Comparing Discrete Choice Experiment with Swing Weighting to Estimate Attribute Relative Importance: A Case Study in Lung Cancer Patient Preferences.

INTRODUCTION: Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR. METHODS: A total of 307 patients with non-small-cell lung cancer in Italy and Belgium completed an online survey assessing preferences for cancer treatment using DCE and SW-DR. The relative importance of the attributes was determined using a random parameter logit model for the DCE and rank order centroid method (ROC) for SW-DR. Differences in relative importance ranking and weights between the methods were assessed using Cohen's weighted kappa and Dirichlet regression. Feedback on ease of understanding and answering the 2 tasks was also collected. RESULTS: Most respondents (>65%) found both tasks (very) easy to understand and answer. The same attribute, survival, was ranked most important irrespective of the methods applied. The overall ranking of the attributes on an aggregate level differed significantly between DCE and SW-ROC (P < 0.01). Greater differences in attribute weights between attributes were reported in DCE compared with SW-DR (P < 0.01). Agreement between the individual-level attribute ranking across methods was moderate (weighted Kappa 0.53-0.55). CONCLUSION: Significant differences in attribute importance between DCE and SW-DR were found. Respondents reported both methods being relatively easy to understand and answer. Further studies confirming these findings are warranted. Such studies will help to provide accurate guidance for methods selection when studying relative attribute importance across a wide array of preference-relevant decisions. HIGHLIGHTS: Both DCEs and SW tasks can be used to determine attribute relative importance rankings and weights; however, little evidence exists empirically comparing these methods in terms of outcomes or respondent usability.Most respondents found the DCE and SW tasks very easy or easy to understand and answer.A direct comparison of DCE and SW found significant differences in attribute importance rankings and weights as well as a greater spread in the DCE-derived attribute relative importance weights.

The psychometric properties of the Italian adaptation of the Health Orientation Scale (HOS).

BACKGROUND: A novel approach suggested that cognitive and dispositional features may explain in depth the health behaviors adoption and the adherence to prevention programs. The Health Orientation Scale (HOS) has been extensively used to map the adoption of health and unhealthy behaviors according to cognitive and dispositional features. Coherently, the main aim of the current research was to assess the factor structure of the Italian version of the HOS using exploratory and confirmatory factor analysis and testing the construct validity of the scale by assessing differences in health orientations between tobacco cigarette smokers and nonsmokers. METHOD: The research protocol was organized in two studies. Study 1 evaluated the dimensionality of the HOS in a sample of Northern Italian healthy people. Three hundred and twenty-one participants were enrolled; they were 229 women (71.3%) and 92 men (28.7%). In Study 2, the factor structure and construct validity of the HOS Italian version was assessed trough confirmatory factor analysis using a tobacco cigarette smokers and nonsmokers population. Two hundred and nineteen participants were enrolled; they were 164 women (75.2%) and 55 men (24.8%). RESULTS: In Study 1, a seven factors solution was obtained explaining 60% of cumulative variance instead of 10 factors solution of the original version of the HOS. In Study 2, the factor structure of the Italian version of the HOS was confirmed and applied to the smokers and nonsmokers; nonsmokers reported higher values than smokers in Factor 1 (MHPP) [t (208) = - 2.739 p < .007] (CI 95-4.96% to -.809), Factor 2 (HES) [t (209) = - 3.387 p < .001] (CI 95-3.93% to -. 1.03), Factor 3 (HIC) [t(213) = - 2.468 p < .014] (CI 95-2.56% to -.28) and Factor 7 (HEX) [t(217) = - 3.451 p < .001] (CI 95%- 1.45 to .39). CONCLUSIONS: Results of the Italian adaptation of HOS lead to a partial redistribution of items and confirmed 7 subscales to distinguish psycho-cognitive dispositional dimensions involved in health orientation styles.

Evaluation of isavuconazole MIC strips for susceptibility testing of Aspergillus and Scedosporium species.

Isavuconazole is a new triazole with an expanded-spectrum and potent activity against moulds and yeasts. It has been authorized for use in adults for the treatment of invasive aspergillosis and for mucormycosis. The only commercially available isavuconazole susceptibility test is the minimum inhibitory concentration (MIC) strip isavuconazole test. The objective of this study was to assess the in vitro activity of isavuconazole using gradient concentration MIC strips, compared with the EUCAST broth microdilution reference method. A total of 147 clinically relevant fungal isolates comprising 120 Aspergillus sp. and 27 Scedosporium apiospermum complex were tested for susceptibility to isavuconazole using the EUCAST broth microdilution method and by the MIC strip isavuconazole test. The percent essential agreement between the two methods was calculated within a 1-fold dilution. The geometric means for the MICs using the EUCAST reference methods and the strip test were respectively: 0.60 mg/l and 0.65 mg/l for A. fumigatus, 0.70 mg/l and 0.77 mg/l for A. flavus, 1.50 mg/l and 1.25 mg/l for A. niger, 0.41 mg/l and 0.38 mg/l for A. terreus, 1.22 mg/l and 1.08 mg/l for S. apiospermum complex. The isavuconazole MIC strips showed good agreement with the EUCAST reference method. Isavuconazole MIC strips could be useful for susceptibility testing of Aspergillus sp. and S. apiospermum complex.

Cognitive training in Alzheimer's disease: a controlled randomized study.

This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to moderate Alzheimer's disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

PURPOSE: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). METHODS: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. RESULTS: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). CONCLUSIONS: The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting.

MYC activity is negatively regulated by a C-terminal lysine cluster.

The MYC oncogene is not only deregulated in cancer through abnormally high levels of expression, but also through oncogenic lesions in upstream signalling cascades. Modelling MYC deregulation using signalling mutants is a productive research strategy. For example, the MYC threonine-58 to alanine substitution mutant (T58A) within MYC-homology box 1 is more transforming than wild-type (WT) MYC, because of decreased apoptosis and increased protein stability. Understanding the regulatory mechanisms controlling T58 phosphorylation has led to new approaches for the development of MYC inhibitors. In this manuscript, we have extensively characterized a MYC signalling mutant in which six lysine residues near the highly conserved MYC homology box IV and basic region have been substituted to arginines (6KR). Previous literature suggests these lysines can undergo both ubiquitylation and acetylation. We show MYC 6KR is able to fully rescue the slow growth phenotype of HO15.19 MYC-null fibroblasts, and promote cell cycle entry of serum-starved MCF10A cells. Remarkably, 6KR increased anchorage-independent colony growth compared with WT MYC in both SH-EP and MCF10A cells. Moreover, it was also more potent in promoting xenograft tumour growth of Rat1A and SH-EP cells. Combined, our data identify this region and these six lysines as important residues for the negative regulation of MYC-induced transformation. Mechanistically, we demonstrate that, unlike T58A, the increased transformation is not a result of increased protein stability or a reduced capacity for 6KR to induce apoptosis. Through expression analysis and luciferase reporter assays, we show that 6KR has increased transcriptional activity compared with WT MYC. Combined, through a comprehensive evaluation across multiple cell types, we identify an important regulatory region within MYC. A better understanding of the full scope of signalling through these residues will provide further insights into the mechanisms contributing to MYC-induced tumorigenesis and may unveil novel therapeutic strategies to target Myc in cancer.

Detection of fungal DNA in lysis-centrifugation blood culture for the diagnosis of invasive candidiasis in neonatal patients.

We report data concerning the detection of fungal DNA directly from lysis-centrifugation blood culture to assess its value in the detection of fungaemia in 86 of the 347 patients admitted to the neonatal intensive-care unit between January 2009 and December 2010. The sensitivity and specificity of the PCR were 87.5% and 98.5%, respectively, with a positive predictive value of 93.3% and a negative predictive value of 97.1%. Detection of fungal DNA directly from blood culture Isolator 1.5 microbial tubes, without prior cultivation, is a promising approach for the rapid detection of Candida spp. in neonates with suspected candidaemia.

New model systems provide insights into Myc-induced transformation.

The ability of Myc to promote cellular transformation is well established; however, a better understanding of the mechanisms through which Myc mediates tumorigenesis is essential for the development of therapeutic approaches to target this potent oncoprotein. Structure-function studies in rodent fibroblast cells have provided the basis for much of our current understanding of these mechanisms. To build on these approaches, we have characterized three novel human cell line models of Myc-dependent transformation: MCF10A, SH-EP Tet21/N-Myc, and LF1/TERT/LT/ST cells. We have also evaluated Myc family proteins (c-Myc and L-Myc), a naturally occurring isoform of Myc (MycS), and a set of N-terminal domain mutants (ΔMBII, W135E, T58A) for their ability to promote anchorage-independent growth in these models. Taken together, these results provide the field with three new human cell-based models to study Myc activity, highlight the importance of cellular context, and challenge the paradigm that the ability of Myc to promote tumorigenesis is exclusively MBII-dependent.

Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome.

OBJECTIVE: To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by Candida species, of late-onset sepsis and neurological outcome in preterm newborns. STUDY DESIGN: A prospective study was conducted in 249 preterms who were subdivided into three groups: one group (n=83) was supplemented with Lactobacillus (L.) reuteri, one group with L. rhamnosus (n=83) and the other with no supplementation (n=83). The fungal colonization in the gastrointestinal tract, the late onset of sepsis and clinical parameters were recorded. A neurological structured assessment was further performed at 1 year of age. RESULT: Candida stool colonization was significantly higher (P<0.01) in the control group than in the groups treated with probiotics. The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups. Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group. CONCLUSION: The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by Candida, in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms.

Contamination of preservation fluid in kidney transplantation: single-center analysis.

INTRODUCTION: Contamination of preservation fluid is common, with a reported incidence of 2.2% to 28.0%, and may be a major cause of early morbidity after transplantation. Herein, we report our experience with routine examination of preservation fluid collected just before implantation, focusing on the rate of contamination and the clinical consequences to recipients. MATERIALS AND METHODS: We analyzed 62 samples of preservation fluid for microbial and fungal contamination. RESULTS: Twenty-four samples (38.7%) were contaminated with at least 1 organism. Bacterial contamination alone was observed in 18 samples; all patients received prophylactic treatment with intravenous piperacillin/tazobactam, 4.5 g/d for 10 days, without clinical sequelae. Six samples were contaminated with Candida species; all patients received prophylactic treatment with fluconazole, 100 mg/d for 3 months. One patient developed reversible acute renal failure due to ureteral obstruction by fungus balls at 30 days after transplantation. CONCLUSION: Contamination of preservation fluid occurs frequently after kidney transplantation. Bacterial contamination evolved without symptoms in most patients treated with prophylactic antibiotic therapy. Fungal contamination may be potentially life-threatening. However, graft nephrectomy is not mandatory if the involved Candida species is identified correctly and appropriate antifungal therapy is rapidly prescribed.

In vitro susceptibility of nondermatophyte molds isolated from onycomycosis to antifungal drugs.

Despite many advances in antifungal drug development and therapy, onychomycosis due to nondermatophyte molds (NDM) remains difficult to treat. Using a reference microdilution method (CLSI M38-A), the antifungal susceptibility to bifonazole, ciclopiroxolamine, fenticonazole, itraconazole, ketoconazole, miconazole, terbinafine and tioconazole of 64 molds isolated from toenail onychomycosis was studied. All the strains showed good susceptibility to ciclopiroxolamine. Aspergillus had excellent susceptibility to itraconazole followed by miconazole, ketoconazole, tioconazole, fenticonazole and terbinafine. The isolated species had variable susceptibility to bifonazole. Scopulariopsis had wide MIC ranges for all antifungal drugs tested except ciclopiroxolamine. Fusarium and Acremonium had reduced susceptibility to antifungal drugs tested. Nevertheless, some strains show low MICs for ketoconazole, miconazole and tioconazole.Studies to evaluate in vitro susceptibility testing using CLSI methods for NDM onychomycosis should be undertaken.

Experience with the Platelia Candida ELISA for the diagnosis of invasive candidosis in neonatal patients.

This preliminary study evaluated the use of the Platelia Candida antigen kit for the diagnosis of invasive candidosis in 70 of 184 pre-term infants admitted to a neonatal intensive care unit between March 2004 and March 2006. The frequency of confirmed candidaemia was 6.5%. The sensitivity and specificity of the assay were 94.4% and 94.2%, respectively, with a positive predictive value of 85% and a negative predictive value of 98%. These results suggest that the inclusion of regular serological surveillance for mannanaemia in some pre-term infants would complement blood cultures for the early detection of candidosis.

In vitro activity of fluconazole, voriconazole and caspofungin against clinical yeast isolates.

Predicting the clinical outcome of a systemic mycosis is often a difficult task, especially when microbiological resistance is one of the factors contributing to therapeutic failure. Some of these factors are host-related--e.g. immune state, site and severity of infection, poor compliance to therapy--while others are associated with the drug's characteristics--e.g. dosage, type of compound (fungistatic/fungicidal), pharmacokinetic properties and drug-drug interactions. In the last few years, clinicians have been confronted with the problem of selecting the most appropriate antifungal therapy for systemic infections and have highlighted the need for a reliable method to assay the in vitro susceptibility of yeasts and molds to different antifungal agents, which would allow them to institute a tailored therapy. Using the CLSI micromethod--the reference method for clinically relevant yeast testing--we assayed 70 clinical yeast isolates ( Candida spp., collected from patients with systemic mycosis) for susceptibility against fluconazole, voriconazole and caspofungin. Data obtained from our in vitro susceptibility assays revealed good activity of azoles against the majority of Candida spp. In particular, 88.6% of the assayed isolates were susceptible to fluconazole, with minimum inhibitory concentrations (MICs) ranging from =0.125 microg/mL to 8 microg/mL; 97.1% of the isolates were susceptible to voriconazole, with MICs ranging from 0.008 microg/mL to 1 microg/mL; regarding caspofungin 72.9% of the isolates had MICs ranging from 0.25 microg/mL to 1 microg/mL.

Detection of Salmonella enterica somatic groups C1 and E1 by PCR-enzyme-linked immunosorbent assay.

Objectives of this study were to develop a PCR-based enzyme-linked immunosorbent assay (PCR-ELISA) for identification of Salmonella enterica somatic groups C1 and E1 and to evaluate this procedure along with a PCR-ELISA procedure for S. enterica somatic groups B, C2, and D in a masked study. Primers were selected from the rfb gene cluster, which is responsible for biosynthesis of O antigens of Salmonella lipopolysaccharide. Previously serogrouped Salmonella isolates (n = 169) were used to determine the sensitivity and specificity of the PCR-ELISA procedure. DNA from all isolates was amplified using the PCR procedure for selected somatic groups and amplified products were visualized on agarose gels, as well as subjected to the ELISA procedure. The PCR-ELISA technique correctly identified 97% of somatic group C1 and 87% of somatic group E1. The sensitivity of this procedure to correctly identify S. enterica somatic group C1 was 97% and 88% for somatic group E1. The specificity was 98% for both somatic groups C1 and E1. The PCR-ELISA techniques correctly identified 93% of Salmonella isolates belonging to somatic groups B, C1, C2, D, and E1. The overall sensitivity of this procedure to correctly identify S. enterica somatic groups was 96% and the specificity was 98%. Ninety-one percent of somatic group D, 92% of somatic group B, and 97% of somatic group C2 were identified correctly with this procedure. Results of this study indicate that the PCR-ELISA procedure is a rapid and accurate method for serogrouping Salmonella isolates. Utilization of the PCR-ELISA procedure for Salmonella serogrouping would aide in identification, surveillance, prevention, and control of Salmonella.

Multicenter comparative evaluation of six commercial systems and the national committee for clinical laboratory standards m27-a broth microdilution method for fluconazole susceptibility testing of Candida species.

Fluconazole susceptibility among 800 clinical Candida isolates (60% C. albicans) and two control strains (C. krusei ATCC 6258 and C. parapsilosis ATCC 22019) was tested with the NCCLS M27-A method (gold standard) and six commercial products (Candifast, disk, Etest, Fungitest, Integral System Yeasts, and Sensititre YeastOne). Results were classified as susceptible, susceptible-dose dependent, or resistant using M27-A breakpoints or, for Fungitest, Integral System Yeasts, and Candifast, as susceptible, intermediate, or resistant, according to the manufacturers' instructions. Concordance with NCCLS M27-A results was analyzed with the chi(2) test. Intra- and interlaboratory reproducibility was also evaluated. NCCLS M27-A (90.1%), Etest (93.1%), Sensititre YeastOne (93.1%), disk (96.7%), Fungitest (92.6%), Integral System Yeasts (40.6%), and Candifast (6.0%) classified the indicated percentages of C. albicans isolates as susceptible. Among non-C. albicans strains, the percentages of susceptible isolates were as follows: NCCLS M27-A, 74.0%; Etest, 83.8%; Sensititre YeastOne, 64.1%; disk, 60.6%; Fungitest, 76.6%; Integral System Yeasts, 28.3%; and Candifast, 27.4%. All methods except Candifast and Integral System Yeasts showed good agreement with NCCLS M27-A results for both C albicans and non-C. albicans isolates. Intralaboratory reproducibility was excellent for NCCLS M27-A, Etest, Sensititre YeastOne, disk, and Fungitest (88 to 91%). Similar results emerged from the interlaboratory reproducibility evaluation. Our findings indicate that some commercial methods can be useful for fluconazole susceptibility testing of clinical Candida isolates. Those characterized by a lack of medium standardization and/or objective interpretative criteria should be avoided. Particular caution is necessary when testing is being done for clinical and epidemiological purposes.

An experimental model for the acute and chronic evaluation of intra-aneurysmal pressure.

PURPOSE: To develop an animal model for the acute and chronic monitoring of pressure within abdominal aortic aneurysms (AAAs) to be treated with endovascular grafts. METHODS: A strain-gauge pressure transducer was placed within an AAA created from a prosthetic vascular graft. Prosthetic aneurysms were implanted into 17 canine infrarenal aortas. The intra-aneurysmal pressure was monitored and correlated with noninvasive forelimb sphygmomanometry for 2 weeks. After this time, an intravascular manometer catheter was passed into the aneurysm. Simultaneous pressure measurements were obtained using the implanted strain-gauge pressure transducer, the manometer catheter, and the forelimb sphygmomanometer. Angiography was performed to assess intraluminal morphology, aneurysm anastomoses, and adjoining aortic vessels. In addition, two control animals underwent intra-aneurysmal pressure monitoring after standard surgical aneurysm repair. RESULTS: There was excellent correlation (r = 0.97) between the pressure measurements obtained with the implanted strain-gauge pressure transducer and the intravascular manometer. Close correlation was also observed between the implanted strain-gauge transducer and the forelimb sphygmomanometer (r = 0.88) during postprocedural monitoring. Intra-aneurysmal pressure was lowered dramatically by surgical exclusion (aneurysm: 15/5 +/- 7/4 mmHg; systemic: 124/66 +/- 34/17 mmHg; p < 0.001). The prosthetic aneurysms were successfully imaged with angiography. CONCLUSIONS: This animal model provides an accurate and reproducible means for measuring intra-aneurysmal pressure on an acute and chronic basis. It may be possible to use this model in the assessment of endovascular devices to determine their efficacy in reducing intra-aneurysmal pressure. Evaluation of complications associated with their use, such as patent aneurysm side branches, perigraft channels, and perianastomotic reflux, may also be possible.

Relative inhibition index of antifungal drugs by diffusion agar susceptibility test.

The diffusion agar susceptibility test for the antifungal drugs has not been validated yet. The aim of this work has been the analysis of the dose-response line, the relative diffusion rate and the residual activity concerning inhibition zone formation in home-made medium for amphotericin B, 5-flucytosine, fluconazole and itraconazole. Furthermore, the Relative Inhibition Index was calculated. With our methods it is possible to better discriminate the results of "in vitro" antifungal activity above all with those which are less diffused in agar medium.