Kristy Seidel

Background Childhood obesity increases the risk of obesity in adulthood, but how parental obesity affects the chances of a child's becoming an obese adult is unknown. We investigated the risk of obesity in young adulthood associated with both obesity in childhood and obesity in one or both parents.

OBJECTIVE: At 5 to 6 years of age, body fatness normally declines to a minimum, a point called adiposity rebound (AR), before increasing again into adulthood. We determined whether a younger age at AR was associated with an increased risk of adult obesity and whether this risk was independent of fatness at AR and parent obesity. DESIGN: A retrospective cohort study using lifelong height and weight measurements recorded in outpatient medical records. SETTING: Group Health Cooperative of Puget Sound (GHC), a health maintenance organization based in Seattle, Washington. PARTICIPANTS: All 390 GHC members (and their parents) born at GHC between January 1, 1965, and January 1, 1971, who had at least one recorded adult height and weight measurement plus two visits with recorded height and weight measurements in each of three age intervals: 1.5 to 4, 4 to 8, and 8 to 16 years. MAIN OUTCOME MEASURES: We calculated the mean body mass index (BMI) of each subject during young adulthood (age 21 to 29 years) and the BMI of the parents when each subject was 1.5 years of age. Adult obesity was defined as a BMI >/=27.8 for males and >/=27. 3 for females. Curves were fit to each subject's BMI values between ages 1.5 and 16 years, and the age and BMI at AR were calculated from these curves. Subjects were divided into tertiles of age at AR (early, middle, and late), BMI at AR, and parent BMI (heavy, medium, and lean). RESULTS: The mean age at AR was 5.5 years, and 15% of the cohort was obese in young adulthood. Adult obesity rates were higher in those with early versus late AR (25% vs 5%), those who were heavy versus lean at AR (24% vs 4%), those with heavy versus lean mothers (25% vs 5%), and those with heavy versus lean fathers (21% vs 5%). After adjusting for parent BMI and BMI at AR, the odds ratio for adult obesity associated with early versus late AR was 6.0 (95% CI, 1.3-26.6). CONCLUSION: An early AR is associated with an increased risk of adult obesity independent of parent obesity and the BMI at AR. Future research should examine the biological and behavioral determinants of AR.

Two randomized, placebo-controlled trials previously showed that fluconazole (400 mg/d) administered prophylactically decreases the incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in improved survival in allograft recipients. Reported here are the results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and the incidence of invasive fungal infections early (less than 110 days) and late (more than 110 days) after BMT. After 8 years of follow-up, survival is significantly better in fluconazole recipients compared with placebo recipients (68 of 152 vs 41 of 148, P =.0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with fluconazole (30 of 148 vs 4 of 152, P <.001). More patients who received placebo died with candidiasis early (13 of 148 vs 1 of 152, P =.001) and late (8 of 96 vs 1 of 121, P =.0068) after BMT. The incidence of severe GVHD involving the gut was higher in patients who did not receive fluconazole (20 of 143 vs 8 of 145, P =.02), and fewer patients who received fluconazole died with this complication. Thus, administration of fluconazole (400 mg/d) for 75 days after BMT appears to be associated with decreased gut GVHD, a persistent protection against disseminated candidal infections and candidiasis-related death, resulting in an overall survival benefit in allogeneic BMT recipients.

The prophylactic use of fluconazole is common in blood and marrow transplant (BMT) recipients. To evaluate how fluconazole has influenced the development of azole resistance and candidemia, weekly mouthwashings were done, and fluconazole susceptibility was determined for 1475 colonizing and invasive isolates obtained from patients undergoing BMT. Of 585 patients, 256 (44%) were colonized with Candida species during the course of BMT. Of these, 136 patients (53%) had at least 1 mouthwashing sample that yielded Candida species other than C. albicans on culture. Only 4.6% of patients developed candidemia. Overall, C. albicans was the most common colonizing isolate, but it caused only 7% of cases of candidemia. About 5% of colonizing C. albicans strains and 100% (2 of 2) invasive C. albicans strains were fluconazole-resistant. Colonization, cytomegalovirus disease, and bacteremia are risk factors for the development of candidemia. The use of prophylactic fluconazole is associated with a low incidence of candidemia and attributable mortality, despite colonization with azole-resistant Candida species in BMT recipients.