Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture.

In Africa, the beta-globin gene cluster haplotype may be associated with variation of Hb F levels in subjects with sickle cell anemia (SS). These observations have not yet been conclusively confirmed in SS out of Africa, perhaps because of small sample sizes, the predominance of haplotype heterozygotes, and diverse influences, including gender, upon Hb F levels. We studied 384 adult African-American SS patients (mean age, 31 years) and explored the relationship of gender, beta-globin gene cluster haplotype, and alpha thalassemia to hematological values and Hb F levels. Both haplotype and gender influenced Hb F concentration. In the total sample, Hb F was higher in females than in males (8.2 vs. 6.5%). In 35 males who were either homozygous for the Senegal chromosome or had the Senegal/Benin haplotype, the mean percent Hb F (8.0%) was equivalent to the Hb F level in females with Benin and Bantu haplotypes (approximately 7.5%). Both females and males homozygous for the Senegal haplotype chromosome or with the Senegal/Benin combination had a significant increase in Hb F compared to other groups. In 44 Senegal/Senegal or Senegal/Benin females the Hb F was 10.9%, or 1.0 g/dl, the highest value observed in all primary analysis groups. Preliminary analyses suggested that the presence of a Bantu chromosome blunted the gender-associated difference in Hb F, but Hb F differences between females with the Senegal/Benin haplotype (11.2%) and the Senegal/Bantu haplotype (8.8%) were not statistically significant. Hemoglobin concentrations were higher in males than in females except in subjects with at least one Senegal haplotype chromosome, where hemoglobin levels were equal. As expected, alpha thalassemia reduced the MCV, increased hemoglobin concentration, and lowered reticulocyte counts, regardless of haplotype. Hb F levels were not affected by the presence of alpha thalassemia in any group. We conclude that gender and beta-globin gene cluster haplotype interact significantly in the modulation of Hb F and anemia in adults with SS.

In 113 black American adults with sickle cell anemia (HbSS), we examined nine polymorphic restriction sites, including the Xmnl site 5' to the G gamma gene, to see whether haplotype is related to the level of HbF and the proportion of G gamma chains or if it influences the hematological and clinical features of the disease. Seventy-five percent of the patients were homozygous or heterozygous for the Benin (no. 19) or Central African Republic (Bantu, no. 20) haplotypes; 13.3% were homozygous or heterozygous for the Senegal (no. 3) haplotype, while 11.5% had other genotypes. Of the subjects, 14.2% were either homozygous or heterozygous for the Xmnl restriction site 5' to the G gamma gene. We found no effect of haplotype on HbF levels. The level of G gamma chains was 60.5% +/- 17.0% in individuals heterozygous or homozygous for haplotype no. 3 and was 46.9% +/- 11.6% in individuals with other haplotypes. Subjects with the Xmnl site 5' to the G gamma gene had G gamma globin levels of 59.5% +/- 16.7% while those lacking that site had an average of 47.2% +/- 12.1%. There were no significant differences among these groups in hemoglobin concentration, packed cell volume, mean cell volume, or clinical indicators of vaso-occlusive severity, including crises, hospitalizations per year, aseptic bone necrosis, acute chest syndrome, or leg ulcers. While the presence of haplotype 3 and the 5' G gamma Xmnl site were associated with increased G gamma chains, there was no effect on HbF level or other hematological and clinical features that might reflect disease severity. It is likely that determinants unrelated to haplotype, linked or unlinked to the beta-globin gene cluster, are the major effectors of differences in the levels of HbF in American patients with sickle cell anemia.

In a 10-week trial of the effect of 80 mEq KCl/day on blood pressure, the following biochemical changes were noted: plasma renin activity (PRA), originally significantly lower in blacks than whites, increased to the same level as whites after K supplementation. A similar trend was noted with aldosterone. KCl increased creatinine excretion in blacks and whites, and lowered Ca excretion in blacks. These results suggest that the low PRA found in blacks is due, at least in part, to low K intake, and not to genetic causes.

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The development and evaluation of new combination vaccines is an important public health endeavor. Trials to evaluate these vaccines are customarily designed and analyzed as noninferiority studies. We explain the concept of noninferiority and highlight important issues that can be challenging in the statistical evaluation of these vaccines. Topics covered include end points, hypotheses, and analyses for comparing geometric mean concentrations (or titers) of antibody and proportion of vaccine recipients responding; covariate adjustment; the problem of multiplicity and its impact on sample size; and choice of a meaningful difference to rule out.

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