Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.

Recommendations for Off-Label Drug Use in Ophthalmology in China: A Clinical Practice Guideline.

Off-label drugs use is widespread in ophthalmology due to the delay in drug approvals and package inserts update. It has been found to vary among different medical institutions in China, leading to safety problems since inappropriate use. Guidance is urgently needed regarding how best to use the drugs for unapproved indications and routes of administration. We aimed to develop an evidence-based guideline to guide off-label drugs used in ophthalmology in China. The practice guideline was developed by the Hospital Pharmacy Professional Committee, Chinese Pharmaceutical Association, following the WHO handbook for guideline development. The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2021CN096). The clinical questions included in the guideline were identified through a three-round Delphi vote. Databases search was performed in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and WanFang Database from their inception to 31 March 2021. Systematic reviews and meta-analyses for each clinical question were conducted individually to synthesize available scientific evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and grade the recommendations' strengths. The multidisciplinary guideline groups were set up, including ophthalmologists, pharmacists, methodology experts, pharmacologists, pharmacoeconomists, and lawyers. The guideline identified 25 clinical questions included. A total of 32 systematic reviews, including 24 conducted by the systematic review group and eight high-relevance published within 2 years, were referred to address these questions. Finally, the guideline presented 32 recommendations addressing 25 clinical questions, involving five strong recommendations and 27 weak recommendations for the treatment of ocular fundus, corneal disease, glaucoma, and endophthalmitis. Current evidence from clinical studies supports the off-label drugs used in ophthalmology. We developed an evidence-based guideline using a rigorous multidisciplinary approach to guide these usages in route clinical practice.

Alarming increase in poisonings from recreational nitrous oxide use after a change in EU-legislation, inquiries to the Dutch Poisons Information Center.

BACKGROUND: After the change in EU-legislation in 2014, recreational use of nitrous oxide (N2O) increased in the Netherlands from 2015 onwards. We studied the effect on N2O poisonings during an 11 year period. METHODS: A retrospective observational study was performed on the incidence rate of N2O poisonings, relative to all recreational drug poisonings reported to the Dutch Poisons Information Center (DPIC) from 2010-2020. Secondary outcomes were the frequency of heavy use, frequent use, co-exposures, and toxicity in 2019 and 2020. RESULTS: 433 N2O poisonings were included. The incidence rate increased exponentially from 0.12% in 2010 to 11% in 2020, with an average monthly rate of 3.8%. In 2019 and 2020, 79% of the patients indicated heavy use, frequent use or both, and 42% used from large cylinders. Chronic toxicity (signs of peripheral neuropathy) was reported in 38% of the patients. CONCLUSION: The rate of N2O poisonings increased alarmingly in the Netherlands. An increasing proportion of patients reported problematic heavy or frequent use, accompanied by chronic toxicity.

Patrones de consumo de drogas en adolescentes ingresados en el Hospital Pediátrico Provincial de Camagüey / Drug consumption patterns in adolescents admitted to the Provincial Pediatric Hospital of Camagüey

RESUMEN Las drogas por sus graves consecuencias están consideradas como un problema social. Los adolescentes son uno de los grupos vulnerables ante su consumo. El trabajo tuvo como objetivo caracterizar los patrones de consumo de drogas en adolescentes ingresados en la Unidad de Intervención en Crisis del Hospital Pediátrico Provincial de Camagüey durante el periodo 2015-2019. Se utilizó la metodología cuanticualitativa mediante métodos teóricos y empíricos. Para la recolección de los datos fue preciso la revisión de las Historias Clínicas. La investigación comprendió una muestra de 83 adolescentes. El estudio posibilitó determinar el aumento del número de ingresos por consumo de sustancias desde el año 2016 hasta 2019 y el grupo de edades más numeroso estuvo conformado entre 16 y 18 años. La curiosidad, el placer y la influencia del grupo de amigos resultaron los principales motivos para las adicciones.

ABSTRACT The objective of the work was to characterize the consumption patterns of drugs in adolescents admitted to the Intervention Unit in Crisis of the Provincial Pediatric Hospital of Camagüey. It was used the quantitative methodology through theoretical and empirical methods. To collect the data, the medical records were reviewed. The research comprised a sample of 83 adolescents. The study made possible to determine the increase in the number of income from consumption of substances from 2016 to 2019 and the most numerous age group was conformed between 16 and 18 years. Curiosity, pleasure and the influence of the group of friends were the main reasons for addictions.

Porta giratória no acolhimento de crianças e adolescentes usuários de drogas: desafios e manejos / Puerta giratoria en la acogida de niños y adolescentes consumidores de drogas: desafíos y gestiones / Revolving door in the care for children and adolescents drug users: challenges and management

Resumo O estudo teve como objetivo descrever características relacionadas ao fenômeno da porta giratória em uma Unidade de Acolhimento infantojuvenil e analisar o modo como o serviço maneja este fenômeno. Foi realizado estudo de caso qualitativo com análise de: entrevistas semiestruturadas; observação participante com registro em caderno de campo; documentos e grupo focal. A partir da análise, foram construídos três temas: Vínculos rompidos: "Se a família não se cuidar a gente não consegue" (questões geracionais, vínculo familiar, adesão ao tratamento); Subfinanciamento: "Eles fazem milagre com os recursos que têm" (subfinanciamento estatal, preconceito e investimento privado); Políticas públicas: "Esse problema não é meu" (segmentação do cuidado, falta de apoio comunitário e informação/preparo das instituições). Esses pontos constituem entraves no tratamento de crianças e adolescentes usuários de drogas e remetem ao fenômeno da porta giratória.

Resumen El objetivo del estudio fue describir características relacionadas con el fenómeno de la puerta giratoria en una Unidad de Acogida de Niños y Adolescentes y analizar la forma en que el servicio maneja este fenómeno. Se realizó un estudio de caso cualitativo con el análisis de: entrevistas semiestructuradas; observación participante registrada en cuaderno de campo; documentos y grupos focales. A partir del análisis se construyeron tres temas: Vínculos rotos: "Si la familia no se cuida, no podemos hacerlo" (cuestiones generacionales, vínculo familiar, adherencia al tratamiento); Falta de financiación: "Hacen milagros con los recursos que tienen" (falta de financiación estatal, prejuicios e inversión privada); Políticas públicas: "Este no es mi problema" (segmentación de la atención, falta de apoyo comunitario e información/preparación de las instituciones). Estos puntos constituyen barreras en el tratamiento de los niños, niñas e adolescentes consumidores de drogas y se refieren al fenómeno de la puerta giratoria.

Abstract The study aimed to describe characteristics related to the revolving door phenomenon in a Child and Adolescent Shelter Unit and to analyze the way in which the service manages this phenomenon. A qualitative case study was carried out with the analysis of: semi-structured interviews; participant observation recorded in a field notebook; documents and a focus group. From the analysis, three themes were constructed: Broken bonds: "If the family does not take care of itself, we can't" (generational issues, family bonds, adherence to treatment); Underfunding: "They work miracles with the resources they have" (state underfunding, prejudice and private investment); Public policies: "This is not my problem" (segmentation of care, lack of community support and information/preparation of the institutions). These points constitute barriers in the treatment of children and adolescents that use drugs and highlight the revolving door phenomenon.

Ranking the Harm of Psychoactive Drugs Including Prescription Analgesics to Users and Others-A Perspective of German Addiction Medicine Experts.

Background: Over the past 15 years, comparative assessments of psychoactive substance harms to both users and others have been compiled by addiction experts. None of these rankings however have included synthetic cannabinoids or non-opioid prescription analgesics (NOAs, e.g., gabapentinoids) despite evidence of increasing recreational use. We present here an updated assessment by German addiction medicine experts, considering changing Western consumption trends-including those of NOAs. Methods: In an initial survey, 101 German addiction medicine physicians evaluated both physical and psychosocial harms (in 5 dimensions) of 33 psychoactive substances including opioids and NOAs, to both users and others. In a second survey, 36 addiction medicine physicians estimated the relative weight of each health and social harm dimension to determine the overall harm rank of an individual substance. We compared our ranking with the most recent European assessment from 2014. Results: Illicit drugs such as methamphetamine, heroin, cocaine and also alcohol were judged particularly harmful, and new psychoactive drugs (cathinones, synthetic cannabinoids) were ranked among the most harmful substances. Cannabis was ranked in the midrange, on par with benzodiazepines and ketamine-somewhat more favorable compared to the last European survey. Prescribed drugs including opioids (in contrast to the USA, Canada, and Australia) were judged less harmful. NOAs were at the bottom end of the ranking. Conclusion: In Germany, alcohol and illicit drugs (including new psychoactive substances) continue to rank among the most harmful addictive substances in contrast to prescribed agents including opioid analgesics and NOAs. Current laws are incongruent with these harm rankings. This study is the first of its kind to include comparative harm rankings of several novel abused substances, both licit/prescribed and illicit.

Sexualidad, alcohol y sustancias psicoactivas en relación con el embarazo no deseado en universitarios / Sexuality, alcohol, psycoative substances and relation with unwanted pregnancy in university students / Sexualidade, álcool e substancias psicoactivas em relação com a gravindez não desejada em universitarios

Objetivo: determinar la relación entre sexualidad, consumo de alcohol, consumo de sustancias psicoactivas y embarazo no deseado en estudiantes universitarios Métodos: estudio descriptivo de corte transversal con intención analítica. Se aplicó una encuesta sobre salud sexual y reproductiva y bienestar basada en el cuestionario Reig-Ferrer. Las variables cualitativas se analizaron mediante frecuencias y porcentajes y las cuantitativas mediante medidas de tendencia central y dispersión. Se calcularon razones de prevalencia utilizando la prueba chi cuadrado que evaluó relación entre embarazo no deseado y algunas conductas de riesgo. Resultados: participaron 2767 estudiantes con edad promedio de 21 (RIC: 19-23) años. La mediana de edad de inicio las relaciones sexuales fueron de 16 (RIC: 15-18) años. El 56,1% refirió consumir alcohol y el 12,7% sustancias psicoactivas (SPA), con alguna frecuencia. Respecto a las mujeres; el 18,9 % ha estado embarazada, y de éstas, el 61,4% ha tenido un embarazo no deseado. El análisis bivariado mostró relación estadísticamente significativa entre el embarazo no deseado y variables como la edad de inicio de las relaciones sexuales, el consumo de SPA y el mantener o no relaciones sexuales bajo el efecto del alcohol y SPA. Conclusiones: el estudio mostró condiciones que pueden favorecer los problemas relacionados con la salud sexual y reproductiva de jóvenes universitarios. Se pone de manifiesto la necesidad de estudiar algunas conductas de riesgo de manera particular, mediante un abordaje integral que permita posteriormente reorientar las actividades de la promoción de la salud sexual en pro de re-conocer conductas de cuidado y de riesgo.

Objective: To determine the relationship between sexuality, alcohol consumption, psychoactive substance consumption and unwanted pregnancy in university students. Methods: Cross sectional study with analytical intention. A sexual and reproductive health and wellness survey based on the Reig-Ferrer questionnaire was applied. The qualitative variables were analyzed using frequencies and percentages, and the quantitative variables using measures of central tendency and dispersion. Prevalence ratios were calculated using the chi square test that evaluated the relationship between unwanted pregnancy and some risk behaviors. Results: A total of 2767 students with an average age of 21 (RIC: 19-23) years participated. The median age of onset of sexual intercourse was 16 (RIC: 15-18) years. Overall, 56.1% reported consuming alcohol and 12.7% psychoactive substances (PS), with some frequency. Regarding women, 18.9% have been pregnant, and of these, 61.4% have had an unwanted pregnancy. The bivariate analysis showed a statistically significant relationship between unwanted pregnancy and variables such as the age of onset of sexual intercourse, the consumption of PS and whether or not to have sexual intercourse under the influence of alcohol and PS. Conclusions: The study showed conditions that can favor the problems related to the sexual and reproductive health of young university students. The need to study some risk behaviors in a particular way through a comprehensive approach that allows reorienting the activities of sexual health promotion in order to re-know care and risk behaviors, is highlighted.

Objetivo: determinar a relação entre sexualidade, consumo de álcool, consumo de substâncias psicoativas e gravidez não desejado em estudantes universitários Métodos: estudo descritivo de corte transversal com intenção analítica. Aplicou-se uma enquete sobre saúde sexual e reprodutiva e bem-estar baseada no questionario Reig-Ferrer. As variáveis qualitativas se analisaram mediante frequências e porcentagens e as quantitativas mediante medidas de tendência central e dispersão. Calcularam-se razões de prevalência utilizando a prova chi quadrado que avaliou relação entre gravidez não desejado e algumas condutas de risco. Resultados: participaram 2767 estudantes com idade média de 21 (RIC: 19-23) anos. A mediana de idade de início as relações sexuais foram de 16 (RIC: 15-18) anos. O 56,1% referiu consumir álcool e o 12,7% substancias psicoativas (SPA), com alguma frequência. Respeito às mulheres; o 18,9 % tem estado gravidas, e destas, o 61,4% tem tido uma gravidez não desejado. O analise bivariado amostrou relação estatisticamente significativa entre uma gravidez não desejado e variáveis como a idade de início das relações sexuais, o consumo de SPA e o manter ou não relações sexuais baixo o efeito do álcool e SPA. Conclusões: O estudo amostrou condições que podem favorecer os problemas relacionados com a saúde sexual e reprodutiva de jovens universitários. É preciso criar a necessidade de estudar algumas condutas de risco de maneira particular, mediante uma abordagem integral que permita posteriormente reorientar as atividades da promoção da saúde sexual em pro de reconhecer condutas de cuidado e de risco.

Antiseizure drugs use during pregnancy and congenital malformations: A retrospective review from the United Arab Emirates.

OBJECTIVE: To observe the incidence of congenital malformations occurring in foetuses exposed to antiseizure drugs (ASDs) during the first trimester and to identify individual drug associations in a population cohort from the United Arab Emirates (UAE). METHODS: Pregnancy outcomes were observed and reported from women with epilepsy (WWE), attending the Obstetric Medicine Neurology Clinic at Corniche Hospital in Abu Dhabi, United Arab Emirates (UAE) from February 2008 to December 2015. RESULTS: Outcome data were available for 179 pregnancies in 112 WWE. There were 139 pregnancies who received ASD treatment during the first trimester, of these 124 were on monotherapy. Thirteen (7.26 %) congenital malformations (CMs) were observed in this cohort, seven were major ones and six were minor. Thirteen of the CMs were from the group with ASDs while one had no ASD-exposure. From the ASD-group, we identified 32 (23.0 %) with poor pregnancy outcomes, including 13 (9.3 %) with CMs and 19 (13.7 %) miscarriages. These figures were significantly higher than that of the no ASD-exposure group (7.9 %) (p = 0.04, Fisher test). The most commonly used ASDs in monotherapy were levetiracetam (25.6 %), carbamazepine (16.2 %), valproate (13.4 %), and lamotrigine (7.3 %). There were 57 (31.8 %) consanguineous marriages in this cohort; there was no statistically significant difference in the CM rate within the consanguineous group between those with and without exposure to ASD. CONCLUSION: This study was the first to report pregnancy outcomes in a WWE cohort from the Middle East and North Africa (MENA) region. It is the first step towards establishing a national / regional pregnancy registry to create a database on ASD use and pregnancy outcomes among the WWE.

Preconceptional paternal antiepileptic drugs use and risk of congenital anomalies in offspring: a nationwide cohort study.

Recent studies have shown that certain pharmacological agents used by fathers before conception may increase the risk of adverse neonatal outcomes in offspring. However, little is known about the effect of paternal use of antiepileptic drugs (AEDs) on congenital anomalies in children. Based on Danish national registers, we conducted a cohort study of 733, 282 singletons born from 1997 to 2008, with follow-up throughout 2013. The children whose fathers used AEDs during the 3 months before conception were categorized as the exposed. Logistic regression model was used to examine association between paternal AEDs use before conception and the risk of congenital anomalies in offspring. Compared with unexposed children, the exposed had a 23% increased risk of congenital anomalies (odds ratios (OR) 1.23, 95% confidence interval [CI] 1.10-1.37) after adjusting for potential confounders. When extending the exposure window to 1 year before conception to the end of pregnancy, except for those using AEDs during 3 months before conception (the susceptible period of exposure), the increased risks were also observed in children whose fathers were former users (i.e., those using AEDs only from 1 year to 3 months before conception) (OR 1.29, 95%CI 1.03-1.61) and later users (i.e., those using AEDs only during pregnancy) (OR 1.35, 95%CI 1.12-1.65). This study suggested that the mildly increased risk of congenital anomalies in the offspring associated with paternal AEDs use before conception may be attributable to the underlying indications related to AEDs use.

Consumo de antimicrobianos seleccionados en el Cardiocentro Pediátrico William Soler durante el periodo 2011-2015 / Consumption of selected antimicrobials at William Soler Pediatric Cardiocenter, 2011-2015

Introducción: El uso irracional de antimicrobianos es un problema de salud. En el Cardiocentro Pediátrico William Soler existe una amplia utilización de ellos, sin embargo, no se conoce el comportamiento del consumo de este grupo farmacológico en la institución. Objetivo: Describir el consumo de antimicrobianos seleccionados en la institución en el periodo 2011-2015. Método: Estudio descriptivo, longitudinal del tipo estudio de utilización de medicamentos de consumo de 11 antimicrobianos, de uso restringido y elevado costo (cefepime, meropenem, levofloxacina oral y parenteral, linezolida, teicoplanina, vancomicina, colistina, aztreonam y amoxicilina/sulbactam oral y parenteral). El consumo en unidades físicas se obtuvo a partir de las tarjetas de estiba del almacén de medicamentos de la farmacia intrahospitalaria. Para el cálculo se utilizó la fórmula establecida por la Organización Mundial de la Salud, expresado en dosis diaria definida/100 camas/día (DDD/100 camas/día). Resultados: Se observó un incremento de 7,28 DDD/100 camas/día, los años 2013 y 2015 se mostraron como los de mayor consumo. Los fármacos más consumidos fueron el meropenem con un incremento de 2,71 DDD/100 camas/día; el cefepime con un incremento de 1,68 DDD/100 camas/día y la linezolida con un aumento de 1,15 DDD/100 camas/día. La terapia 1 y la sala 1A mostraron los mayores valores de consumo. Conclusiones: Los antimicrobianos han reducido de manera importante la amenaza de enfermedades infecciosas y son una herramienta indispensable en el tratamiento de los pacientes en los hospitales. El consumo de antimicrobianos seleccionados en el Cardiocentro Pediátrico William Soler, considerados de alto costo y utilización restringida, evidencia una tendencia al incremento, lo cual muestra la necesidad de desarrollar un programa de optimización de uso de estos medicamentos en la institución(AU)

Introduction: The irrational use of antimicrobials is a health problem. In William Soler Pediatric Cardiocenter there is a wide use of them; however, the behavior of the consumption of this pharmacological group in the institution is not known. Objective: To describe the consumption of selected antimicrobials in the institution in the period 2011-2015. Method: Descriptive, longitudinal study of the use of medicines for the consumption of 11 antimicrobials, of restricted use and high cost (cefepime, meropenem, oral and parenteral levofloxacin, linezolid, teicoplanin, vancomycin, colistin, aztreonam and amoxicillin / oral and parenteral sulbactam). The average consumption in physical units was obtained from the stowage cards of the drug store of the in-hospital pharmacy. For the calculation, the formula established by the World Health Organization was used and this is expressed in a defined daily dose / 100 beds / day (DDD / 100 beds / day). Results: An increase of 7.28 DDD / 100 beds / day was observed; the years 2013 and 2015 were shown as those with the highest consumption. The most consumed drugs were meropenem with an increase of 2.71 DD / 100 beds / day; cefepime with an increase of 1.68 DD / 100 beds / day; and linezolid with an increase of 1.15 DDD / 100 beds / day. Therapy room 1 and room 1A showed the highest consumption values. Conclusions: Antimicrobials have reduced in a crucial way the threat that infectious diseases represent, and they are also an indispensable tool in the treatment of patients in hospitals. The consumption of selected antimicrobials considered of high cost and restricted use in William Soler Pediatric Cardiocenter shows a tendency to increase, which shows the need to develop a program to optimize the use of antimicrobials in the institution(AU)

Consumo de antimicrobianos seleccionados en el Cardiocentro Pediátrico William Soler durante el periodo 2011-2015 / Consumption of selected antimicrobials at William Soler Pediatric Cardiocenter, 2011-2015

Introducción: El uso irracional de antimicrobianos es un problema de salud. En el Cardiocentro Pediátrico William Soler existe una amplia utilización de ellos, sin embargo, no se conoce el comportamiento del consumo de este grupo farmacológico en la institución. Objetivo: Describir el consumo de antimicrobianos seleccionados en la institución en el periodo 2011-2015. Método: Estudio descriptivo, longitudinal del tipo estudio de utilización de medicamentos de consumo de 11 antimicrobianos, de uso restringido y elevado costo (cefepime, meropenem, levofloxacina oral y parenteral, linezolida, teicoplanina, vancomicina, colistina, aztreonam y amoxicilina/sulbactam oral y parenteral). El consumo en unidades físicas se obtuvo a partir de las tarjetas de estiba del almacén de medicamentos de la farmacia intrahospitalaria. Para el cálculo se utilizó la fórmula establecida por la Organización Mundial de la Salud, expresado en dosis diaria definida/100 camas/día (DDD/100 camas/día). Resultados: Se observó un incremento de 7,28 DDD/100 camas/día, los años 2013 y 2015 se mostraron como los de mayor consumo. Los fármacos más consumidos fueron el meropenem con un incremento de 2,71 DDD/100 camas/día; el cefepime con un incremento de 1,68 DDD/100 camas/día y la linezolida con un aumento de 1,15 DDD/100 camas/día. La terapia 1 y la sala 1A mostraron los mayores valores de consumo. Conclusiones: Los antimicrobianos han reducido de manera importante la amenaza de enfermedades infecciosas y son una herramienta indispensable en el tratamiento de los pacientes en los hospitales. El consumo de antimicrobianos seleccionados en el Cardiocentro Pediátrico William Soler, considerados de alto costo y utilización restringida, evidencia una tendencia al incremento, lo cual muestra la necesidad de desarrollar un programa de optimización de uso de estos medicamentos en la institución(AU)

Introduction: The irrational use of antimicrobials is a health problem. In William Soler Pediatric Cardiocenter there is a wide use of them; however, the behavior of the consumption of this pharmacological group in the institution is not known. Objective: To describe the consumption of selected antimicrobials in the institution in the period 2011-2015 Method: Descriptive, longitudinal study of the use of medicines for the consumption of 11 antimicrobials, of restricted use and high cost (cefepime, meropenem, oral and parenteral levofloxacin, linezolid, teicoplanin, vancomycin, colistin, aztreonam and amoxicillin / oral and parenteral sulbactam). The average consumption in physical units was obtained from the stowage cards of the drug store of the in-hospital pharmacy. For the calculation, the formula established by the World Health Organization was used and this is expressed in a defined daily dose / 100 beds / day (DDD / 100 beds / day). Results: An increase of 7.28 DDD / 100 beds / day was observed; the years 2013 and 2015 were shown as those with the highest consumption. The most consumed drugs were meropenem with an increase of 2.71 DD / 100 beds / day; cefepime with an increase of 1.68 DD / 100 beds / day; and linezolid with an increase of 1.15 DDD / 100 beds / day. Therapy room 1 and room 1A showed the highest consumption values. Conclusions: Antimicrobials have reduced in a crucial way the threat that infectious diseases represent, and they are also an indispensable tool in the treatment of patients in hospitals. The consumption of selected antimicrobials considered of high cost and restricted use in William Soler Pediatric Cardiocenter shows a tendency to increase, which shows the need to develop a program to optimize the use of antimicrobials in the institution(AU)

Insights into the Effects of Crack Abuse on the Human Metabolome Using a NMR Approach.

Approximately 255 million people consume illicit drugs every year, among which 18 million use cocaine. A portion of this drug is represented by crack, but it is difficult to estimate the number of users since most are marginalized. However, there are no recognized efficacious pharmacotherapies for crack-cocaine dependence. Inflammation and infection in cocaine users may be due to behavior adopted in conjunction with drug-related changes in the brain. To understand the metabolic changes associated with the drug abuse disorder and identify biomarkers, we performed a 1H NMR-based metabonomic analysis of 44 crack users' and 44 healthy volunteers' blood serum. The LDA model achieved 98% of accuracy. From the water suppressed 1H NMR spectra analyses, it was observed that the relative concentration of lactate was higher in the crack group, while long chain fatty acid acylated carnitines were decreased, which was associated with their nutritional behavior. Analyses of the aromatic region of CPMG 1H NMR spectra demonstrated histidine and tyrosine levels increased in the blood serum of crack users. The reduction of carnitine and acylcarnitines and the accumulation of histidine in the serum of the crack users suggest that histamine biosynthesis is compromised. The tyrosine level points to altered dopamine concentration.

A ciência baseada em evidências nas políticas públicas para reinvenção da prevenção ao uso de álcool e outras drogas / La ciencia basada en evidencias en las políticas públicas para la reinvención de la prevención al uso del alcohol y otras drogas / Evidence-based science in public policies for reinventing alcohol and drugs use prevention

As políticas públicas baseadas em evidências precisam responder às vulnerabilidades sociais na superação das iniquidades. A presente revisão de literatura, do tipo narrativa, analisa os desafios de adaptação na difusão de práticas de prevenção ao uso de álcool e outras drogas baseadas em evidências no Brasil. As teorias de Difusão de Inovações (Rogers) e de Implementação de práticas baseadas em evidências (Aarons et al.) embasaram a crítica aos modelos existentes. Conclui-se que a implantação de uma ação preventiva baseada em evidências, mas que não é culturalmente relevante, corre o risco de não incidir nas vulnerabilidades. Ao mesmo tempo, as adaptações, mesmo que promovam altos níveis de aceitabilidade, podem comprometer a efetividade do programa caso sejam realizadas sem o embasamento em evidências e podem descaracterizar a inovação, passando a servir na reprodução de iniquidades, as quais a inovação compromete-se a mudar.(AU)

Las políticas públicas basadas en evidencias necesitan responder a las vulnerabilidades sociales en la superación de las iniquidades. La presente revisión de la literatura, del tipo narrativa, analiza los desafíos de adaptación en la difusión de prácticas de prevención al uso del alcohol y otras drogas basadas en evidencias en Brasil. Las teorías de "Difusión de innovaciones" (Rogers) y de "Implementación de práctica basada en evidencia" (Aarons et al.) sirvieron de base a la crítica a los modelos existentes. Se concluye que la implantación de una acción preventiva con base en evidencias, pero que no es culturalmente relevante, corre el riesgo de no incidir en las vulnerabilidades. Al mismo tiempo, las adaptaciones, aunque promueven altos niveles de aceptabilidad, pueden comprometer la efectividad del programa caso se realicen sin base en evidencias y pueden desvirtuar la innovación pasando a servir en la reproducción de iniquidades que la innovación se compromete a cambiar.(AU)

The evidence-based public policies need to address the social vulnerabilities in order to overcome the inequities. This narrative literature review analyzes the challenges of adaptation in the dissemination of the evidence-based alcohol and drugs prevention practices within the context of the Brazilian public policies. The critique of existing models is based on the theories of "Diffusion of Innovations" (Rogers) and "Implementation of the evidence-based practices" (Aarons et al). We concluded that the implantation of an evidence-based preventive action, if culturally not relevant, risks not impacting on the vulnerabilities. The adaptations may promote higher levels of acceptance and adhesion. In spite of that, if those adaptations are performed without the evidence base, they may reduce the effectiveness, as well as de-characterize the innovation, ending up in the reproduction of the inequities it aimed to reduce.(AU)

[Complications of intracameral cefuroxime in cataract surgery]. / Oslozhneniia vnutrikamernogo vvedeniia tsefuroksima v khirurgii katarakty.

Intracameral injection of cefuroxime during phacoemulsification is considered effective in preventing endophthalmitis. Its widespread usage has led to the accumulation of data on local and systemic adverse reactions. The analysis of complications of cataract surgery with cefuroxime injections described in literature has allowed identifying a few different clusters of toxic and allergic reactions to intracameral cefuroxime for the first time. These clusters included toxic anterior segment syndrome, serous retinal detachment with macular edema, retinal hemorrhagic infarction and anaphylactic reaction. The first two types develop in the cases of both correct and incorrect dosages, and both have favorable prognosis. Retinal hemorrhagic infarction was observed in cases with more than 50 mg intracameral antibiotic injected in the anterior chamber and was accompanied by persistent irreversible visual deterioration. Anaphylactic shock in response to a standard dose of intracameral cefuroxime was described in patients allergic to penicillin. Every clinical variant has specific complication mechanisms, prevention and treatment options. Antibiotic dilution done by medical staff accounts for the risk of incorrect dosage and related complications. Clinical manifestations of the complications of antibiotic prophylaxis should be considered when specifying the causes of decreased vision in the early postoperative period.

Impact of alcohol disorder and the use of illicit drugs on tuberculosis treatment outcomes: a retrospective cohort study.

BACKGROUND: Alcohol and illicit drugs are associated with the discontinuation of tuberculosis (TB) treatment and can compromise the immune system. We estimated the impact of alcohol disorder and the use of illicit drug on TB treatment outcomes, considering the interaction of both substances in patients from São Paulo state, Brazil. METHODS: This is a retrospective cohort of patients diagnosed with TB from 2011 to 2015. We estimated the relative risk (RR) of an unsuccessful outcome associated with alcohol disorder, use of illicit drugs and their interaction using a multiple regression model. We used the adjusted RR to estimate the population attributable fraction. RESULTS: Out of a total 77,212 TB patients, 22.2% used at least one of the substances of interest during treatment, while 17% presented an unsuccessful outcome of TB treatment. Compared with no exposure to any substance, alcohol disorder alone (adjusted RR: 1.48; 95% CI: 1.4-1.56), drug use alone (adjusted RR: 2.1; 95% CI: 1.98-2.21) and exposure to both substances (adjusted RR: 2.09; 95% CI: 1.97-2.21) were all associated with a higher risk of an unsuccessful outcome. The adjusted RR of an unsuccessful outcome for people exposed to both substances was 32.7% (95% CI: 26.8-38.2%) and 15.8% (95% CI: 11.5-20.1%) lower than expected on the multiplicative and additive scales respectively. Among all TB patients, 15.8% (95% CI: 15-16.5%) of unsuccessful outcomes was attributable to those exposures. CONCLUSIONS: We identified a negative interaction between alcohol disorder and the use of illicit drugs on TB treatment outcomes. Despite this, interventions to reduce substance use in TB patients could have a meaningful contribution to preventing unsuccessful treatment outcomes.

The Clinical Efficacy of Mindfulness-Based Treatments for Alcohol and Drugs Use Disorders: A Meta-Analytic Review of Randomized and Nonrandomized Controlled Trials.

INTRODUCTION: The current study aims to evaluate if and to what extent mindfulness-based interventions (MBIs) could promote an incremental effectiveness compared to interventions usually provided in clinical practice to treat Alcohol and Drugs Use Disorders. In line with this aim, we accomplished a meta-analytic review of randomized and nonrandomized controlled trials, considering primary and secondary outcomes that comprehensively operationalize treatment efficacy. METHODS: We conducted the online research up to August 31st 2017. Adequate procedures for Cohen's d computation were applied. Heterogeneity indexes, moderators, bias of publication, and Orwin's fail-safe number were also estimated. RESULTS: Thirty-seven studies were included (n = 3,531 patients). We observed null effect sizes for attrition rate and overall mental health. Small effect sizes were detected in abstinence, levels of perceived stress, and avoidance coping strategies. Moderate effect sizes were revealed in anxiety and depressive symptoms. Large effect sizes were associated to levels of perceived craving, negative affectivity, and post-traumatic symptoms. CONCLUSION: MBIs seemed to show clinically significant advantages compared to other clinical approaches in relation to specific primary and secondary outcomes. Conversely, treatment retention was independent of the therapeutic approach.

Drogas - Pra que te quero? Drogadição e Adolescência na Voz dos Socioeducadores / Drugs - Why do I want them? Drug Addiction and Adolescence According to Social Educators

RESUMO Foi estudada a compreensão de seis socioeducadores sobre a relação entre o uso de drogas e a prática infracional de adolescentes em cumprimento de medida socioeducativa em meio aberto. O método qualitativo descritivo foi instrumentalizado por entrevistas semiestruturadas, e a análise se deu a partir das interpretações por eles atribuídas para o uso de drogas. Para os socioeducadores, tal uso está relacionado às condições históricas de exclusão social, ressaltando a dificuldade de acesso ao lazer e aos serviços de tratamento. A relação com a prática infracional foi constatada para um pequeno grupo poliusuário de drogas. Uma política para estes adolescentes deve atentar para além do ato infracional e da relação com as drogas, reconhecendo o sofrimento social na origem de tais eventos.

ABSTRACT We investigated the knowledge of six social educators about the connection between the use of drugs and the offence practice of adolescents serving a social-educational measure in an open environment. The descriptive qualitative method was instrumented through semi-structured interviews, and the analysis was based on the interpretations that the social educators attributed to the use of drugs. To them, drug use is related to the historical conditions of social exclusion, emphasizing the difficulty of access to leisure and treatment services. The relation between drug use and the offence practice was observed in a little group of poly-drug users. A policy for these adolescents should not only take into account the infraction and the connection with drugs, but also the social suffering that has these events as an origin.

The appropriate use of human albumin in a Brazilian University Hospital: therapeutic indication and dosage regimen

The objective of the study was to evaluate the use of human albumin in a Brazilian university hospital, in compliance with the institutional protocol and other clinical guidelines, taking into account the therapeutic indications and the dosage regimens. Data was obtained from the pharmacy dispensing records of human albumin, the requests for use it and, when available, the patient's records between January and October 2017. After evaluation the therapeutic indications and the dosage regimens were classified as "appropriate" and "inappropriate". The analysis of 98 requests showed that, when compared to the institutional protocol, 54 (55.1%) requests had an inappropriate therapeutic indication. However, when a comparison was made between 25 medical records (54 requests) and other clinical guidelines, it was observed that the therapeutic indication had none classified as inappropriate. In addition, 16 (29.7%) requests were considered inappropriate in relation to dosage regimens. From these results, it was possible to conclude that although the use of human albumin in the hospital was associated to a clinical protocol, it was outdated. Thus, it is possible to affirm that not only the adoption of a clinical protocol, but its periodical updating is an important strategy to promote the rational use of drugs.

Use of unlicensed and off-label drugs in neonates in a Brazilian university hospital

ABSTRACT This study was designed to investigate the use of off-label and unlicensed drugs in a Neonatal Care Unit (NCU) and to compare the frequency of use of off-label drugs according to the drug regulatory agencies in Brazil (Agência Nacional de Vigilância Sanitária-ANVISA) and the United States Food and Drug Administration (FDA). A prospective observational study was carried out in the NCU. Prescriptions were classified as off-label and unlicensed using both ANVISA and FDA criteria. A total of 157 newborns and 1187 prescriptions were analyzed. The most prescribed drug was fentanyl (9.3%), followed by multivitamin (8.4%) and gentamicin (7.9%). According to ANVISA criteria, there were 665 (56.0%) off-label prescriptions and 86 (7.2%) unlicensed prescriptions and 95.5% of newborns received at least one drug off-label. By contrast, according to FDA criteria, there were 592 (49.9%) off-label prescriptions and 84 (7.1%) unlicensed prescriptions, and 72.0% of newborns received at least one drug off-label. The off-label use of drugs registered by ANVISA differed significantly from that of drugs registered by the FDA. There was a high frequency of off-label and unlicensed drug use in the investigated NCU, and there was an inverse relationship between off-label and unlicensed usage and the gestational age of the newborns.

Relation of new-type drugs using intention to self-efficacy and perceived stress in secondary vocational school students / 中国心理卫生杂志

Objective:To explore the relation of new-type drug using intention,self-efficacy,and perceived stress in secondary vocational school students.Methods:A total of 2692 secondary vocational school students in Zhaoqing,Guangdong Province were selected.The questionnaire of new-type drugs using intention,General Self-Efficacy Scale (GSES),and Perceived Stress Scale (PSS) were respectively used to assess the secondary vocational school students'new-type drugs using intention,self-efficacy,and perceived stress.Path analysis model was used to analyze the relationship of new-type drugs using intention,self-efficacy,and perceived stress among secondary vocational school students.Results:There were 13.6％ (295/2165) of the secondary vocational school students reported an intention to use new-type drugs.The total scores of GSES and PSS were (2.4 ±0.5) and (18.8 ±5.0),respectively.The results of path analysis showed that,after controlling for age,gender,and residence,the scores of GSES were negatively correlated with the scores of PSS (γ =-0.21,P ＜0.001),and the scores of PSS were positively correlated with the scores of questionnaire of new-type drugs using intention (γ =0.05,P ＜ 0.05).However,the scores of GSES showed no significant direct correlation with the scores of questionnaire of new-type drugs using intention (γ =0.04,P ＞ 0.05).Conclusion:The secondary vocational school students' level of perceived stress are positively correlated with their intention to use new-type drugs.Self-efficacy might moderate the individual's level of perceived stress,thus to show indirect correlation to the secondary vocational school students' intention.