a Lehmann alternative used for comparing two distribution functions and the other based on a proportional odds model. These criteria are applied to the marginal distributions of a square table. For each case, a statistic measuring lack of marginal homogeneity and its variance are computed for each independent square table of a factorial design. Given such statistics, one can estimate a set of linear contrasts and compute its dispersion matrix for making inference. A numerical example is given.

Multistage test procedure for testing Blackwelder's hypothesis of equivalence.

Suppose, in a clinical trial, the interest is to show that the effectiveness of an experimental therapy is no worse than that of the standard therapy by more than a specified amount, say delta units. Blackwelder (1) discussed this problem in clinical trials where the outcome of interest is dichotomous. The group sequential procedures developed by DeMets and Ware (2) are valid to test Blackwelder's hypothesis for the case delta = 0. In this paper, the asymmetric procedure of DeMets and Ware is modified to handle the case delta > 0. A two-stage procedure is considered in a drug interaction study that focuses on a specific side effect as the event of interest.

Sample size for a dose-response study.

This paper deals with a method of sample size allocation for a dose-response study assuming a logistic model for the dose-response curve. The method is based on the precision with which one wishes to estimate the dose that would produce the efficacy resulting in a clinically important difference from a placebo. An example is given to illustrate the methodology. The main development of the paper is for a binary response and is suitably modified for a continuous variable.

Comparison of treatments in a combination therapy trial.

Although the min test proposed by Laska and Meisner (1) for testing superiority of a combination to each of its components is the uniformly most powerful monotone test, it is conservative in the neighborhood of origin. Considering a restricted null hypothesis, we analyze a general linear model. The p value associated with the proposed test and a confidence interval for the shortest distance between the combination therapy and component therapies are computed. Analysis of a design with two or more combinations is proposed. A numerical example is given and a problem of optimal allocation of the sample sizes and other relevant design issues are discussed.

A Markovian model for comparing incidences of side effects.

For clinical trials that entail observations at successive visits for the occurrence of a side effect, this paper considers a likelihood-based method to compare side effect incidence rates. The method, which employs the assumption of a Markov chain of order one for the vectors of binary responses, handles missing data due to premature withdrawals. An actual numerical example and a simulated example illustrate the technique.

Analysis of two-period crossover design in a multicenter clinical trial.

A technique is discussed for analyzing a two-period crossover design for a multicenter trial using identical study protocols. The technique is a modification of the analysis originally proposed by Grizzle (1965, Biometrics 21, 467-480; 1974, Biometrics 30, 727) for analyzing a two-period crossover design when study is not a factor. A mixed model using the first baseline as a covariate is analyzed to increase the power of the test of significance of the treatment-by-period interaction. The baseline values are also used in a preliminary test.