Mark A. Weaver

OBJECTIVE: To estimate the frequency with which results of large randomized clinical trials registered with ClinicalTrials.gov are not available to the public. DESIGN: Cross sectional analysis SETTING: Trials with at least 500 participants that were prospectively registered with ClinicalTrials.gov and completed prior to January 2009. DATA SOURCES: PubMed, Google Scholar, and Embase were searched to identify published manuscripts containing trial results. The final literature search occurred in November 2012. Registry entries for unpublished trials were reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database. MAIN OUTCOME MEASURES: The frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in the ClinicalTrials.gov database. RESULTS: Of 585 registered trials, 171 (29%) remained unpublished. These 171 unpublished trials had an estimated total enrollment of 299,763 study participants. The median time between study completion and the final literature search was 60 months for unpublished trials. Non-publication was more common among trials that received industry funding (150/468, 32%) than those that did not (21/117, 18%), P=0.003. Of the 171 unpublished trials, 133 (78%) had no results available in ClinicalTrials.gov. CONCLUSIONS: Among this group of large clinical trials, non-publication of results was common and the availability of results in the ClinicalTrials.gov database was limited. A substantial number of study participants were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results.

Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.

The contamination of corn (maize) by fungi and the accumulation of mycotoxins are a serious agricultural problem for human and animal health. One particular devastating group of mycotoxins, called aatoxins, has been intensely studied since the 1960s. Studies of Aspergillus avus, the agriculturally relevant pro- ducer of aatoxins, have led to a well-characterized biosynthetic pathway for aatoxin production, as well as a basic understanding of the organism’s life cycle. Unfortunately, these eorts have not resulted in corn production practices that substantially reduce aatoxin contamination. Similarly, the use of agrochemicals (e.g., fungicides) results in very limited reduction of the fungus or the toxin. Thus, cultural management (fertility and irrigation) coupled with aggressive insect management is current recommendation for inte- grated aatoxin management. The development of resistant hybrids appears to be a very promising tech- nology, but commercial hybrids are still not available. Thus, biocontrol appears to be the most promising available avenue of reducing aatoxin accumulation. Biocontrol utilizes nontoxigenic strains of Aspergillus to reduce the incidence of toxin-producing isolates through competitive displacement. To maximize the eectiveness of biocontrol, a thorough knowledge of the environmental factors inuencing colonization and growth of Aspergillus is needed. A. avus not only colonizes living plant tissue, but it also grows sapro- phytically on plant tissue in the soil. These residues serve as a reservoir for the fungus, allowing it to over- winter, and under favorable conditions it will resume growth and release new conidia. The conidia can be transmitted by air or insects to serve as new inoculum on host plants or debris in the eld. This complex ecology of Aspergilli has been studied, but our understanding lags behind what is known about biosynthe- sis of the toxin itself. Our limited understanding of Aspergilli soil ecology is in part due to limitations in eval- uating Aspergilli, aatoxin, and the biosynthetic genes in the varying aspects of the environment. Current methods for assessing Aspergillus and aatoxin accumulation rely heavily on cultural and analytical meth- ods that are low throughput and technically challenging. Thus to understand Aspergillus ecology and envi- ronmental eects in contamination to maximize biocontrol eorts, it is necessary to understand current treatment eects and to develop methodologies capable of assessing the fungal populations present. In this manuscript we discuss the current knowledge of A. avus ecology, the application of selected molecu- lar techniques to eld assessments, and crop practices used to reduce aatoxin contamination, focusing on chemical treatments (fungicides and herbicides), insect management, and crop management.

OBJECTIVE: To examine inter-relationships among stress due to infant appearance and behavior in the neonatal intensive care unit (NICU), parental role alteration stress in the NICU, depressive symptoms, state anxiety, posttraumatic stress symptoms, and daily hassles exhibited by African-American mothers of preterm infants and to determine whether there were subgroups of mothers based on patterns of psychological distress. METHOD: One hundred seventy-seven African-American mothers completed questionnaires on their psychological distress at enrollment during infant hospitalization and 2, 6, 12, 18, and 24 months after term. RESULTS: Psychological distress measures were intercorrelated. There were four latent classes of mothers: the low distress class with low scores on all measures; the high NICU-related stress class with high infant appearance and parental role stress and moderate scores on other measures; the high depressive symptoms class with high depressive symptoms and state anxiety and moderately elevated scores on NICU-related stress and posttraumatic stress symptoms; the extreme distress class with the highest means on all measures. Infants in the high stress class were sicker than infants in the other classes. The extreme distress class mothers averaged the lowest educational level. The classes differed on distress measures, worry about the child, and parenting stress through 24 months with the extreme distress class having the highest values. CONCLUSION: Although different types of maternal psychological distress were substantially related, there were distinct subgroups of mothers that were identifiable in the NICU. Moreover, these subgroups continued to differ on trajectories of distress and on their perceptions of the infants and parenting through 24 months after term.