Adherence to oral anticancer treatments: network and sentiment analysis exploring perceived internal and external determinants in patients with metastatic breast cancer.

PURPOSE: Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to analyze the main themes and attributes related to OATs in MBC patients. This research is part of a project titled "Enhancing Therapy Adherence Among Metastatic Breast Cancer Patients" designed to produce a predictive model of non-adherence, a decision support system, and guidelines to improve adherence to OATs. METHODS: The study consists of an exploratory observational and qualitative analysis using a focus group method. A semi-structured interview guide was developed to handle relevant OAT themes. Wordcloud plots, network analysis, and sentiment analysis were performed. RESULTS: Nineteen female MBC patients participated in the protocol (age mean 55.95, SD = 6.87). Four main themes emerged: (theme 1) individual clinical pathway; (theme 2) barriers to adherence; (theme 3) resources to adherence; (theme 4) patients' perception of new technologies. The Wordcloud and network analysis highlighted the important role of treatment side effects and the relationship with the clinician in the modulation of adherence behavior. This result is consistent with the sentiment analysis underscoring patients experience fear of issues related to clinical values and ineffective communication and discontinuity of the doctor in charge of the patient care. CONCLUSION: The study highlighted the key role of the individual, relational variables, and side effects as internal and external determinants influencing adherence to MBC. Finally, the opportunity offered by eHealth technology to connect with other patients with similar conditions and share experiences could be a relief for MBC patients.

Predictive Models of Psychological Distress, Quality of Life, and Adherence to Medication in Breast Cancer Patients: A Scoping Review.

Purpose: An interplay of clinical and psychosocial variables affects breast cancer patients' experiences and clinical trajectories. Several studies investigated the role of socio-demographic, clinical, and psychosocial factors in predicting relevant outcomes in breast cancer care, thus developing predictive models. Our aim is to summarize predictive models for specific psychological and behavioral outcomes: psychological distress, quality of life, and medication adherence. Specifically, we aim to map the determinants of the outcomes of interest, offering a thorough overview of these models. Methods: Databases (PubMed, Scopus, Embase) have been searched to identify studies meeting the inclusion criteria: a breast cancer patients' sample, development/validation of a predictive model for selected psychological/behavioral outcomes (ie, psychological distress, quality of life, and medication adherence), and availability of English full-text. Results: Twenty-one papers describing predictive models for psychological distress, quality of life, and adherence to medication in breast cancer were included. The models were developed using different statistical approaches. It has been shown that treatment-related factors (eg, side-effects, type of surgery or treatment received), socio-demographic (eg, younger age, lower income, and inactive occupational status), clinical (eg, advanced stage of disease, comorbidities, physical symptoms such as fatigue, insomnia, and pain) and psychological variables (eg, anxiety, depression, body image dissatisfaction) might predict poorer outcomes. Conclusion: Predictive models of distress, quality of life, and adherence, although heterogeneous, showed good predictive values, as indicated by the reported performance measures and metrics. Many of the predictors are easily available in patients' health records, whereas others (eg, coping strategies, perceived social support, illness perceptions) might be introduced in routine assessment practices. The possibility to assess such factors is a relevant resource for clinicians and researchers involved in developing and implementing psychological interventions for breast cancer patients.

Thymus and meat physicochemical measurements to discriminate calves treated with anabolic and therapeutic doses of dexamethasone.

To preserve the Europe consumers' health, the use of glucocorticoids as growth promoters is prohibited in cattle fattening. In 2008, the Italian Ministry of Health associated to the official control a national monitoring plan based on the histological thymus analysis to identify animals illegally treated with corticosteroids. However, since corticosteroids are authorized and widely used for therapeutic purposes, it is necessary to verify whether the thymus histological test and some physicochemical traits in meat are able to discriminate doped calves from dexamethasone therapeutic treated ones. The aims of this study were (i) to establish whether the therapeutic and illicit corticosteroid treatments of calves could be differentiated through histological evaluation of thymus and by physicochemical meat traits; (ii) to identify a restricted number of physicochemical traits that could differentiate dexamethasone treated from untreated calves. Three groups of 15 calves each were included in this study: group dexamethasone therapeutic treatment treated with dexamethasone 21-phosphate disodium salt at a therapeutic dose (2 mg/kg of live weight for three consecutive days); group dexamethasone anabolic treatment orally treated with dexamethasone 21-phosphate disodium salt according to a presumed anabolic protocol (0.4 mg/day per animal for 20 days); group placebo control treated with a placebo served as control. Results demonstrated that groups could be easily discriminated by thymus microscopy as well as by two meat markers, namely, cooking loss and shear firmness or Warner-Bratzler shear force. The combination of thymus microscopic features and meat physicochemical traits could be used as a practical, economic and accurate screening strategy to discriminate between meat from illegally and therapeutically treated calves. This new reliable and simple tool could contribute to identify animals treated with dexamethasone in those countries where glucocorticoids are illegally used as growth promoters. More in general, this system could be included in the framework of official controls, and applied to verify suppliers' reliability by the meat industry.

Wild rats as urban detectives for latent sources of asbestos contamination.

Based on a large body of evidence asbestos minerals have been classified as carcinogens. Despite the Italian ban on asbestos in 1992 and the subsequent remediation activities, latent sources of contamination may still represent a hazard where asbestos were particularly used. Using wild rats as sentinel animals, this study aimed at uncovering sites with the greatest potential for non-occupational exposure to asbestos in the city of Casale Monferrato (Piedmont Region, Italy), where the largest Italian manufacturing plant of asbestos-cement had been active. During the study period (2013-2015) a total of 40 wild rats were captured from 16 sampling capture points. The lungs of wild rats have been investigated by using scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS). The SEM-EDS detected the presence of asbestos fibers (tremolite/actinolite, amosite, and chrysotile) in rats' lungs from 11 sampling points. The hypothetical rats' home-range and the observed site-specific concentration of asbestos fibers per gram of dry lung tissue were used to identify areas to be targeted by additional search of latent sources of asbestos. In conclusion, our results showed that the use of wild rats as sentinel animals may effectively integrate the strategies currently in use to reduce the exposure to asbestos.

Quantification of natural and synthetic glucocorticoids in calf urine following different growth-promoting prednisolone treatments.

Over the last few years, low levels of prednisolone have been reported in several cattle urine samples by a number of laboratories within the EU at an average concentration of 2.0 ng mL(-1). The occurrence of prednisolone residues together with increased levels of hydrocortisone and cortisone in urine and tissue samples of untreated animals seems to demonstrate that traces of this steroid can be produced endogenously during stressful situations. Therefore, the endogenous origin of prednisolone makes difficult to correlate positive samples to a potential illicit treatment. An experimental study was developed to investigate the presence of natural and synthetic glucocorticoids and to evaluate levels of excreted prednisolone following growth-promoting treatments. Urine samples from calves undergone oral treatment with prednisolone, alone and in association with dexamethasone, were analyzed by a LC-MS/MS method, validated according to the Commission Decision 2002/657/EC. We also investigated if urinary free 6ß-hydroxyhydrocortisone/hydrocortisone ratio could be a reliable biomarker of illicit treatment with prednisolone and dexamethasone in calves. Our data revealed that urinary levels of prednisolone after both oral prednisolone treatments, never exceeded the value of 1.1 ng mL(-1). Similar prednisolone levels were found in urine samples of untreated calves. Moreover the presence of 6ß-hydroxyhydrocortisone below the CCα value made possible to estimate the 6ß-hydroxyhydrocortisone/hydrocortisone ratio only in a very limited number of samples. Obtained data suggest that further criteria have to be considered to allow correct decisions about the urinary presence of prednisolone during control activities.

Identification by a proteomic approach of a plasma protein as a possible biomarker of illicit dexamethasone treatment in veal calves.

Corticosteroids have become the most widespread illegal growth promoters in veal calves and beef cattle. Testing for corticosteroids relies on either direct detection of compounds or their metabolites or indirect detection to identify changes in biological pathways. We used a comparative proteomic approach, based on two-dimensional electrophoresis (2DE), to identify plasma protein markers after short-term dexamethasone administration in veal calves. Twenty-three male Friesian veal calves were treated experimentally with dexamethasone sodium phosphate: 10 received low-dose administration of the drug (0.4 mg day⁻¹ per os) for 20 consecutive days (treatment group); 10 received the drug at therapeutic dosage (2-4 mg kg⁻¹ i.m.) for 3 consecutive days (comparison group). Three animals were not treated (control group). Plasma samples were collected from each animal at six time points (T1-T6; treatment and control group) and at four time points (T1-T4; comparison group) and stored at -80°C until analysis. Plasma proteins were quantified and analysed in triplicate by 2DE. The images were analysed with Bionumerics® software. Comparison of 2DE maps obtained from blood samples at T1 (before treatment) and at T6 (final sampling) showed a significant disappearance (p < 0.001) of two protein spots at T6 in the treatment group. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and immunoblotting identified these isoforms as serum paraoxonase/arylesterase 1 precursor (PON1). Synthesised in the liver and released into the blood, PON1 has an important role in lipid metabolism. The absence of variation of this protein in the comparison group suggests that the marker has good specificity for detecting illicit corticosteroid treatment.

Granulomatous lesions in a wild mullet population from the eastern Ligurian Sea (Italy): mycobacteriosis vs. pseudotuberculosis.

Mycobacterium spp. and Photobacterium damselae subsp. piscicida are recognized as the most frequent causative agents of granulomatous lesions in fish. Although frequent episodes of mycobacterial infections have been reported in wild fish worldwide, only sporadic cases have been documented to date in Italy. To investigate for the presence of lesions referable to mycobacteriosis and to identify the mycobacterial species involved, a total of 159 wild mullets were fished from the eastern coast of the Ligurian Sea, killed and necropsied. Liver and spleen samples were collected from all fish for histopathological and microbiological analyses. Molecular investigations for identification of Photobacterium damselae subsp. piscicida were performed. Gross examination revealed granulomatous lesions in one animal; microscopically, 42.14% of fish displayed granulomas with various histological features, 19.50% resulted positive at Ziehl-Neelsen staining, and were confirmed as mycobacterial lesions by culture. The identified colonies were characterized as M. fortuitum, M. abscessus, M. flavescens, M. chelonae, M. septicum and M. nonchromogenicum. In all, 35% of animals resulted positive for Photobacterium damselae subsp. piscicida. These data suggest widespread mycobacterial infection also by Photobacterium damselae subsp. piscicida infections in wild fish. Moreover, the pathogenicity of some mycobacterial species, previously considered as saprophytic, was demonstrated.

Histopathology as a simple and reliable method to detect 17ß-oestradiol illegal treatment in male calves.

17ß-Oestradiol is a steroid hormone banned as a growth promoter in food-producing animals all over Europe because of its carcinogenicity. Despite mandatory monitoring of illegal treatment all over Europe, official analytical methods in use test negative a few days after 17ß-oestradiol administration, requiring new sensitive tools to ensure a high level of protection for consumers. The aim of this work was the evaluation of the accuracy of histopathology and immunohistochemistry for progesterone receptor (PR) as a screening method for the detection of low-dosage illegal treatments with 17ß-oestradiol. Fresian male calves (153) were farmed under controlled conditions, and 89 of them were treated with 17ß-oestradiol (5 mg/animal once a week for 4 weeks). After 15 days of suspension, all animals were slaughtered and sexual accessory glands (prostate and bulbo-urethral glands) were sampled for histological examination and immunohistochemical staining with anti-PR antibody (clone hPRa 2). Microscopically 86 out of 89 bulbo-urethral glands showed mild to severe metaplasia, while mild metaplasia was observed only in 1 control. Eighteen out of 89 samples of prostate did not show metaplastic lesions. Immunopositivity for PR characterised all treated animals, while no signal was detected in controls. These findings show that metaplasia of the sexual accessory glands is a sensitive and specific parameter for illegal 17ß-oestradiol treatment in calves at the slaughterhouse, while the appliance of immunohistochemistry for PR can improve to 100% the accuracy of this highly reliable histological approach.

Application of absolute qPCR as a screening method to detect illicit 17ß-oestradiol administration in male cattle.

It has been previously demonstrated that the progesterone receptor gene is up-regulated in the sex accessory glands of pre-pubertal and adult male bovines after 17ß-oestradiol treatment. In the present study, a qualitative screening method was optimised to detect 17ß-oestradiol treatment using absolute quantification by qPCR of the progesterone receptor gene to determine the amount of gene expression in bulbo-urethral glands. An external standard curve was generated and developed with TaqMan® technology. Based on two in vivo experiments, the decision limit CCα, sensitivity and specificity of this screening method were established. Trial 1 consisted of 32 Friesian veal calves divided into two groups: group A (n = 12), consisting of animals treated with four doses of 17ß-oestradiol (5 mg week(-1) per animal); and group B (n = 20), consisting of control animals. Trial 2 was performed on 26 Charolaise beef cattle that either received five doses of 17ß-oestradiol (group C; 20 mg week(-1) per animal; n = 6) or remained untreated (group D; n = 20). Further, progesterone receptor gene expression was evaluated in beef and veal calves for human consumption. A specific CCα on 20 Piedmontese control beef cattle was calculated to include these animals in a field investigation. Five out of 190 beef cattle and 26 out of 177 calves tested expressed the progesterone receptor gene above their respective CCα and they were classified as being suspected of 17ß-oestradiol treatment. Additionally, 58% of veal calves that tested suspect via qPCR exhibited histological lesions of the bulbo-urethral gland tissue, which are typical of oestrogen administration and are consistent with hyperplasia and metaplasia of the glandular epithelium.

Histology as a valid and reliable tool to differentiate fresh from frozen-thawed fish.

Selling fish products as fresh when they have actually been frozen and thawed is a common fraudulent practice in seafood retailing. Unlike fish products frozen to protect them against degenerative changes during transportation and to extend the product's storage life, fish intended for raw consumption in European countries must be previously frozen at -20° C for at least 24 h to kill parasites. The aim of this study was to use histological analysis to distinguish between fresh and frozen-thawed fish and to evaluate this method for use as a routine screening technique in compliance with the requirements of European Commission Regulation No. 882/2004 on official food and feed controls. Method performance (i.e., accuracy and precision) was evaluated on tissue samples from three common Mediterranean fish species; the evaluation was subsequently extended to include samples from 35 fish species in a second experiment to test for method robustness. Method accuracy was tested by comparing histological results against a "gold standard" obtained from the analysis of frozen and unfrozen fish samples prepared for the study. Method precision was evaluated according to interrater agreement (i.e., three laboratories with expertise in histopathology in the first experiment and three expert analysts in the second experiment) by estimating Cohen's kappa (and corresponding 95 % confidence intervals) for each pair of laboratories and experts and the combined Cohen's kappa for all three experts and laboratories. The observed interrater agreement among the three laboratories and the three experts indicated high levels of method accuracy and precision (high sensitivity and specificity) and method reproducibility. Our results suggest that histology is a rapid, simple, and highly accurate method for distinguishing between fresh and frozen-thawed fish, regardless of the fish species analyzed.

Development of tertiary lymphoid structures in the kidneys of pigs with chronic leptospiral nephritis.

Tertiary lymphoid organs (TLOs) are structures that are morphologically and functionally similar to secondary lymphoid organs. TLOs usually arise in a background of chronic inflammation. Several histological patterns of interstitial nephritis have been documented in porcine leptospirosis. Among them the lympho-follicular pattern is characterized by infiltrates of mononuclear cells organized in lymphoid follicle-like structures. Immunohistological analysis of 5 cases of porcine lympho-follicular nephritis associated with Leptospira Pomona infection demonstrated the presence of inflammatory cell populations, including B cells, T cells, macrophages and follicular dendritic cells (FDCs), which were compartmentalized as in TLOs. Immunohistochemistry for Leptospira Pomona revealed an intimate association between leptospiral antigen and FDCs. Overexpression of MHCII in different populations of both professional and non-professional antigen presenting cells was also demonstrated. FDCs play role during TLOs induction for their ability to retain non-self antigens in the form of immune complexes, thus causing persistent T cell activation, generation of a complex cytokine network and stimulation of humoral immunity. Sustained bacterial antigen presentation in the context of chronic leptospiral nephritis, may also lead to autoimmune mechanisms involved in the generation of TLOs. Whether lymphoid neogenesis and TLOs play a protective role in porcine leptospiral nephritis is still unclear.

Development of an enhanced histopathological approach to detect low-dose dexamethasone illicit treatment in veal calves.

Dexamethasone is one of a number of synthetic corticosteroids illegally used to promote growth in food-producing animals. Since these low-level drug cocktails evade detection by currently available chemical methods, simple biological indicators that can aid in laboratory analysis are needed. In an attempt to devise an accurate biological method that could detect illicit drug treatment in food-producing animals, we characterized microscopic morphologic alterations of the thymus in veal calves administered low-dose dexamethasone versus control animals. For this purpose, 122 male calves were farmed for 6 months in controlled condition: 81 animals were orally administered dexamethasone (0.4 mg day(-1)) for 20 days during the sixth month and the remaining 41 were kept as control. Urine samples were collected systematically during the treatment period, the suspension period and at the slaughterhouse. All animals were slaughtered 10 per day starting from 10 days after the last dexamethasone administration and the thymus was sampled for histological examination. The difference between the two animal groups was evaluated by means of a non-parametric test of hypothesis. No residues were detected in the urines collected since the third day after the last administration, whereas morphometric analysis of the thoracic thymus revealed a significant decrease in the cortex:medulla ratio in the treated animals (p<0.0005). We can conclude that this histological approach offers encouraging prospects as a screening method to overcome current limitations in controlling growth promoter abuse.