An observational study on adverse drug reaction profile in patients on long-term treatment with proton pump inhibitors

Background: Proton pump inhibitors (PPI) are most commonly prescribed medications in the world which are highly effective drugs in treatment of upper gastrointestinal disorders, but there are concerns regarding its long term use. Aim and Objective: To assess the pattern of reported adverse drug reactions (ADR) in patients with long term use of PPI and to estimate the frequency of adverse drug effects. Materials and Methods: A study conducted as an observational study among 100 consecutive patients who attended the medical-gastro inpatient and outpatient department on treatment with PPI for more than 4 months, according to inclusion and exclusion criteria. After attaining the written informed consent, data regarding patient’s demographic details, occupational status, addictions, co-morbidities, and lab investigations were recorded in pre-prepared proforma after interviewing the patient and referring the case sheet. Details including PPI used and per day dose of the drug with any ADR developed were noted. Data collected were analyzed using appropriate statistical method. Categorical variables are expressed as frequency (percentage) and continuous variables as mean (standard deviation). Chi-square test was used to find out the association between PPI and ADR. Results: Out of 100 study participants, 57% case reported ADR which included 19 cases (33.3%) of hypomagnesemia, 8 cases (14%) each of hypocalcemia, and hyperkalemia, 7 cases (12.3%) of anemia, and 5 cases (8.9%) of acute kidney injury. Out of the 57 reported adverse events, 29 (50.9%) were caused by Rabeprazole followed by 18 (31.6%) by Pantoprazole, then Esomeprazole: 8 (14%), and least by Omeprazole (3.5%). Conclusion: Long-term use of PPI can lead to various ADR which requires the withdrawal of drug. Since PPIs are easily available without prescriptions, self-medication with PPIs are increasing alarmingly. With every antibiotic one PPI is always prescribed, as a result, there is irrational use of PPIs which is of concern and requires attention. These adverse events could be reduced by preventing self-medication of long duration and reducing the irrational prescribing of PPIs. Doctors should be sensitized about the ADRs. The patient should be educated about the long-term adverse effects of PPIs.

Long-term effectiveness and safety of endoxifen in the treatment of bipolar mania: a case report

Bipolar disorder (BD) displays abnormalities in protein kinase C (PKC) signaling, and evidence suggests that inhibiting PKC may help treat mania. Endoxifen a potent inhibitor of the PKC signaling pathway, is effective in controlling acute bipolar mania, atdoses of 8 mg OD, for a period of 3-weeks. Here we present the case of a patient with severe mania, increased alcohol consumption administered endoxifen 8 mg BID for a period of 3-months, to achieve a better response. High-dose, long-term treatment with endoxifen was efficacious in controlling manic symptoms, with no adverse effects. Additionally, the patient didn抰 consume alcohol during the course of treatment. This case showed the long-term effectiveness and safety of high-dose endoxifen to control mania in a patient with BD.

Effect of Long-Term Use of Eurycoma Longifolia Jack on Histopathological Changes in the Liver in Rats

Presently, the use of Eurycoma longifolia Jack (ELJ) (Tongkat Ali) has increased dramatically in Southeast Asia especially Malaysia where it is widely used as aphrodisiac and anti-malarial agent. Interestingly, its consumption has become popular in daily life as beverage to enhance energy and stamina especially among males. However, its effect on the safety of vital organs of the body has not been studied adequately. Hence, the main objective of this study was to determine whether or not long-term use of ELJ any has side effects on the liver in rats. Methods: Three different concentrations of aqueous extract of ELJ were prepared and dissolved in distilled water. A total of 32 Sprague-Dawley male rats were used and randomly divided into three test groups and control. The test groups were given different doses (low dose 250 mg/kg bw, medium dose 500mg/kg bw and high dose 1000 mg/kg bw) of aqueous extract of ELJ, respectively. Control group was given distilled water alone. Doses were given orally and daily for 5 weeks. After 5 weeks, animals were sacrificed; whole liver tissues were obtained, fixed in 10 percent formaldehyde overnight for histological examination. Result: Histological observations showed mild to moderate degrees of hemorrhage, hepatocytes degeneration and severe fatty changes in liver tissue of the test groups treated with ELJ as compared to control. Conclusion: In conclusion, the long-term daily consumption of ELJ in large quantity as beverage may cause fatty changes, hemorrhage and hepatocytes degeneration in the liver tissue.

Effects of long-term fluoxetine treatment on adrenergic plasticity in rat vas deferens

Chronic antidepressant administration increases neurotrophin levels in the central and peripheral nervous system, leading to an increase of neuronal sprouting, reestablishment of neural networks and neurotransmitter levels. Injured peripheral nerves regenerate at very slow rates. However, the recovery of the hypogastric nerve in rodents after injury is significantly improved with neurotrophin administration. Accordingly, our goal was to determine whether treatment with the antidepressant fluoxetine affects catecholamine levels and neuronal function, after surgical denervation of the rat vas deferens. Noradrenaline levels in the denervated vas deferens were higher in fluoxetine-treated animals than in the vehicle-treated group, as measured by high performance liquid chromatography. In functional studies of smooth muscle contraction, the responses induced by phenylephrine or ATP, as well as pre-synaptic α2-adrenoceptor reactivity, were not modified by chronic treatment with the antidepressant. However, the contraction mediated by neuronal release of noradrenaline induced by tyramine was increased on days 7 and 21 after denervation in rats treated with fluoxetine. These data indicate that fluoxetine can improve functional recovery after rat vas deferens denervation.

A administração crônica de antidepressivos aumenta os níveis de neurotrofinas no sistema nervoso central, levando a um aumento da arborização neuronal, restabelecendo a rede neural e os níveis de neurotransmissores. Lesões do sistema nervoso periférico mostram uma regeneração muito lenta. Entretanto, a recuperação após a lesão do nervo hipogástrico em roedores é significativamente melhorada após a administração de neurotrofinas. Nesse sentido, nosso objetivo foi verificar se o tratamento com o antidepressivo, fluoxetina, interfere nos níveis de catecolaminas e na função neuronal, após a desnervação cirúrgica do ducto deferente de rato. Nos vasos deferentes desnervados, os níveis de catecolaminas nos grupos tratados com fluoxetina foram maiores que no grupo veículo, quantificados em cromatografia líquida de alta eficiência (CLAE). Nos estudos funcionais, a contração da musculatura lisa induzida pela fenilefrina ou pelo ATP, assim como a reatividade pré-sináptica α2-adrenérgica, não foram modificadas com o tratamento crônico de fluoxetina. Contudo, nas contrações mediadas pela liberação neuronal de norepinefrina induzida por tiramina, observou-se aumento da contração nos dias 7 e 21 após a desnevação em ratos tratados com fluoxetina. Esses dados indicam que a fluoxetina pode melhorar a recuperação funcional do vaso deferente de rato após a desnervação.

Recomendações para uso de opioides no Brasil: parte I / Recommendations for the use of opioids in Brazil: part I

JUSTIFICATIVA E OBJETIVOS: O emprego adequado de opioides ainda é um grande desafio no mundo contemporâneo. Diversas são as inadequações na prática clínica, apesar do uso desses agentes ter se iniciado desde a década de 1980. Compreendendo a importância desse tema, a Sociedade Brasileira de Estudo da Dor convidou vários profissionais para desenvolver recomendações que facilite; baseado na literatura médica existente, a composição de um guia prático para o tratamento adequado dos pacientes. CONTEÚDO: Nessa revisão foram discutidas as seguintes recomendações: indicação de terapia com opioides, sua titulação e retirada; rotação de opioides, monitoração de resultados, evidenciando a boa prática clínica. CONCLUSÃO: É importante eleger de maneira adequada os pacientes que utilizarão opioide em longo prazo, avaliando os efeitos adversos e adequando a dose a cada situação clínica.

BACKGROUND AND OBJECTIVES: The adequate use of opioids is still a major challenge to date. There are several mismatches in the clinical practice although these agents have started to be used in the 1980s. Understanding the importance of such subject, the Brazilian Society for the Study of Pain has invited a number of professionals to develop recommendations, based on existing literature, to help the composition of a practical guide for patients' adequate treatment. CONTENTS: This review has discussed the following recommendations: indication of opioid therapy, its titration and weaning; opioids rotation and monitoring of results, thus evidencing good clinical practice. CONCLUSION: It is important to adequately elect patients to receive long-term opioids, by evaluating adverse effects and matching the dose to each clinical situation.

Is long-term use of lithium safe on the kidneys? Do we really know the answer? A critical review

Background: Despite its long history for treating bipolar disorder, lithium use has declined recently due to concerns about its long-term side effects, mainly on the kidneys. Objective: This report provides a summary of the recent findings on this issue. Discussion: Possible intermediate factors in causing kidney damage include: frequent lithium toxicity, prolonged use, nephrogenic diabetes insipidus, and presence of concurrent morbidities known to affect the kidneys. Conclusion: Although data have accumulated about safety of short-term lithium use, the literature on the longterm effects on the kidneys is plagued by poor quality, differing methodology, and small sample size, making it very difficult to approach this issue with confidence. Key message: The literature on the long-term effects on the kidneys is plagued by poor quality; it is difficult to reach an answer to this dilemma with affirmation.

Clinical analysis of central venous catheter related infection (CRI) / 中华急诊医学杂志

Objective To investigate the characteristics of pathogens and risk factors of the catheterassociated infection (CAI) in emergency ICU (EICU) in order to design an appropriately therapeutic strategy for the future.Methods From January 2008 to December 2010,a total of 1363 patients were enrolled for this retrospective study.Blood sample taken from the vein with indwelling catheterization and the tips of catheters cut in 5 cm after withdrawn from the veins in 1363 patients were collected for bacterial culture.Results Of 1363 catheters,pathogens were found in 147 (10.79％) after venous catheterization.The daily occurrences of CAI were 3.05 ones per 1000 catheters.Of 147 cases of infection,46.94％ pathogens were gram-negative bacilli,40.14％ gram-positive cocci,and 12.92％ fungi.Unconditional Logistic regression analysis suggested that repeated catheterization,femoral vein catheterization,the application of multi-lumen catheter and long-term indwelling catheterization were the independent risk factors responsible for CAI.Conclusions The risk factors responsible for catheter related infections should be controlled to prevent the occurrence of nosocomial infection.

Clinical analysis of central venous catheter-related infections in patients in the emergency ICU / 世界急诊医学杂志（英文）

BACKGROUND:Catheter-related infection (CRI) of the central vein is a common cause of nosocomial infection. This study was undertaken to investigate the pathogen culturing and risk factors of CRI in emergency intensive care unit (EICU) in order to provide the beneficial reference.METHODS:From January 2008 to December 2010, a total of 1363 patients were subjected to catheterization. In these patients, the peak CRI rate of the patients was determined by bacterial cultivation and blood bacterial cultivation.RESULTS:CRI happened in 147 of the 1363 patients using the central venous catheter. The peak rate of CRI was 10.79％, with an incidence of 3.05 episodes per 1000 catheter days. Of the 147 patients, 46.94％ had gram-negative bacilli, 40.14％ had gram-positive cocci, and 12.92％ had fungi. Unconditional logistic regression analysis suggests that multiple catheterization, femoral vein catheterization, the application of multicavity catheter, and the duration of catheterization were the independent risk factors for CRI.CONCLUSION:The risk factors for catheter-related infections should be controlled to prevent the occurrence of nosocomial infection.

Características demográficas y clínicas asociadas a la dependencia a benzodiacepinas en pacientes psiquiátricos / Demographic and clinical features related to benzodiazepine dependence in psychiatric patients

Introduction Inappropriate use and dependence to prescription drugs has been considered as a growing health problem in recent years. It has been recognized that benzodiazepines (BZD) are one of the most commonly prescribed drugs due to their rapid therapeutic effect, high efficacy and favorable side effect profile when compared to other psychotropic medications. Despite the desirable therapeutic actions of BZD, mainly for the treatment of anxiety disorders, concerns about the dependence producing or addictive nature of these drugs have been expressed for decades. BZD dependence, unlike dependence to other substances, is a condition generally circumscribed to a therapeutic framework. It is well known that BZD use generally starts legitimately by a medical prescription for the treatment of anxiety symptoms or insomnia. Persons with psychiatric disorders are at a greater health risk for BZD dependence than other groups as BZD are highly used for the treatment of several psychiatric symptoms. BZD dependence in these patients may have a negative clinical impact in the medical treatment of the primary psychiatric disorder and may also affect patients' quality of life as the BZD dependence is added as a comorbid diagnosis that also requires clinical management. In this way, the need for clinical useful information for the prevention or early detection of BZD dependence emerges. Although inconsistent associations have been encountered in the scientific literature, some sociodemographic variables, such as gender and level of education, as well as the characteristics of BZD use, have been identified as potential risk factors for the development of BZD dependence. This information is of easy access for the mental health professional during the initial or subsequent clinical interview with patients, and if significant findings are obtained in Mexican psychiatric patients, these variables may become useful clinical tools for a closer follow-up of those patients with high risk of presenting BZD dependence. Objective To determine sociodemographic variables and characteristics of BZD use that may be risk factors for the development of BZD dependence in a sample of psychiatric patients from Mexico City. Method Subjects. Subjects were consecutively recruited at the outpatient services of the Instituto Nacional de Psiquiatría Ramón de la Fuente (INPRF) in Mexico City. All patients with BZD consumptions were included indistinctly of their psychiatric diagnosis of attendance in the institution. All patients gave their written informed consent after receiving a comprehensive explanation of the nature of the study. The Ethics Review Board of the INPRF approved the study. Assessment procedure Psychiatric diagnoses were made with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and BZD dependence was determined with an adapted version of the substance dependence section of the SCID-I designed to assess BZD use exclusively. Sociodemographic features and characteristics of BZD use were registered in a previously designed format and information was obtained by a personal interview with each patient and main caregiver. The Benzodiazepine Dependence Questionnaire in its Mexican version (BDEPQ-MX) is a self-administered questionnaire used to assess the subjective experience with BZD in the last month in three main areas: perceived dependence, BZD pleasant effects and perceived need of BZD consumption. Results The sample comprised 150 psychiatric patients. A total of 70.0% (n=105) were women and 30.0% (n = 45) were men. Their mean age was 45.9±14.1 with a mean educational level of 11.6±3.9 years. Diagnoses of the sample were mainly anxiety disorders (n = 76, 50.7%) and affective disorders (38.0%). According to the SCID-I, a total of 73 (48.7%) patients met the diagnostic criteria for BZD dependence. Sixty seven percent of the men included in the study reported BZD dependence in contrast to 41.0% of the women. Also, patients with BZD dependence exhibited a higher level of education and a longer time consumption of BZD. A longer duration of BZD consumptions was the main indicator for BZD dependence conferring a risk 10.4 higher for its development. Male gender and psychiatric diagnoses different to anxiety and affective disorders were also significant predictors for BZD dependence. Discussion Numerous potential risk factors relating to BZD dependence have been found and our results support the influence of sociodemographic features and characteristics of BZD consumption for dependence development in a Mexican sample of psychiatric patients. In general, it has been described that men are more prone to substance abuse and dependence and our results showed this same pattern. Nevertheless, this result must be replicated in future studies as for BZD dependence men and women may exhibit similar patterns of consumption and dependence. High rates of BZD prescription, coupled with an elevated risk of substance dependence in diagnoses different to anxiety disorders, highlight the need for a careful review of the costs-benefits of BZD use for the treatment of anxiety emergent symptoms, as other additional medications with lower dependence effect can be used to minimize the potential risk of BZD dependence in these patients. One of the biggest controversies surrounding BZD use has been its long-term use, which has been reported and replicated in our studies as the main indicator for BZD dependence development. Treatment with BZD may be useful for short-term periods of time, and specific goals and objectives of their therapeutic benefits must be established since the initial treatment plans for each patient. The clinical relevance of the present study relies in standing out the high prevalence of BZD dependence found in patients treated with BZD and had not been treated for this comorbid condition. It is important to promote in the mental health professional attendance team strategies for the prevention and early detection of BZD dependence in psychiatric patients.

Introducción El uso inapropiado de los fármacos de prescripción y la dependencia a ellos conforman un problema de salud que va en aumento en la actualidad. A diferencia de la dependencia a otras sustancias, la dependencia a BZD es una condición generalmente circunscrita a un marco terapéutico, ya que el primer contacto frecuentemente se presenta en un contexto clínico. Por el es necesario contar con información que pudiera ser de utilidad clínica para prevenir o detectar de forma oportuna la dependencia en pacientes tratados con BZD. Objetivo Determinar las variables sociodemográficas relacionadas con el patrón de consumo de BZD que pudieran ser predictoras de dependencia a BZD en una muestra de pacientes psiquiátricos de la Ciudad de México. Método Sujetos. Se reclutó a los pacientes que acudieron de forma consecutiva al servicio de Consulta Externa del Instituto Nacional de Psiquiatría Ramón de la Fuente (INPRF) que presentaron uso de BZD, indistintamente del diagnóstico psiquiátrico por el que acudieron a recibir atención especializada. Instrumentos El diagnóstico psiquiátrico y de dependencia a BZD de los pacientes se realizó mediante la entrevista SCID-I. Los principales datos sociodemográficos y las características del consumo de BZD fueron registrados en un formato diseñado ad hoc. El Cuestionario de Dependencia a Benzodiazepinas en su versión para México (BDEPQ-MX) se utilizó para evaluar la experiencia subjetiva del consumo de BZD. Resultados Se incluyó a un total de 150 pacientes con una edad promedio de 45.9±14.1 años. El 48.7% de los pacientes presentaron dependencia a BZD. Los pacientes con dependencia a BZD fueron con mayor frecuencia hombres, con una mayor escolaridad y presentaron un mayor tiempo de consumo. El ser hombre, presentar un diagnóstico distinto a un trastorno de ansiedad o afectivo y tener un mayor tiempo de consumo de BZD fueron los principales factores predictores de dependencia en el presente estudio. Discusión Los hallazgos del presente estudio sustentan la influencia de variables demográficas y del consumo de BZD en el riesgo para desarrollar dependencia. Se observa un mayor riesgo para el desarrollo de dependencia en los hombres. Para los pacientes con diagnósticos distintos a los trastornos de ansiedad es necesario evaluar el costo-beneficio de utilizar las BZD como parte del tratamiento para el manejo de síntomas relacionados con la ansiedad. El uso crónico de BZD fue el principal predictor de dependencia en la presente investigación, lo que pone de manifiesto la importancia de restringir el uso de BZD a periodos cortos de tiempo, estableciendo metas y objetivos claros de sus beneficios terapéuticos. Es fundamental fomentar en el personal médico y paramédico la prevención y detección oportuna de la dependencia a BZD en pacientes psiquiátricos.