The purpose of this study is to examine whether there is a change in physician's behavior because of increased competition in the primary care market. The hypothesis is that increased competition in the healthcare market increases the physician's tendency to prescribe drugs in order to attract patients. Therefore, this paper aims to examine whether the number of opioids prescribed has increased due to a Swedish reform known as the System of Choice that was implemented between 2007-2010, whose target was to increase the competition in the healthcare market. A difference-in-difference method is applied to examine the causal relationship between the reform and the number of prescriptions of opioids. This method is applicable since the counties introduced the reform at different points in time. The result is not statistically significant but the estimate is positive which corresponds to previous literature. However, the result could indicate that the System of Choice has had no effect on the number of opioids prescribed.

Thesis advisor: Alexa H. Veemena / Across species, the juvenile period is characterized by increased social interaction with peers and heightened novelty-seeking behavior, as compared to any other life stage. These behaviors are likely to be highly adaptive during this developmental phase. Still, an excessive novelty-seeking phenotype may predispose individuals to risk-taking and substance abuse, while too little social engagement and low novelty-seeking are characteristics of neuropsychiatry disorders such as autism. The over-arching aim of this dissertation research has been to elucidate the neural mechanisms underlying juvenile social novelty-seeking behavior. Central activation of oxytocin, vasopressin V1a, and µ-opioid receptors (OTR, V1aR, and MOR, respectively) have been implicated in the regulation of adult social behavior, but our understanding of the expression and function of OTR, V1aR, and MORs in the juvenile brain is incomplete. Therefore, in Studies 1 and 2, age differences in binding density of OTR, V1aR, and MOR throughout the rat brain were identified using receptor autoradiography. Next, in Study 3, I established the social novelty preference test, a new paradigm designed to assess the preference of juvenile rats to interact with either a novel or a familiar (cage mate) conspecific. Using this social novelty preference test, in Studies 3, 4, and 5, the functional involvement of OTR, V1aR, and MOR in the regulation of juvenile social novelty preference was characterized using both intracerebroventricular and local in-vivo pharmacological manipulations. The results of these experiments demonstrate that both OTR and MOR activation in the brain are involved in the regulation of juvenile social novelty preference, particularly acting within the nucleus accumbens. Finally, in Study 5, I investigated the impact of social isolation on juvenile social novelty preference. My findings show that social isolation potently reduces social novelty preference, which, in turn, can be restored by MOR activation in the nucleus accumbens. Taken together, this body of work significantly advances our understanding of the neural systems underlying juvenile social novelty preference, and suggests that both oxytocin and opioid systems in the brain may be potential clinical targets for restoring social novelty-seeking behavior in neurodevelopmental disorders, such as autism.

Objetivou-se comparar os efeitos de duas doses de nalbufina em relação ao tramadol após infusão contínua de fentanil durante cirurgia de osteotomia de nivelamento de platô tibial. Realizou-se estudo clínico encoberto com 28 cães (idade 5,6±1,2 anos e peso 34,7±4,2 kg), pré-medicadas com acepromazina (0,03 mg/kg, IM), induzidas com propofol (4 mg/kg, IV), mantidas com isofluorano (EtISO 1,3 V%) e fentanil (bólus de 3 &micro;g/kg, seguido por 0,3 &micro;g/kg/min, IV), randomizados ao final da cirurgia nos grupos: NAL 0,1: 0,1 mg/kg de nalbufina (n=9), NAL0,3: 0,3 mg/kg de nalbufina (n=9) ou TRA: 3 mg/kg de tramadol, (n=10). Avaliou-se os parâmetros fisiológicos, escores de sedação e de dor (Colorado, Glasgow e VAS) a cada 30 minutos após a administração dos tratamentos, por seis horas ou até o resgate (tramadol 4 mg/kg e dipirona 30 mg/kg, quando VAS &ge; 4, Glasgow &ge; 5 e/ ou Colorado &ge; 2). Coletas de sangue para mensuração para gasometria arterial foram realizadas. Avaliou-se ainda os tempos de extubação (TE), recuperação da respiração espontânea (TRE) e decúbito esternal (TDE). Os tempos de recuperação foram avaliados por meio de ANOVA, com pós-teste de Tukey, enquanto as escalas foram avaliadas pelos testes de Friedman e Kruskal-Wallis, seguidos por pós-teste de Dunn quando necessário, com nível de significância de 95%. Os animais que receberam tramadol apresentaram maior grau de sedação em todos os momentos avaliados (p < 0,05), além de maior TE, TRE e TDE que NAL0,1 e NAL0,3 (p<0,001). Quando comparado ao momento basal, o grupo TRA apresentou redução significativa do pH do HCO3 e elevação da PaCO2 em T 30. Na comparação entre grupos, o grupo TRA apresentou menor pH em T30 quando comparado a NAL 0,1 e NAL 0,3. Na escala de avaliação de dor de Glasgow, Colorado e na EAV, o grupo NAL 0,1 apresentou média &#177;DP significativamente mais alta do que NAL 0,3 (p<0,05) e TRA (p<0,001) em T60, T120 e T180. O tempo para administração do resgate foi de 133&#177;50 minutos no grupo NAL0,1, 220&#177;30 minutos no NAL0,3 e 360 minutos no grupo TRA. Com os dados obtidos conclui-se que a administração de nalbufina reduz o tempo de recuperação anestésica, necessitando, porém, de resgate analgésico mais precocemente que o tramadol / The aim of this study was to compare the effects of two nalbuphine doses versus tramadol after fentanyl continuous infusion during tibial plateau leveling osteotomy surgery. A clinical study with 28 dogs (5.6&#177;1.2 years old and 34.7&#177;4.2 kg), pre-medicated with acepromazine (0.03 mg/kg, IM), followed by propofol induction (4 mg/kg, IV), isoflurane (EtISO 1.3 V%) and fentanyl (bolus of 3 &micro;g/kg, following 0,3 &micro;g/kg/min, IV) maintenance; were randomized distributed in the following groups: NAL0.1: 0.1 mg/kg of nalbuphine (n=9), NAL0.3: 0.3 mg/kg of nalbuphine (n=9) or TRA: 3 mg/kg of tramadol (n=10). Physiological parameters, sedation and pain scale (Colorado, Glasgow and VAS) were evaluated every 30 minutes after treatment administration, during six hours, or until rescue medication (tramadol 4 mg/kg and dipyrone 30 mg/kg, when VAS &ge; 4, Glasgow &ge; 5 and/or Colorado &ge; 2). Arterial blood gas sampling were collected. Furthermore, time of extubation (TE), spontaneous respiration recovery (TRE) and sternal decubitus (TDE) were registered. Recovery periods were analyzed using ANOVA, followed by Tukey test, while the pain scales were evaluated using Friedman and Kruskal-Wallis, followed by Dunn&#39;s test, when necessary, with significance level of 95%. Animals that received tramadol exhibited higher sedation score in all evaluated moments (p < 0.05), and also higher TE, TRE and TDE than NAL0.1 and NAL0.3 (p<0.001). TRA group showed significate pH of HCO3 reduction when comparing to baseline and PaCO2 elevation in T30. When comparing between groups, TRA showed significate smaller pH in T30 than NAL0.1 e NAL0.3. Considering Glasgow, Colorado and EAV pain scale, NAL0.1 group produced average &#177;SD significant higher than NAL0.3 (p<0.05) and TRA (p<0.001) in T60, T120 and T180.Rescue pain medication time was 133&#177;50 minutes in NAL0.1 group, 220&#177;30 minutes in NAL0.3 group and 360 minutes in TRA group. The results of this investigation shows that nalbuphine administration decreases anesthesia recovery time, requiring, however, early rescue pain medication than tramadol

Introdução: A dor é o principal motivo de procura ao atendimento médico. Organizações internacionais de saúde indicam o alívio da dor como um direito humano básico. A literatura indica subutilização de opioides devido ao conhecimento insuficiente, o receio quanto ao potencial de adição, efeitos adversos e mitos persistentes sobre estes analgésicos por parte dos profissionais de saúde. Objetivo: Avaliar grau de conhecimento de profissionais de saúde no manejo da dor e no uso de opioides em três unidades pediátricas (Pediatria, UTI e Oncologia). Metodologia: Estudo transversal realizado em um hospital universitário do Sul do Brasil. Um questionário autoaplicável foi entregue para 182 profissionais (médicos, enfermeiros, farmacêuticos, técnicos e auxiliares de enfermagem), entre dezembro de 2011 e março de 2012. Resultados: A taxa de retorno foi de 67% (122). O percentual médio de acertos foi de 63,2 ± 1,4%. Os erros mais frequentes foram: um opioide não deve ser utilizado sem se saber a causa da dor (47%; 54/115); pacientes desenvolvem depressão respiratória frequentemente (42,3%; 22/52) e confusão entre os sintomas da síndrome de abstinência, tolerância e dependência (81,9%; 95/116). Apenas 8,8% (10/114) relataram o uso de escalas de dor para reconhecer a dor em crianças. A barreira para o controle da dor mais citada foi a dificuldade de medir e localizar a dor em pacientes pediátricos. Finalmente, 50,8% (62/122) não receberam nenhum treinamento sobre dor. Conclusões: Foram identificados problemas nos processos de identificação, mensuração e tratamento da dor. Os resultados sugerem a necessidade de investimento na formação continuada dos profissionais e no desenvolvimento de protocolos que busquem aperfeiçoar a terapia analgésica, impedindo um aumento desnecessário do sofrimento da criança. / Introduction: Pain is the main reason to seek medical care. Health international organizations indicate pain relief as a basic human right. The literature indicates underuse of opioids due to insufficient knowledge, fears about the potential for addiction, side effects and persistent myths about these analgesics by health professionals. Objective: To assess degree of knowledge and attitudes of health professionals about management of pain in three pediatric units (Pediatric, ICU and Oncology). Methods: Cross-sectional study in a teaching hospital in southern Brazil. A self-administered questionnaire was delivered to 182 professionals (doctors, nurses, pharmacists, technicians and nursing assistants), between December 2011 and March 2012. Results: The rate of return was 67% (122). The average percentage of correct responses was 63.2 ± 1.4%. The most frequent errors were: an opioid should not be used without knowing the cause of pain (47%, 54/115); patients often develop respiratory depression (42.3%, 22/52); and confusion between symptoms of the syndrome withdrawal, tolerance and dependence (81.9%, 95/116). Only 8.8% (10/114) reported using pain scales to recognize pain in children. The barrier to pain control most cited was the difficulty to measure and locate the pain in pediatric patients. Finally, 50.8% (62/122) received no training on pain. Conclusions: The study identified problems in the process of recognizing, measuring and treating pain. The results suggest the need for investment in training to health care team and development of protocols that seek to optimize analgesic therapy, preventing an unnecessary increase the suffering of the child.

Background: The opioid epidemic is particularly worrisome in the pregnant population, wherein concerns are raised about the health of a mother and her child, resulting in an alarming incidence and prevalence of Neonatal Abstinence Syndrome (NAS). The 2016 National Survey on Drug Use and Health (NSDUH) show the rate of illicit psychoactive substance use among the females aged 12 or older was 15.5% in the past year. Among pregnant women aged 15 to 44, 6.3% were illicit psychoactive substance users. In Tennessee, the number of hospital discharged NAS cases from 2002 to 2013 increased from 1.50 to 16.6 cases per 1,000 live births. This number is triple the national incidence of NAS cases over the same time period. Between 2013 and 2016, at least 52.5% of children diagnosed with NAS in Tennessee have had exposure to one prescription drug, while 27.2% were exposed to a combination of prescribed medications and illicit substances. We examined the behavioral correlates that determine the wish to quit opioids or not to quit opioids among opioid-dependent pregnant and non-pregnant women in rural Appalachia. Methods: Ten women of childbearing age, whether pregnant or not, who were receiving prescribed opioids, were recruited to join the study. All the participating women were also receiving physician-managed Medication Assisted Treatment (MAT) therapy for the treatment of severe opioid use disorder, or are currently being prescribed an opioid medication. Study variables included age, Hamilton Depression Rating Scale (HAM-D), Visual Analogue Scale – Pain (VAS-P), the Modified Opiate Craving Scale (MOCS), the Visual Analog Commitment to Quit Opiates, the McGill Pain Index (MPI), prescriptions, tobacco and nicotine use, illicit substance use, the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), and the Adverse Childhood Experience (ACE) questionnaire. The HAM-D, MOCS, MPI, and SOCRATES scores were log-transformed to approximate a normal distribution. Descriptive statistics and the Spearman’s rank correlation (with a 95% Confidence Interval) were conducted to examine significant behavioral correlates for quitting opioids. Results: Descriptive statistics show that women with higher HAM-D and MOCS scores are not likely to express willingness to quit opioids. There is a statistically significant strong positive correlation of 0.679 (pppp Conclusion: Women who recognize the need to quit opioids or are “taking steps” to quit are more likely to quit opioids. Women with high depression and pain scores are not likely to quit opioids. Non-opioid medications may reduce the number of opioid-dependent pregnant and non-pregnant women of childbearing age, and, in turn, lower the currently high incidence and prevalence rates of NAS.

In this study we present feasibility of a mobile monitoring and reporting system that would provide an accurate unbiased screening tool to systematically analyze opioid adherence in Sickle cell disease patients. In addition, the software simultaneously measures pain. The Mobile Applications Rating Scale: a new and validated tool for assessing the quality of health mobile apps for engagement, functionality, aesthetics, information quality, subjective quality, relevance and overall impact was administered post usage to evaluate the application. A total of 28 patients were recruited to review and test the software at one sitting. The majority of the population found the application to be relevant for their care. Patients were also asked to report on the completeness of information within the app, the majority (96%) reported on the application’s completeness while 4% estimated the information to be minimal or overwhelming. The quality of information as it pertains to sickle cell patients was overwhelimingly reported to be relevant (91.7%); only 8.3% found the application to be poorly relevant to sickle cell disease. The application’s performance was positively rated while the ease of its use positively rated at 91.7%. Most participants (85.7%) found the application to be interesting to use while 74% found it entertaining. All users found the application’s navigation to be logical and accurate with consistent and intuitive gestural design. We conclude that surveyed patients believe it is feasible to use a smartphone application specifically targeted to monitor opioid use and behavior in patients with sickle cell disease (SCD)-associated pain

Myelin is an extensive cell membrane produced by oligodendrocytes to ensheath neuronal axons in the central nervous system with the primary goal of maximizing the efficiency of electrochemical impulse transmission. During brain development, oligodendrocytes differentiate into myelin forming cells in a tightly regulated process which makes them vulnerable to multiple insults. Previous results from the laboratory showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogues used for treating pregnant addicts. The mechanism by which these opioids exerted their effects involved two opioid receptors, the μ-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOR). However, the role of these receptors and their endogenous ligands in controlling the timing of myelination under normal physiological conditions of brain development is not known. In this dissertation, we found that the endogenous MOR ligand endomorphin-1 (EM-1) acts as a strong promoter of rat pre-oligodendrocyte differentiation, but surprisingly, this effect is observed only in cells isolated from female pups. Interestingly, the stimulatory action of EM-1 was abolished upon co-incubation with the endogenous NOR ligand, nociceptin. Moreover, injections of NOR antagonist to 9-day-old female and male rat pups accelerated rat brain myelination in female rat pups with no significant changes in their male counterparts. Interestingly, the lack of major sex-dependent differences in developmental brain levels of EM-1 and nociceptin and the presence of the two receptors MOR and NOR in male and female oligodendrocytes suggested that the observed sex-specific responses may be highly dependent on critical intrinsic sex-dependent differences within these cells. Although nociceptin alone did not exert observable effects on pre-oligodendrocyte maturation, it increased the number of cells expressing Ki-67, a cell proliferation indicator, in oligodendrocyte progenitor cultures. These results suggest that nociceptin may be playing a stage specific role in oligodendrocyte development during brain maturation. The finding of critical functions of EM-1 and nociceptin in the developing female oligodendrocytes and brain myelination highlights the need for considering sexual dimorphism in the design of safer and more effective therapeutic approaches for treating opioid abuse, pain, and demyelinating disease as multiple sclerosis.

Opioids acting at the mu (morphine) receptor represent the vast majority of clinically used opioids and remain the most effective analgesics for treating moderate to severe pain. The use of morphine and similar compounds for the management of pain is limited by adverse side effects including respiratory depression, abuse potential, motor impairment and cognitive deficits. Novel mu opioid receptor agonists developed in our laboratory are based on the structure of the endogenous ligands (endomorphins) and provide potent antinociception. Studies from our laboratory indicate that these endomorphin (EM) analogs produce fewer adverse side-effects in rodents than morphine, including reduced respiratory depression, motor impairment, tolerance, and abuse potential. Recent studies have indicated that repeated injection of morphine, for as little as a few days, can induce glial activation, an inflammatory response that can led to a “paradoxical” morphine-induced pain (Watkins et al, 2005, 2007). Morphine is recognized by glia cells similarly to a foreign antigen via toll-like receptor 4 (Hutchinson et al., 2010; Watkins et al., 2009). Since endomorphin analogs are more similar in structure to endogenous peptides, we hypothesized that they would not be recognized by the immune system as pathogenic. In support of this hypothesis, our laboratory showed activation of microglia in the spinal cord after treatment with morphine, but not endomorphin analogs (Zadina et al., 2012). This may be of particular importance in the treatment of pain in patients already vulnerable to inflammation-induced pathologies, including during older adulthood and after traumatic brain injury (TBI). The focus of this project was to evaluate the cognitive effects of morphine and endomorphin analogs using aging and TBI models. Morphine impaired cognition after both acute and chronic drug administration but EM analogs did not, despite equal or greater duration of antinociception relative to morphine. Chronic studies using young, middle-aged, and old rats revealed that middle-aged rats were more susceptible to cognitive deficits caused by morphine than younger or older rats. Likewise, morphine exacerbated cognitive deficits produced by TBI. Electrophysiology experiments revealed that morphine altered hippocampal long-term potentiation to a greater extent than an EM analog. Immunohistochemistry of the hippocampus indicated that astrocytes are activated after treatment with morphine, but not an EM analog. In TBI studies, morphine treatment led to a reduction in the number of neurons in the dentate gyrus despite an increase in volume, which may be due to increased glial activation. Thus, EM analogs may serve as safer analgesics as indicated by several models, and differential effects of morphine and EM analogs are likely mediated, in part, by alterations in glial activation. / acase@tulane.edu

No description available.

Abstract not available