Impact of Pre-Analytical Time on the Recovery of Pathogens from Blood Cultures: Results from a Large Retrospective Survey

Prompt identification of bloodstream pathogens is essential for optimal management of patients. Significant changes in analytical methods have improved the turnaround time for laboratory diagnosis. Less attention has been paid to the time elapsing from blood collection to incubation and to its potential effect on recovery of pathogens. We evaluated the performance of blood cultures collected under typical hospital conditions in relation to the length of their pre-analytical time. We carried out a large retrospective study including 50,955 blood cultures collected, over a 30-month period, from 7,035 adult septic patients. Cultures were accepted by the laboratory only during opening time (Mon-Fri: 8am\ub14pm; Sat: 8am\ub12pm). Samples collected outside laboratory hours were stored at room temperature at clinical wards. All cultures were processed by automated culture systems. Day and time of blood collection and of culture incubation were known for all samples. A maximum pre-analytical interval of 2 hours is recommended by guidelines. When the laboratory was open, 57% of cultures were processed within 2 h. When the laboratory was closed, 4.9% of cultures were processed within 2 h (P<0.001). Samples collected when the laboratory was closed showed pre-analytical times significantly longer than those collected when laboratory was open (median time: 13 h and 1 h, respectively, P<0.001). The prevalence of positive cultures was significantly lower for samples collected when the laboratory was closed compared to open (11% vs 13%, P<0.001). The probability of a positive result decreased of 16% when the laboratory was closed (OR:0.84; 95%CI:0.80\ub10.89, P<0.001). Further, each hour elapsed from blood collection to incubation resulted associated with a decrease of 0.3% (OR:0.997; 95%CI:0.994\ub10.999, P<0.001) in the probability of a positive result. Delayed insertions of cultures into automated systems was associated with lower detection rates, with potentially important consequences for patients. In each hospital setting the logistic factors able to shorten pre-analytical time should be carefully investigated and specifically targeted

Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy

Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1: 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies

Evaluation of Occupational Exposure to Perchlorethylene in a Group of Italian Dry Cleaners Using Noninvasive Exposure Indices

Recent data suggest a general trend in decreased occupational exposure to perchlorethylene (PCE) in the dry-cleaning sector. The aims of this study were to confirm this trend to lower exposure levels in a group of Italian dry cleaners and to evaluate the current occupational PCE exposure in these works using noninvasive biological indices. Environmental exposure was assessed by personal sampling in 60 operators working in 21 dry cleaning shops in North Italy. PCE in the exhaled alveolar air (PCEalv), urinary concentration of PCE and of trichloroacetic acid (TCA) (PCEu and TCAu respectively), were measured as biological exposure indices. Median PCE environmental concentration in the whole sample was 10.6 mg/m3 (i.e., less than the 25% of the levels measured in the same area in a previous study). All values were less than 10% of the occupational limits. PCEu measured in samples collected at the end of the work shift resulted the biological markers having the strongest correlation with environmental PCE (r = 0.81). PCEalv also resulted in a high correlation (r = 0.66), while a lower correlation was found for TCAu measured at the end shift (r = 0.32). According to our results, PCEu can be proposed as a valid, noninvasive, and easily reliable exposure index to evaluate PCE exposure at the low levels currently observed in dry cleaners, therefore representing a promising alternative to invasive blood sample collections needed to determine PCE blood concentration

Development and characterization of a novel human 3D model of bone metastasis from breast carcinoma in vitro cultured

Breast cancer frequently metastasizes to the skeleton causing significant morbidity. Here, we set-up a novel and advanced ex vivo model by using fresh tissue from human vertebral bone metastasis from breast carcinoma patients able to retain the tumor microenvironment and tumor cells heterogeneity

Environmental, climatic, socio-economic factors and non-pharmacological interventions: A comprehensive four-domain risk assessment of COVID-19 hospitalization and death in Northern Italy

Introduction: Up to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, most of them focused on viral spread than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. Methods: Our population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (no. 68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021. Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. Results: Several significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. Conclusions: Our findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly

Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants

Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs

Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 \u3bcM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 \u3bcM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability

Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform

According to the World Health Organization, more than 1 billion people are at risk of or are affected by neglected tropical diseases. Examples of such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all of which are prevalent in Africa, South America, and India. Our aim within the New Medicines for Trypanosomatidic Infections project was to use (1) synthetic and natural product libraries, (2) screening, and (3) a preclinical absorption, distribution, metabolism, and excretion\u2013toxicity (ADME-Tox) profiling platform to identify compounds that can enter the trypanosomatidic drug discovery value chain. The synthetic compound libraries originated from multiple scaffolds with known antiparasitic activity and natural products from the Hypha Discovery MycoDiverse natural products library. Our focus was first to employ target-based screening to identify inhibitors of the protozoan Trypanosoma brucei pteridine reductase 1 (TbPTR1) and second to use a Trypanosoma brucei phenotypic assay that made use of the T. brucei brucei parasite to identify compounds that inhibited cell growth and caused death. Some of the compounds underwent structure-activity relationship expansion and, when appropriate, were evaluated in a preclinical ADME-Tox assay panel. This preclinical platform has led to the identification of lead-like compounds as well as validated hits in the trypanosomatidic drug discovery value chain

Influenza vaccination coverage among medical residents: An Italian multicenter survey

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P < 0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. © 2014 Landes Bioscience

Impact of Referral Sources and Waiting Times on the Failure to Quit Smoking: One-Year Follow-Up of an Italian Cohort Admitted to a Smoking Cessation Service

In Italy, the National Health Service offers specialized evidence-based support to smokers who would like to quit through smoking cessation (SC) services. We conducted a two-year prospective study, involving all 288 subjects treated for smoking cessation at the SC service of Reggio Emilia, to assess the association of referral sources and waiting times with the risk of treatment failure, by following participants up to one year after the quit date. We performed Cox-regression analysis, including demographic and smoking-related characteristics as confounding variables. The treatment failure rate at 12 months was 59.4% (171/288), including only 12 subjects lost to follow-up. The main mode of entry was self-referral (42.4%), followed by 32.6% from general practice, 17.4% from hospital and 7.6% from other sources. Only 27.8% participants were involved in the SC-program within 60 days of the first contact, as the guidelines suggest. The risk of treatment failure at 12 months showed little association with the type of referral source, while it correlated with waiting times &ge; 60 days (hazard ratio = 1.59; 95% confidence interval 1.10&ndash;2.29). This study provides evidence of long-term high quit rates from a SC service, with few subjects lost to follow-up and biochemical verification of almost all abstinent subjects. Timeliness in care provision could further improve the outcome