A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project.

Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.

Quality of life in an Italian cohort of people living with HIV in the era of combined antiretroviral therapy (Evidence from I.A.N.U.A. study-investigation on antiretroviral therapy).

The aims of this study were to assess the Health Related Quality of Life (HRQoL) of People Living with HIV/AIDS (PLWHA) who attend outpatient services in Genoa, Italy, and to evaluate the relationship between HRQoL and clinical factors, primarily: CD4+ cell count, viral load and HIV-Hepatitis C Virus (HCV) coinfection. A cross-sectional study was performed involving a sample of 943 consecutive patients. Firstly the EuroQol-Five Dimensions-Three Level (EQ-5D-3L) self-reported questionnaire was used to evaluate HRQoL, while socio-demographic information was collected using a separate self-administered questionnaire. Descriptive statistical analysis was then used to show the socio-demographic and clinical characteristics of the sample. Having characterized the sample, Pearson's correlation technique was used to assess the relationship between HRQoL and socio-demographic and clinical characteristics. Finally, multivariable linear regression was used to determine factors associated with HRQOL. The median EQ-Visual analogue scale (EQ-VAS) score was 75.4 (SD 18.4). We found statistically significant associations between the EQ-VAS score and age, coinfection with HCV+, education, other drugs taken over cART, hospitalization due to HIV and a CD4+ cell count <200 mm3 compared with CD4+ cell count >500 mm3. Factors independently associated with lower HRQoL were: older age, coinfection with HCV+, other drugs used in addition to cART, hospitalization due to HIV and CD4+ cell count <200 mm3 compared with CD4+ cell count >500 mm3.

Twenty-month Performance of a Universal Bonding System on Simulated-challenged Dentin Substrates Pretreated with Chlorhexidine.

OBJECTIVES: Since the use of dentin antiproteolytic agents with universal adhesives (UAs) can potentially degrade the bonding interface, this study evaluated bond strengths with and without chlorhexidine (CHX) on variously altered dentin surfaces for up to 20 months. METHODS: Human molar specimens (n=20) were categorized by substrates as S=sound, E=eroded, and C=carious, and by pretreatment as W=water or CHX. These specimens were subjected to micro-tensile bond strength (µTBS) testing at 24 hours, 6 months, and 20 months, after 30 seconds of pretreatment with CHX or W, followed by self-etching and bonding (Adper Single Bond Universal, 3M ESPE). Modes of failure were assessed using optical microscopy (40×) and scanning electron microscopy (SEM), and the results were analyzed by 3-way ANOVA and Tukey's statistical tests (α=0.05). RESULTS: Substrate (p<0.001), pre-treatment (p=0.0413), and time (p<0.0001) were statistically significant. The sound-dentin group in initial time (W=39.27/CHX=40.55) yielded the higher µTBS values (MPa) in comparison with altered substrates pre-treated with CHX (E-CHX=19.84; C-CHX=18.24) after 20 months, which showed the lowest values. Under SEM analysis, heterogeneous patterns appeared in the hybrid layer of the CHX-treated group, particularly in the altered substrates. CONCLUSIONS: Bond strength to dentin decreased over a period of 20 months using UA with 10-methacryloyloxydecyl-dihydrogen phosphate (MDP) in self-etching mode. Substrates altered by erosion or caries have impaired adhesion and associated clinical use of UA with MDP and CHX should be avoided.

Exposure to psychotropic medications and COVID-19 course after hospital admission: Results from a prospective cohort study.

OBJECTIVE: There is evidence of a bidirectional association between COVID-19 disease and psychiatric disorders. We aimed to assess whether exposure to psychotropic medications prior to hospitalization was associated with mortality or discharge within 30 days after hospital admission. METHODS: In this prospective study, we included all individuals with a laboratory-confirmed COVID-19 infection who were admitted to the Bologna University Hospital between 1st March 2020 and 31st January 2021. We collected data about pre-existing psychiatric disorders and the use of psychotropic medications at the admission. As univariate analyses, we estimated cumulative incidence functions for 30-day mortality and discharge stratifying by exposure to each of the psychotropic medication classes. Finally, we fitted Cox regression models to estimate cause-specific Hazard Ratios (HR) of 30-day mortality and discharge. Results were adjusted for sociodemographic (age, sex), clinically relevant variables (comorbidity, c-reactive protein levels, severity of disease at presentation, history of smoking, study period), and psychiatric variables (psychiatric disorder diagnosis, number of psychotropic medications). RESULTS: Out of a total of 1238 hospitalized patients, 316 were prescribed psychotropic medications at the time of admission. Among these, 45 (3.6%) were taking a first-generation antipsychotics (FGA) and 66 (5.3%) a second generation antipsychotic (SGA). Exposure to SGA was associated with increased rates of 30-day mortality (HR = 2.01, 95%CI = 1.02-3.97) and exposure to FGA was associated with decreased rates of 30-day discharge (HR = 0.55, 95%CI = 0.33-0.90). CONCLUSION: Patients with COVID-19 infection exposed to FGA and SGA may have worse COVID-19 infection outcomes.

Intraspecific diversity of Edwardsiella ictaluri isolates from diseased freshwater catfish, Pangasianodon hypophthalmus (Sauvage), cultured in the Mekong Delta, Vietnam.

A molecular epidemiology study was conducted on 90 Edwardsiella ictaluri isolates recovered from diseased farmed freshwater catfish, Pangasianodon hypophthalmus, cultured in the Mekong Delta, Vietnam. Thirteen isolates of E. ictaluri derived from diseased channel catfish, Ictalurus punctatus, cultured in the USA were included for comparison. All the E.ictaluri isolates tested were found to be biochemically indistinguishable. A repetitive (rep)-PCR using the single (GTG)(5) primer was shown to possess limited discriminatory power, yielding two similar DNA profiles categorized as (GTG)(5) -PCR group 1 or 2 among the Vietnam isolates and (GTG)(5) -PCR group 1 within the USA isolates. Macrorestriction analysis identified 14 and 22 unique pulsotypes by XbaI and SpeI, respectively, among a subset of 59 E. ictaluri isolates. Numerical analysis of the combined macrorestriction profiles revealed three main groups: a distinct cluster formed exclusively of the USA isolates, and a major and minor cluster with outliers contained the Vietnam isolates. Antibiotic susceptibility and plasmid profiling supported the existence of the three groups. The results indicate that macrorestriction analysis may be regarded as a suitable typing method among the E. ictaluri species of limited intraspecific diversity. Furthermore, the findings suggest that E. ictaluri originating from Vietnam may constitute a distinct genetic group.

Performance of a Universal Bonding System Associated With 2% Digluconate Chlorhexidine in Carious and Eroded Dentin.

CLINICAL RELEVANCE: Carious and eroded dentin represent clinical challenges. The use of a universal bonding system, in a self-etching mode, associated with chlorhexidine (CHX) seems to not improve its longevity. This may be attributed to the competition for calcium between the bonding agent functional monomer and CHX.

Adapted Three-step Restorative Technique: Recovering Dental Substrate Compromised by Complex Erosive Wear in a Young Patient.

CLINICAL RELEVANCE: This article presents the dental restoration of a young female patient complaining of erosive dental wear using a three-step restorative technique, an alternative approach with some novel adjustments. SUMMARY: For successful tooth wear treatment, determining the etiological systemic and local factors is the main priority before deciding on effective and long-term preventive and/or therapeutic restorative approaches. In addition to professional intervention, achieving optimal outcomes requires patients to control their diet and/or gastric issues, thus minimizing the wear process. However, continuous wear constitutes the most challenging scenario, mainly when it affects young patients' dentitions. This article describes the dental restoration of posterior teeth with reestablishment of occlusal vertical dimension before treating the anterior teeth, while educating the patient and providing medical monitoring. The three-step restorative technique seems to be properly applicable in cases of significant dental compromise due mainly to erosive wear and is based on direct procedures, which can assure a reliable and feasible approach.

Bloodstream infections in patients living with HIV in the modern cART era.

Retrospective multicentre study aiming at analysing the etiology, characteristics and outcome of bloodstream infections (BSI) in people living with HIV (PLWHIV) in an era of modern antiretroviral therapy. Between 2008 and 2015, 79 PLWHIV had at least 1 BSI, for a total of 119 pathogens isolated. Patients were mainly male (72.1%), previous intravenous drug users (55.7%), co-infected with HCV or HBV (58.2%) and in CDC stage C (60.8%). Gram-positive (G+) pathogens caused 44.5% of BSI, followed by Gram-negative (G-), 40.3%, fungi, 10.9%, and mycobacteria, 4.2%. Candida spp. and coagulase-negative staphylococci were the most frequent pathogens found in nosocomial BSI (17% each), while E.coli was prevalent in community-acquired BSI (25%). At the last available follow-up, (mean 3.2 ± 2.7 years) the overall crude mortality was 40.5%. Factors associated with mortality in the final multivariate analysis were older age, (p = 0.02; HR 3.8, 95%CI 1.2-11.7) CDC stage C (p = 0.02; HR 3.3, 95%CI 1.2-9.1), malignancies, (p = 0.004; HR 3.2, 95%CI 1.4-7.0) and end stage liver disease (p = 0.006; HR 3.4, 95%CI 1.4-8.0). In conclusion, the study found high mortality following BSI in PLWHIV. Older age, neoplastic comorbidities, end stage liver disease and advanced HIV stage were the main factors correlated to mortality.

Duty to disclose what? Querying the putative obligation to return research results to participants.

Many research ethics guidelines now oblige researchers to offer research participants the results of research in which they participated. This practice is intended to uphold respect for persons and ensure that participants are not treated as mere means to an end. Yet some scholars have begun to question a generalised duty to disclose research results, highlighting the potential harms arising from disclosure and questioning the ethical justification for a duty to disclose, especially with respect to individual results. In support of this view, we argue that current rationales for a duty of disclosure do not form an adequate basis for an ethical imperative. We review policy guidance and scholarly commentary regarding the duty to communicate the results of biomedical, epidemiological and genetic research to research participants and show that there is wide variation in opinion regarding what should be disclosed and under what circumstance. Moreover, we argue that there is fundamental confusion about the notion of "research results," specifically regarding three core concepts: the distinction between aggregate and individual results, amongst different types of research, and across different degrees of result veracity. Even where policy guidance and scholarly commentary have been most forceful in support of an ethical imperative to disclose research results, ambiguity regarding what is to be disclosed confounds ethical action.

A SOA-Based Platform to Support Clinical Data Sharing

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the "Interoperable" Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the "Interoperable" Tier, the current solution actually covers the "Connected" Tier, due to local hospital policy restrictions.

A SOA-Based Platform to Support Clinical Data Sharing.

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the "Interoperable" Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the "Interoperable" Tier, the current solution actually covers the "Connected" Tier, due to local hospital policy restrictions.

Effectiveness, safety, durability and immune recovery in a retrospective, multicentre, observational cohort of ART-experienced, HIV-1-infected patients receiving maraviroc.

The aim of this retrospective, multicentre, observational study was to assess the durability, safety, immune recovery and effectiveness on viral suppression of antiretroviral therapy (ART) in a maraviroc (MVC)-based cohort. We collected clinical, demographical, immunological and virological parameters of adult HIV patients who were infected by CCR5-tropic virus and started an ART regimen containing MVC from 2005 to 2012. We created a longitudinal mixed model to assess the change over time of data. We enrolled 126 drug-experienced patients; the median duration of MVC treatment was 25 months. The probability of stopping ART at one year was 13.3%, and at three years was 27.3%. Statistically significant changes were observed for CD4+ cell count increase ( p < 0.001), HIV-RNA decrease ( p < 0.001) and total cholesterol decrease ( p = 0.005). Ninety-four patients (79.7%) had CD4 ≥ 200 cells/mm3 at baseline while nine of them reached this threshold at nine months (7.6%), 17 (13%) after nine months and six (5%) remained below 200 cells/mm3 at the end of the study. Overall, 114 patients (90.5%) achieved an HIV-RNA ≤ 50 cp/ml. A majority of patients maintained CD4 cell counts of ≥ 200 cells/mm3 and achieved an undetectable HIV viral load within three months. MVC-containing regimens are safe and appear to be a feasible therapeutic option for ART.

Role of Proteolytic Enzyme Inhibitors on Carious and Eroded Dentin Associated With a Universal Bonding System.

OBJECTIVES: The aim of this study was to evaluate the effect of proteolytic inhibitors on the bond strength of a universal adhesive system (etch-and-rinse mode) applied to artificial carious and eroded dentin. METHODS: Ninety molars were prepared and randomly divided into three groups according to the substrate: N, no challenges; ACD, artificial carious dentin simulation and ERO, artificial erosion simulation with orange juice. All groups were redivided into three subgroups according to the dentin pretreatment: W, water; CHX, 2% digluconate chlorhexidine; and E-64 (trans-epoxysuccinyl-L-leucylamido-[4-guanidino] butane), 5 µM E-64 inhibitor. They constituted a total of nine groups (n=10): N-W, N-CHX, N-E64, ACD-W, ACD-CHX, ACD-E64, ERO-W, ERO-CHX, and ERO-E64. All specimens were restored with Adper Single Bond Universal/Filtek Z250. Beams (0.64 mm2) were obtained and subjected to the microtensile test (µTBS) in a universal testing machine at 0.5 mm/min. The failure mode of the interfaces was determined by optical microscopy (40× magnification). Data were statistically analyzed by three-way analysis of variance and Tukey tests (p<0.05). RESULTS: All individual factors (p<0.0001) and the interaction between substrate and treatment (p=0.0011) and between substrate and time (p=0.0003) were statistically significant. The caries substrate contributed negatively to bond strength. Chlorhexidine reduced bond strength for normal and eroded conditions. Only the normal substrate was negatively affected by time despite the pretreatment. CONCLUSIONS: The universal bonding system appears to be a promising bonding strategy for the maintenance of bond strength to affected dentin. E-64 did not affect bonding to the dentin in contrast to the use of chlorhexidine, which, when associated with the universal system, did affect the microtensile bond strength for artificial carious dentin.

Development of a piezoelectric immunosensor for the measurement of paclitaxel.

This paper describes the development of a piezoelectric immunosensor for the measurement of paclitaxel (taxol), a natural anti-cancer agent. An antibody specific for taxanes was immobilized onto the surface of quartz crystals by means of the layer-by-layer self-assembly technique. The immobilization was achieved using electrostatic interactions between a precursor layer and the antibody molecules. The assembly process was monitored by a quartz crystal microbalance (QCM) and the topography of the modified quartz crystals was investigated by means of atomic force microscopy. The specific interaction of the immobilized antibody with paclitaxel in solution at different concentrations was monitored as a change in resonant frequency of the modified crystal. Moreover, the influence of non-specific adsorption was also characterized. The results show that the proposed immunosensor offers a promising alternative to classical analytical methods for a fast and easy determination of paclitaxel.

An experience of microbiological data sharing.

OBJECTIVES: The control of infections and their resistance to antibiotics in hospitals is a matter of vital importance in the follow-up of transplant patients. This project has the purpose of translating microbiological reports from an obsolete file structure to a system which could guarantee a more correct and quick transmission of data, a system of storage which reduces the possibility of errors, a smoother manipulation, consultation and updating of data and, at least, a simple way to compute the cost of analysis, based on the costs determined by the national's DRG. METHODS: The proposed solution is a semiautomatic interface which translates these data into a relational database on a daily basis, interprets the requests coming from external centers and produces reports. The prospective to use this tool for several centers indicates to us the need to choose an HL7 output for the interface. RESULTS: A prototype version of this program was installed in February 2004. In this period, routine work has been recorded with an average of 6.5 samples per day, with a maximum of 23 samples. Moreover, historical data from 1998 has been translated. The main source of errors in these data was due to patient identification problems with an average occurrence of 4.06% in the virology section and of 4.16% in the microbiological division. CONCLUSIONS: A complete reorganization of the system would be desirable but at the moment it is not realistic because of obvious budget problems. The proposed approach, mainly the HL7 interface, seems to be a reasonable compromise.

How to avoid and manage a pneumothorax.

Pneumothorax is one of the most frequent complications during percutaneous central vascular cannulation. When choosing a site for central vascular access, the internal jugular vein is preferable to other vessels, for the lower frequency of related complications, including pneumothorax. This review intends to summarize the current state of the art on how to avoid and, if it occurs, to manage this rare but relevant complication. In order to prevent pneumothorax, as well as other relevant complications of central vein cannulation, it is advisable to use ultrasound guidance whenever possible. If pneumothorax occurs, it is important to recognize its signs and symptoms. To exclude the presence of asymptomatic pneumothorax, in the normal clinical routine a chest X-ray should be obtained within 4 hours from the procedure of central vein cannulation of subclavian and internal jugular veins. If promptly recognized, pneumothorax can be managed quickly and in a relatively easy way. Depending on its size and symptoms, and in particular when a tension pneumothorax is suspected, treatment can vary from simple observation to a chest tube insertion or, in the latter case, to an emergency thoracentesis needle insertion in the pleural space.

Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P < 5 × 10-8 ). Of these, 12 metabolites were significantly higher in plasma samples from volunteers dosed with the OATP1B1 inhibitor, cyclosporine (CSA) vs. placebo (q-value < 0.2). Conjugated bile acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established.

Gender and ethnic differences in hospital-based procedure utilization in California.

OBJECTIVE: To examine several hospital-based procedures for systematic utilization differences between the genders and among ethnic groups (Asian, black, Latino, and white). METHODS: California hospital discharges in 1989 and 1990 were sampled by principal diagnosis. Odds ratios for treatment by demographic class were estimated for heart transplantation, kidney transplantation, extracorporeal shockwave lithotripsy, hip replacement, carotid endarterectomy, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, pacemaker implant, and automatic cardioverter-defibrillator implant. Logistic regression controlled for insurance status, age, diagnosis, and comorbidity count. RESULTS: The following results were statistically significant (P < .05). Males' odds of receiving most procedures exceeded those of females by 115% (odds ratio, 2.15) for coronary artery bypass grafting, 86% for heart transplantation, 38% for defibrillator implants, 34% for angioplasty, 28% for pacemaker implants, and 24% for hip replacement. Whites' odds of receiving several procedures exceeded those of blacks by 204% for kidney transplantation, 186% for defibrillator implant, 144% for coronary artery bypass grafting, 127% for endarterectomy, and 100% for angioplasty. Whites' odds of receiving some procedures also exceeded those of Latinos by 72% for angioplasty, 58% for kidney transplantation, and 49% for coronary artery bypass grafting. Whites' odds of receiving endarterectomy or angioplasty exceeded those of Asians by 108% and 30%, respectively. Asians had 113% higher odds than whites of receiving hip replacement. CONCLUSIONS: The array of utilization differences across 4 demographic comparisons and 9 hospital procedures suggests systematic trends in high-technology allocation. Generally, women received procedures less often than men and minorities less than whites.

[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors.

To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies.