Drug Interactions With New Synthetic Opioids

Fentanyl, fentanyl analogs, and other new synthetic opioids (NSO) have burst onto the illegal drug market as new psychoactive substances (NPS). They are often sold as heroin to unsuspecting users and produce euphoria through their agonist action on μ- opioid receptors. Their high consumption, often combined with other substances, has led to multiple intoxications during recent years. In some countries, such as the United States, the consumption of opioids, whether for medical or recreational purposes, has become epidemic and is considered a public health problem. Fentanyl analogs are more potent than fentanyl which in turn is 50 times more potent than morphine. Furthermore, some fentanyl analogs have longer duration of action and therefore interactions with other substances and medicines can be more serious. This review is focused on the potentially most frequent interactions of opioid NPS taking into account the drugs present in the reported cases of poly-intoxication, including other illegal drugs of abuse and medication. Substances involved are mainly antidepressants, antihistamines, antipsychotics, benzodiazepines, analgesics, anesthetics, psychostimulants, other opioids, alcohol, and illegal drugs of abuse. The interactions can be produced due to pharmacokinetic and pharmacodynamic mechanisms. Naloxone can be used as an antidote, although required doses might be higher than for traditional opioid intoxications. It is crucial that doctors who habitually prescribe opioids, which are often misused by patients and NPS users, be aware of designer opioids' potentially life-threatening drug-drug interactions in order to prevent new cases of intoxication

El uso de películas comerciales para comprender los principios bioéticos en la investigación clínica

[ES] Las películas comerciales se han empleado para ilustrar temas difíciles de comprender totalmente en las clases teóricas. Nuestra hipótesis se basa en que la bioética aplicada a la investigación clínica puede comprenderse mejor si los estudiantes observan situaciones reales o ficticias en películas comerciales. Diseñamos un estudio aleatorizado y paralelo para comparar la eficacia de dos películas, Miss Evers’ Boys (El experimento Tuskegee) y Extreme Measures (Al cruzar el límite), para mejorar el conocimiento de los principios bioéticos en estudiantes de Biología humana. Se les asignó de forma aleatoria a cada grupo experimental y completaron un cuestionario para establecer su mejora subjetiva en el conocimiento de los principios bioéticos aplicados a la investigación clínica. Participaron 94 estudiantes, de los que 50 fueron asignados a Extreme Measures y 44 a Miss Evers’ boys. Los estudiantes consideraron ambas películas como útiles para aprender bioética en investigación clínica. Los principios de justicia y de autonomía se comprendieron mejor que los de beneficencia y no maleficencia. No se observaron diferencias significativas entre ambas películas para ninguna pregunta. Concluimos que la elección de las películas es un elemento crítico en educación y que una lista de preguntas preparadas por los profesores puede ayudar en ocasiones a centrar la atención de los estudiantes en los puntos más importantes. [EN] Popular films have been used to illustrate issues that may be difficult to fully understand in lectures. We hypothesise that bioethics applied to clinical research may be better understood if students are exposed to the real or fictional characters depicted in commercial films. We designed a randomised, parallel study to compare the effectiveness of two popular films, Miss Evers’ Boys and Extreme Measures, to improve the understanding of bioethical principles in students of Human Biology. Students were randomly assigned to each experimental group and they completed a self-administered questionnaire to establish the subjective improvement of their knowledge on bioethical principles applied to clinical research. Ninety-four students participated in the experiment. Fifty students were assigned to Extreme Measures and forty-four to Miss Evers’ Boys. Students rated both films as useful to learn bioethics in clinical research. Principles of justice and autonomy were better understood than beneficence and nonmaleficence. No differences were seen between the films’ scores for each question. Popular films may be useful in teaching the application of bioethical principles to students. We conclude that the choice of film is critical and a list of questions prepared by teachers may eventually help the students to focus on the most important points

Analysis of ECs and related compounds in plasma: artifactual isomerization and ex vivo enzymatic generation of 2-MGs

The analysis of peripheral endocannabinoids (ECs) is a good biomarker of the EC system. Their concentrations, from clinical studies, strongly depend on sample collection and time processing conditions taking place in clinical and laboratory settings. The analysis of 2-monoacylglycerols (MGs) (i.e., 2-arachidonoylglycerol or 2-oleoylglycerol) is a particularly challenging issue because of their ex vivo formation and chemical isomerization that occur after blood sample collection. We provide evidence that their ex vivo formation can be minimized by adding Orlistat, an enzymatic lipase inhibitor, to plasma. Taking into consideration the low cost of Orlistat, we recommend its addition to plasma collecting tubes while maintaining sample cold chain until storage. We have validated a method for the determination of the EC profile of a range of MGs and N-acylethanolamides in plasma that preserves the original isomer ratio of MGs. Nevertheless, the chemical isomerization of 2-MGs can only be avoided by an immediate processing and analysis of samples due to their instability during conservation. We believe that this new methodology can aid in the harmonization of the measurement of ECs and related compounds in clinical samples

Reliability of two measurement indices for gingival enlargement

Background and objective: The objective of this study was to analyze the concordance of the vertical gingival overgrowth index (GOi) and the horizontal Miranda & Brunet index (MBi) and to compare their reliability and reproducibility for an early diagnosis of gingival enlargement. A wide range of methods has been employed to determine the severity of drug-induced gingival enlargement (DIGE) that has resulted in uncertainty with regard to the prevalence of this side effect. In recent studies, different indices have been used to grade DIGE. The large variability observed between studies and the differences between vertical and horizontal gingival-enlargement measurements could be the result of the use of nonreliable indices during the measurement process. Some indices involve invasive procedures that require many measurements, or even a data-processing system, while others are less convenient and technically expensive and complex. In previous studies we used two complementary indices - the vertical GOi and the horizontal MBi. The results of these studies found some differences between both indices, with the MBi rendering higher estimates of DIGE prevalence that was attributed to its greater sensitivity for the detection of minimal changes in gingival thickness. To our knowledge, there are no studies comparing different measurement indices for gingival enlargement that are supported by statistical concordance analysis. Material and methods:   Twelve plaster casts from patients who had worn orthodontic brackets, and who had different degrees of chronic inflammatory gingival enlargement, were analyzed. Three previously trained examiners registered twice the degree of buccal overgrowth, using the GOi and MBi, in all cast models with a minimum interval of 7 d between the first and the second evaluation. In total, from each cast, measurements from 16 gingival sites were taken using the GOi, and from nine gingival units (mesial and distal sites measurements) using the MBi. Concordance analysis of the registered measurements (intra-examiner and among examiners) for each index and between indices was assessed using the nonweighted Kappa index with a confidence interval of 95%. Results: We obtained 648 values for the GOi and the MBi. The overall score 0 (indicating absence of enlargement) was 32.7% and 19.8% for GOi and MBi, respectively, score 1 (light/moderate) was 39.7% and 48.1%, and score 2 (severe) was 27.6% and 32.1%. Concordance analysis for each index showed intra-examiner Kappa values of 0.820 for the GOi and 0.830 for the MBi. Interexaminer Kappa values were 0.720 for the GOi and 0.770 for the MBi. Concordance between indices showed Kappa values for the same examiner of 0.600, whereas concordance among different examiners was 0.550. Discrepancies between indices indicated a systematic skew, with 79-82.1% of discrepancy associated with a higher value for the MBi compared with the GOi. Conclusion: Both gingival enlargement indices analyzed are reliable, complementary and applicable for measuring gingival overgrowth. However, the MBi shows, with fewer measurements, a greater sensitivity than the GOi for the detection of the early stages of gingival enlargement, being adequate for the screening of large populations at risk

Salivary secretory disorders, inducing drugs, and clinical management

Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions

Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

Background: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives

Facial emotion processing in patients with social anxiety disorder and Williams-Beuren syndrome: an fMRI study

Background: social anxiety disorder (SAD) and Williams-Beuren syndrome (WBS) are 2 conditions with major differences in terms of genetics, development and cognitive profiles. Both conditions are associated with compromised abilities in overlapping areas, including social approach, processing of social emotional cues and gaze behaviour, and to some extent they are associated with opposite behaviours in these domains. We examined common and distinct patterns of brain activation during a facial emotion processing paradigm in patients with SAD and WBS. Methods: we examined patients with SAD and WBS and healthy controls matched by age and laterality using functional MRI during the processing of happy, fearful and angry faces. Results: we included 20 patients with SAD and 20 with WBS as well as 20 matched controls in our study. Patients with SAD and WBS did not differ in the pattern of limbic activation. We observed differences in early visual areas of the face processing network in patients with WBS and differences in the cortical prefrontal regions involved in the top-down regulation of anxiety and in the fusiform gyrus for patients with SAD. Compared with those in the SAD and control groups, participants in the WBS group did not activate the right lateral inferior occipital cortex. In addition, compared with controls, patients with WBS hypoactivated the posterior primary visual cortex and showed significantly less deactivation in the right temporal operculum. Participants in the SAD group showed decreased prefrontal activation compared with those in the WBS and control groups. In addition, compared with controls, participants with SAD showed decreased fusiform activation. Participants with SAD and WBS also differed in the pattern of activation in the superior temporal gyrus, a region that has been linked to gaze processing. Limitations: the results observed in the WBS group are limited by the IQ of the WBS sample; however, the specificity of findings suggests that the pattern of brain activation observed for WBS is more likely to reflect a neurobiological substrate rather than intellectual impairment per se. Conclusion: patients with SAD and WBS showed common and specific patterns of brain activation. Our results highlight the role of cortical regions during facial emotion processing in individuals with SAD and WBS

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

Señores docentes, más cine por favor

[ES] La utilización del cine como herramienta para la divulgación y educación médica es el objetivo principal de la Revista de Medicina y Cine. Año tras año y número a número su contenido nos demuestra cómo se pueden enseñar de una forma original, atractiva y divertida algunas partes de las materias de medicina y ciencias biomédicas, ya sea usando las películas de cine comercial o las series y las películas de televisió

Uso del cine comercial en la docencia de Bioética en estudios de Biología

En el presente artículo narramos la experiencia del uso del cine comercial en la docencia de la Bioética con estudiantes de Biología de la Universidad Pompeu Fabra de Barcelona. Durante los tres últimos cursos académicos (2007-2010) proyectamos tres películas para fomentar el aprendizaje de principios bioéticos y para estimular la discusión sobre temas relevantes previstos en el programa de la asignatura. A partir de la participación de los estudiantes y sus resultados académicos, la actividad ha sido muy bien valorada