Economies in Drug Usage in the Irish Healthcare Setting

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Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.

Circuitos de uso de crack na região central da cidade de São Paulo (SP, Brasil)

Apesar de o uso de drogas ser uma prática presente desde os primórdios da humanidade, atualmente o seu abuso adquiriu dimensões preocupantes, configurando-se como um problema de saúde pública. O surgimento do crack, droga derivada da pasta de coca, agravou esse quadro ao aumentar os danos sociais e à saúde dos usuários. Visando conhecer o impacto de sua inserção no cotidiano dos usuários, foi realizado um estudo etnográfico em locais de venda e uso de crack na região central da cidade de São Paulo (SP, Brasil). Foi utilizado um diário de campo para registrar as observações e os diálogos informais efetuados com as pessoas que circulavam no local estudado. Os resultados apontaram os circuitos percorridos pelos usuários, suas dinâmicas e as relações que estabelecem com outros atores sociais, as quais são permeadas por permanente tensão, envolvendo a prática de atos violentos nos quais os usuários são tanto agressores quanto vítimas. O estudo também sugere a importância de outros fatores como a história da região pesquisada, as políticas públicas, questões econômicas e ausência de investimentos sociais e em saúde pública. Sugere-se que o alto grau de degradação da região pesquisada não seria consequência apenas das pessoas e atividades exercidas no local, mas principalmente do processo urbano que gerou tal quadro social.

Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison

OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49) and the acknowledged use of injecting drugs (OR=3.36). Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.

Fulminant hepatitis: a clinical review of 11 years

24 cases of fulminant hepatitis (FH) hospitalized in the Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis. The authors believe that yellow fever should be considered a cause of FH where the clinical picture meets the criteria for such, although its mechanisms of encephalopathy remain obscure. The clinical details of the 3 cases of yellow fever are presented.

Persistent hyperglycemia at 24-48 h in acute hyperglycemic stroke patients is not associated with a worse functional outcome.

BACKGROUND: Recently, it was shown that the relation between admission glucose and functional outcome after ischemic stroke is described by a J-shaped curve, with a glucose range of 3.7-7.3 mmol/l associated with a favorable outcome. We tested the hypothesis that persistence of hyperglycemia above this threshold at 24-48 h after stroke onset impairs 3-month functional outcome. METHODS: We analyzed all patients with glucose >7.3 mmol/l on admission from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). Patients were divided into two groups according to their subacute glucose level at 24-48 h after last well-being time (group 1: ≤7.3 mmol/l, group 2: >7.3 mmol/l). A favorable functional outcome was defined as a modified Rankin Score (mRS) ≤2 at 3 months. A multiple logistic regression analysis of multiple demographic, clinical, laboratory and neuroimaging covariates was performed to assess predictors of an unfavorable outcome. RESULTS: A total of 1,984 patients with ischemic stroke were admitted between January 1, 2003 and October 20, 2009, within 24 h after last well-being time. In the 421 patients (21.2%) with admission glucose >7.3 mmol/l, the proportion of patients with a favorable outcome was not statistically significantly different between the two groups (59.2 vs. 48.7%, respectively). In multiple logistic regression analysis, unfavorable outcome was significantly associated with age (odds ratio, OR: 1.06, 95% confidence interval, 95% CI: 1.03-1.08 for every 10-year increase), National Institute of Health Stroke Score, NIHSS score, on admission (OR: 1.16, 95% CI: 1.11-1.21), prehospital mRS (OR: 12.63, 95% CI: 2.61-61.10 for patients with score >0), antidiabetic drug usage (OR: 0.36, 95% CI: 0.15-0.86) and glucose on admission (OR: 1.16, 95% CI: 1.02-1.31 for every 1 mmol/l increase). No association was found between persistent hyperglycemia at 24-28 h and outcome in either diabetics or nondiabetics. CONCLUSIONS: In ischemic stroke patients with acute hyperglycemia, persistent hyperglycemia (>7.3 mmol/l) at 24-48 h after stroke onset is not associated with a worse functional outcome at 3 months whether the patient was previously diabetic or not.

Redução de danos e o saber-fazer de profissionais de um CAPS ad em Natal-RN

The present study had as a main objective to analyze how the professionals at a CAPS ad unit in Natal-RN conceive the knowledge-practice process with regard to the Harm Reduction Policy (HRP) towards alcohol and other drugs. For the accomplishment of this proposal, it was intended: 1) Verifying the possibilities and limits of the HRP implementation at a CAPS ad unit in Natal-RN; 2) Relating the professionals knowledge at a CAPS ad unit in Natal in regard to the Harm Reduction Policy; 3) Enumerating the HRP programmatic actions at the institution. The research had exploratory, descriptive and qualitative approach aspects, guided by the concepts of biopower and self care proposed by Michel Foucault. Data collection occurred in June and July 2011, in which the focal group technique was used. After that, collect field material was analyzed through the content analysis method proposed by Minayo. The results showed some conceptual and practical approach between the harm reduction strategy and the knowledge-practice of the professionals at this CAPS ad unit. The discursive models about drug usage, especially the moral-legal model, still have a significant role in the daily lives of these professionals, being amplified by some demands of their jobs or even through the instituted discourse. The individuals recognize the need for less prohibited practices and more socializing ones, identifying them with the Harm Reduction (HR) logic, when there is a coherent and well-founded understanding about HR among the professionals. Distorted and reductionist views about HR as considering the simple instrumental function of this strategy (distribution of basic supplies) among the professionals, represent one of the main barriers for its implementation. There are few programmatic activities that are related to the RD strategy at this CAPS ad unit which makes a more effective appropriation by the working team difficult to reach. The working processes and the postures adopted by this CAP ad unit professionals have been showing that many of their practices and conceptions were modified to the detriment of new necessities emerged from the demands. Consequently, the self care notion is revealed which brings the need for the valorization of these care agents roles, that is, their collective and individual contribution.

Urinary levels of catecholamines among individuals with and without sleep bruxism

Sleep bruxism (SB) is characterized by repetitive and coordinated mandible movements and non-functional teeth contacts during sleep time. Although the etiology of SB is controversial, the literature converges on its multifactorial origin. Occlusal factors, smoking, alcoholism, drug usage, stress, and anxiety have been described as SB trigger factors. Recent studies on this topic discussed the role of neurotransmitters on the development of SB.Thus, the purpose of this study was to detect and quantify the urinary levels of catecholamines, specifically of adrenaline, noradrenaline and dopamine, in subjects with SB and in control individuals.Urine from individuals with SB (n = 20) and without SB (n = 20) was subjected to liquid chromatography. The catecholamine data were compared by Mann-Whitney's test (p a parts per thousand currency sign 0.05).Our analysis showed higher levels of catecholamines in subjects with SB (adrenaline = 111.4 A mu g/24 h; noradrenaline = 261,5 A mu g/24 h; dopamine = 479.5 A mu g/24 h) than in control subjects (adrenaline = 35,0 A mu g/24 h; noradrenaline = 148,7 A mu g/24 h; dopamine = 201,7 A mu g/24 h). Statistical differences were found for the three catecholamines tested.It was concluded that individuals with SB have higher levels of urinary catecholamines.

Avaliação da taxa de filtração glomerular e excreção fracionada de eletrólitos de cães com doença renal crônica tratados com dimetilsulfóxido (DMSO)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A eletrocoagulação na terapêutica das lesões intra-epiteliais escamosas de alto grau do colo uterino

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Consumo de drogas: uma comparação entre dois levantamentos com estudantes da rede pública de ensino na cidade de Assis, São Paulo, em 2000 e 2010

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalence and trends of substance abuse in Harris County, Texas, 1989 to 1991

In the late 1980s, Harris County, Texas began experiencing an escalation of drug-related activities. Various indicators used in this analysis tracked drug-related trends from 1989 to 1991 to determine patterns for comparison of local (Houston/Harris County, Texas) to national levels.^ An important indicator of the drug scenario was drug-related activities among youths, which increased during the period of this study. The Harris County Juvenile Probation Department showed that among arrests for drug-related activities, felonies increased from 25% in 1988 to 53% in 1991. With the rise in drug-related crimes, and substance abuse among the student body, school districts were forced to institute drug education programs in an effort to curtail such activities.^ Law enforcement agencies in the county saw increased demands for their services as a result of drug activities. Harris County Sheriffs Department reported a 32% plus increase in drug-related charges between 1986 and 1991. Houston Police Department reported an increase of 109% for the same period.^ Data from the Harris County Medical Examiner, the National Institute of Justice's Drug Use Forecasting System (Houston), and drug treatment facilities around Houston/Harris County, Texas indicated similar drug usage trends. Over a four-year period (1988-91), the drugs most frequently detected during blood and urine analyses were cocaine, followed by marijuana, heroin, LSD, and methamphetamines.^ From 1988 to 1991, most drug rehabilitation organizations experienced increased demands for their services by approximately 35%. Several other organizations experienced as much as a 70 percent increase. Males accounted for roughly 70% and females about 30% of persons seeking treatment. However, the number of females pursuing treatment increased, thereby reducing the gender gap.^ Blacks in Houston/Harris County were at higher risk for drug usage among the general population, but sought treatment more readily than other ethnic groups. Whites sought treatment in similar numbers as Blacks, but overall the risk appeared smaller because they made up a larger portion of the Houston/Harris County population.^ This analysis concluded that drug trends for the Houston/Harris County, Texas did not follow national trends, but showed patterns of its own. It was recommended that other communities carry out similar studies to determine drug use trends particular to their local. ^

Rho-kinase as a therapeutic target in vascular diseases:striking nitric oxide signaling

Rho GTPases are a globular, monomeric group of small signaling G-protein molecules. Rho-associated protein kinase/Rho-kinase (ROCK) is a downstream effector protein of the Rho GTPase. Rho-kinases are the potential therapeutic targets in the treatment of cardiovascular diseases. Here, we have primarily discussed the intriguing roles of ROCK in cardiovascular health in relation to nitric oxide signaling. Further, we highlighted the biphasic effects of Y-27632, a ROCK inhibitor under shear stress, which acts as an agonist of nitric oxide production in endothelial cells. The biphasic effects of this inhibitor raised the question of safety of the drug usage in treating cardiovascular diseases.

Caracterización y prevalencia del compromiso ocular en pacientes con enfermedad autoinmune y autoinflamatoria en un centro de referencia reumatológica en Colombia entre los años 2000 a 2015

RESUMEN Objetivo: Estimar la prevalencia de las diferentes enfermedades oftalmológicas que aparecen en el contexto de una enfermedad autoinmune (EAI) en pacientes de un centro de referencia reumatológica en Colombia, según características clínicas y sociodemográficas durante un período de 15 años, comprendido entre los años 2000 a 2015. Métodos: Se realizó un estudio descriptivo, observacional de prevalencia. El tipo de muestreo fue aleatorio estratificado con asignación proporcional en el programa Epidat 3.4. Los datos se analizaron en el programa SPSS v22.0 y se realizó análisis univariado de las variables categóricas, para las variables cuantitativas se realizaron medidas de tendencia central. Resultados: De 1640 historias clínicas revisadas, se encontraron 634 pacientes (38,65%) con compromiso ocular. Si excluimos los pacientes con SS, que por definición presentan ojo seco, 222 pacientes (13,53%) presentaron compromiso oftalmológico. Del total de pacientes, el 83,3% fueron mujeres. La AR fue la enfermedad autoinmune con mayor compromiso oftalmológico con 138 pacientes (62,2%), y en último lugar la sarcoidosis con 1 solo paciente afectado. La QCS fue la manifestación más común en todos los grupos diagnósticos de EAI, con 146 pacientes (63,5%). De 414 pacientes con Síndrome de Sjögren (SS) y QCS 8 presentaron compromiso ocular adicional, siendo la uveítis la segunda patología ocular asociada en pacientes con SS y la primera causa en las espondiloartropatias (71,4 %). Los pacientes con catarata (4,1%) presentaron la mayor prevalencia de uso de corticoide (88.8%). De 222 pacientes, 28 (12,6%) presentaron uveítis. Del total de pacientes, 16 (7,2%) presentaron maculopatía por antimalaráricos y 6 (18,75%) de los pacientes con LES. Los ANAS se presentaron en el 100% los pacientes con trastorno vascular de la retina. Los pacientes con epiescleritis presentaron la mayor proporción de positivización de anticuerpos anti-DNA. La EAI que más presentó epiescleritis fue LES con 4 pacientes (12,5%) El 22% de paciente con anticuerpos anti-RNP presentaron escleritis y 32,1% de los pacientes con uveítis presentaron HLA-B27 positivo. Las manifestaciones oftalmológicas precedieron a las sistémicas entre un 11,1% y un 33,3% de los pacientes. Conclusión: Las enfermedades oculares se presentan con frecuencia en los pacientes colombianos con EAI (38.65%), siendo la AR la enfermedad con mayor compromiso ocular (62,2%) y la QCS la enfermedad ocular con mayor prevalencia en todas las EAI (63,5%). La uveítis se presentó en 28 pacientes (12,6%). Las manifestaciones oftalmológicas pueden preceder a las sistémicas. El examen oftalmológico debe ser incluido en los pacientes con EAI, por ser la enfermedad ocular una comorbilidad frecuente. Adicionalmente, los efectos oftalmológicos de las medicaciones sistémicas utilizadas en EAI deben ser estrechamente monitorizados, durante el curso del tratamiento.

Using Computer-aided Drug Design and Medicinal Chemistry Strategies in the Fight Against Diabetes

The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics. ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.