The frequency and cost of treatment perceived to be futile in critical care.

IMPORTANCE: Physicians often perceive as futile intensive care interventions that prolong life without achieving an effect that the patient can appreciate as a benefit. The prevalence and cost of critical care perceived to be futile have not been prospectively quantified. OBJECTIVE: To quantify the prevalence and cost of treatment perceived to be futile in adult critical care. DESIGN, SETTING, AND PARTICIPANTS: To develop a common definition of futile care, we convened a focus group of clinicians who care for critically ill patients. On a daily basis for 3 months, we surveyed critical care specialists in 5 intensive care units (ICUs) at an academic health care system to identify patients whom the physicians believed were receiving futile treatment. Using a multivariate model, we identified patient and clinician characteristics associated with patients perceived to be receiving futile treatment. We estimated the total cost of futile treatment by summing the charges of each day of receiving perceived futile treatment and converting to costs. MAIN OUTCOME AND MEASURE: Prevalence of patients perceived to be receiving futile treatment. RESULTS: During a 3-month period, there were 6916 assessments by 36 critical care specialists of 1136 patients. Of these patients, 904 (80%) were never perceived to be receiving futile treatment, 98 (8.6%) were perceived as receiving probably futile treatment, 123 (11%) were perceived as receiving futile treatment, and 11 (1%) were perceived as receiving futile treatment only on the day they transitioned to palliative care. The patients with futile treatment assessments received 464 days of treatment perceived to be futile in critical care (range, 1-58 days), accounting for 6.7% of all assessed patient days in the 5 ICUs studied. Eighty-four of the 123 patients perceived as receiving futile treatment died before hospital discharge and 20 within 6 months of ICU care (6-month mortality rate of 85%), with survivors remaining in severely compromised health states. The cost of futile treatment in critical care was estimated at $2.6 million. CONCLUSIONS AND RELEVANCE: In 1 health system, treatment in critical care that is perceived to be futile is common and the cost is substantial.

The fetal cheek-to-cheek diameter and abdominal circumference: are they correlated?

OBJECTIVE: The cheek-to-cheek diameter (CCD) has been shown to be an indicator of subcutaneous tissue mass in the fetus. However, the correlation between CCD and the abdominal circumference (AC) has not been investigated yet. The objective of the present study was to demonstrate whether a correlation exists between fetal CCD, AC, estimated fetal weight (EFW), and the 1 h, 50 g, glucose challenge test (GCT) levels in patients with and without gestational diabetes mellitus. METHODS: A prospective, institutional review board approved study was performed. The CCD was obtained as part of the ultrasound for obstetric interval growth scans and biophysical profiles. Exams were performed during the third trimester. The CCD was obtained on a coronal view of the fetal face, at the level of the nostrils and lips. Patients were enrolled between November 2005 and May 2006. Pearson correlation coefficient and linear regression modeling were used as appropriate. RESULTS: Eighty-three patients were enrolled, 29 (33%) of them were diabetic. The mean gestational age is 34.8 +/- 3 weeks and the mean maternal age is 29.9 +/- 5.1. A significant linear association was found between CCD and EFW (Pearson coefficient of correlation being 0.51, P = 0.01). The Pearson correlation coefficient of the relationship between the CCD and AC was 0.47 (P = 0.01). Using a linear regression model, controlling for gestational age at performance of the ultrasound, the association between CCD and EFW remained significant (P = 0.021). There were no significant differences between diabetic and non-diabetic patients regarding the CCD (6.2 +/- 0.9 vs. 6.3 +/- 0.9 respectively, P = 0.669) or the EFW (2,527.9 +/- 705 vs. 2,645 +/- 760 g). While AC was significantly correlated with the GCT levels (Pearson coefficient of correlation = 0.46, P = 0.024), no such correlation was demonstrated for CCD (Pearson correlation coefficient = 0.23, P = 0.160). CONCLUSIONS: The cheek-to-cheek diameter is significantly correlated to the abdominal circumference and the estimated fetal weight. However, the abdominal circumference has a tighter correlation with the glucose challenge test.

Using Hoechst 33342 to target radioactivity to the cell nucleus.

We have explored the use of Hoechst 33342 (H33342) to carry radioactivity to the cell nucleus. H33342 enters cells and targets DNA at adenine-thymine-rich regions of the minor groove. Considerable membrane blebbing and ruffling occur in CHO cells within minutes after its addition to the culture medium in micromolar quantities. Blue vesicles are apparent in the cell cytoplasm, and by 30 min the nuclei are stained dark blue. Upon its binding to DNA, a visible emission shift of the dye can be observed with fluorescence microscopy. We have radioiodinated (125I) H33342 and specifically irradiated nuclear DNA by incubating CHO cells with 125I-H33342 at 37 degrees C and accumulating 125I decays at -90 degrees C. At various times, the cells are thawed and assayed for survival (clonogenicity) and DSB (gamma-H2AX) formation. 125I-H33342 decay leads to a monoexponential decrease in cell survival with a D0 of 122 125I decays per cell and a linear increase in DNA DSB induction (equivalent to 15 gamma-H2AX foci/cell). Cell death is not modified by the radioprotective effects of H33342 because we use considerably lower concentrations than those that provide a slight protection against gamma radiation. We conclude that cell killing by 125I-H33342 and the induction of gamma-H2AX foci are highly correlated.

FvVE1 regulates filamentous growth, the ratio of microconidia to macroconidia and cell wall formation in Fusarium verticillioides.

The velvet gene, veA, co-ordinates asexual and sexual development in the homothallic fungal species Aspergillus nidulans. Studies in Aspergillus parasiticus and Aspergillus fumigatus demonstrated that veA also regulates morphological differentiation in these species. Whether veA has the same role in morphogenesis in other fungal genera has not been investigated. In this work, we studied the role of the veA homologue, FvVE1, in the heterothallic fungus Fusarium verticillioides. Deletion of FvVE1 suppressed aerial hyphal growth and reduced colony surface hydrophobicity on solid media. In submerged cultures, FvVE1 deletion caused alterations in hyphal polarity, marked activation of conidiation and yeast-like growth. The latter was promoted by shaking to increase aeration of cultures. In addition, FvVE1 deletion markedly increased the ratio of macroconidia to microconidia. Supplementation of osmotic stabilizers restored the wild-type phenotype to deletion mutants, suggesting phenotypic alterations caused by FvVE1 deletion are related to cell wall defects. This is consistent with the hypersensitivity of FvVE1 deletion mutants to SDS and with the significant reduction in the mannoprotein content of mutants compared with the wild-type strain. However, no dramatic cell wall alterations were observed when mutants were examined by transmission electron microscopy. Our data strongly suggest that FvVE1 is important for cell wall integrity, cell surface hydrophobicity, hyphal polarity and conidiation pattern.