The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

El uso de "virado" como estrategia de reducción de daños entre los usuarios de crack del estado de Pernambuco, Brasil / The use of "virado" as a harm reduction strategy among crack users in the State of Pernambuco, Brazil

RESUMEN El objetivo del estudio es discutir uno de los usos del crack denominado "virado", como estrategia de reducción de daños entre las personas que usan crack en Pernambuco, Brasil. Se realizó una investigación cualitativa y transversal. Desde marzo hasta agosto de 2016, se realizaron entrevistas semiestructuradas sobre la cultura del uso de crack a 39 personas que usan esta substancia. El límite de participantes se estableció por el criterio de saturación. Los datos se analizaron con la técnica de análisis de contenido. Las personas que participaron relataron que el virado es una manera distinta de utilizar el crack y, al comparar su efecto con el uso fumado o inhalado, mencionaron que el virado produce menos impacto en las relaciones interpersonales y en la libido, además de reducir el uso compulsivo de crack, cuestiones que se podrían considerar como estrategias de reducción de daños. Un aspecto negativo es que comparten los canutos para aspirar el virado, lo cual es una situación de riesgo para la transmisión de enfermedades infecciosas. Conocer la cultura del uso del crack en distintas formas y situaciones es imprescindible para la planificación y desarrollo de acciones de atención a la salud.

ABSTRACT The aim of the study is to discuss the use of crack in the form of "virado" as a harm reduction strategy in Pernambuco, Brazil. This is a cross-sectional study with a qualitative approach in which semi-structured interviews were conducted regarding aspects related to the culture of crack use with 39 crack users between March and August 2016. Participants were recruited using saturation criteria and data were analyzed through content analysis. Respondents discussed the use of "virado" and compared its effects in relation to crack, addressing improvement in interpersonal relationships, libido, and non-compulsive drug use, which can all be understood as harm reduction strategies. On the other hand, equipment sharing for the use of "virado" was identified as a high-risk practice with regards to the transmission of infectious diseases. Knowing about the culture of crack use in different contexts is essential in order to plan and develop health care actions.

Cannabis use among the drug users with compulsory detained detoxification treatment in China / 北京大学学报(医学版)

OBJECTIVE@#To explore the epidemic situation of cannabis use among drug users with compulsory detained detoxification treatment in China.@*METHODS@#Using the data from the Drug Abuse Population Estimation in the Key Cities of the Ministry of Public Security, we analyzed the sociodemographic characteristics and substance use of cannabis abusers with compulsory detained detoxification treatment in 55 provincial capital cities and key cities of China. Chi-square test, Fisher exact test and Kruskal-Wallis rank sum test were used to compare the prevalence of cannabis, heroin, synthetic and mixed drug use among patients with detoxification treatment, as well as the differences in polydrug use and areas among cannabis users.@*RESULTS@#In the study, 25 366 drug users with compulsory detained detoxification treatment were recruited, of whom 2.2% (546/25 366) used cannabis in the previous year before the treatment. The proportion of males was 83.5%, and the proportion of ethnic minorities was 41.0%. Those who received junior high school education or above accounted for 30.8%, and the unemployed accounted for 44.1%. The average age was (33.3±8.2) years, the average age of beginning drug use was (24.8±7.7) years, and the average duration between the first drug abuse and first detoxification treatment was (5.4±4.6) years. The prevalence of cannabis use was higher among those drug users who were 35-year-old and younger, ethnic minorities, employees and residents in Xinjiang. Of the cannabis users, 91.4% used polydrug, 13.6% combined with heroin alone, 42.1% combined with synthetic drugs alone and 35.7% combined with both of heroin and synthetic drugs. Of the cannabis users, 49.6% came from 3 regions: Xinjiang Uygur Autonomous Region, Jiangsu Province and Shanghai City. The cannabis users in Xinjiang had a high proportion of ethnic minorities who received junior high school education and below. Moreover, 79.6% of them combined cannabis use with heroin. The cannabis users in Jiangsu, Zhejiang and Shanghai areas had a higher proportion of ethnic Han who received better education (high school and above). Moreover, 92.7% of them combined cannabis use with methamphe-tamine.@*CONCLUSION@#The prevalence of cannabis use among the population with compulsory detained detoxification treatment is higher than that among drug users under surveillance, but there are obvious regional cluster effect and high possibility of polydrug abuse. Thus, it's important to strengthen the monitoring of cannabis use, to increase the control of cannabis and to formulate China's anti-cannabis policy among different population.

Craving for heroin: difference between methadone maintenance therapy patients with and without ADHD / Fissura por heroína: diferença entre pacientes em terapia de manutenção com metadona com e sem TDAH

Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. Method Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney's U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk's test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. Results A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. Conclusion Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

Resumo Introdução O transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento que persiste na idade adulta em 40-60% dos casos. Estudos clínicos e de neuroimagem sugerem que pacientes afetados tanto por adição quanto por TDAH apresentam maiores índices de fissura (craving) por droga do que pacientes sem TDAH. Este estudo piloto aberto investigou os efeitos do TDAH sobre fissura por heroína em pacientes em terapia de manutenção com metadona. Método Os pacientes foram recrutados em serviços ambulatoriais em uma unidade de tratamento de adição na cidade de Alba, Itália. Eles foram avaliados usando os seguintes instrumentos: Structured Clinical Interview for DSM-5 (SCID-5), SCID-5 for Personality Disorders (SCID-5-PD), Diagnostic Interview for Adult TDAH, second edition (DIVA 2.0) e Clinical Opiate Withdrawal Scale (COWS). Variáveis categóricas foram examinadas utilizando o teste do qui-quadrado, e variáveis contínuas, o teste t e o teste U de Mann-Whitney para dados com distribuição normal e não normal, respectivamente. A distribuição dos dados foi avaliada usando o teste de Shapiro-Wilk. O nível de significância foi estabelecido em p=0,05. A correção de Bonferroni foi aplicada (0,0063) para evitar erro tipo I. Resultados Um total de 104 pacientes foram incluídos no estudo: 14 com TDAH (13,5%) e 90 sem (86,5%). Pacientes com TDAH mostraram maior intensidade de fissura por heroína do que pacientes sem TDAH na ausência de sintomas de abstinência. Conclusão Adição e TDAH compartilham mecanismos neurobiológicos que influenciam mutuamente a evolução dos dois transtornos. Em particular, a disfunção da dopamina em vários circuitos cerebrais pode influenciar os níveis de impulsividade, motivação, controle inibitório, funções executivas e comportamento, e, portanto, a intensidade da fissura.

Vocal assessment of addicts on methadone therapy via the RBH scale and objective acoustic parameters / Avaliação da voz de drogaditos em terapia com metadona através da escala de rugosidade, soprosidade e aspereza, e parâmetros acústicos objetivos

Abstract Introduction: A large number of people around the world struggle daily to become free of their addiction to illegal psychoactive substances. In order to create an atmosphere of improved supervision, established communication and improved quality of life for drug addicts, centers have been set up to provide methadone as a substitute. Objective: The aim of the research was to assess the vocal features of drug addicts on methadone therapy via subjective and objective parameters, to ascertain if vocal damage has occurred and to determine whether subjective and objective acoustic vocal parameters are related, and how. Methods: The research included 34 adults of both genders who were undergoing methadone treatment. A subjective vocal evaluation assessed voice pitch and clarity, while the subjective acoustic analysis utilized the Roughness-Breathiness-Hoarseness scale of roughness-breathiness-hoarseness. Objective acoustic analysis was conducted after recording and analyzing an uninterrupted vocal /a/ of at least three seconds duration, using the "GllotisController" software. Results: The subjective acoustic analysis using the Roughness-Breathiness-Hoarseness scale showed pathological values in 52.9% male and 47% female participants. The average values of the roughness-breathiness-hoarseness for the entire sample were 0.91, 0.38 and 0.50, respectively. Lower roughness was associated with a higher fundamental frequency (f0) and lower jitter and shimmer values (p < 0.05). There was a statistically significant correlation between breathiness, jitter (p < 0.01) and shimmer (p < 0.05), and between hoarseness and jitter (p < 0.01). Conclusion: A statistically significant correlation was found between the two subjective vocal assessments, voice clarity and pitch, and Roughness-Breathiness-Hoarseness scale, and the parameters of the objective acoustic vocal assessment.

Resumo Introdução: Um grande número de pessoas em todo o mundo luta diariamente para livrar-se de seu vício em substâncias psicoativas ilegais. Com o objetivo de criar uma atmosfera de supervisão melhorada, comunicação estabelecida e melhora da qualidade de vida para drogaditos, foram criados centros que fornecem a substância substitutiva metadona. Objetivo: Avaliar a voz de drogaditos que recebem terapia com metadona através de parâmetros subjetivos e objetivos, para determinar o eventual dano à voz, bem como determinar se os parâmetros vocais acústicos subjetivos e objetivos estão interligados e como isso ocorre. Método: A pesquisa incluiu 34 participantes, usuários de terapia com metadona, de ambos os sexos. A avaliação vocal subjetiva consistiu na avaliação do tom (pitch) e clareza da voz, enquanto a análise acústica subjetiva consistiu no uso da escala RSA, de rugosidade, soprosidade e aspereza. A análise acústica objetiva foi realizada após a gravação e análise da vocalização ininterrupta de /a/ com duração de no mínimo três segundos, com o software GllotisController. Resultados: A análise acústica subjetiva utilizando a escala RSA mostrou valores patológicos em 52,9% de homens e 47% em mulheres. Os valores médios dos parâmetros rugosidade, soprosidade e aspereza para toda a amostra foram 0,91, 0,38 e 0,50, respectivamente. O parâmetro rugosidade mais baixo esteve associado a valores mais altos de frequência fundamental (f0) e menor jitter e o shimmer (p < 0,05). Entre o parâmetro soprosidade e o jitter (p < 0,01) e o shimmer (p < 0,05) houve uma correlação estatisticamente significante, bem como entre o parâmetro aspereza e o jitter (p < 0,01). Conclusão: Foi encontrada uma correlação estatisticamente significante entre a avaliação vocal subjetiva da clareza e do tom (pitch) da voz e os parâmetros da avaliação vocal acústica objetiva, bem como os parâmetros da análise vocal acústica subjetiva utilizando a escala de rugosidade, soprosidade e aspereza e os parâmetros acústicos objetivos.

Efectividad del cambio de tratamiento desde Metadona a Buprenorfina/Naloxona en dependientes a opiáceos, Bilbao - España / Effectiveness of treatment change from methadone to Buprenorphine / Naloxone in opiate dependents, Bilbao - Spain

A nivel mundial la dependencia a opiáceos es un problema vigente, y los pacientes afectados por esta condición requieren programas de tratamiento sustitutivo farmacológico, que utilizan tradicionalmente Metadona. Actualmente, existe debate sobre el hecho de que la Buprenorfina/Naloxona podria ser utilizada como un reemplazo adecuado del fármaco tradicional. Las investigaciones aún no son totalmente concluyentes, faltando estudios que prueben los resultados en la práctica clínica. Objetivos: Determinar la efectividad del tratamiento con Buprenorfina/Naloxona como reemplazo de la metadona en pacientes dependientes de opiáceos tratados en un Módulo de Asistencia Psicosocial en la ciudad de Bilbao, España. Métodos: Se realizó un estudio cuasiexperimental, cuantitativo, longitudinal, prospectivo, con 21 pacientes dependientes de opiáceos que formaban parte del Programa de mantenimiento con Metadona con dosis inferiores o iguales a 40 mg/día, en quienes se sustituyó ese tratamiento por el de Buprenorfina/Naloxona (8mg/2mg) siguiendo para esto los criterios de la Guía para el tratamiento de la adicción a opiáceos con Buprenorfina/Naloxona de la Sociedad Científica Española de estudios sobre alcohol, el alcoholismo y otras toxicomanías del 2010. Resultados: Después de tres meses de cambio de terapéutica a Buprenorfina/Naloxona se evidencio una reducción estadísticamente significativa en el consumo de opiáceos ilegales, medido a través de los controles de substancias en orina desde un promedio de 2,67 controles positivos con metadona, a 2,24 controles con Buprenorfina/Naloxona. La adherencia, se mantuvo similar a la previa, presentando además una retención del 100% de los pacientes. La calidad de vida, medida con el Test TECVASP, presento una mejora estadísticamente significativa, desde una puntuación de 76,76 cuando recibían Metadona (DE 6,41) hasta 90,33 (DE 5,77 ) con la nueva terapéutica. Conclusiones: Cambiar la terapia de mantenimiento con Metadona, en pacientes dependientes de opioides, por buprenorfina/naloxona es una buena opción, ya que tiene una efectividad similar en términos de adherencia y retención, y produce una mayor reducción en el uso de opiáceos ilegales, al tiempo que mejora la calidad de vida del paciente.

At the global level, opioid dependence is an ongoing problem, and patients with this condition require pharmacological substitution treatment programs, which traditionally use methadone. Currently there is debate over whether Buprenorphine / Naloxone could be used as a suitable replacement for the traditional drug. The investigations are not yet totally conclusive, lacking studies that prove the results in the clinical practice. Objectives: To determine the effectiveness of treatment with Buprenorphine / Naloxone as a replacement for Methadone in opioid dependent patients treated in a Psychosocial Assistance Module in the city of Bilbao, Spain. Methods: A quasi-experimental, quantitative, longitudinal, prospective study was conducted with 21 opioid-dependent patients that were part of the maintenance program with Methadone at doses lower than or equal to 40 mg / day, in which treatment was replaced by that of Buprenorphine / Naloxone (8 mg/2 mg) following for this the criteria of the Guide for the treatment of the addiction to opiates with Buprenorphine / Naloxone of the Spanish Scientific Society of studies on alcohol, alcoholism and other drug addictions of 2010. Results: After a three-month change in therapy to Buprenorphine / Naloxone, a statistically significant reduction in illegal opioid use was observed, measured through urine substance controls from an average of 2.67 methadone-positive controls 2.24 controls with Buprenorphine / Naloxone. The Adherence remained similar to the previous one, presenting a retention of 100% of the patients. Quality of life, measured with the TECVASP test, showed a statistically significant improvement, from a score of 76.76 when receiving Methadone (DE 6.41) to 90.33 (DE 5.77) with the new therapy. Conclusions: Changing maintenance therapy with methadone, in opioid-dependent patients, by buprenorphine/naloxone is a good option, because it has a similar effectiveness in terms of adherence and retention, and produces a greater reduction in the use of illegal opiates, and the same time improves the quality of life of the patient.

Satisfação com os cuidados de enfermagem em usuários de drogas: evolução de uma escala / Satisfacción con la atención de enfermería en los consumidores de drogas: evolución de una escala / Satisfaction with nursing care in drug users: the evolution of a scale

RESUMO Objetivos Identificar o grau de satisfação com os cuidados de enfermagem, as variáveis significativas e contribuir para a evolução da escala. Métodos Pesquisa descritiva, correlacional, transversal com 180 usuários de drogas. Dados coletados com a escala "Satisfação dos Utentes com os Cuidados de Enfermagem no Centro de Saúde26", entre fevereiro e dezembro de 2012, em três unidades de tratamento na região de Lisboa e Vale do Tejo, em Portugal. Resultados Os usuários assinalaram 83,3% de satisfação. A dimensão "Individualização da informação" foi a mais assinalada (98,5%). Quanto mais estabilidade nos programas, abstinência de estimulantes e benzodiazepinas e mais intervenções de enfermagem, maior a satisfação. Contribuíram ainda para a satisfação, melhores condições de trabalho, especialização em saúde mental, menor idade e menor experiência profissional dos enfermeiros. Extraíram-se 4 itens da escala assumindo nova designação SUCECS22. Conclusões A satisfação foi elevada, influenciada por variáveis estruturais dos usuários, dos enfermeiros e das condições de trabalho. A escala revelou-se adequada à avaliação nesta população.

RESUMEN Objetivo Identificar el grado de satisfacción con la atención de enfermería, las variables significativas y contribuir a la evolución de la escala. Método Estudio descriptivo, correlacional, transversal, con 180 usuarios de drogas. Datos recogidos con la escala "Satisfacción del paciente con el cuidado comunitario de enfermería26", entre febrero y diciembre de 2012, en tres unidades de tratamiento, en la región de Lisboa y el Vale do Tejo, Portugal. Resultados Los usuarios indicaron 83.3% de satisfacción. La dimensión "Individualización de la formación" fue la más marcada (98,5%). La mayor estabilidad en los programas, la abstinencia de estimulantes y benzodiacepinas y más intervenciones de enfermería, mayor es la satisfacción. Contribuyeron a la satisfacción, mejores condiciones de trabajo, especialidad en salud mental, más joven y menos experiencia de las enfermeras. Se extrajeron cuatro ítems de la escala asumiendo nueva designación SUCECS22. Conclusiones La satisfacción es alta, influenciada por las variables estructurales de los usuarios, de las enfermeras, y las condiciones de trabajo. La escala se reveló adecuada a la evaluación en esta población.

ABSTRACT Objectives To identify the degree of satisfaction with nursing care, the significant variables and contribute to the evolution of the scale. Methods Descriptive, correlational, cross study, with 180 drug users. Data collected using the scale called "Satisfaction of users with the Nursing Health Center26", between February and December 2012 in three treatment units in the region of Lisbon and Vale do Tejo, Portugal. Results Users indicated 83.3% satisfaction. The dimension "Information individualization" was the most marked (98.5%). The more stability in the programs, abstinence from stimulants and benzodiazepines and more nursing interventions, the greater the satisfaction. Better working conditions, specializing in mental health, younger ages and less experience of nurses also contributed to satisfaction. Four items of the scale were extracted, assuming new SUCECS22 designation. Conclusions Satisfaction was high, influenced by structural variables of users, nurses and working conditions. The scale has proved suitable for assessment in this population.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Clinical pharmacology of methadone in neonates and in their mothers. A review / Farmacologia clínica da metadona em neonatos e suas mães: revisão

The outstanding properties of methadone are its analgesic activity, its efficacy by oral route, its extended duration of action in suppressing of withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. The analgesic activity of methadone, a racemate, is almost entirely the result of its R-methadone content. Respiratory depression is the chief hazard associated with methadone, and its peak respiratory depressant effects typically occur later, and persist for longer than its peak analgesic effect, particularly in the early dosing period. Methadone undergoes extensive metabolism in the liver and the major metabolic pathway is N-demethylation by CYP3A4 and CYP2B6. There is a remarkable interindividual variability in the rate of methadone metabolism. Mothers with opioid addiction are often placed on methadone before delivery in an attempt to reduce illicit opioid usage. Methadone is useful because it can be taken orally, only requires one or two daily doses and has a long-lasting effect. Weaning should not be attempted during pregnancy and, because of increased clearance, the dose of methadone may need to be increased in the last 3 months of pregnancy. Significant positive correlations were found for umbilical cord methadone concentrations, methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. In conclusion, umbilical cord methadone concentrations were correlated to methadone dose. A total of 55-94% of infants born to opioid-dependent mothers in US show signs of opioid withdrawal. Methadone is useful to avoid use of opioid illicit drugs.

As mais importantes propriedades da metadona são sua atividade analgésica, a sua eficácia por via oral, a sua prolongada acão supressora de sintomas de abstinência em indivíduos fisicamente dependentes e a persistência de seus efeitos com administração repetida. A actividade analgésica de metadona, um racemato, é quase inteiramente o resultado do seu teor de R-metadona. A depressão respiratória é o principal risco associado a seu uso, e o pico de depressão respiratória normalmente ocorre tardiamente e persiste após o fim de seu efeito analgésico especialmente durante as fases iniciais de seu uso terapêutico. A metadona é metabolizada no fígado e a principal via metabólica é a N-desmetilação por CYP3A4 e CYP2B6. Há uma variabilidade interindividual notável em relação à sua taxa de metabolisacão. Mães com dependência de opiáceos são frequentemente colocadas em terapêutica com metadona antes do parto, na tentativa de reduzir o uso de opiáceos ilícitos. A metadona é útil porque pode ser tomada por via oral, só precisa de uma ou duas doses diárias e tem efeito de longa duração. O desmame não deve ser executado durante a gravidez; por causa do aumento da depuração, a dose de metadona pode precisar ser aumentada nos últimos três meses de gravidez. Correlações positivas significativas foram encontradas para a metadona entre os seguintes parâmetros: concentrações no cordão umbilical, dose média diria, dose durante o terceiro trimestre, e dose diária média cumulativa. Em conclusão, as concentrações de cordão umbilical de metadona foram correlacionados com a dose de metadona. Entre 55% e 94% dos recém-nascidos de mães dependentes de opiáceos nos Estados Unidos mostram sinais de abstinência a opiáceos. A metadona é útil para evitar o uso de drogas ilícitas opióides.

Effects of psychological counseling intervention on increasing methadone dosage and reducing heroin use among patients receiving methadone maintenance treatment / 中华流行病学杂志

<p><b>OBJECTIVE</b>To learn about the effects of psychological counseling intervention on reducing heroin use, increasing methadone dosage and improving compliance rate of methadone maintenance treatment (MMT).</p><p><b>METHODS</b>Subjects who had had at least one positive result for regular urine morphine tests during the past three months were recruited from 16 MMT clinics. During the three-month intervention period, the subjects received regular psychological counseling provided by doctors (once every other week) and peer education (once a week). Positive rates of urine morphine tests, average days receiving MMT during three months before the intervention and during the intervention, and average daily dosage of methadone during the last week before intervention and during the last week of the intervention programs conducted were recorded and compared.</p><p><b>RESULTS</b>A total of 492 patients receiving MMT were surveyed. There were significant changes in positive rates for urine morphine tests, average daily dosage, and average days on MMT before and during the intervention programs. The positive rate for urine morphine tests dropped from 50.1% to 27.1%; the average daily dosage of methadone increased from 63.0 mg to 72.6 mg; the average days receiving MMT increased from 69.4 days to 73.9 days.</p><p><b>CONCLUSION</b>Intensive psychological counseling intervention was effective in reducing heroin use, increasing methadone dosage and improving compliance rate of MMT among patients receiving MMT.</p>

Impact of antiretroviral therapy on drug-using and high risk sexual behaviors among HIV-positive methadone maintenance treatment clients: a qualitative study / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand that whether initiation of antiretroviral therapy (ART) would impact on the change and its reasons regarding the HIV-related high risk behaviors among HIV-positive clients who attending the methadone maintenance treatment (MMT).</p><p><b>METHODS</b>In-depth interviews were conducted among 34 MMT clients in Yunnan province who were under ART. The related contents would include information on general demographic charicteristics, HIV infection,MMT, number of sexual partners before and after ART, sexual behavior and frequency of condom use, drug use, needle sharing, changes in risk behaviors before and after the ART, reasons for high-risk behavior, of the clients.</p><p><b>RESULTS</b>The average age of the interviewees was 38.5 years, and most of them were male (70.6%). The clients under this study all admitted that the frequencies of unsafe sex and needle sharing did not increase after the ART initiation, with the main reasons as increasing HIV related awareness, the use of methadone, high accessibility of free condoms and access to clean needles etc. However, 12 of 34 reported being relapsed and 3 reported inconsistent condom use. The interaction of ART and dosage of methadone were connected to the episodes of relapsing and the ART optimism would result in inconsistent condom use.</p><p><b>CONCLUSION</b>No evidence supported that the ART initiation would increase the risk behaviors among the HIV-infected MMT clients. However, attention needs to be paid to the new challenges caused by high expectation of ART.</p>

Association between negative emotion and interpersonal sensitivity among patients in methadone maintenance treatment / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analyze interpersonal sensitivity level and influencing factors among patients in methadone maintenance treatment.</p><p><b>METHODS</b>From 2010 June to 2011 June, the research was performed in Center of Methadone Maintenance Treatment of Nanjing Baixia District Hospital. A total of 272 methadone maintenance treatment was studied using a self-designed questionnaire, interpersonal sensitivity scale in symptom check list (SCL-90), self-rating depression scale (SDS), self-rating anxiety scale (SAS). If interpersonal sensitivity level ≥ 2 points, it was positive. In this study, through independent sample t test, analysis of the social demographic characteristics, depression and anxiety, interpersonal sensitivity level. Non conditional logistic regression analysis was used to explore a variety of factors, and the relationship of these factors with interpersonal sensitivity.</p><p><b>RESULTS</b>The depression score, the anxiety score and the level of interpersonal relationship sensitivity in 272 methadone maintenance treatment (1.65 ± 0.51, 47.66 ± 8.58, 42.38 ± 9.40) was higher than the national norm (1.65 ± 0.51, 41.88 ± 10.57, 29.78 ± 0.46) (t values were 8.23, 17.63 and 22.27, respectively; all P values < 0.001). In 272 methadone maintenance treatment, the percentage of men was 75.0% (204/272) and the percentage of women was 25.0% (68/272). SDS score of male and female was (48.38 ± 8.30) and (45.90 ± 9.34) points (t = 5.67, P = 0.037); Aged 20-29, 30-39, 40-49 and ≥ 50 years old group, SDS scores were (48.26 ± 7.59), (47.73 ± 8.38), (47.79 ± 9.22) and (48.09 ± 6.33) points (F = 3.90, P = 0.046); According to the drug's time, divided into 1-3, 4-6 and ≥ 7 years group, SDS scores were (45.92 ± 7.47), (47.41 ± 7.57) and (48.07 ± 8.57) points (F = 4.49, = 0.039). SAS score of male and female was (41.21 ± 9.53) and (42.91 ± 9.42) points (t = 2.23, P = 0.043). The positive rate of interpersonal sensitivity was 47.1% (128/272). Multivariate analysis showed that, with SDS and SAS scores increased by 1, respectively, interpersonal sensitivity increased 23.23 (8.62-96.68) and 11.97 (6.42-19.27) points.</p><p><b>CONCLUSION</b>Interpersonal sensitivity level in methadone maintenance treatment was higher than normal and depression; anxiety and depression both were the risk factors of interpersonal sensitivity level.</p>

Estimation of out-of-pocket costs of patients at the methadone maintenance therapy clinic in Malaysia

Out-of-pocket [OOP] payments may burden Methadone Maintenance Clinic patients. Since treatment is fully .subsidized by the government, financial constraint might lead to patients being made to pay or be given incentive for inconvenience of therapy. This study thus evaluates the characteristic and commitment of methadone therapy patient's in terms of OOP cost, Willingness-To-Pay [WTP]and Willingness-To-Accept [WTA]concept. This survey utilizes the questionnaire by Boris ova and Goodman [2003] on the OOP, WTP and WTA. The forty adult patient's selected medical records from year 2009-2011 were from an urban government methadone clinic. Subject's selection was by convenient sampling based on the predetermined criteria. Most were male [95%] and Malay [60%] was the predominant group. Patients were group into three income groups; /=RM1000 - /=RM3000. The average OOP cost per month was RM391.30 [s.d RM337.50], which is about 35% of employed patient's monthly income. The wide variation could be attributed by high inter-individual and significant differences between patients in terms of transport, times taken to clinic, cost per trip and weekly household income [p=<0.05]. Patients with income of less than RM1000 showed the highest tendency to pay for treatment, asked for the least money for inconvenience and many are unwilling to accept any payments. These findings showed that WTP and WTA is less of a concern for patients in the low-income group. To conclude, OOP payment is not a treatment barrier for most of the urban MMT patients

Club-based drug use and its associated risk factors among HIV-positive methadone maintenance treatment clients / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe club-based drug use and to explore the determinants on those HIV-positive methadone maintenance treatment (MMT) clients.</p><p><b>METHODS</b>This study was conducted in 5 MMT clinics in Yunnan province and 612 MMT clients who met the survey criteria were recruited for the study. Urine sample was tested as a biological marker to identify if heroin, methamphetamine, methylene-dioxy-methyl-amphetamine, buprenorphine or benzodiazepine had been used.</p><p><b>RESULTS</b>The average age among the 612 clients was 38.9 ± 6.3 years. Among these, 78.9% were males, with the average years of education as 8.0 ± 3.4 years. There were 60.5% clients who had good relationship with their families. 153 (25.0%) clients reported having used club-related drugs in the last 12 months. Results from the urine test showed that the positive rate on morphine was 14.4%, while the positive rate for club-related drugs was 26.6%. Factors as residential area, casual sexual partners, retention on MMT and occasionally use of heroin were associated with urine results on club-related drugs and the prevalence of self-reported club drug use (P < 0.05).</p><p><b>CONCLUSION</b>Club-related drug use was common among HIV-positive MMT clients. Inspection and supervision for club-related drugs and the education and intervention programs on related high risk behaviors should be strengthened.</p>

Analysis of characteristics and therapy of clients in the extension methadone maintenance therapy clinic / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy.</p><p><b>METHODS</b>From December 20, 2010 to March 10, 2011, the system sampling method was used to get the cases. A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi, Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture, Yunnan province were interviewed, and the demographic characteristics, quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared. A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment.</p><p><b>RESULTS</b>Of the 462 cases, 239 cases were from standard MMT clinic, and 223 cases were from the extension MMT clinic. Among them, 117 cases were new research objects into the group during the investigation. Among the clients of extension MMT clinic, 96.7% (147/152) of them were males, 37.5% (57/152) were Dai nationality, and 61.2% (93/152) were married, 38.8% (59/152) with primary school education, 95.4% (145/152) lived with their family or relatives, 96.7% (147/152) could arrive at the clinic from their habitation within 15 minutes. The positive detection rates 72% (13/18), 71% (24/34), 58% (30/52), 29% (15/52), 14% (6/44), 14% (4/29), 15% (5/34), 17% (6/35), 6% (2/33), 16% (5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ(2) = 61.04, P < 0.05). The period of retention of the clients in extension MMT clinics was 175-days averagely, with an average retention 122 days of when withdrawing. The retention rates of the clients were 52% (37/71)and 61% (28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively. There was no difference in the retention rate between those of two types of clinics (χ(2) = 0.82, P = 0.37) .</p><p><b>CONCLUSION</b>Most of the clients in extension MMT clinics lived with their family or relatives, and spent less time on the way to the clinics. After 9 months methadone maintenance therapy, the quality of life of clients in extension clinics was improved while addiction among them decreased. The extension clinic was an effective strategy for retention in remote areas.</p>

Predictors of treatment retention in a major methadone maintenance treatment program in Iran: a survival analysis

To identify correlates related to retention time of a cohort study of the opioid-dependent patients participating in the Methadone Maintenance Treatment [MMT] program offered by a major addiction treatment clinic in Tehran, Iran between April 2007 and March 2011. Several parametric Survival models assuming Weibull, Log-normal and Log-logistic distributions were compared to search for association between covariates and risk of relapse and dropping out of treatment among 198 patient participants. According to Akaike Information Criterion [AIC], Log-normal model had the best fitting. Estimates of this model indicated that increase in average methadone dosage was associated with longer retention time. Correlates associated with shorter retention time were suffering from mental disorders, using stimulant drugs, being poly-substance dependents and having prior treatments. Findings of this study provide support for giving more attention to patients who are poly-substance or stimulant-drug dependents, have non-substance psychiatric comorbidity and the ones with addiction treatment history. Independent of patient characteristics, retention improved as the dose of methadone increased

Health economic evaluation for the extension clinics of methadone maintenance treatment / 中华预防医学杂志

<p><b>OBJECTIVE</b>To discuss the cost, cost-effectiveness, and cost-utility of the extension methadone maintenance treatment (MMT) clinics and provide the evidences of the strategy of scaling up the extension MMT clinics.</p><p><b>METHODS</b>A study was conducted in Dehong prefecture, Yunnan province, including Mang, Ruili city, Longchuan, Yingjiang, Lianghe county. 117 newly enrolling heroin addict patients in 17 extension MMT clinics were recruited as subjects from December 2010 to February 2011. An interview was conducted by the trained interviewers for the quality of life score of patients, and the cost of drug use was calculated. Table of outpatient costs of methadone maintenance treatment clinic of Dehong prefecture in Yunnan was used for collecting and calculating the fixed cost, operating cost of the clinics, and the unit cost and incremental cost of the patients from 2008 to 2010. Cost-effectiveness and cost-utility of the extension clinics were analyzed by using the Markov model.</p><p><b>RESULTS</b>The total spending of extension clinics for 2008, 2009, and 2010 on average was ¥57 294, ¥80 752 and ¥74 739 respectively, or about ¥4379 annually per patient. The cost of averting one HIV infection was ¥316 509; the cost of averting one acquired immune deficiency syndrome (AIDS) patients was ¥508 676; and the cost of averting one death was ¥152 330. The cost of obtaining one life year (LY) was ¥3696 and the cost of obtaining one quality adjusted life year (QALY) was ¥9014. Comparing with drug users, the incremental cost utility ratio (ICUR) of the patients of the extension MMT clinics were -7074 yuan/QALY and -7162 yuan/LY.</p><p><b>CONCLUSION</b>The extension MMT clinic service is lower in cost, and better in cost-effectiveness and cost-utility.</p>

effects of gabapentin on methadone based addiction treatment: a randomized controlled trial

Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups [34 in treatment group and 26 in control group]; one group was prescribed combination of methadone [40-120 mg] and gabapentin [300 mg] as group A, and the other group was given methadone [40-120] and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9 +/- 9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B [73.8 +/- 19.5 mg daily vs. 58.9 +/- 11 mg daily and cumulatively 1550.7 +/- 409.7 mg vs. 238.3 +/- 238.2 mg, p= 0.001]. When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption

Effectiveness of relapse prevention cognitive- behavioral model in opioid - dependent patients participating in the methadone maintenance treatment in Iran

To evaluate the effectiveness of relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment [MMT] in Iran. The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies [INCAS]. Participatns were randomized into two groups: educational intervention group [N=46] and control group [N=46]. The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instruments. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 [P<0.01]. Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 [P<.03], 0.31 [P<.02], and 0.43 [P<.02] respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group. Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance