One-star rating for a five-star program: evaluating 'Hospital Compare'.

OBJECTIVES: For healthcare systems of any size, it is important to minimize costs while maximizing outcomes. One idea of how to achieve these goals has been the reduction in hospital-related complications, including infection and surgical complications, among others. In the United States, policy makers recently adopted the 'Hospital Compare' program as a way to encourage consumers and improve hospitals. This article evaluates the effectiveness of this policy. STUDY DESIGN: This article uses an observed cohort study of most US hospitals across four different indices. METHODS: Each observed hospital was evaluated at least once each year over a span of three years for rates of hospital-acquired infections and compared to what reasonably ought to have been the rate based on hospital factors. Hospitals poorly rated in the base year were compared against remaining institutions for their ability to meet national benchmarks in future years. RESULTS: Despite government attempts to show individuals the comparative quality of hospitals, there is little evidence that these informed consumer choices were substantially enough to motivate changes. Across most metrics used, poorly rated hospitals were unlikely to improve at rates that the designers of Hospital Compare would have envisioned. CONCLUSIONS: Although it is possible that the effects could shift over time, it is unlikely that the Hospital Compare program properly understood and anticipated patient calculus for choosing a hospital. Technical complexity and other issues further undermined the program. Despite this, the goal of reducing complications is worthwhile, but a different strategy should be pursued.

Bone Abnormalities in Mice with Protein Kinase A (PKA) Defects Reveal a Role of Cyclic AMP Signaling in Bone Stromal Cell-Dependent Tumor Development.

Protein kinase A (PKA) is an important enzyme for all eukaryotic cells. PKA phosphorylates other proteins, thus, it is essential for the regulation of many diverse cellular functions, including cytoplasmic trafficking and signaling, organelle structure and mitochondrial oxidation, nuclear gene expression, the cell cycle, and cellular division. The PKA holoenzyme is composed of 2 regulatory and 2 catalytic subunits. Four regulatory (R1α, R1ß, R2α, and R2ß) and 4 catalytic subunits (Cα, Cß, Cγ, and Prkx) have been identified, giving rise to mainly PKA-I (when the 2 regulatory subunits are either R1α or R1ß), or PKA-II (when the 2 regulatory subunits are either R2α or R2ß). Mutations in the PKA subunits can lead to altered total PKA activity or abnormal PKA-I to PKA-II ratio, leading to various abnormalities in both humans and mice. These effects can be tissue-specific. We studied the effect of PKA subunit defects on PKA activity and bone morphology of mice that were single or double heterozygous for null alleles of the various PKA subunit genes. Bone lesions including fibrous dysplasia, myxomas, osteo-sarcomas, -chondromas and -chondrosarcomas were found in these mice. Observational and molecular studies showed that these lesions were derived from bone stromal cells (BSCs). We conclude that haploinsufficiency for different PKA subunit genes affected bone lesion formation, new bone generation, organization, and mineralization in variable ways. This work identified a PKA subunit- and activity-dependent pathway of bone lesion formation from BSCs with important implications for understanding how cyclic AMP affects the skeleton and its tumorigenesis.

Engineering Approaches for Understanding Osteogenesis: Hydrogels as Synthetic Bone Microenvironments.

The microenvironment, which can be considered the sum of all the components and conditions surrounding a particular cell, is critical to moderating cellular behavior. In bone, interactions with the microenvironment can influence osteogenic differentiation, and subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs, can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic polymer networks, are popularly used for cell culture constructs due to their substantial water content and their ability to be tailored for specific applications. As synthetic microenvironments, a level of control can be exerted on the hydrogel structure and material properties, such that individual contributions from the scaffold on cellular behavior can be observed. Both biochemical and mechanical stimuli have been shown to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive ligands, include osteoinductive moieties, vary mechanical properties, and be subject to external mechanical stimulation, all of which have been shown to affect osteogenic differentiation. Following "bottom-up" fabrication methods, levels of complexity can be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic bone microenvironments to observe both individual and synergistic effects from biochemical and mechanical signals on osteogenic differentiation. Ultimately, a better understanding of how material properties can influence cellular behavior will better inform design of tissue engineering scaffolds, not just for studying cell behavior, but also for regenerative medicine purposes.

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Acute massive pulmonary embolism in a Jehovah's witness: successful treatment with catheter thrombectomy.

A 71-year-old woman presented with an acute, massive pulmonary embolism. As a Jehovah's Witness, she was not willing to accept thrombolysis because of the potential risk of bleeding requiring blood transfusion. The patient was successfully treated with catheter thrombectomy, using rheolytic and fragmentation devices. (CHEST 2000; 117:594-597)

Unilateral absent pulmonary perfusion due to bronchogenic carcinoma.

Ventilation-perfusion lung scans are commonly done in the diagnosis of pulmonary thromboembolic disease. We describe a patient in whom absent perfusion involving an entire lung was due to bronchogenic carcinoma. Echocardiography and chest computed tomography were essential tests in evaluating a nonembolic etiology.

Early bronchoscopic diagnosis of concomitant tuberculosis and Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection.

Pulmonary infections, including mixed infections, are common in patients with human immunodeficiency virus (HIV), and a specific diagnosis is desirable to direct therapy. In a retrospective study of patients suspected of having Pneumocystis carinii pneumonia, we examined the usefulness of fiberoptic bronchoscopy in the immediate diagnosis of tuberculosis. In 267 patients, pneumocystis pneumonia was diagnosed in 115 (43%), of whom 5 (4%) also had concomitant tuberculosis. Bronchoalveolar lavage gave an immediate diagnosis of tuberculosis by positive acid-fast bacilli stain in 3 patients, while the transbronchial biopsy was suggestive in a fourth. Four of these patients developed respiratory failure, and 2 died. In patients with pneumocystis pneumonia, respiratory failure was significantly more common in those with tuberculosis (P = .0077). In 156 (58%) of the 267 cases, bronchoalveolar lavage was negative for pneumocystis pneumonia, while tuberculosis was diagnosed in 14 (9%), and an immediate diagnosis was made in 10 (71%). In a series of HIV-infected patients suspected mainly of having pneumocystis pneumonia, tuberculosis was found instead in 19 (7%), and both diseases were present in 5 (2%). Bronchoscopy provided an early diagnosis of tuberculosis in 63%. Patients with concomitant pneumocystis pneumonia and tuberculosis had a high rate of respiratory failure.

Pressure measurements in the normal and occluded rabbit maxillary sinus.

Occlusion of the maxillary ostium is considered to be a key factor in the pathogenesis of maxillary sinusitis. In this study, the authors determined the effect of ostial occlusion on pressure in the rabbit maxillary sinus which, like most humans, has only one ostium. We compared pressures in the normal and occluded maxillary sinus and the nasal cavity during spontaneous breathing in anesthetized adult animals. Serial pressure measurements were obtained from sinuses with patent ostia in nasal-breathing rabbits and with occluded ostia in both nasal-breathing and tracheotomized animals. Sinuses with patent ostia showed pressure curves synchronous with the respiratory cycle. Inspiratory and expiratory pressures in the nasal cavity and the sinus were isobaric. Sinuses with occluded ostia initially developed a positive pressure followed by a negative pressure that reached a subatmospheric plateau of -28.2 +/- 7.3 mm H2O (mean +/- standard deviation [SD]) within 20 to 50 minutes. This is the first quantitative study of sinus pressures using the rabbit as an animal model. The findings may contribute to a better understanding of the role of ostial occlusion in the pathogenesis of maxillary sinusitis in humans.

Respiratory failure in pregnancy due to Pneumocystis carinii: report of a successful outcome.

BACKGROUND: The incidence of infection with the human immunodeficiency virus (HIV) is rising rapidly among women of reproductive age. Pneumocystis carinii pneumonia during pregnancy may be the first manifestation of HIV infection. If respiratory failure ensures, the outcome has been reported as almost invariably fatal. CASE: A 31-year-old African-American woman at 28 weeks' gestation was admitted with bilateral perihilar interstitial infiltrates. Laboratory evaluation revealed hypoxemia and an elevated serum lactic dehydrogenase level. Although she denied risk factors for HIV infection, she was treated immediately for P carinii infection with trimethoprim-sulfamethoxazole and methylprednisolone. Her respiratory status deteriorated and she required intubation. Bronchoscopy confirmed the diagnosis, and CD4 lymphocyte depletion confirmed immunosuppression. The patient responded to treatment and recovered completely. CONCLUSION: A high index of suspicion must be maintained for the diagnosis of P carinii and previously unsuspected HIV infection during pregnancy. The early manifestations may be subtle and progress over weeks until respiratory failure rapidly ensues. With timely diagnosis and management, the outcome of P carinii pneumonia in pregnancy can be successful.

Changes in hepatocyte NADH fluorescence during prolonged hypoxia.

Deprivation of oxygen reduces oxidative phosphorylation and rapidly causes an increase in cellular NADH which can be monitored by fluorimetry. Previous studies have established that increases in NADH fluorescence accurately reflect the impairment in oxidative phosphorylation which occurs during brief periods of acute hypoxia. However, the potential usefulness of fluorimetry for following longer, clinically relevant periods of ischemia has not been explored. We studied changes in NADH fluorescence in rat hepatocyte suspensions and in isolated-buffer-perfused rat livers during hypoxia (pO2 < 50 mm Hg) for periods as long as 180 min. NADH fluorescence of hepatocyte suspensions consistently increased by about 15% after 13 to 15 min of hypoxia and coincided with a marked decrease in tissue ATP levels. Reoxygenation after 15 or 30 min of hypoxia resulted in recovery of ATP and NADH with minimal loss of viability, as measured by trypan blue exclusion. After 60 to 180 min hypoxia, the initial increase in NADH fluorescence was followed by a progressive, irreversible decline which correlated with decreased cell viability. Similar changes in NADH fluorescence were observed in isolated-perfused rat livers in which NADH fluorescence was monitored at the liver surface with a fiberoptic probe. Hypoxia for 30 min had no effect on NADH fluorescence, but hypoxia for longer periods caused a steady increase in fluorescence after 45-60 min. When hypoxia was prolonged (120 or 180 min), fluorescence peaked after 60-75 min and then declined progressively to levels below baseline. The greatest decrease in fluorescence was seen after 180 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhodococcus equi endobronchial mass with lung abscess in a patient with AIDS.

An endobronchial lesion with lung abscess in a patient with AIDS was due to Rhodococcus equi. The patient responded to triple chemotherapy.

Use of a chlorhexidine dressing to reduce microbial colonization of epidural catheters.

We performed a prospective randomized controlled trial to assess the efficacy of a chlorhexidine dressing in reducing the microbial flora at the insertion site of epidural catheters. These catheters were used for acute pain management and were dressed either by a standardized method or with a CHX/urethane sponge composite. Microbial colonization of the catheter developed in 9 of 31 controls (29.0%) and 1 of 26 (3.8%) catheters with the CHX dressing (P less than 0.05%). The CHX dressing caused no adverse effects. The data suggest that delivery of antiseptic to the catheter wound site reduces catheter colonization with a possible reduction in the risk of epidural catheter-related infection.

An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial.

PURPOSE: Percutaneously inserted central venous catheters are widely used. Catheter-related bacteremia or fungemia is the most frequent serious complication of these catheters. In an attempt to reduce the frequency of such infections, a subcutaneous cuff constructed of a biodegradable collagen matrix impregnated with bactericidal silver was developed. Our goal was to assess, in a multicenter clinical trial, the effectiveness of this cuff in preventing catheter-related infection. MATERIALS AND METHODS: Central venous catheters needed for fluid or drug therapy, hemodynamic monitoring, or hyperalimentation in patients in three centers were randomly assigned to be inserted with or without the cuff. Patients and catheters in the two groups were comparable in terms of risk factors predisposing to infection, including colonization of skin about the insertion site. RESULTS: The results with 234 catheters inserted into a new site showed that catheters inserted with the cuff were threefold less likely to be colonized on removal (more than 15 colony-forming units) than were control catheters (28.9 percent versus 9.1 percent, p = 0.002) and were nearly fourfold less likely to produce bacteremia (3.7 percent versus 1.0 percent). Adverse effects from the cuff were not seen. The cuff did not confer protection, however against infection with catheters inserted over a guidewire into old sites. Most of the catheter-related infections identified in this study, including four of the six bacteremias, appear to have been caused by microorganisms colonizing skin about the insertion site, affirming the pathogenetic basis for benefit seen with the cuff in this clinical trial; two may have derived from contamination of the catheter hub. CONCLUSION: This novel, silver-impregnated, attachable cuff can substantially reduce the incidence of catheter-related infection with most percutaneously inserted central venous catheters, can extend the time catheters can be left in place safely, and can prove cost-beneficial.

Leukotriene D4 increases extravascular lung water in the dog.

The peptide leukotrienes have been detected in animals that have received endotoxin injections and also have been associated with patients suffering from the adult respiratory distress syndrome (ARDS). The ability of leukotriene D4 (LTD4) to cause pulmonary capillary permeability changes was investigated in ten anesthetized mongrel dogs. Four dogs were used as controls and six dogs received intravenous LTD4 (0.25 microgram/kg). There was a variable response in that two treated animals showed no apparent effect of LTD4. Analysis of the results from the remaining four treated animals demonstrated a significant increase in extravascular lung water (EVLW) that peaked 3 hr after LTD4 from 5.4 +/- 0.6 to 10.3 +/- 0.5 ml/kg (P less than .01). In these four dogs, EVLW increased before slight, but statistically significant, rises in pulmonary artery wedge pressure (4 +/- 1 to 9 +/- 1 mm Hg, P less than .01) and mean pulmonary artery pressure (13 +/- 1 to 17 +/- 1 mm Hg, P less than .01) occurred. During the same period, cardiac output decreased 56 +/- 7% (P less than .01), but no change in airway resistance was observed. This study is the first in vivo demonstration that LTD4 directly alters pulmonary fluid balance in the dog. We conclude LTD4 can cause increases in EVLW and may be an important mediator of the permeability changes observed in various clinical events that lead to the adult respiratory distress syndrome.

Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.