Optimization of decision support tool using medication regimens to assess rehospitalization risks.

BACKGROUND: Unnecessary hospital readmissions are costly for the U.S. health care system. An automated algorithm was developed to target this problem and proven to predict elderly patients at greater risk of rehospitalization based on their medication regimens. OBJECTIVE: Improve the algorithm for predicting elderly patients' risks for readmission by optimizing the sensitivity of its medication criteria. METHODS: Outcome and Assessment Information Set (OASIS) and medication data were reused from a study that defined and tested an algorithm for assessing rehospitalization risks of 911 patients from 15 Medicare-certified home health care agencies. Odds Ratio analyses, literature reviews and clinical judgments were used to adjust the scoring of patients' High Risk Medication Regimens (HRMRs). Receiver Operating Characteristic (ROC) analysis evaluated whether these adjustments improved the predictive strength of the algorithm's components. RESULTS: HRMR scores are composed of polypharmacy (number of drugs), potentially inappropriate medications (PIM) (drugs risky to the elderly), and Medication Regimen Complexity Index (MRCI) (complex dose forms, dose frequency, instructions or administration). Strongest ROC results for the HRMR components were Areas Under the Curve (AUC) of .68 for polypharmacy when excluding supplements; and .60 for PIM and .69 for MRCI using the original HRMR criteria. The "cut point" identifying MRCI scores as indicative of medication-related readmission risk was increased from 20 to 33. CONCLUSION: The automated algorithm can predict elderly patients at risk of hospital readmissions and its underlying criteria is improved by a modification to its polypharmacy definition and MRCI cut point.

Significance of new lung infiltrates in outpatients after lung and heart-lung transplantation.

BACKGROUND: Infection and rejection represent major complications following lung transplantation and are often associated with pulmonary infiltrates. The differential diagnosis of these infiltrates depends on their timing after transplantation. The aim of this study was to characterize lung transplant recipients (LTR) presenting with new pulmonary infiltrates. METHODS: A retrospective analysis of all LTR and heart-lung transplant recipients attending outpatient follow-up at our institution between September 1, 2006 and October 14, 2011 was performed. All patients presenting with new pulmonary infiltrates on chest x-ray who underwent bronchoscopy were included. RESULTS: A total of 913 patients accounted for 13,156 attendances, with 3,912 bronchoscopies being performed. Seventy-eight patients (9%) exhibited new pulmonary infiltrates and proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile range [IQR] 5-39) months after transplantation. Forty-eight patients (62%) were male, and median patient age was 47 (IQR 29-57) years. Subsequent investigation revealed pneumonia to be the underlying cause in 63 patients (81%). In the remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in 6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients. Overall 1-year survival in LTR presenting with new infiltrates was 97%, compared with 96% for all LTR attending our Outpatient Department. CONCLUSIONS: New pulmonary infiltrates occurring after the first month in LTR are most likely due to infection. Through prompt diagnosis and treatment, early mortality appears unaffected. Late mortality remains attributable to CLAD.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

Absence of indigenous specific West Nile virus antibodies in Tyrolean blood donors.

In the last several years, West Nile virus (WNV) was proven to be present especially in the neighboring countries of Austria, such as Italy, Hungary, and the Czech Republic, as well as in eastern parts of Austria, where it was detected in migratory and domestic birds. In summer 2010, infections with WNV were reported from Romania and northern Greece with about 150 diseased and increasingly fatal cases. We tested the sera of 1,607 blood donors from North Tyrol (Austria) and South Tyrol (Italy) for antibodies against WNV by using IgG enzyme-linked immunosorbent assay (ELISA). Initial results of the ELISA tests showed seroprevalence rates of 46.2% in North Tyrol and 0.5% in South Tyrol, which turned out to be false-positive cross-reactions with antibodies against tick-borne encephalitis virus (TBEV) by adjacent neutralization assays. These results indicate that seropositivity against WNV requires confirmation by neutralization assays, as cross-reactivity with TBEV is frequent and because, currently, WNV is not endemic in the study area.

Self-expanding metallic stent placement with laryngeal mask in lung transplant recipients.

BACKGROUND: Bronchial stent insertion is a suitable method to treat airway complications. We present our experience with laryngeal mask airway (LMA) for stent insertion in lung transplant (LT) recipients. METHODS: From April 2007 to March 2009, 27 LT recipients underwent insertion of self-expanding nitinol stents to manage airway complications after LT, using LMA for general anesthesia. All procedures were performed with flexible fiberoptic bronchoscopy without fluoroscopy; stent release was visualized with ultrathin bronchoscopes. We followed technical success, safety, improvement of lung function, and clinical symptoms. RESULTS: Forty-one stents were inserted in 27 patients in 32 sessions. The indications for stent insertion were necrotic lesions (7%) and obstructive lesions (90%). Technical success and safety were 94%. Twice, the stent dislocated, requiring replacements. In 91% of patients, postinterventional improvement in graft function (1 minute forced expiratory volume) was >10% after the intervention. Improvement of clinical symptoms was achieved in 94%. The median procedure time was 38 minutes (range, 30-85 minutes). CONCLUSIONS: LMA offered an excellent condition for stent insertion in LT recipients with airway complications. It provided adequate ventilation and safe airway control during the procedure. This technique may serve as alternative to established techniques using fluoroscopy and rigid bronchoscopy.

[Lung transplantation. Indications, long-term results and special impact of follow-up care]. / Lungentransplantation. Indikationen, Langzeitergebnisse und die besondere Bedeutung der Nachsorge.

Lung transplantation has been established as an appropriate ultimate treatment strategy in end-stage lung disease, when all conventional therapeutic options have been exhausted. A successful transplantation should result in an improved quality of life as well as an increase in life-expectancy for certain diseases (cystic fibrosis, pulmonary fibrosis and pulmonary hypertension). There is still a critical need regarding the number of available donor organs. Presently, one out of six patients dies on the waiting list. In order to identify suitable candidates for transplantation a number of criteria require consideration. These include the exact etiology of the pulmonary or cardiac disease, but also patient age, physical mobility, nutritional and muscular status as well as a comprehensive assessment to exclude significant extra-pulmonary co-morbidities. Complications arising after transplantation occur because of general perioperative risks, but also as a result of specific issues such as acute or chronic graft rejection, airway stenoses, infections of the newly immunosuppressed patient as well as a complete spectrum of secondary extra-pulmonary conditions. Comprehensive follow-up care in lung transplantation patients remains a vital issue. Analyses have shown a relevant improvement in long-term outcome, when follow-up care is delivered in cooperation with an established large volume transplant centre.

Are metallic stents really safe? A long-term analysis in lung transplant recipients.

Airway complications affect 20% of all lung transplant recipients. Self-expandable metallic stents (SEMS) are one treatment option but their use in benign airway disorders is controversial. We studies the long-term safety of SEMS in lung transplant recipients. Between January 1998 and February 2008, all lung transplant recipients with SEMS were analysed retrospectively at a single centre. Complications were recorded until September 2008. In 65 (9.2%) out of 706 recipients, 111 (91% noncovered) bronchial SEMS were implanted a median (range) 133 (55-903) days after lung transplantation; follow-up was 777 (7-3.655) days. Clinical improvement was noted in 80% of recipients. The forced expiratory volume in 1 s increased by (mean+/-SD) 21+/-33%. Most frequent early complications were migration (3%) and mucus plugging (11%). No procedure-related deaths were noted. Re-stenosis occurred in 34 (52%) out of 65 recipients 85 (7-629) days after insertion. In multivariate analysis, stent insertion before post-operative day 90 was independently associated with an increased risk of re-stenosis (HR 3.29, 95% CI 1.50-7.18; p = 0.003). In 40% of recipients, new bacterial airway colonisation occurred after SEMS insertion. In SEMS patients, 5-yr survival was significantly lower than in the total cohort (60% versus 76%; p = 0.02). Late complications in lung transplant recipients treated with SEMS are frequent. The major problems are re-stenosis and airway colonisation.

Indicators for steroid response in biopsy proven acute graft rejection after lung transplantation.

OBJECTIVE: Acute rejection (AR) after lung transplantation (LTx) requires prompt intervention. Most episodes respond to steroid pulse therapy. The aim of this study was to evaluate clinical indicators for non-response to steroid treatment in biopsy proven AR after the early postoperative period. METHODS: We prospectively analysed 85 patients more than 6 months after LTx with symptomatic biopsy proven AR (>or=grade A1) from Jan. 2005 until Nov. 2007 in a single centre. In 47 patients, AR was steroid-sensitive (group 1), 38 patients did not respond to steroid pulse therapy (group 2). All AR episodes were associated with clinical symptoms. Fifty-seven (67%) were low-grade rejections (ISHLT A1). RESULTS: Independent clinical predictors for steroid response vs. non-steroid response in biopsy proven AR were "days after transplantation" (p=0.01, adjusted hazard ratio (HR) 1.2), "decline in home spirometry slope" (p=0.03, HR 0.97), "adherence to home spirometry" (p=0.05, HR 0.98) and "serum CRP" (p=0.02, HR 0.87). Eight patients (21%) of group 2 developed BOS during the following 6 months. CONCLUSIONS: Early detection of deterioration in graft function seems to be crucial for effective treatment of AR. Home spirometry seems to be useful in detecting early changes in graft function and surveillance protocols could be potentially helpful in predicting patients likely to demonstrate a steroid response.

Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis.

Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.

A 1-year Aspergillus terreus surveillance study at the University Hospital of Innsbruck: molecular typing of environmental and clinical isolates.

Aspergillus terreus appears to have become an increasingly frequent cause of opportunistic infections in the University Hospital of Innsbruck (UHI) and is of serious concern because of in vivo and in vitro resistance to amphotericin B. In order to determine the possible relationship between environmental contamination by A. terreus and the occurrence of invasive aspergillosis, a 1-year prospective study (2004-2005) was carried out in the UHI. Isolates obtained from air samples of various high-risk settings and those from surveillance cultures of proven and probable aspergillosis (EORTC/MSG criteria) were examined by genotyping. Within 1 year, 34 and 15 A. terreus isolates were collected from the environment and from patients, respectively. Genotypic analysis with rapid amplification of polymorphic DNA (RAPD) PCR and the combination of three different primers (R108, CII, P4) revealed 46 distinct genotypic profiles (types 1-46). No strain similarity was detected among and within the patients and environmental areas, indicating a great genomic diversity in A. terreus, which is common in the environment of Innsbruck and a source of invasive infections in immunosuppressed patients. Genotypical diversity was found in clinical and environmental A. terreus isolates.

Immune evasion by acquisition of complement inhibitors: the mould Aspergillus binds both factor H and C4b binding protein.

Pathogenic fungi represent a major threat particularly to immunocompromised hosts, leading to severe, and often lethal, systemic opportunistic infections. Although the impaired immune status of the host is clearly the most important factor leading to disease, virulence factors of the fungus also play a role. Factor H (FH) and its splice product FHL-1 represent the major fluid phase inhibitors of the alternative pathway of complement, whereas C4b-binding protein (C4bp) is the main fluid phase inhibitor of the classical and lectin pathways. Both proteins can bind to the surface of various human pathogens conveying resistance to complement destruction and thus contribute to their pathogenic potential. We have recently shown that Candida albicans evades complement by binding both Factor H and C4bp. Here we show that moulds such as Aspergillus spp. bind Factor H, the splicing variant FHL-1 and also C4bp. Immunofluorescence and flow cytometry studies show that the binding of Factor H and C4bp to Aspergillus spp. appears to be even stronger than to Candida spp. and that different, albeit possibly nearby, binding moieties mediate this surface attachment.

The central nervous system in mucosal vaccination of rhesus macaques with simian immunodeficiency virus Deltanef.

We studied the central nervous system (CNS) of rhesus macaques during series of vaccination experiments in which attenuated simian immunodeficiency virus (SIV), SIVmac239Deltanef, was applied to the tonsils and the animals were later challenged with pathogenic SIVmac251 or SHIV/89.6P via tonsils or rectum. The pathologic lesions were graded on a scale of 0-5. The lesions were in general very mild, with a score of 0.5, except for one case, in which the animal had progressed to simian AIDS (SAIDS) and had severe lesions of grade 4. Except for the SAIDS case, the most common lesions were meningitis, ependymitis, inflammation of choroid plexus, and astrocytosis. Invasion of the challenge virus, SIVmac251, and pathologic lesions were detected 4 days post infection. The main features of the pathological lesions were similar during short-term follow-up (4 days to 2 weeks) and long-term follow-up (23 to 56 weeks) after challenge. No significant difference was found between unvaccinated controls infected with the challenge viruses and vaccinated and challenged animals. The pathological lesions in the one SAIDS case consisted of extensive lesions of the white matter in connection with confluent ependymitis, indicating an invasion through the choroid plexus. The lesions were characterized by a myriad of multinucleated giant cells of macrophage origin, which showed, together with individual macrophages, strong labelling for viral RNA and proteins. Productive infection of astrocytes was a very rare finding. In three cases infected via tonsils with SIVmac239Deltanef without challenge, we detected expression of Nef-derived peptides, indicating a selective pressure for Nef functions in the CNS.

Influence of amphotericin B and amphotericin B colloidal dispersion on the functions of human phagocytes in defence against Aspergillus species.

This study investigated the in vitro effects of amphotericin B and amphotericin B colloidal dispersion (ABCD) on phagocytosis and inhibition of germination of clinical isolates of Aspergillus spp. by monocyte-derived macrophages (MDMs). Both amphotericin B and ABCD caused significant reductions in uptake of conidia of Aspergillus spp. by MDMs (p < 0.01). The inhibition of germination was superior with conidia of Aspergillus fumigatus, Aspergillus niger and Aspergillus terreus isolates. Aspergillus flavus growth was significantly less inhibited of either antimycotic as compared to A. fumigatus and A. terreus (p < 0.01).We demonstrate that amphotericin B or ABCD acts as a potent inhibitor of Aspergillus germination. By contrast, treatment of MDMs with these antimycotics diminished phagocytosis of conidia in vitro.

Lack of microbial DNA in tissue specimens of patients with abdominal aortic aneurysms and positive Chlamydiales serology.

In a case-control study that included a total of 98 patients and 83 controls, the possible link between various pathogens and abdominal aortic aneurysms was investigated. For 68 patients with abdominal aortic aneurysm and age-matched controls, no differences were detected in the levels of immunoglobulin (Ig)A and IgG Chlamydiaceae and Chlamydophila pneumoniae antibodies. Patients with IgA titers positive for Chlamydophila pneumoniae showed progressive disease (defined as an annual increase of the aneurysm diameter of > or = 0.5 cm) more frequently than patients with negative IgA titers (p = 0.046). Polymerase chain reactions performed to detect DNA for Chlamydophila pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, human cytomegalovirus, Borrelia burgdorferi and Helicobacter pylori in tissue specimens of 30 patients and 15 controls were negative. In summary, Chlamydophila pneumoniae may contribute to aortic aneurysm disease progression, but DNA of this and other pathogens was not found in patients' specimens.

Minimal residual disease in ovarian cancer as a target for complement-mediated mAb immunotherapy.

Ovarian cancer is potentially well suited for local monoclonal antibody (mAb) immunotherapy, because it remains within the peritoneal cavity for a long period of time before giving rise to distant metastases. At the stage of minimal residual disease, the cells appear to be in a state of dormancy (G(0)) or at least have lower rates of tumour cell proliferation. They should be a promising target for immunotherapy. Here we first examined the cell-cycle expression of CD59 and decay-accelerating factor (DAF; CD55) on four different ovarian carcinoma cell lines, using simultaneous flow cytometric analysis of DNA content or the cell-cycle-specific nuclear proliferation protein Ki67 and CD59 or DAF surface expression. We found that CD59 and DAF are stably expressed throughout the cell cycle. The polyvalent approach to target-independent antigens to improve the efficiency of mAb complement (C)-mediated damages was promising, and tumour cells become sensitive to C damage, when incubated with cross-linked mAb against different tumour-associated antigens. Although, such immune complex-mediated C activation was rather ineffective in killing the cells, it could be potentiated by the addition of blocking mAb against CD59 and DAF. Our results suggest that the activities of intrinsic C regulators must be neutralized to make minimal residual disease a promising target for antibody therapy.

Characterization of methicillin-resistant Staphylococcus aureus from Ulaanbaatar, Mongolia.

In order to expand current knowledge of the types of methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in central Asia, six MRSA strains collected from hospitals in Ulaanbaatar, Mongolia during 2000-2002 were examined. Three strains possessed a staphylococcal cassette chromosome mec (SCCmec) element of type IV c, were sequence type (ST) 154 according to multilocus sequence typing (MLST), and contained lukS-lukF (Panton-Valentine leukocidin). Another three strains contained a SCCmec element of type III and were MLST type ST 239. Using automated ribotyping, the six MRSA strains were divided into four different EcoRI ribotypes, and two groups of isolates were distinguished by means of SmaI-macrorestriction patterns. In comparison to other countries, the incidence of MRSA in Mongolia is low.

Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157: indications for an animal reservoir.

This study investigates a sorbitol-fermenting enterohaemorrhagic Escherichia coli (SF EHEC) O157 infection in a farmer's family in the Austrian province of Salzburg. The investigation commenced after a 10-month-old boy was admitted to hospital with the clinical diagnosis of a haemolytic-uraemic syndrome (HUS) and his stool specimen grew SF EHEC O157:H-. In a subsequent environmental survey, a stool specimen of the 2-year-old brother and faecal samples of two cattle from the family's farm were also found to be positive for SF EHEC O157:H-. All four isolates had indistinguishable phenotypic and molecular characteristics and were identical to the first strain detected in Bavaria in 1988. Despite identical isolates being demonstrated in Bavaria after 1988, and until this report, increased surveillance in neighbouring Austria had not found this organism. We propose that the strain may have recently spread from Bavaria to Austria. Although SF EHEC O157:H- strains are still rare, they may represent a considerable health threat as they can spread from farm animals to humans and between humans.

Targeting human immunodeficiency virus type 1 with antibodies derived from patients with connective tissue disease.

During the budding process, human immunodeficiency virus (HIV) acquires several cellular proteins from the host. Thus, antibodies against self antigens found in sera patients with autoimmune disorders may cross react with host-derived or the HIV-specific proteins gp120 and gp41 on the viral envelope and probably neutralize HIV infection. To verify this hypothesis, 88 sera from HIV negative patients suffering from systemic lupus erythematosus (SLE) and other autoimmune disorders were analysed for cross reacting antibodies against HIV-1 by Western blot and FACS analysis indicating that antibodies cross-react with epitopes expressed on HIV infected or non-infected cells. Virus capture assays revealed that HIV-1(IIIB) was directly recognized by 60% of sera from patients with autoimmune disorders. Sera were also tested in HIV neutralization assays with stimulated T cells. Reduction of the viral load by patient sera correlated with their reactivity in Western blot analysis. Complement further enhanced the reduction of viral titres, although no complement-mediated lysis was observed. These data suggest a possible protective role of auto-antibodies against HIV infection in lupus patients.

Interaction of serotonin with Candida albicans selectively attenuates fungal virulence in vitro.

In this study we investigated whether the direct interaction between Candida albicans CBS 5982 and 5-hydroxytryptamine (5-HT) alters candidial virulence. Hyphae elongation, phospholipase activity and the production of secreted aspartyl proteinases (Saps) following 5-HT treatment were investigated. 5-HT treatment of C. albicans significantly (P < 0.05) affected hyphal extension, phospholipase activity and the production of Saps at concentrations of 118-0.46 mM. In conclusion, our findings suggest that the interaction between 5-HT and C. albicans may diminish the virulence properties of this fungal pathogen.