Lexical patterns, features and knowledge resources for coreference resolution in clinical notes

Generation of entity coreference chains provides a means to extract linked narrative events from clinical notes, but despite being a well-researched topic in natural language processing, general- purpose coreference tools perform poorly on clinical texts. This paper presents a knowledge-centric and pattern-based approach to resolving coreference across a wide variety of clinical records comprising discharge summaries, progress notes, pathology, radiology and surgical reports from two corpora (Ontology Development and Information Extraction (ODIE) and i2b2/VA). In addition, a method for generating coreference chains using progressively pruned linked lists is demonstrated that reduces the search space and facilitates evaluation by a number of metrics. Independent evaluation results show an F-measure for each corpus of 79.2% and 87.5%, respectively, which offers performance at least as good as human annotators, greatly increased performance over general- purpose tools, and improvement on previously reported clinical coreference systems. The system uses a number of open-source components that are available to download

Monthly Increase in Vitamin D Levels upon Supplementation with 2000 IU/Day in Healthy Volunteers: Result from “Integriamoci”, a Pilot Pharmacokinetic Study

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina(®)) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10–26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78–35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60–5.68) after 7 days and 8.85 ng/mL (IQR 2.85–13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment

Tuberculosis After Gastrectomy, Plasmatic Concentration of Antitubercular Drugs

We report pharmacokinetic data on two gastrectomized, patients affected by tuberculosis. Drugs plasmatic concentrations were measured after seven days of oral therapy by a validated high performance liquid chromatography-mass spectrometry (HPLC-MS) method and the area under the concentration-time-curve (AUC) over 24 hours (AUC0–24) was calculated. A sub-therapeutic level of isoniazid was found in a patient with total gastrectomy with a Cmax of 0,395 mg\L and AUC0–24 level of 4.75 hr*mg/L. The level of the other antitubercular drugs was adequate. These findings support the need to monitor anti tubercular drug levels to facilitate early detection of therapeutic failure, above all in patients treated with isoniazid and with potential problems on oral drugs absorption

Cannabis-Based Oral Formulations for Medical Purposes: Preparation, Quality and Stability

Current legislation in Italy provides that medical Cannabis may be administered orally or by inhalation. One of the fundamental criteria for the administration of oral formulations is that they deliver a known consistent quantity of the active ingredients to ensure uniform therapies leading to the optimisation of the risks/benefits. In 2018, our group developed an improved Cannabis oil extraction technique. The objective of the present work was to carry out a stability study for the oil extracts obtained by this method. Furthermore, in order to facilitate the consumption of the prescribed medical Cannabis therapy by patients, a standard procedure was defined for the preparation of a single-dose preparation for oral use (hard capsules) containing the oil extract; thereafter, the quality and stability were evaluated. The hard capsules loaded with the oil extract were analysed and found to be uniform in content. The encapsulation process did not alter the quantity of the active molecule present in the oil. The stability tests yielded excellent results. Since the capsule dosage form is easily transported and administered, has pleasant organoleptic properties and is stable at room temperature for extended periods of time, this would facilitate the adherence to therapy by patients in treatment

Analysing product development process and plm features in the food and fashion industries

The food and fashion industries are well-known as areas of excellence representing Italy globally. Their products include innovative features, have short lifecycles and a high level of customisation. Both the pipelines have to respond quickly to unpredictable demand in order to minimize stock-outs, forced markdowns, obsolete inventory and they focus their Supply Chain (SC) strategies on quality and time-to-market. Although they are characterized by many different aspects, both leverage on the same point of strength: their internal Product Development (PD) process. The opposite occurs in the automotive industry, with its standard and functional products and its efficient pipeline centred on cost reduction. Starting from previous works presented during the last PLM conference (PLM16), the research aims at investigating similarities and differences between these sectors, focusing on their PD process and their main critical success factors. Moreover, the authors analyse how Food and Fashion companies are managing the entire set of information throughout PD and the strategic role of Product Lifecycle Management (PLM). In order to reach these goals, a multiple case study analysis has been performed, involving companies belonging to the Food and Fashion industries. The results will be relevant both for academics and practitioners. Indeed, there is a literature gap about this topic, because of the lack of researches concerning Food and Fashion PD. From the practitioners point of view, the results of this work will help Food and Fashion companies to support their business analysing the PD process and to better understand how the use of the PLM system could improve it

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations

Development and In-House Validation of an Enzyme-Linked Immunosorbent Assay and a Lateral Flow Immunoassay for the Dosage of Tenofovir in Human Saliva

Highly active antiretroviral therapy (HAART) includes very potent drugs that are often characterized by high toxicity. Tenofovir (TFV) is a widely used drug prescribed mainly for pre-exposure prophylaxis (PreP) and the treatment of human immunodeficiency virus (HIV). The therapeutic range of TFV is narrow, and adverse effects occur with both underdose and overdose. The main factor contributing to therapeutic failure is the improper management of TFV, which may be caused by low compliance or patient variability. An important tool to prevent inappropriate administration is therapeutic drug monitoring (TDM) of compliance-relevant concentrations (ARCs) of TFV. TDM is performed routinely using time-consuming and expensive chromatographic methods coupled with mass spectrometry. Immunoassays, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFIAs), are based on antibody&ndash;antigen specific recognition and represent key tools for real-time quantitative and qualitative screening for point-of-care testing (POCT). Since saliva is a non-invasive and non-infectious biological sample, it is well-suited for TDM. However, saliva is expected to have a very low ARC for TFV, so tests with high sensitivity are required. Here, we have developed and validated a highly sensitive ELISA (IC50 1.2 ng/mL, dynamic range 0.4&ndash;10 ng/mL) that allows the quantification of TFV in saliva at ARCs and an extremely sensitive LFIA (visual LOD 0.5 ng/mL) that is able to distinguish between optimal and suboptimal ARCs of TFV in untreated saliva

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR. This study enrolled 245 patients treated with SOF; 245 samples were analyzed for pharmacogenetics and 50 were analyzed for IC pharmacokinetics. The GS-331007 IC concentration at 30 days was associated with its plasma concentration determinate at 30, 60 and 90 days of SOF-therapy and with daclatasvir concentrations at 7 days of therapy. No genetic polymorphism affected IC exposure. In linear multivariate analysis, ledipasvir treatment, baseline albumin and estimated glomerular filtration rate were significant predictors of IC exposure. This study presents data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. These results could be useful for regions where SOF–RBV treatment is considered the standard of care; moreover, they could further deepen the knowledge of IC exposure for similar drugs in the future