Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial

Context  Ventilator management protocols shorten the time required to wean adult patients from mechanical ventilation. The efficacy of such weaning protocols among children has not been studied. Objective  To evaluate whether weaning protocols are superior to standard care (no defined protocol) for infants and children with acute illnesses requiring mechanical ventilator support and whether a volume support weaning protocol using continuous automated adjustment of pressure support by the ventilator (ie, VSV) is superior to manual adjustment of pressure support by clinicians (ie, PSV). Design and Setting  Randomized controlled trial conducted in the pediatric intensive care units of 10 children's hospitals across North America from November 1999 through April 2001. Patients  One hundred eighty-two spontaneously breathing children (<18 years old) who had been receiving ventilator support for more than 24 hours and who failed a test for extubation readiness on minimal pressure support. Interventions  Patients were randomized to a PSV protocol (n = 62), VSV protocol (n = 60), or no protocol (n = 60). Main Outcome Measures  Duration of weaning time (from randomization to successful extubation); extubation failure (any invasive or noninvasive ventilator support within 48 hours of extubation). Results  Extubation failure rates were not significantly different for PSV (15%), VSV (24%), and no protocol (17%) (P = .44). Among weaning successes, median duration of weaning was not significantly different for PSV (1.6 days), VSV (1.8 days), and no protocol (2.0 days) (P = .75). Male children more frequently failed extubation (odds ratio, 7.86; 95% confidence interval, 2.36-26.2; P<.001). Increased sedative use in the first 24 hours of weaning predicted extubation failure (P = .04) and, among extubation successes, duration of weaning (P<.001). Conclusions  In contrast with adult patients, the majority of children are weaned from mechanical ventilator support in 2 days or less. Weaning protocols did not significantly shorten this brief duration of weaning.      

The role of superoxide and nuclear factor-kappaB signaling in N-methyl-D-aspartate-induced necrosis and apoptosis

N-Methyl-D-aspartate (NMDA) receptor-mediated cell death is complex, probably involving elements of necrosis and apoptosis. The mechanisms underlying this phenomenon are incompletely understood but have been suggested to involve reactive oxygen species such as nitric oxide and superoxide anion (O(2)) and nuclear factor-kappaB (NF-kappaB) signaling. In this study, we used a selective nonpeptidyl superoxide dismutase mimetic (M40403) and SN50, a peptide inhibitor of NF-kappaB translocation, to investigate the role of O(2) and the potential downstream signaling molecules in cell death induced by activation of the NMDA receptor. Application of NMDA to a mixed neuronal/glial forebrain culture resulted in an early increase in the release of cytoplasmic lactate dehydrogenase (LDH), which peaked at 4 h. This was followed by a reduction in mitochondrial metabolism of the dye MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] that continued to decrease throughout the 20-h exposure. A substantial increase in DNA fragmentation as measured by an enzyme-linked immunosorbent assay (ELISA) specific for DNA-associated histone proteins (nucleosomes) was observed at 7 and 20 h. M40403 and SN50 blocked NMDA-induced changes in LDH release at 2, 4, and 20 h, MTT metabolism at 4 and 20 h, and DNA fragmentation at 20 h as measured by the ELISA and by an increase in terminal dUTP-nick end labeling. M40403 also prevented NMDA-induced nuclear transport of NF-kappaB and increased expression of Bax relative to Bcl-X(L). SN50 was also able to block NMDA-induced cell death as well as the increased Bax/Bcl-X(L) ratio. Time course studies and experiments with SN50 and M40403 suggest that O(2) production and NF-kappaB translocation may be involved in necrosis and apoptosis, but the latter also requires an increased expression of Bax. The ability of M40403 to prevent NMDA-induced cell death relatively early in this cascade suggests its potential therapeutic utility in central nervous systems diseases such as stroke that are associated with increased NMDA receptor-mediated production of O(2).     

Summary of the 2000 Surgeon General's listening session: toward a national action plan on overweight and obesity

OBJECTIVE: To provide insight into discussions at the Surgeon General's Listening Session, "Toward a National Action Plan on Overweight and Obesity," and to complement The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. RESEARCH METHODS AND PROCEDURES: On December 7 and 8, 2000, representatives from federal, state, academic, and private sectors attended the Surgeon General's Listening Session and were given an opportunity to recommend what to include in a national plan to address overweight and obesity. The public was invited to comment during a corresponding public comment period. The Surgeon General's Listening Session was also broadcast on the Internet, allowing others to view the deliberations live or access the archived files. Significant discussion points from the Listening Session have been reviewed by representatives of the federal agencies and are the basis of this complementary document. RESULTS: Examples of issues, strategies, and barriers to change are discussed within five thematic areas: schools, health care, family and community, worksite, and media. Suggested cooperative or collaborative actions for preventing and decreasing overweight and obesity are described. An annotated list of some programmatic partnerships is included. DISCUSSION: The Surgeon General's Listening Session provided an opportunity for representatives from family and community groups, schools, the media, the health-care environment, and worksites to become partners and to unite around the common goal of preventing and decreasing overweight and obesity. The combination of approaches from these perspectives offers a rich resource of opportunity to combat the public health epidemic of overweight and obesity.     

Evolutionary health promotion

Health promotion's promise is enormous, but its potential is, as yet, unmatched by accomplishment. Life expectancy increases track more closely with economic prosperity and sanitary engineering than with strictly medical advances. Notable achievements in the past century--the decreased incidences of epidemic infections, dental caries, and stomach cancer--are owed to virologists, dentists, and (probably) refrigeration more than to physicians. Prevention speaks against tobacco abuse with a single voice, but in many other areas contradictory research findings have generated skepticism and even indifference among the general public for whom recommendations are targeted. Health promotion's shortcomings may reflect lack of an overall conceptual framework, a deficiency that might be corrected by adopting evolutionary premises: (1) The human genome was selected in past environments far different from those of the present. (2) Cultural evolution now proceeds too rapidly for genetic accommodation--resulting in dissociation between our genes and our lives. (3) This mismatch between biology and lifestyle fosters development of degenerative diseases. These principles could inform a research agenda and, ultimately, public policy: (1) Better characterize differences between ancient and modern life patterns. (2) Identify which of these affect the development of disease. (3) Integrate epidemiological, mechanistic, and genetic data with evolutionary principles to create an overarching formulation upon which to base persuasive, consistent, and effective recommendations.     

A comparison of thermal injury, healing patterns, and postoperative adhesion formation following CO2 laser and electromicrosurgery

To further define the role of CO2 laser in infertility surgery, the authors compared the immediate tissue damage and the subsequent healing patterns that followed the randomized use of CO2 laser and electrocautery on opposite sides of the reproductive tracts of 20 mature, female rabbits. Blind histopathologic evaluations were performed on the ovarian and uterine tissues immediately to compare the extent of the acute thermal damage, and 4 weeks postoperatively to compare the healing patterns. There were no differences in the depth of thermal damage, extent of collagen deposition, or in postoperative adhesion formation between CO2 laser and electrocautery. However, the mean depth of the acute thermal damage was significantly less on the ovary than on the uterus, and the area of fibrosis was significantly less when the incised uterine surfaces were approximated.     

Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis

We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal (GABHS) pharyngitis in 260 children. After a throat culture had been obtained, each child was evaluated for the presence of predetermined signs and symptoms, and was then randomized in a double-blind manner to receive penicillin V, cefadroxil, or placebo. Of the 194 children with throat cultures positive for GABHS, 68 received penicillin V, 70 received cefadroxil, and 56 received placebo. Approximately 18 to 24 hours later, each patient returned for reevaluation. Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo. In addition, the evaluating physician, parents, and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement.