Crises and Turnaround Management: Lessons Learned from Recovery of New Orleans and Tulane University Following Hurricane Katrina.

By their very nature both man-made and natural disasters are unpredictable, and so we recommend that all health-care institutions be prepared. In this paper, the authors describe and make a number of recommendations, regarding the importance of crisis and turnaround management using as a model the New Orleans public health system and Tulane University Medical School post-Hurricane Katrina. Leadership skills, articulation of vision, nimble decision making, and teamwork are all crucial elements of a successful recovery from disaster. The leadership team demonstrated courage, integrity, entrepreneurship, and vision. As a result, it led to a different approach to public health and the introduction of new and innovative medical education and research programs.

The "for-benefit" academic medical center: a solution for survival.

Academic medical centers (AMCs) are the backbone of the U.S. health care system. They provide a disproportionate share of charity care and serve as a training ground for future physicians. Yet, AMCs face profound economic challenges, from changes in funding to changes in the health care market. To survive, many AMCs will need to form integrated health systems, a process expected to cost tens, if not hundreds, of millions of dollars. Nearly all AMCs are structured as not-for- profit entities, which places restrictions on their ability to forge partnerships, pursue joint ventures, and access private capital, often essential elements for forming such integrated systems. An alternative model known as the "for-benefit" corporation can allow AMCs to retain their important social mission and the other advantages of their not-for-profit status while allowing them flexibility and access to both investment and philanthropic capital. To pursue the for-benefit pathway, AMCs have two options-either they could work within the constraints of existing laws to restructure themselves as for-benefit entities, or they could create, under federal law, a new for-benefit AMC model, allowing for the orderly conversion of not-for-profit AMCs. Essential components of a for-benefit AMC include a social purpose, access to multiple forms of capital, the use of earnings to support its purpose, transparency, aligned compensation, and tax exemptions. Restructuring an AMC as a for-benefit entity enables it to both advance shareholder value and further the public good.

A case for change: disruption in academic medicine.

Disruptive technologies allow less expensive and more efficient processes to eventually dominate a market sector. The academic health center's tripartite mission of education, clinical care, and research is threatened by decreasing revenues and increasing expenses and is, as a result, ripe for disruption. The authors describe current disruptive technologies that threaten traditional operations at academic health centers and provide a prescription not only to survive, but also to prosper, in the face of disruptive forces.

Light-scattering spectroscopy differentiates fetal from adult nucleated red blood cells: may lead to noninvasive prenatal diagnosis.

Present techniques for prenatal diagnosis are invasive and present significant risks of fetal loss. Noninvasive prenatal diagnosis utilizing fetal nucleated red blood cells (fNRBC) circulating in maternal peripheral blood has received attention, since it poses no risk to the fetus. However, because of the failure to find broadly applicable identifiers that can differentiate fetal from adult NRBC, reliable detection of viable fNRBC in amounts sufficient for clinical use remains a challenge. In this Letter we show that fNRBC light-scattering spectroscopic signatures may lead to a clinically useful method of minimally invasive prenatal genetic testing.

Medical school dean as a turnaround agent.

Taking on the role as a new medical school Dean in a new city after Hurricane Katrina posed many challenges. To facilitate turnaround, 3 principles were applied: hit the ground running, promote community involvement, and gain a common vision for the future. This article describes Tulane University's process for implementing change and expands on its vision for the future.

Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia?

OBJECTIVE: Twin pregnancies are a risk factor for preeclampsia with a reported incidence of 2-3 times higher than singleton pregnancies. Soluble fms-like tyrosine kinase 1 (sFlt1), which is a circulating antiangiogenic molecule of placental origin, plays a central role in preeclampsia by antagonizing placental growth factor (PlGF) and vascular endothelial growth factor signaling in the maternal vasculature. Increased sFlt1 and the ratio sFlt1/free PlGF have been shown to antedate clinical signs in preeclampsia. Although the cause of the upregulated sFlt1 in preeclampsia still is not understood clearly, placental ischemia with accompanying hypoxia is thought to play an important role. We therefore hypothesized that the higher risk of preeclampsia in twin pregnancies results from high sFlt1 (or sFlt1/PlGF) and that the sFlt1 upregulation was due to either relative placental hypoxia and/or increased placental mass. STUDY DESIGN: Maternal serum samples and placentas from third-trimester twin and singleton pregnancies without preeclampsia were used. Serum samples were analyzed for levels of sFlt1 and free PlGF by enzyme-linked immunosorbent assay and reported as means (in nanograms per milliliter and picograms per milliliter, respectively). Placentas were weighed and examined for content of sFlt1 and PlGF messenger RNA (mRNA) by quantitative polymerase chain reaction and hypoxia inducible factor-1alpha (HIF-1alpha) protein by Western blot. RESULTS: Soluble Flt1 concentrations in twin pregnancy maternal serum were 2.2 times higher than those that were measured in singleton pregnancy maternal serum samples (30.98 +/- 9.78 ng/mL vs 14.14 +/- 9.35 ng/mL, respectively; P = .001). Free PlGF concentrations were not significantly different between twin and singleton maternal serum samples, but the mean sFlt1/PlGF ratio of twin pregnancy maternal serum samples was 2.2 times higher than the equivalent ratio in singleton pregnancy samples (197.58 +/- 126.86 ng/mL vs 89.91 +/- 70.63 ng/mL, respectively; P = .029). Quantitative polymerase chain reaction for sFlt1 and PlGF mRNA revealed no significant differences between the 2 study groups. Western blot analysis of placental samples for HIF-1alpha revealed a mean ratio HIF-1alpha/actin of 0.53 vs 0.87, for the twins vs singletons placental samples respectively (twins showed lower HIF-1alpha, not higher). The mean weights of twin and singleton placentas were 1246 vs 716 g, respectively (P < .001). Importantly, the placental weights correlated very well with the circulating sFlt1 levels (R(2) = .75). CONCLUSION: In twin pregnancies, circulating sFlt1 levels and sFlt1/PlGF ratios were twice as high as those in singleton pregnancies. The increased serum sFlt1 levels in twin pregnancies were not accompanied by any changes in the levels of sFlt1 mRNA and HIF-1alpha protein in the twin placentas but were correlated with increased placental weight. These findings suggest that the increased risk of preeclampsia in twin pregnancies may be due to increased placental mass that leads to increased circulating levels of sFlt1.

Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels.

This article reports the development of an optical imaging technique, confocal light absorption and scattering spectroscopic (CLASS) microscopy, capable of noninvasively determining the dimensions and other physical properties of single subcellular organelles. CLASS microscopy combines the principles of light-scattering spectroscopy (LSS) with confocal microscopy. LSS is an optical technique that relates the spectroscopic properties of light elastically scattered by small particles to their size, refractive index, and shape. The multispectral nature of LSS enables it to measure internal cell structures much smaller than the diffraction limit without damaging the cell or requiring exogenous markers, which could affect cell function. Scanning the confocal volume across the sample creates an image. CLASS microscopy approaches the accuracy of electron microscopy but is nondestructive and does not require the contrast agents common to optical microscopy. It provides unique capabilities to study functions of viable cells, which are beyond the capabilities of other techniques.

Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy.

OBJECTIVE: The objective of this pilot study was to evaluate the clinical utility of soluble fms-like tyrosine kinase 1 (sFlt 1) and soluble endoglin (sEng) in the differential diagnosis of hypertension in late pregnancy. STUDY DESIGN: We analyzed serum levels of sFlt 1 and sEng in women with gestational hypertension (GHTN; n = 17), chronic hypertension (CHTN; n = 19), preeclampsia (n = 19), and normal pregnancy (n = 20) in the third trimester. We calculated the sensitivity, specificity, and positive and negative likelihood ratio (LR) for each factor in diagnosing preeclampsia. RESULTS: The sensitivity and specificity of sFlt 1 in differentiating preeclampsia from normal pregnancy were 90% and 90%, respectively, and 90% and 95% for sEng. In women with GHTN, they were 79% and 88% for sFlt 1; 84% and 88% for sEng; 90% and 63% for uric acid. In women with CHTN, they were 84% and 95% for sFlt 1; 84% and 79% for sEng; 68%; and 78% for uric acid. The positive LR for preeclampsia was 9 for sFlt 1 and 7 for sEng in women with normal pregnancy; in women with GHTN; 6.7 for sFlt 1 and 7.2 for sEng; in CHTN, 16 for sFlt 1 and 4 for sEng. Serum uric acid had a positive LR of only 2.4 in women with GHTN and 3.1 in women with CHTN. CONCLUSION: Both sFlt 1 and sEng may prove useful in differentiating preeclampsia from other hypertensive diseases of pregnancy. A prospective cohort study should be performed determine the clinical utility of measuring these proteins.

Effects of teamwork training on adverse outcomes and process of care in labor and delivery: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of teamwork training on the occurrence of adverse outcomes and process of care in labor and delivery. METHODS: A cluster-randomized controlled trial was conducted at seven intervention and eight control hospitals. The intervention was a standardized teamwork training curriculum based on crew resource management that emphasized communication and team structure. The primary outcome was the proportion of deliveries at 20 weeks or more of gestation in which one or more adverse maternal or neonatal outcomes or both occurred (Adverse Outcome Index). Additional outcomes included 11 clinical process measures. RESULTS: A total of 1,307 personnel were trained and 28,536 deliveries analyzed. At baseline, there were no differences in demographic or delivery characteristics between the groups. The mean Adverse Outcome Index prevalence was similar in the control and intervention groups, both at baseline and after implementation of teamwork training (9.4% versus 9.0% and 7.2% versus 8.3%, respectively). The intracluster correlation coefficient was 0.015, with a resultant wide confidence interval for the difference in mean Adverse Outcome Index between groups (-5.6% to 3.2%). One process measure, the time from the decision to perform an immediate cesarean delivery to the incision, differed significantly after team training (33.3 minutes versus 21.2 minutes, P=.03). CONCLUSION: Training, as was conducted and implemented, did not transfer to a detectable impact in this study. The Adverse Outcome Index could be an important tool for comparing obstetric outcomes within and between institutions to help guide quality improvement. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT00381056 LEVEL OF EVIDENCE: I.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

BACKGROUND: Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in the pathogenesis of preeclampsia. Since soluble endoglin, another antiangiogenic protein, acts together with sFlt1 to induce a severe preeclampsia-like syndrome in pregnant rats, we examined whether it is associated with preeclampsia in women. METHODS: We performed a nested case-control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial. The study included all 72 women who had preterm preeclampsia (<37 weeks), as well as 480 randomly selected women--120 women with preeclampsia at term (at > or =37 weeks), 120 women with gestational hypertension, 120 normotensive women who delivered infants who were small for gestational age, and 120 normotensive controls who delivered infants who were not small for gestational age. RESULTS: Circulating soluble endoglin levels increased markedly beginning 2 to 3 months before the onset of preeclampsia. After the onset of clinical disease, the mean serum level in women with preterm preeclampsia was 46.4 ng per milliliter, as compared with 9.8 ng per milliliter in controls (P<0.001). The mean serum level in women with preeclampsia at term was 31.0 ng per milliliter, as compared with 13.3 ng per milliliter in controls (P<0.001). Beginning at 17 weeks through 20 weeks of gestation, soluble endoglin levels were significantly higher in women in whom preterm preeclampsia later developed than in controls (10.2 ng per milliliter vs. 5.8 ng per milliliter, P<0.001), and at 25 through 28 weeks of gestation, the levels were significantly higher in women in whom term preeclampsia developed than in controls (8.5 ng per milliliter vs. 5.9 ng per milliliter, P<0.001). An increased level of soluble endoglin was usually accompanied by an increased ratio of sFlt1:PlGF. The risk of preeclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone. CONCLUSIONS: Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia.

Circulating angiogenic proteins in trisomy 13.

OBJECTIVE: Women who are carrying a trisomy 13 fetus are more prone to develop preeclampsia. Excess circulating soluble fms-like tyrosine kinase-1 has been implicated recently in the pathogenesis of preeclampsia. Since the fms-like tyrosine kinase-1/soluble fms-like tyrosine kinase-1 gene is located on chromosome 13q12, we hypothesized that the extra copy of this gene in trisomy 13 may lead to excess circulating soluble fms-like tyrosine kinase-1, reduced free placental growth factor level, and increased soluble fms-like tyrosine kinase-1/placental growth factor ratio. This may then contribute to the increased risk of preeclampsia that has been observed in these patients. Our objective was to characterize the maternal circulating angiogenic proteins in trisomy 13 pregnancies. STUDY DESIGN: Maternal serum samples of trisomy 13, 18, 21 and normal karyotype pregnancies were obtained from first and second trimester screening programs. We chose 17 cases of trisomy 13 that were matched for maternal age, freezer storage time, and parity with 85 normal karyotype control samples. Additionally, 20 cases of trisomy 18 and 17 cases of trisomy 21 were included. Cases and control samples were assayed for levels of soluble fms-like tyrosine kinase-1 and placental growth factor by enzyme-linked immunosorbent assay in a blinded fashion. Because of the skewed distributions of soluble fms-like tyrosine kinase-1 and placental growth factor, nonparametric analytic techniques were used, and the results are reported as median and ranges. RESULTS: In early pregnancy trisomy 13 cases and control samples, the median circulating soluble fms-like tyrosine kinase-1/placental growth factor ratios were 17.0 (range, 1.2-61.3) and 6.7 (range, 0.8-62.9), respectively (P = .003). The median soluble fms-like tyrosine kinase-1/placental growth factor ratios in trisomy 18 and 21 were 4.8 (range, 0.9-53.9) and 5.1 (range, 1.0-18.1), which were not significantly different than the control samples. Furthermore, the differences between trisomy 13 and control samples were more pronounced in the second trimester specimens than in the specimens from the first trimester. CONCLUSION: These data suggest that alterations in circulating angiogenic factors may be involved intimately in the pathogenesis of preeclampsia in trisomy 13. A larger clinical study that measures these factors longitudinally and correlates them with pregnancy outcomes is needed to further establish the link between trisomy 13, altered angiogenic factors, and preeclampsia.

Recent advances in understanding of preeclampsia.

Despite intensive research, preeclampsia still accounts for significant morbidity and mortality for the mother and the neonate, especially in developing countries. Recent studies have suggested that excess secretion of a naturally occurring anti-angiogenic molecule of placental origin referred to as soluble fms-like tyrosine kinase-1 (sFlt-1, also referred to as sVEGFR-1) may contribute to the pathogenesis of preeclampsia. sFlt-1 acts by antagonizing two pro-angiogenic molecules - vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Abnormalities in the angiogenic balance have been proposed as having a major role in the molecular cascade leading to proteinuria, hypertension, and endothelial dysfunction. Further evidence supports the hypothesis that angiogenic balance is crucial to differentiation and invasion of cytotrophoblasts. The abnormal placentation and the accompanying hypoxia may, in turn, result in more sFlt-1 production, thus leading to a vicious cycle of sFlt-1 production, eventually causing preeclampsia. These recent discoveries may facilitate the development of novel strategies for the diagnosis and therapy of preeclampsia.

Vaginal birth after cesarean delivery: practice patterns of obstetrician-gynecologists.

OBJECTIVE: To assess obstetrician-gynecologists' current practice patterns and opinions regarding vaginal birth after cesarean delivery (VBAC). STUDY DESIGN: Questionnaires were mailed to a random sample of 1,200 American College of Obstetricians and Gynecologists (ACOG) fellows in July 2003. Information was gathered on percentage of cesarean and VBAC deliveries performed, factors influencing changes in these rates in the past 5 years, hospital protocol regarding VBAC and factors influencing the recommendation of VBAC. RESULTS: Fifty-three percent of questionnaires were returned to ACOG after 3 mailings. Approximately 49% of respondents reported that they were performing more cesarean deliveries than they were 5 years earlier. The primary reasons for this increase were the risk of liability and patient preference for delivery method. More than 25% of physicians reported that they practiced in hospitals that do not follow the ACOG guidelines with respect to resources and immediate availability. Almost all (98.2%) respondents agreed that they knew the risks and benefits of VBAC. However, only 61% reported feeling competent in determining which patients will have a successful VBAC. CONCLUSION: Obstetrician-gynecologists seem to be aware of the risks and benefits of VBAC; however, there is some doubt as to who should be offered a trial of labor and what predicts a successful VBAC.

Urinary placental growth factor and risk of preeclampsia.

CONTEXT: Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth factor (PlGF), a proangiogenic protein, predict subsequent development of preeclampsia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too large a molecule to be filtered into the urine, while PlGF is readily filtered. OBJECTIVE: To test the hypothesis that urinary PlGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preeclampsia. DESIGN, SETTING, AND PATIENTS: Nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US university medical centers during 1992-1995. Each woman with preeclampsia was matched to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at -70 degrees C. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens obtained before labor. MAIN OUTCOME MEASURE: Cross-sectional urinary PlGF concentrations, before and after normalization for urinary creatinine. RESULTS: Among normotensive controls, urinary PlGF increased during the first 2 trimesters, peaked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of preeclampsia the pattern of urinary PlGF was similar, but levels were significantly reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the disease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PlGF in women with preeclampsia was 32 pg/mL, compared with 234 pg/mL in controls with fetuses of similar gestational age (P<.001). The adjusted odds ratio for the risk of preeclampsia to begin before 37 weeks of gestation for specimens obtained at 21 to 32 weeks, which were in the lowest quartile of control PlGF concentrations (<118 pg/mL), compared with all other quartiles, was 22.5 (95% confidence interval, 7.4-67.8). CONCLUSION: Decreased urinary PlGF at mid gestation is strongly associated with subsequent early development of preeclampsia.

Circulating angiogenic factors and the risk of preeclampsia.

BACKGROUND: The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. METHODS: We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. RESULTS: During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. CONCLUSIONS: Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia.