New Synthetic Opioids Use among Patients in Treatment for an Opioid Use Disorder in Barcelona.

INTRODUCTION: New synthetic opioids (NSO), a class of new psychoactive substances (NPS), have recently emerged and pose an upcoming global public health challenge. The effects produced by NSO are similar to those from morphine, but they present greater pharmacological potency and abuse potential. Due to the increasing number of fatal overdoses and seizures in which NSO have been detected as heroin substitutes or adulterants, individuals with Opioid Use Disorder (OUD) represent a vulnerable population. The aim of our study was to describe and characterize from a gender perspective a Spanish cohort of potential conscious or unconscious NSO users. METHODS: A cross-sectional study was conducted in a cohort of OUD participants under treatment in addiction care services in Barcelona and Badalona, Spain. Clinical evaluation was performed through an ad hoc survey, a scale to evaluate reasons to use an opioid without prescription (range 0-4) and the Wellbeing Index (WHO-5) (range 0-100). Objective consumption of NSO was assessed by urinalysis carried out by two validated methods: high-sensitivity gas chromatography-mass spectrometry (MS) and ultra-high-performance liquid chromatography-high-resolution MS. RESULTS: A total of 154 participants with OUD were enrolled. They were mainly men (72.7%), mean age 47.8 years. Methadone was the predominant medication for opioid agonist treatment (mean dose 61.25 mg/day). A total of 32 (20.8%) participants reported having consumed some opioid to become "high" in the previous 3 months. The principal reasons for consuming illicit opioids were Replacing other drugs (mean 2.03) and Availability (mean 1.62), although Low price, was more highly valued by men (p = 0.045) and Shorter effect duration, most highly rated by women (p = <0.001). In the WHO-5, the mean score was 55 (SD = 30.1) without differences by gender. Fentanyl and derivatives or/and metabolites were detected in 7 (6.1%) participants, but illicit/non-prescribed NSOs were found in 5 out of 114 patients (4.4%), and other non-fentanyl opioids in 36 participants (26 men and 10 women). CONCLUSION: A non-negligible consumption of NSO-fentanyl's (positive detection in 6.1% of biological samples) was detected. The reasons for using these substances and also the well-being differed between the genders. There is therefore both voluntary and involuntary NSO consumption in our country which highlights the importance of approaching this potential public health problem.

Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry and High-Sensitivity Gas Chromatography-Mass Spectrometry Screening of Classic Drugs and New Psychoactive Substances and Metabolites in Urine of Consumers.

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 µm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100-1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40-550 m/z). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.

Cocaine and depressive disorders: When standard clinical diagnosis is insufficient. / Trastorno por uso de cocaína y depresión: Cuando el diagnóstico clínico no es suficiente.

BACKGROUND: Cocaine use is a growing global health problem and patients with cocaine use disorders (CUD) present several complications, including high rates of major depression. These subjects present two types of major depressive disorder (MDD): primary major depressive disorder (P-MDD) and cocaine-induced major depressive disorder (CI-MDD). To improve treatment, it is necessary to distinguish between both types. The aim of this study was to assess the differences in depressive symptomatology criteria (P-MDD vs CI-MDD) in CUD patients. METHODS: Secondary data analysis was carried out with a cross-sectional sample of 160 patients presenting CUD and MDD. Clinical assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). A differential diagnosis was obtained between P-MDD and CI-MDD. RESULTS: Men represented 80% of the sample, the mean age was 38.61 years, and 64.5% had elementary studies. CI-MDD diagnosis (61.3%) was more frequent than P-MDD (38.7%). There was a younger age of CUD onset in CI-MDD patients. In addition, 79.4% of the patients had another substance use disorder diagnosis. The criterion "Changes in weight or appetite" was more prevalent (57.1%) in P-MDD group. CONCLUSIONS: We found differences in the criterion "Changes in weight or appetite". Further research is needed in this field to establish a differential diagnosis and thus provide better treatment for CUD patients.

Antecedentes: El consumo de cocaína es un creciente problema de salud en todo el mundo. Además, los pacientes con trastorno por consumo de cocaína (TCC) presentan una alta comorbilidad con el trastorno depresivo mayor (TDM). Estos pacientes pueden presentar dos tipos de TDM: trastorno depresivo mayor primario (TDM-P) y trastorno depresivo mayor inducido por cocaína (TDM-IC). El objetivo de este estudio es evaluar las diferencias en la sintomatología depresiva (TDM-P vs. TDM- IC) en los pacientes con TCC para mejorar su tratamiento. Métodos: Se llevó a cabo un análisis secundario en una muestra transversal de 160 pacientes que presentaban TCC y algún TDM. La evaluación clínica, así como el diagnóstico diferencial entre TDM-P y TDM-IC, se realizó utilizando la entrevista PRISM. Resultados: Los hombres representaron el 80% de la muestra con una edad media de 38,61 años y el 64,5% sólo tenía estudios primarios. El diagnóstico de TDM-IC (61,3%) fue más frecuente que el de TDM-P (38,7%). Los pacientes con TDM-IC mostraron una edad de aparición más temprana para el TCC. El 79,4% de los pacientes cumplían criterios para otro trastorno por consumo de sustancias. Únicamente el criterio "Cambios en el peso o en el apetito" fue estadísticamente más prevalente (57,1%) en los pacientes con TDM-P. Conclusiones: Existen diferencias en el criterio "Cambios en el peso o en el apetito" entre TDM-P y TDM-IC. Se necesita más investigación a fin de obtener un diagnóstico diferencial entre los dos tipos de depresión y proporcionar un mejor tratamiento para los pacientes con TCC.

Focal high-dose-rate brachytherapy for localized prostate cancer: toxicity and preliminary biochemical results.

BACKGROUND: This study aimed to evaluate the outcomes and the toxicity of focal high-dose-rate (HDR) brachytherapy in selected localized prostate cancer patients. METHODS: Fifty patients were treated with focal high-dose-rate brachytherapy between March 2013 and November 2017, representing 5% of the cases treated by our group during this period. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The prescribed dose for the focal volume was 24 Gy. RESULTS: The treated volume corresponded to a mean value of 32% of the total prostatic volume. The mean focal D90 in our series was 23 Gy (range 16-26 Gy). The mean initial IPSS was 8.2 (range 0-26), at 6 months 7.5 (range 0-23), and at 24 months 6.7 (range 0-18). No acute or late urinary retention was seen. When the ICIQ-SF score was 0 at the end of treatment, it remained nil thereafter at 1 and 2 years for all patients. No intraoperative or perioperative complications occurred. No rectal toxicity was reported after treatment. Of the total patients identified as potent, only three patients had a very slight decrease of the mean IIEF5. The mean initial PSA was 6.9 ng/mL (range 1.9-13.4). At the last follow-up visit, the mean PSA was 3 ng/ml (range 0.48-8.11). CONCLUSION: HDR focal brachytherapy in selected patients with low intermediate-risk prostate cancer could achieve the same satisfactory results in terms of relapse-free survival as conventional whole prostate brachytherapy with less toxicity.

Surgical delay is a risk factor of delirium in hip fracture patients with mild-moderate cognitive impairment.

AIM: To investigate the relationship between onset of delirium and time to surgery in hip fracture (HF) patients with a different degree of cognitive impairment. METHODS: Retrospective analysis of a prospective database of 939 older adults, aged ≥ 75 years admitted with a fragility HF. Subjects underwent a Comprehensive Geriatric Assessment on admission, evaluating health status, prefracture functional status in basic and instrumental activities of daily living, and walking ability. According to the Short Portable Mental Status Questionnaire score, patients were stratified into three categories: cognitively healthy (0-2 errors), mildly to moderately impaired (3-7 errors) and severely impaired (8-10 errors). Time to surgery (from admission) was expressed as days. The occurrence of delirium was ascertained daily by Confusion Assessment Method. RESULTS: Two hundred ninety-two (31.1%) patients experienced delirium during in-hospital stay. They were older, with a higher degree of comorbidity and functional impairment compared to patients without delirium. In multivariate analysis, surgical delay resulted a significant independent risk factor for delirium (HR 1.11, 95% CI 1.01-1.24), along with age, prefracture functional disability and cognitive impairment. When the analysis was performed accounting for the cognitive categories, surgical delay demonstrated to increase the risk of delirium only in the subcategory of mildly to moderately impaired patients, while no significant effect was demonstrated in patients cognitively healthy or severely impaired. CONCLUSIONS: The study supports the concept that older adults with HF should undergo surgery quickly. Patients with mild-to-moderate cognitive impairment should be primarily considered as the best target for interventions aiming to reduce time to surgery.

Autoantibodies to cytoplasmic rods and rings in patients with hepatitis C virus infection treated with direct-acting antivirals: The role of prior treatment with interferon plus ribavirin.

INTRODUCTION: The cytoplasmic rods-rings (RR) pattern is found in hepatitis C (HCV) patients treated with interferon-ribavirin when studied with ANA-IIF. Ribavirin aggregates/induces antigenic changes in IMPDH-2, an enzyme necessary for ribavirin action. PATIENTS AND METHOD: Prospective search for anti-RR autoantibodies (HEp-2, INOVA) in patients treated with direct-acting antivirals (DAAs) from October 2015 to June 2017. HCV-negative patients from up to June 2016 acted as controls. Anti-RR was analyzed at baseline and, mainly, during treatment and follow-up. The Chi-square test, Student's t-test and a logistic regression analysis were performed. RESULTS: Between October 2015 and June 2016, 1258 men and 2389 women who were HCV-negative and 137 men and 112 women who were HCV-positive patients were studied. Approximately 22.9% of HCV-negative and 13.2% of HCV-positive were ANA-IIF-positive (p<0.05). Three HCV-negative (0.08%) and 23 (9.2%) HCV-positive patients had anti-RR (p<0.001). A total of 122 patients received DAAs; 30 received DAA+RBV; 46 pre-treated with IFN-RBV received DAA; 31 pre-treated with IFN-RBV received DAA+RBV; 16 received IFNpeg-RBV; and 24 received IFN-RBV-DAA. None of the 122 DAA-treated patients showed anti-RR; anti-RR were identified in 14.8% of those treated with DAA-RBV; in 25.9% of those pre-treated with IFN-RBV receiving DAA; in 22.2% of IFN-RBV-pre-treated patients who received DAA+RBV; in 7.4% of those treated with IFNpeg-RBV and in 29.6% of those treated with IFNpeg-RBV-DAA. The multivariate analysis showed significant associations between anti-RR and "Exposure to IFN" and "Time of exposure to RBV". CONCLUSIONS: Anti-RR autoantibodies were detected only in patients with current or past treatments with RBV, even in cases in which only DAAs were later administered.

Understanding the interactions of diruthenium anticancer agents with amino acids.

The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-κO)-2-methyl-4-(1H)-pyridinonato-κO4](η6-p-cymene)-ruthenium(II)}alkane (PyRu 2n ) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein-DNA and DNA-DNA crosslinking ability. We report here studies on the reactions of the diruthenium organometallics PyRu 26 and PyRu 28 in comparison with a mononuclear analogue PyRu3 with amino acids using mass spectrometry and NMR spectroscopy. The compounds behave very similarly, independent of the spacer length between the metal center and of the nuclearity of the complexes. Incubation with L-cysteine (Cys) results in fast release of the pyridone ligand, with the Ru complexes able to form Cys adducts. In contrast, L-methionine forms, initially, adducts with the metal centers, but over time, the adducts decompose. Similar behavior was observed for the reaction with L-histidine with [Ru(η6-p-cymene)(L-histidine)] species detected.

Long-term outcomes in patients younger than 60 years of age treated with brachytherapy for prostate cancer.

PURPOSE: The purpose of the study was to report the outcomes and late toxicities in patients younger than 60 years of age with long-term follow-up treated with low dose rate (LDR) brachytherapy for localized prostate cancer. METHODS: Between January 2000 and December 2009, 270 consecutive patients were treated with favourable localized prostate cancer; the median follow-up was 111 months (range 21-206). All patients received one implant of LDR brachytherapy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Events, Version 4.0 (CTAE v4.02) by the National Cancer Institute. RESULTS: The overall survival according to Kaplan-Meier estimates was 99 (±1%) at 17 years. The 17-year rate for failure in tumour-free survival (TFS) was 97% (±1%), whereas for biochemical control it was 95% (±1%) at 17 years, 97% (±1%) of patients being free of local recurrence. No intraoperative or perioperative complications occurred. Acute genitourinary (GU) grade II toxicity was 4% at 12 months. No other chronic toxicity was observed after treatment. At 6 months, 94% of patients reported no change in bowel function. CONCLUSIONS: LDR brachytherapy provides patients younger than 60 years of age with low and intermediate-risk prostate cancer excellent outcomes and has a low risk of significant long-term GU or gastrointestinal morbidity.

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer. Longterm results.

OBJECTIVES: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. METHODS AND MATERIALS: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the "Phoenix consensus". Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. RESULTS: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. CONCLUSIONS: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer.

Risk of infections related to endovascular catheters and cardiac implantable devices in hemodialysis patients.

Patients requiring dialysis are extremely vulnerable to infectious diseases. The high burden of comorbidities and weakened immune system due to uremia and previous immunosuppressive therapy expose the patient on dialysis to more infectious events than the general population. The infectious risk is further increased by the presence of endovascular catheters and implantable cardiologic devices. The former is generally placed as urgent vascular access for dialysis and in subjects requiring hemodialysis treatments without autogenous arteriovenous fistula. The high frequency of cardiovascular events also increases the likelihood of implanting indwelling implantable cardiac devices (CIED) such as pacemakers (PMs) and defibrillators (ICDs). The simultaneous presence of CVC and CIED yields an increased risk of developing severe prosthetic device-associated bloodstream infections often progressing to septicemia. Although, antibiotic therapy is the mainstay of prosthetic device-related infections, antibiotic resistance of biofilm-residing bacteria reduces the choice of infection eradication. In these cases, the resolution of the infection process relies on the removal of the prosthetic device. Compared to CVC removal, the extraction of leads is a more complex procedure and poses an increased risk of vessel tearing. As a result, the prevention of prosthetic device-related infection is of utmost importance in hemodialysis (HD) patients and relies principally on avoiding CVC as vascular access for HD and placement of a new class of wireless implantable medical devices. When the combination of CVC and CIED is inevitable, prevention of infection, mainly due translocation of skin bacteria, should be a mandatory priority for healthcare workers.

Liquid biopsy to personalize treatment for metastatic prostate cancer.

Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It complements invasive tissue biopsy and involves the assessment of various biomarkers in body fluids such as blood, semen, and urine. Liquid biopsy analyzes circulating tumor cells, extracellular vesicles, circulating tumor DNA, and the secretome. This is particularly important given the heterogeneity of prostate cancer and the need for better prognostic biomarkers. Liquid biopsy can personalize the treatment of homonosensitive and castration-resistant metastatic prostate cancer by acting as a predictive and prognostic tool. This review discusses various biomarkers, assay techniques, and potential applications in daily clinical practice, highlighting the exciting possibilities that this emerging field holds for improving patient outcomes.

Evaluation of an integrated system for classification, assessment and comparison of services for long-term care in Europe: the eDESDE-LTC study.

BACKGROUND: The harmonization of European health systems brings with it a need for tools to allow the standardized collection of information about medical care. A common coding system and standards for the description of services are needed to allow local data to be incorporated into evidence-informed policy, and to permit equity and mobility to be assessed. The aim of this project has been to design such a classification and a related tool for the coding of services for Long Term Care (DESDE-LTC), based on the European Service Mapping Schedule (ESMS). METHODS: The development of DESDE-LTC followed an iterative process using nominal groups in 6 European countries. 54 researchers and stakeholders in health and social services contributed to this process. In order to classify services, we use the minimal organization unit or "Basic Stable Input of Care" (BSIC), coded by its principal function or "Main Type of Care" (MTC). The evaluation of the tool included an analysis of feasibility, consistency, ontology, inter-rater reliability, Boolean Factor Analysis, and a preliminary impact analysis (screening, scoping and appraisal). RESULTS: DESDE-LTC includes an alpha-numerical coding system, a glossary and an assessment instrument for mapping and counting LTC. It shows high feasibility, consistency, inter-rater reliability and face, content and construct validity. DESDE-LTC is ontologically consistent. It is regarded by experts as useful and relevant for evidence-informed decision making. CONCLUSION: DESDE-LTC contributes to establishing a common terminology, taxonomy and coding of LTC services in a European context, and a standard procedure for data collection and international comparison.

A matter of fat: insulin resistance and oxidative stress.

BACKGROUND: Obesity is linked to insulin resistance (IR), which can lead to type 2 diabetes mellitus. Oxidative stress present in early obesity may favor the progression to comorbid conditions. OBJECTIVE: To examine the relationship between oxidative stress biomarkers and the severity of IR in a group of obese children. METHODS: Forty obese children with a body mass index (BMI) Z-score ≥ 2 were divided into two groups using the median obtained for the homeostasis model assessment of IR (HOMA-IR). Anthropometric parameters (including body fat composition by bioelectrical impedance) and biochemical parameters were assessed. The following biomarkers of oxidative stress were measured: malondialdehyde (MDA), carbonyl groups (CG), reduced glutathione, oxidized low-density lipoprotein, and vitamin E. Comparisons were adjusted for gender and Tanner stage. RESULTS: Children with high values of HOMA-IR were more likely to have high body fat percentage and waist circumferences. However, the BMI Z-score did not correlate to the level of IR. Children with higher values of HOMA-IR presented increased levels of markers of oxidative stress in lipids (MDA, p = 0.005) and proteins (CG, p = 0.015). Moreover, MDA increased with increasing levels of HOMA-IR (r = 0.50, p = 0.002), suggesting that lipoperoxidation increases as IR worsens. In a multivariate regression model, only HOMA-IR was predictive of MDA values, irrespective of adiposity parameters and other metabolic risk factors (r2 = 0.22, p = 0.002). CONCLUSIONS: Oxidative stress increases in obese children according to the severity of IR, which could be linked to the development of comorbidities.

First Human Case of Tick-Borne Encephalitis in Non-Endemic Region in Italy: A Case Report.

Tick-borne encephalitis (TBE), a human viral infectious disease caused by the tick-borne encephalitis virus (TBEV), is emerging in Italy, especially in the north-eastern area. No human cases of autochthonous TBE have been reported in Italy's central regions (such as Emilia-Romagna, Italy). However, here we describe the first human case of TBEV infection in this region, pointing to endemic transmission of TBEV, supporting the concept of circulation of TBEV and of the presence of a possible hot spot in the Serramazzoni region in the Emilian Apennines.

Intraoperative Neurovascular Bundle Preservation with Hyaluronic Acid during Radical Brachytherapy for Localized Prostate Cancer: Technique and MicroMosfet In Vivo Dosimetry.

PURPOSE: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance from NB to the radioactive sources. METHODS: This is the first published report in the medical literature that studies a new approach to decrease neurovascular bundle toxicity and improve quality of life for patients with prostate cancer treated with radical brachytherapy as monotherapy. Transperineal HA injection on the side of the prostate into the lateral aspect of the prostate fat was used to consistently displace several autonomic fibers and vessels on the lateral wall of the prostate away from radiation sources. RESULTS: When a protection in the form of an HA layer is placed, the reduction effect at the maximum dose is between 46% and 54% (calculated values), which means that the method for protection is highly recommended. The values of the absorbed dose calculated in this project have been compared with the ones given by the treatment planning system. CONCLUSIONS: This newly created space decreases absorbed dose in the NB, calculated with the TPS and measured by microMOSFET due to the thickness of HA.

Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images.

BACKGROUND AND OBJECTIVES: Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. RESULTS: We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. CONCLUSIONS: The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.

Synthetic cannabinoids use in a sample of opioid-use disorder patients.

Cannabis is the most widely consumed illegal drug in the world and synthetic cannabinoids are increasingly gaining popularity and replacing traditional cannabis. These substances are a type of new psychoactive substance that mimics the cannabis effects but often are more severe. Since, people with opioids use disorder use widely cannabis, they are a population vulnerable to use synthetic cannabinoids. In addition, these substances are not detected by the standard test used in the clinical practice and drug-checking is more common in recreational settings. A cross-sectional study with samples of 301 opioid use disorder individuals was carried out at the addiction care services from Barcelona and Badalona. Urinalysis was performed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high -resolution mass spectrometry (UHPLC-HRMS). Any synthetic cannabinoid was detected in 4.3% of the individuals and in 23% of these samples two or more synthetic cannabinoids were detected. Among the 8 different synthetic cannabinoids detected, most common were JWH-032 and JWH-122. Natural cannabis was detected in the 18.6% of the samples and only in the 0.7% of them THC was identified. Several different synthetic cannabinoids were detected and a non-negligible percentage of natural cannabis was detected among our sample. Our results suggest that the use of synthetic cannabinoids may be related to the avoidance of detection. In the absence of methods for the detection of these substances in clinical practice, there are insufficient data and knowledge making difficult to understand about this phenomenon among opioid use disorder population.

New Psychoactive Substances Consumption in Opioid-Use Disorder Patients.

(1) Background: Since the beginning of the 21st century, the large number and wide chemical variety of new psychoactive substances (NPS) that enter the market every year has become a public health problem. Given the rapidity with which the drug market is changing, many NPS are not clinically investigated and their effects and health risks are unknown. Drug testing is a very useful tool for this purpose, but, unfortunately, it is not very widespread in individuals with opioid-use disorder under detoxification treatment. The aim of this study is to investigate the use of illicit drugs and NPS in opioid-use disorder (OUD) patients on opioid agonist treatment. (2) Methods: A multicenter, descriptive, cross-sectional study was conducted at two addiction care services in Barcelona and Badalona, Spain. Urine samples were collected from OUD individuals attending these two centers, who anonymously donated a urine sample at the time of a periodical visit. Samples were analyzed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high -resolution mass spectrometry (UHPLC-HRMS). (3) Results: Out of the 187 collected and analyzed urine samples, 27.3% were positive for any type of NPS and 8.6% were positive for new synthetic opioids, including fentanyl and its derivatives (NSO). Other frequently detected substances were benzodiazepines in 46.0% of samples, antipsychotics in 27.8% of samples, or cocaine and cannabis in 23.5% of samples. (4) Conclusion: A wide number of NPS, including NSO, have been detected in urine samples from an OUD population. A lack of NPS detection in standard drug screening among drug users can hide the identification of a potential public health problem.

A Gender Perspective of Addictive Disorders.

PURPOSE OF REVIEW: Substance use disorders (SUD) affect differentially women and men. Although the prevalence has been reported higher in men, those women with addictive disorders present a more vulnerable profile and are less likely to enter treatment than men. The aim of this paper is to present an overview of how sex and gender may influence epidemiology, clinical manifestations, social impact, and the neurobiological basis of these differences of women with SUD, based on human research. RECENT FINDINGS: The differences in prevalence rates between genders are getting narrower; also, women tend to increase the amount of consumption more rapidly than men, showing an accelerated onset of the SUD (telescoping effect). In respect to clinical features, the most important differences are related to the risk of experience psychiatric comorbidity, the exposure to intimate partner violence, and the associated high risks in sexual and reproductive health; and those who are mothers and addicted to substances are at risk of losing the custody of children accumulating more adverse life events. Some of these differences can be based on neurobiological differences: pharmacokinetic response to substances, sensitivity to gonadal hormones, differences in neurobiological systems as glutamate, endocannabinoids, and genetic differences. SUMMARY: Specific research in women who use drugs is very scarce and treatments are not gender-sensitive oriented. For these reasons, it is important to guarantee access to the appropriate treatment of women who use drugs and a need for a gender perspective in the treatment and research of substance use disorders.

Global Oral Health Policies and Guidelines: Using Silver Diamine Fluoride for Caries Control.

Silver diamine fluoride (SDF) was developed in Japan in the 1960s. It is a clear solution containing silver and fluoride ions. Because of its anti-bacterial and remineralizing effect, silver diamine fluoride has been used in managing dental caries for decades worldwide. This paper aims to summarize and discuss the global policies, guidelines, and relevant information on utilizing SDF for caries management. SDF can be used for treating dental caries in most countries. However, it is not permitted to be used in mainland China. Several manufacturers, mainly in Australia, Brazil, India, Japan, and the United States, produce SDF at different concentrations that are commercially available around the world. The prices differ between contents and brands. Different government organizations and dental associations have developed guidelines for clinical use of SDF. Dental professionals can refer to the specific guidelines in their own countries or territories. Training for using SDF is part of undergraduate and/or postgraduate curriculums in almost all countries. However, real utilization of SDF of dentists, especially in the private sector, remains unclear in most places because little research has been conducted. There are at least two ongoing regional-wide large-scale oral health programs, using SDF as one of the components to manage dental caries in young children (one in Hong Kong and one in Mongolia). Because SDF treatment does not require caries removal, and it is simple, non-invasive, and inexpensive, SDF is a valuable strategy for caries management in young children, elderly people, and patients with special needs. In addition, to reduce the risk of bacteria or virus transmission in dental settings, using SDF as a non-aerosol producing procedure should be emphasized under the COVID-19 outbreak.