Impact of commercial over-reimbursement on hospitals: the curious case of central Indiana.

An employer coalition in Indiana sponsored a study by the Rand Corporation examining commercial insurer payments as a percent of Medicare. The employers sought to understand why their health care costs were high and increasing. The study showed that, on average, their insurer was paying three times what Medicare pays for the same services. In this, a follow-up study, we demonstrate that these high payments resulted in very high profit margins for central Indiana's major health systems, along with elevated costs and poor performance on key efficiency measures. We also see indications that hospitals appear to be using aggressive revenue cycle management techniques. The paper concludes with a discussion of policy issues.

Pitfalls in Serological Diagnosis of Cryptococcus gattii Infections.

The detection of cryptococcal antigen by latex agglutination tests (LATs), enzyme-linked immunoassays (ELISA), or lateral flow assay (LFA) is an important tool for diagnosis of a Cryptococcus infection. Cerebrospinal fluid and/or serum samples of 10 patients with cryptococcosis due to Cryptococcus gattii or a hybrid of Cryptococcus neoformans and C. gattii were examined by three LATs (the IMMY Latex-Crypto(®) test, the Pastorex(TM) Crypto Plus, and the Remel Cryptococcus Antigen Test Kit) and the LFA made by Immuno-Mycologics. LATs based on monoclonal antibodies (mAbs) like the Pastorex(TM) Crypto Plus or the Remel Cryptococcus Antigen Test Kit turned out to have an insufficient sensitivity to detect four out of 10 C. gattii infections, including one infection by a hybrid between C. gattii and C. neoformans. Reflecting the ongoing expansion of C. gattii in geographical zones outside of tropical and subtropical areas like Mediterranean countries, Vancouver Island (British Columbia, Canada) and the Pacific Northwest region (USA), these findings are alarming because of the risk of delayed diagnosis of infections caused by C. gattii. Therefore, the preliminary serological screening for cryptococcal antigen in the case of a suspected Cryptococcus infection should be performed by using an assay with a broad range specificity and sensitivity for C. neoformans and C. gattii, including their hybrids.

Capacity, commitment, and culture: The 3 Cs of staff development in a learning organization.

TOPIC: If an agency desires changes in practice and a consistent approach to services, psychiatric rehabilitation staff development requires more than a single session of training. PURPOSE: This column describes one agency's approach to a comprehensive staff training and development program, designed to enhance the 3 Cs of capacity, commitment, and culture. SOURCES USED: The program described has been in place, with frequent adjustments, for over 20 years, and the experiences of the authors and their colleagues form the primary source for the paper. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Staff development requires an ongoing investment--competency-based training, supervision congruent with the service vision and mission, accountability through performance evaluation, and opportunities for growth. We have a firm belief that our employees learn to treat others, in part, from how they are treated by our agency leadership.

Cluster analysis of Scedosporium boydii infections in a single hospital.

Scedosporiosis is a rare, but often fatal mycotic infection occurring in immunosuppressed as well as in immunocompetent patients. Over a period of 14 months, Scedosporium boydii isolates were sent to our reference laboratory from six immunocompetent patients treated at a single hospital in Germany. In analogy to the EORTC/MSG criteria, four patients were classified as proven invasive scedosporiosis cases, and two patients as probable or possible cases. Of note, in five patients scedosporiosis was diagnosed between 1 and 14 months (median 5.0 months) after cardiac surgery. Despite antimycotic treatment two patients died, and three were lost for long-term follow-up. All clinical S. boydii isolates were characterized by molecular analysis using multilocus sequence typing (MLST). An identical MLST type was found in five patients who had been treated in the surgery unit, suggesting a link between these infections. The source of S. boydii has not been identified. Within an observation period of 2 years before and after this cluster of infections no further cases of scedosporiosis were reported from this hospital.

Promoting readiness for discharge for long-term state hospital residents.

OBJECTIVE: This project was designed to increase readiness for change for long-stay state hospital residents who were unwilling to move to the community. METHODS: Project staff designed customized strategies to build relationships, increase awareness of personal and environmental influences on deciding if, when, and where to relocate, and increase commitment to making a change. RESULTS: Of 10 participants, eight successfully relocated to the community in less than two years. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Readiness development strategies designed specifically for individuals can be effective in facilitating change. Staff expertise in readiness assessment and creativity in designing interventions, as well as staff commitment to this program, were critical to success.

Successful treatment of relapsing disseminated coccidioidomycosis with cutaneous involvement with posaconazole.

A 52-year-old woman with pulmonary sarcoidosis on immunosuppressive therapy developed pulmonary infiltrates and cutaneous granulomatous abscesses after a trip to the USA in April 2005. A hyphomycete was identified, further characterized by a gene probe as Coccidioides spp. and then definitively identified as Coccidioides posadasii by polymerase chain reaction and sequencing. Antibodies towards Coccidioides spp. were detected. The infection was successfully treated with posaconazole (Noxafil), 2 x 400 mg/d.

Re-identification of clinical isolates of the Pseudallescheria boydii-complex involved in near-drowning.

Fungal infections caused by the members of the genera Pseudallescheria and/or Scedosporium are important complications in patients after near-drowning. As the taxonomy of Pseudallescheria and Scedosporium has been revised, clinical isolates from 11 patients, after near-drowning, previously identified as P. boydii or S. apiospermum had to be re-identified. S. apiospermum, now separated from P. boydii as a distinct species, was found most frequently (n = 8), while S. aurantiacum, recently described as new species and P. boydii were less common (n = 2 and n = 1, respectively). Three patients near-drowned during the Tsunami 2004 were infected by different species of the P. boydii complex. In vitro testing resulted in lowest minimal inhibitory concentration (MICs) for voriconazole (range 0.25-2.0 microg ml(-1)).

Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin.

This is the first report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 microg/ml, independently from the species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different.

Hassallidin B--second antifungal member of the Hassallidin family.

The cyanobacterium Hassallia sp. produces a family of four compounds which exhibit a broad spectrum of antifungal activities. So far only one of these members has been isolated and its structure elucidated. In this study, we present a second member of this group. Mass spectrometry, one- and two-dimensional NMR and chiral GC-MS analysis revealed the same peptidic and fatty acid core for hassallidin B as the first member hassallidin A with an additional carbohydrate unit, a rhamnose attached to the 3-hydroxyl group of the C(14)-acyl side chain. The antifungal potential of hassallidin B is nearly identical to that of hassallidin A.

Validation of the 'Marburg bone bank system' for thermodisinfection of allogenic femoral head transplants using selected bacteria, fungi, and spores.

The Marburg Bone Bank System 'Lobator sd-2' is widely used to process human femoral heads removed during aseptic surgery by thermal disinfection. The inactivating capacity of the thermodisinfection system was validated in compliance with current standards using a newly developed femoral head model. The following micro-organisms, bacteria and fungi, taken from the American Type Culture Collection were investigated: Staphylococcus aureus, Staphyloccus epidermidis, Enterococcus faecium, Pseudomonas aeruginosa, Bacillus subtilis including spores, Clostridium sporogenes, Mycobacterium terrae, Candida albicans and Aspergillus niger spores. Highly enriched suspensions of these micro-organisms were applied to the centre of the femoral heads. The reduction in the number of micro-organisms was determined by counting the colony-forming units (cfu) before and after processing the spiked test device in the 'Lobator sd-2' system. Vegetative bacteria, fungi and fungal spores were completely inactivated (reduction factor >/=6 log(10)). The numbers of B. subtilis and C. sporogenes spores, both known to be heat-resistant, were reduced by one to two orders of magnitude. These bacteria serve as a model for spore forming pathogens which are not relevant in femoral heads from living donors. By processing human femoral heads from living donors by thermal disinfection using the Marburg Bone Banking system, a high level of safety is achieved regarding clinically relevant pathogens. To further increase the safety of the thermally treated femoral heads, we recommend that the medical history and present state of the donor, as well as the necessary serological tests should be taken into account.

Peracetic acid-ethanol treatment of allogeneic avital bone tissue transplants--a reliable sterilization method.

OBJECTIVES: Based on the European Standard EN 1040, the validation guidelines of the German Federal Institute for Drugs and Medical Devices and CPMP guidelines we tested the antimicrobial effectiveness of a peracetic acid-ethanol sterilization procedure (PES) in allogenic avital bone transplants. STUDY DESIGN: Delipidated human bone spongiosa cubes (15 x 15 x 15 mm) served as tissue. Three enveloped viruses (human immunodeficiency virus type 2, pseudorabies virus, bovine virus diarrhoea virus) and three non-enveloped viruses (hepatitis A virus, poliovirus, porcine parvovirus) were used. The reduction of virus infectivity was measured as TCID50/ml in neutralized supernatants and bone homogenates. Staphylococcus aureus. Enterococcus faecium, Pseudomonas aeruginosa. Bacillus subtilis. Clostridium sporogenes, Mycobacterium terrae. Candida albicans, Aspergillus niger as well as spores of Bacillus subtilis were tested additionally. PES led to a reduction of virus titres by more than 4 log10. Only HAV showed a reduction below 4 log10 (2.87) with residual infectivity. After including a delipidating step for HAV-infected cells, a reduction of over 7 log10 HAV titre was found. For viable bacteria, fungi and spores a titre reduction below the detection level (5 log10) was achieved after an incubation time of 2 hours. CONCLUSIONS: The peracetic acid-ethanol procedure proved to be a reliable method for the sterilization of human bone transplants (layer thickness < or = 15 mm). However, additional safety measures (anamnestic informations, infectious serology, HIV-/HBV-/HCV-PCR in case of multiorgan donors) should be taken.

Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors.

The hydroxypyridone ciclopirox olamine belongs to the antimycotic drugs used for the treatment of superficial mycoses. In contrast to the azoles and other antimycotic drugs, its specific mode of action is only poorly understood. To investigate the mode of action of ciclopirox olamine on fungal viability, pathogenicity, and drug resistance, we examined the expression patterns of 47 Candida albicans genes in cells grown in the presence of a subinhibitory concentration (0.6 micro g/ml) of ciclopirox olamine by reverse transcription-PCR. In addition, we used suppression-subtractive hybridization to further identify genes that are up-regulated in the presence of ciclopirox olamine. The expression of essential genes such as ACT1 was not significantly modified in cells exposed to ciclopirox olamine. Most putative and known virulence genes such as genes encoding secreted proteinases or lipases had no or only moderately reduced expression levels. In contrast, exposure of cells to ciclopirox olamine led to a distinct up- or down-regulation of genes encoding iron permeases or transporters (FTR1, FTR2, FTH1), a copper permease (CCC2), an iron reductase (CFL1), and a siderophore transporter (SIT1); these effects resembled those found under iron-limited conditions. Addition of FeCl(3) to ciclopirox olamine-treated cells reversed the effect of the drug. Addition of the iron chelator bipyridine to the growth medium induced similar patterns of expression of distinct iron-regulated genes (FTR1, FTR2). While serum-induced yeast-to-hyphal phase transition of C. albicans was not affected in ciclopirox olamine-treated cells in the presence of subinhibitory conditions, a dramatic increase in sensitivity to oxidative stress was noted, which may indicate the reduced activities of iron-containing gene products responsible for detoxification. Although the Candida drug resistance genes CDR1 and CDR2 were up-regulated, no change in resistance or increased tolerance could be observed even after an incubation period of 6 months. This was in contrast to control experiments with fluconazole, in which the MICs for cells incubated with this drug had noticeably increased after 2 months. These data support the view that the antifungal activity of ciclopirox olamine may at least be partially caused by iron limitation. Furthermore, neither the expression of certain multiple-drug resistance genes nor other resistance mechanisms caused C. albicans resistance to this drug even after long-term exposure.

Susceptibility testing of fungi--current status and open questions.

The increase of fungal infections and the improvement of therapeutical options demand reliable antifungal susceptibility testing. In vitro susceptibility testing of fungi--in contrast to bacteria--is not yet established as a routine method. The NCCIS (National Committee for Clinical Laboratory Standards) guidelines for susceptibility testing of yeasts (and proposed for hyphomycetes) are most important for standardization. Meanwhile, essential parts of this test procedure are accepted, but it should still be improved. The concept of using only one test medium for all drugs and test organisms is not realized so far. There are also some test situations that prevent the NCCLS standard from being applied. Based on our experience, this article describes the NCCLS methods and their modifications. It places emphasis on lipophilic drugs showing controversies despite standardization. Furthermore, the prediction of MICs on the clinical outcome is discussed. Since there are some pitfalls in testing antifungals, this should be done in experienced laboratories only. The MIC has to be regarded as only one, but an important, factor in the management of fungal diseases. Host-, drug-, and pathogen-specific data should be considered simultaneously.

Multicenter comparison of Fungitest for susceptibility testing of Candida species.

In four laboratories the reproducibility of Fungitest, a colorimetric breakpoint method for antifungal susceptibility testing, was examined. The interlaboratory agreement of test results from 50 Candida strains was dependent on the antifungal agents and ranged from 56% to 100%. Itraconazole showed the poorest, amphotericin B and flucytosine (100% and 96%, respectively) the highest concordance. When minor discrepancies were disregarded the agreement increased to 94% to 100% for all agents. In total, major discrepancies were only seen in 2.7%. The overall agreement between concordant results and the NCCLS standard method was high, ranging between 96.4% and 100%. Generally, sensitive strains showed a better agreement with Fungitest. Since the concordance in multisite studies with Fungitest will always depend on the isolates chosen, further studies with this test are necessary.

Adherence of different Candida dubliniensis isolates in the presence of fluconazole.

BACKGROUND: The recently described yeast species Candida dubliniensis is closely related to C. albicans and has been recovered predominantly from the oral cavities of HIV-infected individuals and AIDS patients who are often receiving fluconazole as prophylactic or therapeutic treatment for oropharyngeal candidiasis. Like C. albicans, C. dubliniensis secretes aspartic proteinases which in C. albicans have been shown to be involved in adherence. OBJECTIVE: To explain the increasing prevalence of C. dubliniensis in AIDS patients and to investigate the virulence factors of this yeast. METHODS: An in vitro assay was developed to compare the adherence to epithelial cells of C. dubliniensis from HIV-patients with that of C. albicans. RESULTS: All C. albicans isolates adhered better than the 22 C. dubliniensis isolates. In the presence of fluconazole, the C. dubliniensis isolates tested showed increased adherence as compared with controls without fluconazole. In contrast, all C. albicans isolates decreased in adherence to epithelial cells in the presence of fluconazole independently of their in vitro susceptibility to this drug. Proteinase antigens are present on the surface of C. dubliniensis cells adherent to epithelial target cells. In the presence of fluconazole this proteinase antigen was more strongly expressed. CONCLUSION: Increased adherence of C. dubliniensis strains in the presence of fluconazole could explain its high recovery rate from HIV-positive patients in recent years. The induction of proteinase secretion in the presence of fluconazole found for most of the C. dubliniensis isolates could be one of the factors involved in adherence.