Memantine Inhibits Calcium-Permeable AMPA Receptors.

Memantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimer's. NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine blocks CP-AMPAR ion channels in a unique mechanism of action from NMDARs. Furthermore, we demonstrate that memantine reverses a gain of function AMPAR mutation found in a patient with a neurodevelopmental disorder and inhibits CP-AMPARs in nerve injury. Our findings alter the paradigm for the memantine mechanism of action and provide a blueprint for therapeutic approaches targeting CP-AMPARs.

The use of healthcare services and disabling chronic pain: results from the cross-sectional population-based Andalusian Health Survey.

BACKGROUND: Several factors seem to be related to the use of healthcare services, and chronic pain (CP) is among these characteristics. The objective is to describe the number of visits to a doctor's surgery or emergency rooms, and the periods of hospitalization; to identify characteristics associated with frequent healthcare use, including disabling chronic pain (DCP) and non-disabling chronic pain (n-DCP). METHODS: Representative population-based cross-sectional study of 6569 people older than 16 years from southern Spain was collected. The frequency of visits to a doctor's surgery or emergency rooms and periods of hospitalization were defined as at or above the 90th percentile. Binary logistic regression analyses were conducted separately on women and men to identify characteristics associated with being frequent visitors. RESULTS: People with DCP are more frequent visitors to a doctor's surgery and emergency rooms and endure longer periods of hospitalization compared to people with n-DCP and without pain. In logistic regression models, people with DCP are twice as likely to over-visit a doctor's surgery; to endure longer periods of hospitalization and more visits to an emergency room service. No relationship was found in n-DCP. CONCLUSIONS: Disability seems to modulate a greater use of health services among the population with CP, doubling it when compared to n-DCP and n-CP, both in women and men. Understanding the role of disability in the use of healthcare services for individuals with CP allows for the identification of needs and strategies to optimize resources.

Novel pentafluorosulfanyl-containing triclocarban analogs selectively kill Gram-positive bacteria.

Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization. IMPORTANCE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.

Understanding the Impact of Chronic Non-Cancer Pain on Daily Life from a Gender Perspective Using the PAIN_Integral Scale©.

The experience of chronic non-cancer pain differs between women and men due to gender-related factors. This study (1) assessed the difference in responses to the impact of chronic non-cancer pain on daily life in women and men using the PAIN_Integral Scale© and (2) evaluated its invariance through multigroup confirmatory factor analysis. This was conducted by means of an analysis of invariance through a multigroup confirmatory factor analysis. A cross-sectional sample of 400 participants over 18 years of age with Chronic Non-Oncological Pain in Pain Units and Primary Care Centres belonging to the Spanish Public Health System was recruited (January to March 2020). An analysis was performed to assess whether any of the items in the instrument showed different behaviours. All analyses were performed using AMOS® v.26 software. The results showed that the structure of the PAIN_Integral© Scale remained adequate when analysing its invariance in women and men, showing no metric, scalar and/or strict invariance. Therefore, these results indicated that the PAIN_Integral Scale© instrument has a different interpretation for women and men, identifying eight items with a singular functioning in both sexes and belonging to the subscales of proactivity, resilience and support network. These findings can be explained by gender stereotypes, since the dimensions where there are differences have an important social burden.

A rare case of Salmonella-associated acute pancreatitis in a patient with ulcerative colitis.

Inflammatory bowel disease is a known risk factor for enteric infections such as Salmonella. This infection can affect almost all major organs. Acute Salmonella pancreatitis is a rare complication. This is the case of a 61-year-old man with ulcerative colitis who developed acute pancreatitis complicating Salmonella infection.

Ozone responses to reduced precursor emissions: A modeling analysis on how attainable goals can improve air quality in the Mexico City Metropolitan Area.

High tropospheric ozone (O3) concentrations prevent the improvement of the air quality in the Mexico City Metropolitan Area (MCMA). Although the problem has improved considerably since the 1990s, a rebound in O3 levels in recent years has raised concerns about the deteriorating air quality. The nonlinear relationship between O3 formation and the emissions of its main precursors, i.e., volatile organic compounds (VOCs) and nitrogen oxides (NOx), is a challenge when measures are enacted for effective mitigation of the O3 problem. This study evaluated the reduction in precursors, VOCs and NOx, using an up-to-date regional air quality model (HERMES-Mex-WRF-CMAQ). For evaluating realizable scenarios, the decline in VOC achieved in Japan after policy implementation was the targeted VOC reduction (40 % from area sources), and the NOx reduction observed in the MCMA during the COVID-19 pandemic was the targeted NOx reduction (40 % from mobile sources). The analysis evaluated the O3 responses to changes in a single precursor and a combination of both during a period of high O3 concentrations (April 2019). The results showed that 40 % reduction in VOC emissions would decrease the O3 8-h maximum concentrations by 16 %. However, 40 % reduction in NOx emissions would increase O3 by >15 %. The simultaneous reduction of both precursors did not significantly affect O3 levels. The diagnosis of ozone sensitivity using the H2O2/HNO3 ratios reinforced the simulation findings, indicating that VOC emissions limited ozone formation in most MCMA areas. As the simulated scenarios were based on factual case studies, our research offers insights into the realistic aims of MCMA policies to reduce O3 levels.

Novel molecular mechanism driving neuroprotection after soluble epoxide hydrolase inhibition: Insights for Alzheimer's disease therapeutics.

BACKGROUND: Neuroinflammation is widely recognized as a significant hallmark of Alzheimer's disease (AD). To combat neuroinflammation, the inhibition of the soluble epoxide hydrolase (sEH) enzyme has been demonstrated crucial. Importantly, sEH inhibition could be related to other neuroprotective pathways described in AD. AIMS: The aim of the study was to unveil new molecular pathways driving neuroprotection through sEH, we used an optimized, potent, and selective sEH inhibitor (sEHi, UB-SCG-51). MATERIALS AND METHODS: UB-SCG-51 was tested in neuroblastoma cell line, SH-SY5Y, in primary mouse and human astrocytes cultures challenged with proinflammatory insults and in microglia cultures treated with amyloid oligomers, as well as in mice AD model (5XFAD). RESULTS: UB-SCG-51 (10 and 30 µM) prevented neurotoxic reactive-astrocyte conversion in primary mouse astrocytes challenged with TNF-α, IL-1α, and C1q (T/I/C) combination for 24 h. Moreover, in microglial cultures, sEHi reduced inflammation and glial activity. In addition, UB-SCG-51 rescued 5XFAD cognitive impairment, reducing the number of Amyloid-ß plaques and Tau hyperphosphorylation accompanied by a reduction in neuroinflammation and apoptotic markers. Notably, a transcriptional profile analysis revealed a new pathway modulated by sEHi treatment. Specifically, the eIF2α/CHOP pathway, which promoted the endoplasmic reticulum response, was increased in the 5XFAD-treated group. These findings were confirmed in human primary astrocytes by combining sEHi and eIF2α inhibitor (eIF2αi) treatment. Besides, combining both treatments resulted in increased in C3 gene expression after T/I/C compared with the group treated with sEHi alone in cultures. DISCUSSION: Therefore, sEHi rescued cognitive impairment and neurodegeneration in AD mice model, based on the reduction of inflammation and eIF2α/CHOP signaling pathway. CONCLUSIONS: In whole, our results support the concept that targeting neuroinflammation through sEH inhibition is a promising therapeutic strategy to fight against Alzheimer's disease with additive and/or synergistic activities targeting neuroinflammation and cell stress.

Tobacco Mild Green Mosaic Virus (TMGMV) Isolates from Different Plant Families Show No Evidence of Differential Adaptation to Their Host of Origin.

The relevance of tobamoviruses to crop production is increasing due to new emergences, which cannot be understood without knowledge of the tobamovirus host range and host specificity. Recent analyses of tobamovirus occurrence in different plant communities have shown unsuspectedly large host ranges. This was the case of the tobacco mild green mosaic virus (TMGMV), which previously was most associated with solanaceous hosts. We addressed two hypotheses concerning TMGMV host range evolution: (i) ecological fitting, rather than genome evolution, determines TMGMV host range, and (ii) isolates are adapted to the host of origin. We obtained TMGMV isolates from non-solanaceous hosts and we tested the capacity of genetically closely related TMGMV isolates from three host families to infect and multiply in 10 hosts of six families. All isolates systemically infected all hosts, with clear disease symptoms apparent only in solanaceous hosts. TMGMV multiplication depended on the assayed host but not on the isolate's host of origin, with all isolates accumulating to the highest levels in Nicotiana tabacum. Thus, results support that TMGMV isolates are adapted to hosts in the genus Nicotiana, consistent with a well-known old virus-host association. In addition, phenotypic plasticity allows Nicotiana-adapted TMGMV genotypes to infect a large range of hosts, as encountered according to plant community composition and transmission dynamics.

Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress.

Soluble epoxide hydrolase (sEH) is a drug target with the potential for therapeutic utility in the areas of inflammation, neurodegenerative disease, chronic pain, and diabetes, among others. Proteolysis-targeting chimeras (PROTACs) molecules offer new opportunities for targeting sEH, due to its capacity to induce its degradation. Here, we describe that the new ALT-PG2, a PROTAC that degrades sEH protein in the human hepatic Huh-7 cell line, in isolated mouse primary hepatocytes, and in the liver of mice. Remarkably, sEH degradation caused by ALT-PG2 was accompanied by an increase in the phosphorylated levels of AMP-activated protein kinase (AMPK), while phosphorylated extracellular-signal-regulated kinase 1/2 (ERK1/2) was reduced. Consistent with the key role of these kinases on endoplasmic reticulum (ER) stress, ALT-PG2 attenuated the levels of ER stress and inflammatory markers. Overall, the findings of this study indicate that targeting sEH with degraders is a promising pharmacological strategy to promote AMPK activation and to reduce ER stress and inflammation.

Valoración del liderazgo enfermero en un hospital del Sistema Sanitario Público Andaluz / Leadership in a hospital of the Andalusian Public Health System

Objetivo: Analizar, con perspectiva de género, las características y la percepción de los efectos del liderazgo de las enfermeras y enfermeros de un hospital del Sistema Sanitario Público Andaluz. Metodología: Estudio cualitativo con enfoque fenomenológico. Los/as participantes fueron enfermeras asistenciales y con cargos intermedios con contrato mayor a 6 meses. Se realizó un análisis de contenido cualitativo. Se establecieron 4 fases para el análisis de datos, de donde resultaron 5 categorías. Se utilizó el software NVivo 11 para el análisis de los diálogos. Resultados: Los discursos de los participantes dotan al líder de características que lo definen como una persona referente. La contribución de los mandos intermedios es necesaria para la consecución de los objetivos de las unidades asistenciales y cohesión del grupo, aunque este grupo la perciben solo en relación al manejo de los recursos. El acceso a cargos de gestión no tiene vinculación con el género. Conclusiones: El estilo de liderazgo predominante en los cargos intermedios del Hospital de Lebrija es reconocido como un liderazgo participativo, esencial para el mantenimiento de la gestión eficiente y favorecedor de la promoción y la igualdad entre profesionales; no identificándose sesgos de género en el acceso a dichos cargos.(AU)

Objective: To analyse, from a gender perspective, the characteristics and perception of the effects of leadership of nurses in a hospital of the Andalusian Public Health System. Methodology: Qualitative study with a phenomenological approach. The participants were nurses in care and intermediate positions with a contract of more than 6 months. A qualitative content analysis was carried out. Four phases were established for data analysis, from which 5 categories resulted. NVivo 11 software was used to analyse the dialogues. Results: The participants’ discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender. Conclusions: The participants’ discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender.(AU)

Bienestar eudaimónico y meditación mindfulness en los contextos laborales: una revisión sistemática / Eudaimonic Well-Being and Mindfulness Meditation in the Work-place: A Systematic Review

El objetivo de este estudio es analizar los efectos de las intervenciones basadas en mindfulness (IBMs) sobre variables relacionadas con el bienestar eudaimónico en contextos laborales. Para ello, se realizó una revisión sistemática de ensayos controlados aleatorizados, efectuándose una búsqueda de publicaciones relevantes en las bases de datos PsycInfo, Pubmed y ProQuest (acotando desde enero de 2009 a diciembre de 2019). Los términos de búsqueda incluyeron variables relacionadas con la eudaimonia (p. ej. resilience, maturity, wisdom, etc.). 9006 estudios fueron revisados, de los que 16 fueron incluidos finalmente. Se identificaron 9 variables psicológicas relacionadas con el modelo de bienestar eudaimónico de Ryff (2018). Los estudios diferían en el tipo de IBM, duración de la intervención, tiempo de práctica y variables eudaimónicas evaluadas. En general, las IBMs son eficaces, con tamaños de efecto medios, para mejorar autoaceptación, relaciones positivas y crecimiento personal. No obstante, son necesarios nuevos estudios de mayor calidad.(AU)

This systematic review analyzes the effects of mindfulness-based interventions (MBIs) on variables related to eudaimonic well-being in or-ganizational contexts. A searchfor relevant publications was conducted in the PsycInfo, Pubmed, and ProQuest databases, ranging from January 2009 to December 2019. The search terms included variables related to Ryff's psychological well-being model (2018) (e.g., resilience, maturity, wis-dom, autonomy, etc.). 9006 studies were reviewed following the PRISMA guidelines, of which 16 were included. Nine psychological variables related to eudaimonia were identified. The studies differed in the type of MBI, du-ration of the intervention, time of practice and eudaimonic variables evalu-ated. MBIs are effective, with medium effect sizes, to improve self-acceptance, positive relationships, and personal growth. However, high-quality studies are needed.(AU)

Endoscopic Vacuum Therapy for Upper Gastrointestinal Leaks and Perforations: Analysis From a Multicenter Spanish Registry.

INTRODUCTION: Endoscopic vacuum therapy (EVT) is a novel technique for closing upper gastrointestinal (UGI) defects. Available literature includes single-center retrospective cohort studies with small sample sizes. Furthermore, evidence about factors associated with EVT failure is scarce. We aimed to assess the efficacy and safety of EVT for the resolution of UGI defects in a multicenter study and to investigate the factors associated with EVT failure and in-hospital mortality. METHODS: This is a prospective cohort study in which consecutive EVT procedures for the treatment of UGI defects from 19 Spanish hospitals were recorded in the national registry between November 2018 and March 2022. RESULTS: We included 102 patients: 89 with anastomotic leaks and 13 with perforations. Closure of the defect was achieved in 84 cases (82%). A total of 6 patients (5.9%) had adverse events related to the EVT. The in-hospital mortality rate was 12.7%. A total of 6 patients (5.9%) died because of EVT failure and 1 case (0.9%) due to a fatal adverse event. Time from diagnosis of the defect to initiation of EVT was the only independent predictor for EVT failure (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, P = 0.005). EVT failure (OR 24.5, 95% CI 4.5-133, P = 0.001) and development of pneumonia after EVT (OR 246.97, 95% CI 11.15-5,472.58, P = 0.0001) were independent predictors of in-hospital mortality. DISCUSSION: EVT is safe and effective in cases of anastomotic leak and perforations of the upper digestive tract. The early use of EVT improves the efficacy of this technique.

Design and Synthesis of AMPK Activators and GDF15 Inducers.

Targeting growth differentiation factor 15 (GDF15) is a recent strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Here, we designed, synthesized, and pharmacologically evaluated in vitro a novel series of AMPK activators to upregulate GDF15 levels. These compounds were structurally based on the (1-dibenzylamino-3-phenoxy)propan-2-ol structure of the orphan ubiquitin E3 ligase subunit protein Fbxo48 inhibitor, BC1618. This molecule showed a better potency than metformin, increasing GDF15 mRNA levels in human Huh-7 hepatic cells. Based on BC1618, structural modifications have been performed to create a collection of diversely substituted new molecules. Of the thirty-five new compounds evaluated, compound 21 showed a higher increase in GDF15 mRNA levels compared with BC1618. Metformin, BC1618, and compound 21 increased phosphorylated AMPK, but only 21 increased GDF15 protein levels. Overall, these findings indicate that 21 has a unique capacity to increase GDF15 protein levels in human hepatic cells compared with metformin and BC1618.

Leadership in a hospital of the Andalusian Public Health System.

OBJECTIVE: To analyse, from a gender perspective, the characteristics and perception of the effects of leadership of nurses in a hospital of the Andalusian Public Health System. METHODOLOGY: Qualitative study with a phenomenological approach. The participants were nurses in care and intermediate positions with a contract of more than 6 months. A qualitative content analysis was carried out. Four phases were established for data analysis, from which 5 categories resulted. NVivo 11 software was used to analyse the dialogues. RESULTS: The participants' discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender. CONCLUSIONS: The participants' discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender.

A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid-State NMR.

We compared the anti-influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine-31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a subset of these compounds against viruses with the amantadine-resistant L26F, V27A, A30T, G34E M2 mutant channels. Four compounds inhibited WT M2 virus in vitro with mid-nanomolar potency, with 27 compounds showing sub-micromolar to low micromolar potency. Several compounds inhibited L26F M2 virus in vitro with sub-micromolar to low micromolar potency, but only three compounds blocked L26F M2-mediated proton current as determined by electrophysiology (EP). One compound was found to be a triple blocker of WT, L26F, V27A M2 channels by EP assays, but did not inhibit V27A M2 virus in vitro, and one compound inhibited WT, L26F, V27A M2 in vitro without blocking V27A M2 channel. One compound blocked only L26F M2 channel by EP, but did not inhibit virus replication. The triple blocker compound is as long as rimantadine, but could bind and block V27A M2 channel due to its larger girth as revealed by molecular dynamics simulations, while MAS NMR informed on the interaction of the compound with M2(18-60) WT or L26F or V27A.

A slightly different polyp: melanoma metastasis diagnosed by colonoscopy.

Melanoma metastases are rare in the colon. Its diagnosis is difficult because they do not usually produce symptoms. They can present through the endoscopic image of a non-pigmented polyp. This is the case of a 56-year-old woman diagnosed with melanoma metastasis through polypectomy of an unusual-looking polyp.

Synthesis and Testing of Analogs of the Tuberculosis Drug Candidate SQ109 against Bacteria and Protozoa: Identification of Lead Compounds against Mycobacterium abscessus and Malaria Parasites.

SQ109 is a tuberculosis drug candidate that has high potency against Mycobacterium tuberculosis and is thought to function at least in part by blocking cell wall biosynthesis by inhibiting the MmpL3 transporter. It also has activity against bacteria and protozoan parasites that lack MmpL3, where it can act as an uncoupler, targeting lipid membranes and Ca2+ homeostasis. Here, we synthesized 18 analogs of SQ109 and tested them against M. smegmatis, M. tuberculosis, M. abscessus, Bacillus subtilis, and Escherichia coli, as well as against the protozoan parasites Trypanosoma brucei, T. cruzi, Leishmania donovani, L. mexicana, and Plasmodium falciparum. Activity against the mycobacteria was generally less than with SQ109 and was reduced by increasing the size of the alkyl adduct, but two analogs were ∼4-8-fold more active than SQ109 against M. abscessus, including a highly drug-resistant strain harboring an A309P mutation in MmpL3. There was also better activity than found with SQ109 with other bacteria and protozoa. Of particular interest, we found that the adamantyl C-2 ethyl, butyl, phenyl, and benzyl analogs had 4-10× increased activity against P. falciparum asexual blood stages, together with low toxicity to a human HepG2 cell line, making them of interest as new antimalarial drug leads. We also used surface plasmon resonance to investigate the binding of inhibitors to MmpL3 and differential scanning calorimetry to investigate binding to lipid membranes. There was no correlation between MmpL3 binding and M. tuberculosis or M. smegmatis cell activity, suggesting that MmpL3 is not a major target in mycobacteria. However, some of the more active species decreased lipid phase transition temperatures, indicating increased accumulation in membranes, which is expected to lead to enhanced uncoupler activity.

Evaluation of adherence monitoring in buprenorphine treatment: A pilot study using timed drug assays to determine accuracy of testing.

AIMS: Buprenorphine is effective at reducing relapse to opioid misuse, morbidity and mortality in opioid-dependent patients. Urine drug screening (UDS) to assess adherence is used routinely in opioid agonist treatment (OAT). The primary aim of this study was to determine factors which may be associated with a negative qualitative urine drug screen for buprenorphine in OAT patients. METHODS: This prospective pilot study was conducted at a tertiary addiction medicine centre. Twenty participants on stable treatment underwent supervised administration of sublingual buprenorphine. Matched urine and blood samples were collected prior to and 2, 4 and 6 hours after buprenorphine administration. Qualitative urine drug screen results were obtained using gas chromatography-mass spectrometry (GC-MS), while quantitative blood and urine results were obtained using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Qualitative urine assay yielded a negative result for buprenorphine in 57% of tested samples. The median concentration of urinary buprenorphine was 167 mcg/L (range: 2-1730 mcg/L). Thirty percent of all blood samples did not detect buprenorphine (range 0-18 mcg/L). Positive qualitative urine drug screen results were associated with higher urine (343 mcg/L compared with 75 mcg/L; P < .05) and blood (4 mcg/L compared with 2 mcg/L; P < .05) buprenorphine concentrations. Median urine concentrations of buprenorphine were highest at 2 hours and were higher in participants receiving CYP3A4 inhibitors. CONCLUSION: Interpretation of qualitative urine drug screens to assess adherence in OAT is complex. Poor adherence with treatment cannot be assumed in patients returning a negative qualitative GC-MS urine drug screen.

Factors that influence the impact of Chronic Non-Cancer Pain on daily life: A partial least squares modelling approach.

BACKGROUND: Chronic Non-Cancer Pain is pain of more than three months' duration and is not associated with an oncological condition. There is ample literature that recognises that Chronic Non-Cancer Pain impacts numerous areas of the life of the person who suffers from it. This impact is difficult to determine and quantify because Chronic Pain is a subjective experience. OBJECTIVE: The objective of this study was to test a recursive model of hypothesised factors that comprise the concept of Chronic Non-Cancer Pain Impact on daily life using Partial Least Squares-Structural Equation Modelling. DESIGN: A cross-sectional study was carried out. The sample size was calculated using G*Power V.3.1.9.4 with five parameters (two-tailed, large effect size (f2 = 0.35), power of 0.95, statistical significance of 95% (α = 0.05) and 36 predictors). The minimum number of subjects was considered to be 137. METHODS: A recursive model was built based on data from a sample of 395 people over 18 years of age with Chronic Non-Cancer Pain. Data collection was conducted between January and March 2020 at Pain Units and Primary Healthcare Centres belonging to the Spanish Public Health System in the province of Seville (Spain). Analyses were based on Partial Least Squares-Structural Equation Modelling. The internal consistency, convergent validity and discriminant validity of the internal measurement model were assessed. For the external measurement model, global model adjustment and structural validity were assessed. The predictive capacity of the final model was also evaluated. All analyses were performed using SmartPLS version 3.3.2 in consistent mode. RESULTS: Findings showed an adequate validity of the proposed model, which comprised nine factors: pain catastrophising, hopelessness due to pain, support network, proactivity, treatment compliance, self-care, mobility, resilience, and sleep. The internal validity of the model (Cronbach's alpha and rho_A > 0.70; Average Variance Extracted>0.50; standardised outer loadings>0.60; Heterotrait-Monotrait-Ratio < 0.85), goodness of fit (Standardised Root Mean Square Residuals<0.08; Geodesic and Euclidean distance p-value<0.05) and predictive power with out-of-sample values (Stone-Geisser test>0.5) were adequate. The hypothesised structure of the instrument has also been confirmed (path coefficients>0.3; R2 > 0.1; f2 > 0.2). CONCLUSIONS: The results have shown an adequate internal consistency, convergent validity and discriminant validity of the model. Likewise, the model has shown an adequate goodness of fit, and the validity of its structure and the hypothesis have been confirmed. However, more research is needed in this regard as the possible interaction between the different factors evaluated in the model with the confounding or moderating variables that may exist.