Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect.

Current developments in tissue engineering strategies for articular cartilage regeneration focus on the design of supportive three-dimensional scaffolds and their use in combination with cells from different sources. The challenge of translating initial successes in small laboratory animals into the clinics involves pilot studies in large animal models, where safety and efficacy should be investigated during prolonged follow-up periods. Here we present, in a single study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non-seeded and seeded with fresh ex vivo expanded autologous progenitor cells that were derived from three different cell sources [cartilage, fat and bone marrow (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An ovine model of critical size osteochondral focal defect was used and the test items were implanted arthroscopically into the knees. Evidence of regeneration of hyaline quality tissue was observed at 6 and 12 months post-treatment with variable success depending on the cell source. Cartilage and BM-derived mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the best quality of new cartilage, as judged qualitatively by magnetic resonance imaging and macroscopic assessment, and by histological quantitative scores. Given the limitations in sourcing cartilage tissue and the risk of donor site morbidity, BM emerges as a preferential source of MSC for novel cartilage resurfacing therapies of osteochondral defects using copolymeric poly-D,L-lactide-co-glycolide scaffolds.

Aplicación del modelo alternativo de diagnóstico de Trastorno de la Personalidad DSM-5 para valorar la evolución de una paciente adolescente / Application of the alternative model of DSM-5 Personality Disorder to assess the evolution of an adolescent patient

La quinta edición del Manual Diagnóstico y Estadístico de Trastornos Mentales, en su Sección III, presenta un modelo alternativo para el diagnóstico de los Trastornos de la Personalidad que intenta eliminar algunos de los problemas que aparecen con el modelo oficial presentado en la sección II del manual. Es de considerable interés la posibilidad que ofrece este modelo, cuyos ejes son el funcionamiento de la personalidad y los rasgos de la personalidad, de poder caracterizar con precisión a un paciente que cumple criterios de varios trastornos de la personalidad o no cumple criterios de uno concreto. También se contempla la posibilidad de utilizarlo como herramienta para la valoración de la funcionalidad de un paciente y el diseño de un plan terapéutico en función de su personalidad. En este artículo se presenta a una paciente con alteraciones del comportamiento, se caracteriza su personalidad según este modelo y se observa su evolución

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition, presents in its Section III an alternative model for diagnosing Personality Disorders, which tries to amend some of the problems of the official model, included in Section II. Is it of remarkable interest the possibility that this model, whose main axes are the personality functioning and the personality traits, brings us of being able to characterize with precision a patient that meets criteria of more than one personality disorders or does not fully meet criteria for a single one. The possibility of using it as a tool to evaluate the functioning of a patient and designing a specific treatment plan according to his or her personality is also contemplated. In this article is present a patient whose behaviour is altered, her personality is characterised according to this model and he evolution is observed

Transitory improvement of articular cartilage characteristics after implantation of polylactide:polyglycolic acid (PLGA) scaffolds seeded with autologous mesenchymal stromal cells in a sheep model of critical-sized chondral defect.

Clinical translation of emerging technologies aiming at cartilage resurfacing is hindered by neither the appropriate scaffold design nor the optimal cell source having been defined. Here, critical-sized, chondral-only focal defects were created in sheep and treated with clinical-grade, co-polymeric poly-lactide:polyglycolic acid scaffolds either alone or seeded with 3.3 × 10(6) ± 0.4 × 10(6) autologous bone marrow-derived mesenchymal stromal cells and studied over 12 month follow-up. An untreated group was included for comparison. Second-look arthroscopy performed at 4 months post-treatment evidenced the generation of neocartilage of better quality in those defects treated with cells. However, macroscopic scores in the cell-treated group declined significantly from 7.5 ± 2.3 at 4 months to 3.1 ± 2.6 (p = 0.0098) at 12 months post-treatment, whereas the other two experimental groups remained unaltered during 4-12 month post-treatment. The effectiveness of the cell-based approach proposed in this study is thus restricted to between months 1 and 4 post-treatment.

An arthroscopic approach for the treatment of osteochondral focal defects with cell-free and cell-loaded PLGA scaffolds in sheep.

Osteochondral injuries are common in humans and are relatively difficult to manage with current treatment options. The combination of novel biomaterials and expanded progenitor or stem cells provides a source of therapeutic and immunologically compatible medicines that can be used in regenerative medicine. However, such new medicinal products need to be tested in translational animal models using the intended route of administration in humans and the intended delivery device. In this study, we evaluated the feasibility of an arthroscopic approach for the implantation of biocompatible copolymeric poly-D,L-lactide-co-glycolide (PLGA) scaffolds in an ovine preclinical model of knee osteochondral defects. Moreover this procedure was further tested using ex vivo expanded autologous chondrocytes derived from cartilaginous tissue, which were loaded in PLGA scaffolds and their potential to generate hyaline cartilage was evaluated. All scaffolds were successfully implanted arthroscopically and the clinical evolution of the animals was followed by non invasive MRI techniques, similar to the standard in human clinical practice. No clinical complications occurred after the transplantation procedures in any of the animals. Interestingly, the macroscopic evaluation demonstrated significant improvement after treatment with scaffolds loaded with cells compared to untreated controls.

Non-invasive electrohysterogram recording using flexible concentric ring electrode.

Non-invasive electrohysterogram (EHG) recording could provide valuable information about uterine dynamics. Bipolar EHG has usually been performed using monopolar disposable electrodes. Recently concentric ring electrodes have been used for EHG recordings so as to acquire more localized electrical activity which may be helpful for deducing uterine contraction efficiency. Nevertheless concentric ring electrodes have commonly been implemented in rigid substrates. Therefore they do not adapt to the body surface curvature which may cause discomfort for patients and a poor contact between electrode and skin. The aim of this paper is to examine the feasibility of picking up EHG signals (BC-EHG) using a new flexible tripolar concentric ring (TCR) electrode placed on the abdominal surface, and to compare it with the conventional bipolar recordings. For this purpose, a total of 7 recording sessions were carried out in 7 pregnant women. Each recording implied simultaneous acquisition of one bipolar EHG signal and of two bipolar concentric EHG (BC-EHG) signals using the flexible TCR electrode. Then a set of temporal and spectral parameters was computed from both bipolar EHG and BC-EHG bursts. Experimental results show no noticeable difference in duration and in dominant frequency in Fast Wave High frequency range. Nonetheless, the low frequency content (0.1-0.2 Hz) of BC-EHG records is smaller than that of bipolar record. These results suggest that the new flexible TCR electrode permits to pick up uterine electrical activity and may provide additional information for deducing uterine efficiency.

Asociación entre el gen del transportador de la serotonina y rasgos de personalidad en pacientes con trastorno límite de la personalidad evaluados mediante el Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) / Association between the serotonin transporter gene and personality traits in borderline personality disorder patients evaluated with Zuckerman-Kuhlman Personality Questionnaire (ZKPQ)

Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5-HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder

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Association between the serotonin transporter gene and personality traits in borderline personality disorder patients evaluated with Zuckerman-Zuhlman Personality Questionnaire (ZKPQ).

INTRODUCTION: The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5- HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. METHOD: A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). RESULTS: Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. CONCLUSIONS: The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder.

Impresión clínica global para pacientes con trastorno límite de la personalidad (ICG-TLP): una escala sensible al cambio / The clinical global impression scale for borderline personality disorder patients (CGI-BPD): a scale sensible to detect changes

La ICG-TLP es una adaptación de la escala de Impresión Clínica Global (ICG) diseñada con el objetivo de evaluar tanto la severidad como el cambio postintervención en pacientes diagnosticados de trastorno límite de la personalidad (TLP). Está compuesta por 10 ítems que puntúan los nueve dominios psicopatológicos relevantes del TLP y una puntuación global adicional. La ICG-TLP consta de dos formatos, la ICGTLP- S para evaluar la severidad actual y la ICG-TLP-M para evaluar la mejoría. Para establecer las propiedades psicométricas de la ICG-TLP ésta fue administrada a 78 pacientes (11 hombres y 67 mujeres) en el marco de una intervención terapéutica de 4 meses de duración. La ICG-TLP muestra buenas características de validez, fiabilidad (α de 0,85 y 0,89; CCI: 0,86 y 0,78), una adecuada sensibilidad al cambio y una estructura factorial de dos factores que explican el 67,4% de la varianza total. La ICG-TLP es una escala simple y fácil de administrar que corrige la excesiva generalización característica de su versión original y permite evaluar la severidad y el cambio en pacientes TLP

The CGI-BPD scale is an adaptation of the Clinical Global Impression (CGI) scale designed to assess severity and post-intervention changes in patients with Borderline Personality Disorder (BPD). It contains 10 items that score the nine relevant psychopathological domains of BPD, plus an additional global score. The CGI-BPD has two formats, the CGI-BPD-S, to evaluate the present severity, and the CGIBPD- I to evaluate improvement. To establish the psychometric properties of the CGI-BPD, the test was administered to 78 BPD patients, 11 men and 67 women, within the framework of a 4-month therapeutic intervention. The modified scale showed good validity and reliability (α 0.85 and 0.89; CCI: 0.86 and 0.78), adequate sensitivity to change, and a two-factor structure accounting for 67.4 % of total variance. While remaining simple to administer, the CGI-BPD may correct the excessive generalisation contained in its original version and is a useful tool to evaluate severity and change in BPD patients

The clinical global impression scale for borderline personality disorder patients (CGI-BPD): a scale sensible to detect changes.

The CGI-BPD scale is an adaptation of the Clinical Global Impression (CGI) scale designed to assess severity and post-intervention changes in patients with Borderline Personality Disorder (BPD). It contains 10 items that score the nine relevant psychopathological domains of BPD, plus an additional global score. The CGI-BPD has two formats, the CGI-BPD-S, to evaluate the present severity, and the CGIBPD- I to evaluate improvement. To establish the psychometric properties of the CGI-BPD, the test was administered to 78 BPD patients, 11 men and 67 women, within the framework of a 4-month therapeutic intervention. The modified scale showed good validity and reliability (alpha 0.85 and 0.89; CCI: 0.86 and 0.78), adequate sensitivity to change, and a two-factor structure accounting for 67.4 % of total variance. While remaining simple to administer, the CGI-BPD may correct the excessive generalisation contained in its original version and is a useful tool to evaluate severity and change in BPD patients.

Injectable atypical antipsychotics for agitation in borderline personality disorder.

Agitation is relatively common among Borderline Personality Disorder (BPD) patients in Psychiatric Emergency Services (PES). New injectable atypical antipsychotics are indicated for treatment in agitated psychotic or maniac patients but not for agitated BDP patients. Twenty agitated BPD patients were treated with intramuscular atypical antipsychotics (olanzapine or ziprasidone). Results suggest intramuscular atypical antipsychotics may be effective, fast and safe for treating acute BPD patients.

[Validation of a Spanish version of the Diagnostic Interview for Bordelines-Revised (DIB-R)]. / Validación de la versión española de la Diagnostic Interview for Bordelines-Revised (DIB-R).

INTRODUCTION: Borderline Personality Disorder (BPD) is the most studied Axis II disorders. However, there are no Spanish versions of specific interviews. The Diagnostic Interview for Borderlines-Revised (DIB-R) is a semistructured interview used to determine the diagnosis and severity of BPD patients. The aim of this study was to validate the DIB-R for use in a Spanish-speaking sample. METHOD: The psychometric characteristics of the DIB-R Spanish version were assessed in a sample of 156 patients with the possible diagnosis of borderline personality disorder. There were 29 men and 127 women with a mean age of 27.6 years (SD: 6.5; range: 18-45). The Spanish adaptation of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) was used as gold standard. RESULTS: The DIB-R showed good total internal consistency (Cronbach's alpha: 0.89) and high inter-rater reliability (within-class correlation: 0.94). Using logistic regression analyses the best cut-off was judged to be 6 or more, obtaining high sensitivity (0.81), specificity (0.94) and moderate convergent validity of the diagnosis with the SCID-II (kappa: 0.59). CONCLUSIONS: The Spanish version of the DIB-R showed psychometric characteristics similar to those in the original interview and may be useful to determine BPD presence and severity.

Validación de la versión española de la Diagnostic Interview for Bordelines-Revised (DIB-R) / Validation of a Spanish version of the Diagnostic Interview for Bordelines-Revised (DIB-R)

Introducción. El trastorno límite de la personalidad (TLP) es el trastorno del Eje II más estudiado en la actualidad; sin embargo, no existen versiones españolas de entrevistas específicas. La Diagnostic Interview for Borderlines-Revised (DIB-R) es una entrevista semiestructurada que permite determinar tanto el diagnóstico como la severidad clínica de pacientes con TLP. El objetivo del presente estudio la validación de la DIB-R para su uso en población de habla española. Método. Las características psicométricas de la versión española de la DIB-R fueron evaluadas en una muestra de 156 sujetos con orientación diagnóstica del TLP; 29 hombres y 127 mujeres con una edad media de 27,6 años (desviación estándar: 6,5; rango: 18-45). La adaptación española de la Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) se utilizó como . Resultados. La DIB-R mostró una buena consistencia interna global (alfa de Cronbach de 0.89) y una alta fiabilidad entre evaluadores (coeficiente de correlación intraclase de 0.94). Utilizando un análisis de regresión logística se estableció como punto de corte diagnóstico los valores iguales o superiores a 6, con una elevada convergencia diagnóstica con la SCID-II (kappa de 0,59). Conclusiones. La versión española de la DIB-R mostró unas propiedades psicométrica comparables a las del instrumento original y puede resultar útil para determinar tanto la presencia como la gravedad del TLP (AU)

Introduction. Borderline Personality Disorder (BPD) is the most studied Axis II disorders. However, there are no Spanish versions of specific interviews. The Diagnostic Interview for Bordelines-Revised (DIB-R) is a semistructured interview used to determine the diagnosis and severity of BPD patients. The aim of this study was to validate the DIB-R for use in a Spanish –speaking sample. Method. The psychometric characteristics of the DIB-R Spanish version were assessed in a sample of 156 patients with the possible diagnosis of borderline personality disorder. There were 29 men and 127 women with a mean age of 27.6 years (SD: 6,5; range: 18-45). The Spanish adaptation of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) was used as gold standard. Results. The DIB-R showed good total internal reliability (within-class correlation: 0,94). Using logistic regression analyses the best cut-off was judged to be 6 or more, obtaining high sensitivity (0.81), specificity (0,94) and moderate convergent validity of the diagnosis with the SCIID-II (kappa. 0.59). Conclusions. The Spanish version of the DIB-R showed psychometric characteristics similar to those in the original interview and may be useful to determine BPD presence and severity (AU)