Cases of Adverse Reaction to Psychotropic Drugs and Possible Association with Pharmacogenetics

Directory of Open Access Journals (Sweden)

Irina Piatkov

2012-10-01

Full Text Available Thousands of samples for pharmacogenetic tests have been analysed in our laboratory since its establishment. In this article we describe some of the most interesting cases of CYP poor metabolisers associated with adverse reactions to psychotropic drugs. Prevention of disease/illness, including Adverse Drug Reaction (ADR, is an aim of modern medicine. Scientific data supports the fact that evaluation of drug toxicology includes several factors, one of which is genetic variations in pharmacodynamics and pharmacokinetics of drug pathways. These variations are only a part of toxicity evaluation, however, even if it would help to prevent only a small percentage of patients from suffering adverse drug reactions, especially life threatening ADRs, pharmacogenetic testing should play a significant role in any modern psychopharmacologic practice. Medical practitioners should also consider the use of other medications or alternative dosing strategies for drugs in patients identified as altered metabolisers. This will promise not only better and safer treatments for patients, but also potentially lowering overall healthcare costs.

Extent of poly-pharmacy, occurrence and associated factors of drug-drug interaction and potential adverse drug reactions in Gondar Teaching Referral Hospital, North West Ethiopia

Directory of Open Access Journals (Sweden)

Endalkachew Admassie

2013-01-01

Full Text Available The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug-drug interaction (DDI and potential adverse drug reaction (ADR in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to identify risk factors for the occurrence of DDI and possible ADRs. All the statistical calculations were performed using SPSS; software. A total of 12,334 prescriptions were dispensed during the study period of which, 2,180 prescriptions were containing two or more drugs per prescription. A total of 21,210 drugs were prescribed and the average number of drugs per prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and Minor were analyzed and DDI were detected in 711 (32.6% prescriptions. Sex was not found to be a risk factor for the occurrence of DDI and ADR, while age and number of medications per prescription were found to be significant risk factors for the occurrence of DDI and ADR. The mean number of drugs per prescription was 1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar hospital was able to maintain the limit and prescriptions containing multiple drugs supposed to be taken systemically. Numbers of drugs per prescription as well as older age were found to be predisposing factors for the occurrence of DDI and potential ADRs while sex was not a risk factor.

Potentially inappropriate prescribing and the risk of adverse drug reactions in critically ill older adults

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Galli TB

2016-12-01

Full Text Available Background: Potentially inappropriate medication (PIM use in the elderly is associated with increased risk of adverse drug reactions (ADRs, but there is limited information regarding PIM use in the intensive care unit (ICU setting. Objective: The aim of the study is to describe the prevalence and factors associated with the use of PIM and the occurrence of PIM-related adverse reactions in the critically ill elderly. Methods: This study enrolled all critically ill older adults (60 years or more admitted to medical or cardiovascular ICUs between January and December 2013, in a large tertiary teaching hospital. For all patients, clinical pharmacists listed the medications given during the ICU stay and data on drugs were analyzed using 2012 Beers Criteria, to identify the prevalence of PIM. For each identified PIM the medical records were analyzed to evaluate factors associated with its use. The frequency of ADRs and, the causal relationship between PIM and the ADRs identified were also evaluated through review of medical records. Results: According to 2012 Beers Criteria, 98.2% of elderly patients used at least one PIM (n=599, of which 24.8% were newly started in the ICUs. In 29.6% of PIMs, there was a clinical circumstance that justified their prescription. The number of PIMs was associated with ICU length of stay and total number of medications. There was at least one ADR identified in 17.8% of patients; more than 40% were attributed to PIM, but there was no statistical association. Conclusions: There is a high prevalence of PIM used in acutely ill older people, but they do not seem to be the major cause of adverse drug reactions in this population. Although many PIMs had a clinical circumstance that led to their prescription during the course of ICU hospitalization, many were still present upon hospital discharge. Therefore, prescription of PIMs should be minimized to improve the safety of elderly patients.

Common adverse drug reactions with psychiatric medications and ...

African Journals Online (AJOL)

Common adverse drug reactions with psychiatric medications and an approach to their management: Adverse drug reactions are as important in psychiatric practice as they are in any other branch of medicine.

EXPLORING THE PATTERN OF POLYPHARMACY AND PROPORTION OF DRUG TO DRUG INTERACTIONS AND ADVERSE DRUG REACTIONS IN THE ELDERLY

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Vijayashree Thyagaraj

2017-07-01

Full Text Available BACKGROUND The geriatric population is increasing as a result of advanced medical facilities. This population also faces a number of medical health challenges. They tend to receive multiple medications often leading to Drug-Drug Interactions (DDIs Adverse Drug Reactions (ADRs and other clinical consequences, which compromises their quality of life if not endangering it as well. There are few Indian studies focusing on this problem. Hence, this study was undertaken with the aim to assess the polypharmacy pattern, proportion of DDIs and adverse drug reactions in the geriatric population in a tertiary care hospital. MATERIALS AND METHODS This was a cross-sectional study wherein data from 201 geriatric inpatient’s prescriptions were collected. The prescriptions were assessed for demographic details such as age, gender, comorbidities and drugs prescribed. All prescriptions were evaluated for polypharmacy, DDIs and ADRs. DDIs were assessed using Micromedex software. Patients were stratified into groups and DDIs were compared between the groups, gender and also with number of drugs used. RESULTS There were 201 patients with a mean age of approximately 70 years. Polypharmacy occurred in 73.63% of them with mean number of drugs being 6.23. The number of drugs used increased significantly with age (p=0.0001. Hypertension was the most common comorbidity. Polypharmacy was strongly associated with hypertension and dyslipidaemia. A total of 129 (64.17% patients accounted for 425 potential DDIs. The most common drug involved in DDIs was aspirin. A subset analysis of ADRs showed an occurrence of 50.68% with 10.81% being definitely avoidable. CONCLUSION Elderly individuals are at increased risk of being on polypharmacy. This comes with the risk of several potential DDIs, which in turn may lead to adverse drug reactions, which results in morbidity. Doctors involved in the care of the elderly should be aware of these facts and exercise caution while adding any

3-12 Detection and Management of Adverse Drug React

African Journals Online (AJOL)

MINA SAN

Detection and Management of Adverse Drug Reactions Related to Antiretroviral Drugs among. HIV/AIDS Patients in Kiambu ... of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care .... educational level, perception of ADRs, knowledge of ADRs, detection ...

Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

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Moore N

2015-07-01

Full Text Available Nicholas Moore,1 Charles Pollack,2 Paul Butkerait2 1Department of Pharmacology, Université de Bordeaux, Bordeaux, France; 2Pfizer Consumer Healthcare, Madison, NJ, USA Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. Keywords: adverse effects, nonsteroidal anti-inflammatory drugs, gastrointestinal, cardiovascular, renal

Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

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Maisha Kelly Freeman

2016-06-01

Full Text Available Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders; drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included medical marijuana with a subheading for adverse effect. Only articles in adult patients were considered. In addition, medical marijuana or cannabis plus one of the following search terms were searched: drug interactions, herb-drug interactions, drug-related side effects and adverse drug reactions, substance-related disorders, addiction, and abuse. A free-text search was also conducted to identify articles not included in the MeSH term search. A bibliographic search was also conducted. Articles were included if they addressed adverse effects of medical marijuana for the treatment of a condition. Meta-analyses, randomized controlled clinical trials, and case reports were included in the review if the primary focus of the article related to the adverse effect profile of inhaled medical marijuana. Medical marijuana efficacy studies were not assessed. In the absence of this information, case reports or reports of inhaled recreational marijuana use was used. Studies were excluded if published in languages other than English. In addition, studies highlighting mechanisms of action, studies of pharmacodynamics or pharmacokinetic effects were excluded, unless these effects were due to drug-drug interactions. Prescription products containing marijuana or derivatives were excluded from evaluation. An Internet search was conducted to locate the most up-to-date information on the laws concerning medical marijuana. Key findings: A PubMed search revealed 58 articles and 28 of

iADRs: towards online adverse drug reaction analysis.

Science.gov (United States)

Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

2012-12-01

Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

Ranking Adverse Drug Reactions With Crowdsourcing

KAUST Repository

Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel; Altman, Russ B

2015-01-01

Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

Science.gov (United States)

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is

Computerized surveillance of opioid-related adverse drug events in perioperative care: a cross-sectional study

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Gattis Katherine G

2009-08-01

Full Text Available Abstract Background Given the complexity of surgical care, perioperative patients are at high risk of opioid-related adverse drug events. Existing methods of detection, such as trigger tools and manual chart review, are time-intensive which makes sustainability challenging. Using strategic rule design, computerized surveillance may be an efficient, pharmacist-driven model for event detection that leverages existing staff resources. Methods Computerized adverse drug event surveillance uses a logic-based rules engine to identify potential adverse drug events or evolving unsafe clinical conditions. We extended an inpatient rule (administration of naloxone to detect opioid-related oversedation and respiratory depression to perioperative care at a large academic medical center. Our primary endpoint was the adverse drug event rate. For all patients with a naloxone alert, manual chart review was performed by a perioperative clinical pharmacist to assess patient harm. In patients with confirmed oversedation, other patient safety event databases were queried to determine if they could detect duplicate, prior, or subsequent opioid-related events. Results We identified 419 cases of perioperative naloxone administration. Of these, 101 were given postoperatively and 69 were confirmed as adverse drug events after chart review yielding a rate of 1.89 adverse drug events/1000 surgical encounters across both the inpatient and ambulatory settings. Our ability to detect inpatient opioid adverse drug events increased 22.7% by expanding surveillance into perioperative care. Analysis of historical surveillance data as well as a voluntary reporting database revealed that 11 of our perioperative patients had prior or subsequent harmful oversedation. Nine of these cases received intraoperative naloxone, and 2 had received naloxone in the post-anesthesia care unit. Pharmacist effort was approximately 3 hours per week to evaluate naloxone alerts and confirm adverse drug

HOW ADVERSE DRUG-REACTIONS CAN PLAY A ROLE IN INNOVATIVE DRUG RESEARCH - SIMILARITIES IN ADVERSE DRUG REACTION PROFILES OF CAPTOPRIL AND PENICILLAMINE

NARCIS (Netherlands)

RIKKEN, F; VOS, R

1995-01-01

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We

The validity of a patient-reported adverse drug event questionnaire using different recall periods

NARCIS (Netherlands)

de Vries, Sieta T; Haaijer-Ruskamp, Flora M; de Zeeuw, Dick; Denig, Petra

2014-01-01

PURPOSE: To assess the validity of a patient-reported adverse drug events (ADEs) questionnaire with a 3-month or 4-week recall period. METHODS: Patients receiving at least one oral glucose-lowering drug were asked to report potential ADEs they experienced related to any drug in a daily diary for a

Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

DEFF Research Database (Denmark)

Roitmann, Eva; Eriksson, Robert; Brunak, Søren

2014-01-01

New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse...

Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

Science.gov (United States)

Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

2015-06-01

All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

Science.gov (United States)

van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

2000-12-01

Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

Science.gov (United States)

Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

2018-06-01

Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Ranking adverse drug reactions with crowdsourcing.

Science.gov (United States)

Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel; Altman, Russ B

2015-03-23

There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. The intent of the study was to rank ADRs according to severity. We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.

Ranking Adverse Drug Reactions With Crowdsourcing

KAUST Repository

Gottlieb, Assaf

2015-03-23

Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective: The intent of the study was to rank ADRs according to severity. Methods: We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results: There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions: ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.

Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

Science.gov (United States)

Mangoni, Arduino A

2012-05-01

Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

Science.gov (United States)

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

Directory of Open Access Journals (Sweden)

Glauciene Santana Damasceno

2013-01-01

Full Text Available OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%, the skin and appendages (21.4%, and the central and peripheral nervous systems (14.3%. Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. "Probable reactions" (75% predominated over "possible reactions" (24%. In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6% of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I. A high dropout rate from tuberculosis treatment (24.4% was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs.

Why Clinicians Don't Report Adverse Drug Events: Qualitative Study.

Science.gov (United States)

Hohl, Corinne M; Small, Serena S; Peddie, David; Badke, Katherin; Bailey, Chantelle; Balka, Ellen

2018-02-27

Adverse drug events are unintended and harmful events related to medications. Adverse drug events are important for patient care, quality improvement, drug safety research, and postmarketing surveillance, but they are vastly underreported. Our objectives were to identify barriers to adverse drug event documentation and factors contributing to underreporting. This qualitative study was conducted in 1 ambulatory center, and the emergency departments and inpatient wards of 3 acute care hospitals in British Columbia between March 2014 and December 2016. We completed workplace observations and focus groups with general practitioners, hospitalists, emergency physicians, and hospital and community pharmacists. We analyzed field notes by coding and iteratively analyzing our data to identify emerging concepts, generate thematic and event summaries, and create workflow diagrams. Clinicians validated emerging concepts by applying them to cases from their clinical practice. We completed 238 hours of observations during which clinicians investigated 65 suspect adverse drug events. The observed events were often complex and diagnosed over time, requiring the input of multiple providers. Providers documented adverse drug events in charts to support continuity of care but never reported them to external agencies. Providers faced time constraints, and reporting would have required duplication of documentation. Existing reporting systems are not suited to capture the complex nature of adverse drug events or adapted to workflow and are simply not used by frontline clinicians. Systems that are integrated into electronic medical records, make use of existing data to avoid duplication of documentation, and generate alerts to improve safety may address the shortcomings of existing systems and generate robust adverse drug event data as a by-product of safer care. ©Corinne M Hohl, Serena S Small, David Peddie, Katherin Badke, Chantelle Bailey, Ellen Balka. Originally published in JMIR

The pharmacist and adverse drug reaction reporting.

Science.gov (United States)

Pearson, K

1982-08-01

During premarketing trials, the number of patients exposed to a drug and the length of exposure to a drug are both limited. After marketing, many thousands, frequently millions, of patients are exposed to the drug over considerably longer periods of time, and adverse drug reactions not previously recognized appear. Because of these factors, postmarketing surveillance is extremely important. Pharmacists can contribute to drug safety and improved patient care by understanding and actively participating in the Food and Drug Administration's Spontaneous Reporting Program.

Determination of the frequency and direct cost of the adverse drug events in Argentina.

Science.gov (United States)

Izquierdo, Estela; Rodríguez, Claudio; Pampliega, Eneas; Filinger, Ester

2009-05-01

To determine the frequency and the direct costs of adverse drug reactions, in an ambulatory population of the City of Buenos Aires, Argentina and its area of influence. A retrospective study was done during a period of three months on approximately 300.000 residents of the Buenos Aires area, gathering data according to the selected variables by means of the electronic capture of prescriptions dispensed in pharmacies of the area. This method enables the detection and registration of potential conflicts that may arise between a prescribed drug and factors such as: patient's demographic, clinical and drug profile. The analysis unit was defined as the happening of a moderate or severe adverse event reported by the system. The selected variables were the incidence of these effects and the direct cost was calculated as the value of the drugs that induced the adverse event. The events were classified according to the following interactions: a) drug-drug, b) drug-pediatrics, c) drug-gender, d) drug-pregnancy and abuse of controlled substances. The observed frequency shows great variability and the shortage of available data for ambulatory populations. We found 6.74% of reported events over the total of processed items, which generated an additional cost equivalent to 4.58% of the total pharmaceutical expenses. This study has only evaluated the cost occurred by the use of a drug that will lead to an adverse reaction. Moderate and severe reactions were included regardless of the important indirect costs, hospitalization costs, tests, physician fees, etc.

Adverse drug reactions induced by cardiovascular drugs in outpatients.

Science.gov (United States)

Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

2008-01-01

Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, PPearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

Science.gov (United States)

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

2017-09-01

Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected Pbrand and generics for all three drugs of interest (Breslow-Day Pbrands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

Physician access to drug profiles to reduce adverse reactions

Science.gov (United States)

Yasnoff, William A.; Tomkins, Edward L.; Dunn, Louise M.

1995-10-01

Adverse drug reactions (ADRs) are a major source of preventable morbidity and mortality, especially among the elderly, who use more drugs and are more sensitive to them. The insurance industry has recently addressed this problem through the implementation of drug interaction alerts to pharmacists in conjunction with immediate online claims adjudication for almost 60% of prescriptions (expected to reach 90% within 5 years). These alerts are based on stored patient drug profiles maintained by pharmacy benefit managers (PBMs) which are updated whenever prescriptions are filled. While these alerts are very helpful, the pharmacist does not prescribe, resulting in time-consuming and costly delays to contact the physician and remedy potential interactions. We have developed and demonstrated the feasibility of the PINPOINT (Pharmaceutical Information Network for prevention of interactions) system for making the drug profile and interaction information easily available to the physician before the prescription is written. We plan to test the cost-effectiveness of the system in a prospective controlled clinical trial.

Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov

Directory of Open Access Journals (Sweden)

Eric Wen Su

2017-03-01

Full Text Available Drug repositioning (i.e., drug repurposing is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics and PolyAnalyst (Megaputer were utilized. An I2E query extracts “Serious Adverse Events” (SAE data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer.

Patients’ attention to and understanding of adverse drug reaction warnings

Directory of Open Access Journals (Sweden)

Tresa Muir McNeal

2010-12-01

Full Text Available Tresa Muir McNeal1, Colleen Y Colbert1, Christian Cable1, Curtis R Mirkes1, June G Lubowinski2, John D Myers11Department of Medicine, Texas A&M University System HSC College of Medicine, Scott & White Healthcare, Temple, TX, USA; 2RD Haynes Medical Library, Scott & White Healthcare, Temple, TX, USAIntroduction: Medications are critical to the management of patient conditions, and they can have significant effects on the success or failure of medical interventions. Patient perceptions of drug warnings play an important role in medication compliance and ultimately disease management. Several factors may affect patients’ understanding of drug warnings and drug labeling, including health literacy and interactions with physicians and pharmacists.Purpose: The purpose of this article is to provide a review of the literature related to patient perceptions of drug warnings and drug labeling. Descriptive articles and studies regarding patient perceptions and knowledge of adverse drug reaction warnings were reviewed.Methods: The following databases were utilized to search the literature related to patient perceptions of drug warnings: PubMed, Academic Search Premiere, CINAHL, Medline, Psych Info, Business Source Complete, Alternative Healthwatch, Health Source (both Nursing/Academic and Consumer additions, JSTOR, and Master File Premiere. For the purpose of this review, any peer-reviewed article was eligible. Exclusionary criteria included: articles published in languages other than English, articles/studies on patient perceptions of vaccines and chemotherapy, and articles related to perceptions of medications administered in the inpatient setting. Forty-six articles were included in the review.Results: Health literacy has been shown to have a major impact on patients’ ability to understand potential adverse reactions and instructions on correct dosing of medications. Direct communication with physicians and pharmacists is one of the most important and

Adverse drug reaction monitoring of newer oral anti diabetic drugs – a pharmacovigilance perspective

Directory of Open Access Journals (Sweden)

Ankita Bhattacharjee

2016-04-01

Full Text Available Objective: To monitor and evaluate adverse drug reactions (ADRs of newer oral anti-diabetic drugs in type II diabetics by spontaneous/solicited ADR monitoring.Material and methods: Two hundred and thirty two diabetic patients on newer oral antidiabetic drugs were evaluated prospectively in a cross-sectional study over a period of eighteen months. All patients were followed up for ADRs which were evaluated for incidence, frequency, severity and causality. ADR severity was graded according to University of Virginia Health System Adverse Drug Reaction Reporting program criteria and causality assessment was done using WHO-UMC scale.Results: 190 out of 232 patients (42 patients lost to follow up were evaluated. ADRs were observed in 34 cases (17.9%. Most common ADRs were gastrointestinal (44.2% followed by musculoskeletal (17.6%, metabolic (14.7%, infections (5.9% and others (17.6%. The maximal frequency of ADRs was seen with sitagliptin (6.4% followed by vildagliptin(3.8%, saxagliptin(2.7%, saroglitazar(2.1%, linagliptin(1.6%, canagliflozin(1.6%. 25(73.5%, 8(23.5% and 1(3% ADRs were mild, moderate and severe respectively. 24(70% ADRs were classified as possible, 9(27% probable and 1(3% unlikely on causality assessment. Conclusion: Newer oral antidiabetic drugs like gliptins and SGLT-2 inhibitors have potential to cause ADRs. Gastro-intestinal, musculoskeletal, metabolic were most common ADRs. Active pharmacovigilance should be carried out for risk identification and management. 

HLA Association with Drug-Induced Adverse Reactions

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Wen-Lang Fan

2017-01-01

Full Text Available Adverse drug reactions (ADRs remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs, such as Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01. The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI. In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

Predictive modeling of structured electronic health records for adverse drug event detection.

Science.gov (United States)

Zhao, Jing; Henriksson, Aron; Asker, Lars; Boström, Henrik

2015-01-01

The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and

Automatically Recognizing Medication and Adverse Event Information From Food and Drug Administration's Adverse Event Reporting System Narratives.

Science.gov (United States)

Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P; Yu, Hong

2014-06-27

The Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. The annotated corpus had an agreement of over .9 Cohen's kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance.

Adverse drug reactions induced by cardiovascular drugs in outpatients

Directory of Open Access Journals (Sweden)

Gholami K

2008-03-01

Full Text Available Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs induced by this class of medicinal products seems necessary.Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3% patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5% and the lowest rate with Atenolol (3%. Headache was the most frequent detected ADR (23%. Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05. ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05. With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05. Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

Assessing the proarrhythmic potential of drugs

DEFF Research Database (Denmark)

Thomsen, Morten Bækgaard; Matz, Jørgen; Volders, Paul G A

2006-01-01

Torsades de pointes (TdP) is a potentially lethal cardiac arrhythmia that can occur as an unwanted adverse effect of various pharmacological therapies. Before a drug is approved for marketing, its effects on cardiac repolarisation are examined clinically and experimentally. This paper expresses...... the opinion that effects on repolarisation duration cannot directly be translated to risk of proarrhythmia. Current safety assessments of drugs only involve repolarisation assays, however the proarrhythmic profile can only be determined in the predisposed model. The availability of these proarrhythmic animal...... surrogate parameters possessing predictive power of TdP arrhythmia are reviewed. As these parameters are not developed to finalisation, any meaningful study of the proarrhythmic potential of a new drug will include evaluation in an integrated model of TdP arrhythmia....

Adverse Drug Events and Medication Errors in African Hospitals: A Systematic Review.

Science.gov (United States)

Mekonnen, Alemayehu B; Alhawassi, Tariq M; McLachlan, Andrew J; Brien, Jo-Anne E

2018-03-01

Medication errors and adverse drug events are universal problems contributing to patient harm but the magnitude of these problems in Africa remains unclear. The objective of this study was to systematically investigate the literature on the extent of medication errors and adverse drug events, and the factors contributing to medication errors in African hospitals. We searched PubMed, MEDLINE, EMBASE, Web of Science and Global Health databases from inception to 31 August, 2017 and hand searched the reference lists of included studies. Original research studies of any design published in English that investigated adverse drug events and/or medication errors in any patient population in the hospital setting in Africa were included. Descriptive statistics including median and interquartile range were presented. Fifty-one studies were included; of these, 33 focused on medication errors, 15 on adverse drug events, and three studies focused on medication errors and adverse drug events. These studies were conducted in nine (of the 54) African countries. In any patient population, the median (interquartile range) percentage of patients reported to have experienced any suspected adverse drug event at hospital admission was 8.4% (4.5-20.1%), while adverse drug events causing admission were reported in 2.8% (0.7-6.4%) of patients but it was reported that a median of 43.5% (20.0-47.0%) of the adverse drug events were deemed preventable. Similarly, the median mortality rate attributed to adverse drug events was reported to be 0.1% (interquartile range 0.0-0.3%). The most commonly reported types of medication errors were prescribing errors, occurring in a median of 57.4% (interquartile range 22.8-72.8%) of all prescriptions and a median of 15.5% (interquartile range 7.5-50.6%) of the prescriptions evaluated had dosing problems. Major contributing factors for medication errors reported in these studies were individual practitioner factors (e.g. fatigue and inadequate knowledge

Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

Science.gov (United States)

Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

2014-01-01

The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

Science.gov (United States)

Vilar, Santiago; Hripcsak, George

2016-01-01

Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

Science.gov (United States)

Vilar, Santiago; Hripcsak, George

2017-07-01

Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

Science.gov (United States)

Liu, Xiao; Chen, Hsinchun

2015-12-01

Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. Published by Elsevier Inc.

Prediction of adverse drug reactions using decision tree modeling.

Science.gov (United States)

Hammann, F; Gutmann, H; Vogt, N; Helma, C; Drewe, J

2010-07-01

Drug safety is of great importance to public health. The detrimental effects of drugs not only limit their application but also cause suffering in individual patients and evoke distrust of pharmacotherapy. For the purpose of identifying drugs that could be suspected of causing adverse reactions, we present a structure-activity relationship analysis of adverse drug reactions (ADRs) in the central nervous system (CNS), liver, and kidney, and also of allergic reactions, for a broad variety of drugs (n = 507) from the Swiss drug registry. Using decision tree induction, a machine learning method, we determined the chemical, physical, and structural properties of compounds that predispose them to causing ADRs. The models had high predictive accuracies (78.9-90.2%) for allergic, renal, CNS, and hepatic ADRs. We show the feasibility of predicting complex end-organ effects using simple models that involve no expensive computations and that can be used (i) in the selection of the compound during the drug discovery stage, (ii) to understand how drugs interact with the target organ systems, and (iii) for generating alerts in postmarketing drug surveillance and pharmacovigilance.

Adverse Drug Event Monitoring at the Food and Drug Administration: Your Report Can Make a Difference

OpenAIRE

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treati...

Role of peripheral eosinophilia in adverse cutaneous drug reactions.

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Drago, F; Cogorno, L; Agnoletti, A F; Parodi, A

2015-01-01

The objective of this retrospective study was to verify whether peripheral eosinophilia (PE) may be a marker of severity for adverse cutaneous drug reactions (ACDR). We investigated for PE in sixty-three patients diagnosed as adverse cutaneous drug reactions. All the patients underwent blood tests at baseline visit. Only patients that showed a very likely connection between ACDR and the suspected causative drug were induced in the study. We found that 11 out of 63 patients (17%) presented PE for values ≥ 0.6 x 10(9) cells/l or for a percentage of total leukocytes ≥ 6%. These 11 patients compared to patients without eosinophilia had a longer recovery time, they showed diffuse severe cutaneous reactions and they all needed a systemic therapy compared to the 41% of patients without eosinophilia. These outcomes prompt us to believe that peripheral eosinophilia may be an index of severity for adverse cutaneous drug reactions. Therefore, we suggest physicians to always detect the presence of peripheral eosinophilia in order to not underestimate the reaction and to promptly start an appropriate therapy.

A study on adverse drug reactions in a tertiary care hospital of ...

African Journals Online (AJOL)

Ratan J. Lihite

2016-06-27

Jun 27, 2016 ... Patients of all age and either sex were included. Adverse drug ... adverse drug reactions in majority of the patients. The commonly .... ten prescription drugs were excluded. .... Pneumonia with respiratory distress, Vision problem, Knee pain, .... back of spontaneous reporting system i.e. underreporting. Thus ...

THE PROSPECTIVE OBSERVATIONAL STUDY ON CUTANEOUS ADVERSE DRUG REACTIONS TO CHEMOTHERAPY

Directory of Open Access Journals (Sweden)

Prakash Mani

2016-07-01

Full Text Available INTRODUCTION There are a wide spectrum of adverse cutaneous drug reactions (ACDRs varying from transient maculopapular rash to fatal toxic epidermal necrolysis (TEN. With the advent of newer and targeted therapy in the field of dermatology, the pattern of cutaneous adverse drug eruptions and the drugs responsible for them keep changing every year. Hence, this study was undertaken to ascertain the clinical spectrum of ACDRs and the causative drugs, in a tertiary care centre in South India. MATERIALS AND METHODS This study was a prospective, observational study conducted in Department of Medical Oncology, Government Rajaji Hospital, Madurai Medical College, Madurai during the period of March 2015 - August 2015 (6 months. Severity of the reaction was assessed using CTCAE (Common Terminology Criteria for Adverse Events scale version 4.1. Causality of the drug was assessed using Naranjo Causality Assessment Scale. The scale was calculated first for the regimen and then for individual drugs separately. The adverse events with score of 6 or more (probable and definite adverse events were taken for the study. RESULTS AND CONCLUSION The overall incidence of ACDRs found in this study was 85%. Alopecia was the commonest ACDR occurring in 51.6% of patients. Nail pigmentation and supravenous pigmentation were the next common ACDRs, recorded in 35% and 16% of patients respectively. Imatinib caused generalised hypopigmentation in 40% of patients. Bleomycin induced, flagellate erythema and pigmentation in 17% of patients and stomatitis was seen in 11% of patients. Acneiform eruptions were recorded with erlotinib and gefitinib therapy. Supravenous pigmentation was common with 5-fluorouracil and docetaxel, occurring in 53% & 48% respectively. Newer targeted therapies like EGFR (Epidermal growth factor receptor inhibitors recorded low incidence of ACDRs like alopecia as against conventional antineoplastic agents. The cancer chemotherapeutic drugs are associated

Detecting drug-drug interactions using a database for spontaneous adverse drug reactions : an example with diuretics and non-steroidal anti-inflammatory drugs

NARCIS (Netherlands)

van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

2000-01-01

OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable

Psychiatric Adverse Effects of Dermatological Drugs

Directory of Open Access Journals (Sweden)

Mine Özmen

2010-07-01

Full Text Available Dermatological drugs, mostly corticosteroids and isotretinoin, cause different psychiatric adverse effects. During steroid therapy, a wide range of psychiatric conditions, from minor clinical symptoms like insomnia and anxiety to serious psychiatric syndromes like psychosis and delirium might be seen. In medical literature, a causal connection is usually suggested between “isotretinoin”, which is used for treatment of acne vulgaris and depression and suicide attempts. However, there are no statistically significant double-blind randomized studies that support this connection. Clinicians must know patient’s psychiatric history before using any dermatological treatment known as causing psychiatric adverse effects, and psychiatric consultation should be established whenever necessary.

A continuous GRASP to determine the relationship between drugs and adverse reactions

International Nuclear Information System (INIS)

Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle; Resende, Mauricio G. C.

2007-01-01

Adverse drag reactions (ADRs) are estimated to be one of the leading causes of death. Many national and international agencies have set up databases of ADR reports for the express purpose of determining the relationship between drugs and adverse reactions that they cause. We formulate the drug-reaction relationship problem as a continuous optimization problem and utilize C-GRASP, a new continuous global optimization heuristic, to approximately determine the relationship between drugs and adverse reactions. Our approach is compared against others in the literature and is shown to find better solutions

Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

Science.gov (United States)

Kim, Seonji; Park, Kyounghoon; Kim, Mi-Sook; Yang, Bo Ram; Choi, Hyun Jin; Park, Byung-Joo

2017-10-01

Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals. Copyright © 2017 Elsevier B.V. All rights reserved.

Glycaemic adverse drug reactions from anti-neoplastics used in ...

African Journals Online (AJOL)

235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

The concept of adverse drug reaction reporting: awareness among ...

African Journals Online (AJOL)

Arun Kumar Agnihotri

concept of pharmacovigilance and adverse drug reaction reporting, a section on ... ADR go undocumented worldwide8,9. ... international drug monitoring collaborating centre, ... practitioners to report all suspected ADR, the few .... more with some of the guidelines such as nurses, .... patients: a meta-analysis of prospective.

Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey.

Science.gov (United States)

Bush, Thomas M; Rayburn, Keith S; Holloway, Sandra W; Sanchez-Yamamoto, Deanna S; Allen, Blaine L; Lam, Tiffany; So, Brian K; Tran, De H; Greyber, Elizabeth R; Kantor, Sophia; Roth, Larry W

2007-01-01

Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. The rate of potential and observed adverse herb-drug interactions. Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications.

Detection and Management of Adverse Drug Reactions Related to ...

African Journals Online (AJOL)

The objective of this study was to establish the detection, prevalence and management of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care Centre (CCC) of Kiambu District Hospital. The study was a cross sectional survey where the patients included ...

Knowledge, Attitude and Practice of Adverse Drug Reaction ...

African Journals Online (AJOL)

Erah

. Keywords: Adverse drug reactions; Knowledge, attitude and practice; Health care workers; Yellow card reporting scheme. Received: 24 August 2010. Revised accepted: 22 April 2011. *Corresponding author: E-mail: jofadare@gmail.com ...

IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS

Directory of Open Access Journals (Sweden)

Valentina Galbiati

2016-07-01

Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

Potential drug–drug interactions in Alzheimer patients with behavioral symptoms

Directory of Open Access Journals (Sweden)

Pasqualetti G

2015-09-01

Full Text Available Giuseppe Pasqualetti, Sara Tognini, Valeria Calsolaro, Antonio Polini, Fabio Monzani Geriatrics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Abstract: The use of multi drug regimens among the elderly population has increased tremendously over the last decade although the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses. The elderly populations are particularly at an increased risk of adverse drug reactions considering comorbidity, poly-therapy, physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs and, in some cases, poor compliance due to cognitive impairment and/or depression. In this setting, drug–drug interaction may represent a serious and even life-threatening clinical condition. Moreover, the inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in addition of yet another drug to treat the symptoms, which in turn increases drug–drug interactions. Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, are the most widely prescribed agents for Alzheimer’s disease (AD patients. Behavioral and psychological symptoms of dementia, including psychotic symptoms and behavioral disorders, represent noncognitive disturbances frequently observed in AD patients. Antipsychotic drugs are at high risk of adverse events, even at modest doses, and may interfere with the progression of cognitive impairment and interact with several drugs including anti-arrhythmics and acetylcholinesterase inhibitors. Other medications often used in AD patients are represented by anxiolytic, like benzodiazepine, or antidepressant agents. These agents also might interfere with other concomitant drugs through both pharmacokinetic and pharmacodynamic mechanisms. In this review we focus on the most frequent drug–drug interactions, potentially harmful, in AD patients with

Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

OpenAIRE

Maisha Kelly Freeman; Pilar Z Murphy

2016-01-01

Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders); drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included med...

[Impact of potentially inappropriate drug usage on health insurance business results].

Science.gov (United States)

Kirschke, Malin; Böhme, Jacqueline

2014-09-01

In Germany a list was drawn up that included 83 potentially inappropriate drugs. The PRISCUS list published in 2010 was intended to highlight certain problems in the pharmakotherapy of elderly patients and serve as a support for improved medicine safety. Almost a third of the insurance portfolio of the HALLESCHE Krankenversicherung aged over 75 years takes drugs that are on the PRISCUS list. Benzodiazepine and Z-drugs are taken most frequently. The costs per insurant with potentially inappropriate medication are on average higher than for policyholders who do not take drugs on the PRISCUS list. The costs per insurant are rising, with an increase in the number of PRISCUS agents being taken as well. However, there is still no scientific proof that potentially inappropriate drugs lead to adverse drug events.

Monitoring of Adverse Drug Reactions Associated with Antihypertensive Medicines at a University Teaching Hospital in New Delhi

Directory of Open Access Journals (Sweden)

Fowad Khurshid

2012-09-01

Full Text Available Aim To monitor the adverse drug reactions (ADRs caused by antihypertensive medicines prescribed in a university teaching hospital.Methods:he present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO, Government of India.Results:A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29 % than males, 7 (3.64 %. Combination therapy was associated with more number of adverse drug reactions (66.7 % as against monotherapy (33.3 %. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7, followed by diuretics (n = 5, and beta- blockers (n = 4. Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7, followed by torasemide (n = 3. Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8 % followed by musculo-skeletal complaints (23.8 % and gastro-intestinal disorders (14.3 %. Conclusions:The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.

Adverse events of modern antifungal drugs during treatment of invasive fungal infections

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N. V. Dmitrieva

2014-07-01

Full Text Available Characteristics of adverse events of modern antimycotics by organ systems and comparative frequency between different medicines and their groups are presented. The examples of incompatibility of antifungal drugs with other pharmacological groups are discussed. Records of adverse events and drug compatibility will allow the practitioner to prevent and timely cure possible complications, should they arise.

Adverse events of modern antifungal drugs during treatment of invasive fungal infections

Directory of Open Access Journals (Sweden)

N. V. Dmitrieva

2013-01-01

Full Text Available Characteristics of adverse events of modern antimycotics by organ systems and comparative frequency between different medicines and their groups are presented. The examples of incompatibility of antifungal drugs with other pharmacological groups are discussed. Records of adverse events and drug compatibility will allow the practitioner to prevent and timely cure possible complications, should they arise.

Adverse drug events in the oral cavity.

Science.gov (United States)

Yuan, Anna; Woo, Sook-Bin

2015-01-01

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Cutaneous adverse drug reactions seen at a university hospital department of dermatology

DEFF Research Database (Denmark)

Borch, Jakob E; Andersen, Klaus E; Bindslev-Jensen, Carsten

2006-01-01

Patients with suspected cutaneous adverse drug reactions are often referred to allergy clinics or departments of dermatology for evaluation. These patients are selected compared with patients identified in prospective and cross-sectional studies of hospital populations. This explains the observed...... variation in prevalence of specific reactions and of eliciting drugs. This study investigated the prevalence of cutaneous adverse drug reactions in a university hospital department of dermatology that is specially focused on allergy. An 8-month survey was carried out during the period April-December 2003...

Adverse events in children and adolescents treated with quetiapine: an analysis of adverse drug reaction reports from the Danish Medicines Agency database

DEFF Research Database (Denmark)

Jakobsen, Klaus D.; Wallach-Kildemoes, Helle; Bruhn, Christina H.

2017-01-01

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children...... and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported......, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns....

The validation of an invitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions

International Nuclear Information System (INIS)

Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David

2010-01-01

Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.

Hospitalization due to Adverse Drug Reactions and Drug Interactions before and after HAART

Directory of Open Access Journals (Sweden)

Michelle M Foisy

2000-01-01

Full Text Available OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART (phase 1 and post-HAART (phase 2.

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two "challenging" case reports.

Science.gov (United States)

Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

2013-12-01

Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health.

Toward multimodal signal detection of adverse drug reactions.

Science.gov (United States)

Harpaz, Rave; DuMouchel, William; Schuemie, Martijn; Bodenreider, Olivier; Friedman, Carol; Horvitz, Eric; Ripple, Anna; Sorbello, Alfred; White, Ryen W; Winnenburg, Rainer; Shah, Nigam H

2017-12-01

Improving mechanisms to detect adverse drug reactions (ADRs) is key to strengthening post-marketing drug safety surveillance. Signal detection is presently unimodal, relying on a single information source. Multimodal signal detection is based on jointly analyzing multiple information sources. Building on, and expanding the work done in prior studies, the aim of the article is to further research on multimodal signal detection, explore its potential benefits, and propose methods for its construction and evaluation. Four data sources are investigated; FDA's adverse event reporting system, insurance claims, the MEDLINE citation database, and the logs of major Web search engines. Published methods are used to generate and combine signals from each data source. Two distinct reference benchmarks corresponding to well-established and recently labeled ADRs respectively are used to evaluate the performance of multimodal signal detection in terms of area under the ROC curve (AUC) and lead-time-to-detection, with the latter relative to labeling revision dates. Limited to our reference benchmarks, multimodal signal detection provides AUC improvements ranging from 0.04 to 0.09 based on a widely used evaluation benchmark, and a comparative added lead-time of 7-22 months relative to labeling revision dates from a time-indexed benchmark. The results support the notion that utilizing and jointly analyzing multiple data sources may lead to improved signal detection. Given certain data and benchmark limitations, the early stage of development, and the complexity of ADRs, it is currently not possible to make definitive statements about the ultimate utility of the concept. Continued development of multimodal signal detection requires a deeper understanding the data sources used, additional benchmarks, and further research on methods to generate and synthesize signals. Copyright © 2017 Elsevier Inc. All rights reserved.

A dataset of 200 structured product labels annotated for adverse drug reactions.

Science.gov (United States)

Demner-Fushman, Dina; Shooshan, Sonya E; Rodriguez, Laritza; Aronson, Alan R; Lang, Francois; Rogers, Willie; Roberts, Kirk; Tonning, Joseph

2018-01-30

Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a drug may have, are one of the leading causes of morbidity and mortality during medical care. To date, there is no structured machine-readable authoritative source of known ADRs. The United States Food and Drug Administration (FDA) partnered with the National Library of Medicine to create a pilot dataset containing standardised information about known adverse reactions for 200 FDA-approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to exchange information about drugs and other products, were manually annotated for adverse reactions at the mention level to facilitate development and evaluation of text mining tools for extraction of ADRs from all SPLs. The ADRs were then normalised to the Unified Medical Language System (UMLS) and to the Medical Dictionary for Regulatory Activities (MedDRA). We present the curation process and the structure of the publicly available database SPL-ADR-200db containing 5,098 distinct ADRs. The database is available at https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and validating the data is available at https://github.com/lhncbc/fda-ars.

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

Science.gov (United States)

Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

2017-01-01

Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

ADVERPred-Web Service for Prediction of Adverse Effects of Drugs.

Science.gov (United States)

Ivanov, Sergey M; Lagunin, Alexey A; Rudik, Anastasia V; Filimonov, Dmitry A; Poroikov, Vladimir V

2018-01-22

Application of structure-activity relationships (SARs) for the prediction of adverse effects of drugs (ADEs) has been reported in many published studies. Training sets for the creation of SAR models are usually based on drug label information which allows for the generation of data sets for many hundreds of drugs. Since many ADEs may not be related to drug consumption, one of the main problems in such studies is the quality of data on drug-ADE pairs obtained from labels. The information on ADEs may be included in three sections of the drug labels: "Boxed warning," "Warnings and Precautions," and "Adverse reactions." The first two sections, especially Boxed warning, usually contain the most frequent and severe ADEs that have either known or probable relationships to drug consumption. Using this information, we have created manually curated data sets for the five most frequent and severe ADEs: myocardial infarction, arrhythmia, cardiac failure, severe hepatotoxicity, and nephrotoxicity, with more than 850 drugs on average for each effect. The corresponding SARs were built with PASS (Prediction of Activity Spectra for Substances) software and had balanced accuracy values of 0.74, 0.7, 0.77, 0.67, and 0.75, respectively. They were implemented in a freely available ADVERPred web service ( http://www.way2drug.com/adverpred/ ), which enables a user to predict five ADEs based on the structural formula of compound. This web service can be applied for estimation of the corresponding ADEs for hits and lead compounds at the early stages of drug discovery.

Sharing adverse drug event data using business intelligence technology.

Science.gov (United States)

Horvath, Monica M; Cozart, Heidi; Ahmad, Asif; Langman, Matthew K; Ferranti, Jeffrey

2009-03-01

Duke University Health System uses computerized adverse drug event surveillance as an integral part of medication safety at 2 community hospitals and an academic medical center. This information must be swiftly communicated to organizational patient safety stakeholders to find opportunities to improve patient care; however, this process is encumbered by highly manual methods of preparing the data. Following the examples of other industries, we deployed a business intelligence tool to provide dynamic safety reports on adverse drug events. Once data were migrated into the health system data warehouse, we developed census-adjusted reports with user-driven prompts. Drill down functionality enables navigation from aggregate trends to event details by clicking report graphics. Reports can be accessed by patient safety leadership either through an existing safety reporting portal or the health system performance improvement Web site. Elaborate prompt screens allow many varieties of reports to be created quickly by patient safety personnel without consultation with the research analyst. The reduction in research analyst workload because of business intelligence implementation made this individual available to additional patient safety projects thereby leveraging their talents more effectively. Dedicated liaisons are essential to ensure clear communication between clinical and technical staff throughout the development life cycle. Design and development of the business intelligence model for adverse drug event data must reflect the eccentricities of the operational system, especially as new areas of emphasis evolve. Future usability studies examining the data presentation and access model are needed.

Factors that condition the spontaneous reporting of adverse drug reactions among nurses: an integrative review.

Science.gov (United States)

De Angelis, Alessia; Colaceci, Sofia; Giusti, Angela; Vellone, Ercole; Alvaro, Rosaria

2016-03-01

To describe and synthesise previous research on factors conditioning the spontaneous reporting of adverse drug reactions among nurses. Spontaneous reports of adverse drug reactions by health-care providers, are a main instrument for the continuous evaluation of the risk-benefit ratio of every drug. Under-reporting of adverse drug reactions by all health-care providers, in particular by nurses, is a major limitation to this system. An integrated review of the literature was conducted using MEDLINE, CINAHL, Embase, Scopus databases and Google Scholar. After evaluation for appropriateness related to inclusion/exclusion criteria, 16 studies were included in the final analysis and synthesis. Two factors emerged from the study: (1) intrinsic factors related to nurses' knowledge and attitudes; (2) extrinsic factors related to nurses' interaction with health-care organisations and to the relationship between nurses and physicians. Nurses' attitudes that hinder reporting include ignorance, insecurity, fear and lethargy. Nurses are not fully aware of their role in adverse drug reaction reporting. Nurses must acquire greater knowledge to implement specific skills into their daily clinical practice. To improve nurses' reporting of adverse drug reactions, it is necessary to develop management approaches that modify both intrinsic and extrinsic factors. © 2015 John Wiley & Sons Ltd.

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

Science.gov (United States)

Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M.; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

2013-01-01

Introduction: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. Materials and Methods: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. Results: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Discussion and Conclusion: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health. PMID:24347986

Quality indicators of preventable adverse drug events in patients with type 2 diabetes

DEFF Research Database (Denmark)

Thomsen, Linda Aagaard

associated with HbA1c monitoring and treatment was determined using logistic regression. The fourth step in the model was a health economic evaluation of the cost-effectiveness of shifting patients from inadequate to adequate medical treatment. The database used for the AMI indicator study formed...... the database for this study. Five post AMI treatment scenarios were analysed, and incremental cost-effectiveness ratios calculated. Results: The systematic literature review (Article 1) revealed that preventable adverse drug The systematic literature review (Article 1) revealed that preventable adverse drug......, that from a public health care systems' point of view, providing intensive cardioprotective treatment according to already accepted guidelines to type 2 diabetes patients is cost-effective. The HbA1c study demonstrated how diabetes-related hospital admissions are frequent, and how preventable adverse drug...

Incidence of cutaneous adverse drug reactions among medical inpatients of Sultanah Aminah Hospital Johor Bahru.

Science.gov (United States)

Latha, S; Choon, S E

2017-06-01

Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. A prospective study was conducted among medical inpatients from July to December 2014. A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.

Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

Science.gov (United States)

Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

2013-11-01

The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

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Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

2016-03-16

Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

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Ohyama, Katsuhiro; Inoue, Michiko

2016-01-01

Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

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Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2016-07-01

We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

Predicting Adverse Drug Effects from Literature- and Database-Mined Assertions.

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La, Mary K; Sedykh, Alexander; Fourches, Denis; Muratov, Eugene; Tropsha, Alexander

2018-06-06

Given that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug-target-effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug-target-effect paradigm, can be integrated to facilitate the inference of relationships between these entities. This study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. Cheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C-T-E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson's paradigm to form C-T-E triangles. Missing C-E edges were then inferred as C-E relationships. Unreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C-E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale. The presented workflow, based on free-access databases and an association-based inference scheme, provided novel C-E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C-E inferences, this workflow may provide an effective computational method for

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

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Ding, Wen Yi; Lee, Chew Kek; Choon, Siew Eng

2010-07-01

Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens-Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA-B*1502 and HLA-B*5801 which are genetic markers for carbamazepine-induced SJS/TEN and allopurinol-induced SJS/TEN/DRESS respectively. The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine

Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

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Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

2018-03-01

Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

Adverse reactions analysis and prevention of antiseptic drug in the obstetrics and gynecology nursing.

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Wang, Yongli; Bo, Qing; Zhang, Ying; He, Jing

2018-05-01

Antimicrobial agents are widely used in gynecologic inflammation and surgical period, so as to cure some infectious diseases, reduce the chance of surgical incision infection, but at the same time, there are many adverse reactions. The use of nursing interventions in obstetrics and gynecology can significantly reduce the adverse drug reactions in the treatment. The results showed that the incidence of adverse reactions in the observation group was 8.8%, while that in the control group was 15.6%. The incidence of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05). The results showed that the nursing intervention in obstetrics and gynecology could reduce the adverse drug reactions. In a word, the nursing intervention of obstetrics and gynecology can greatly reduce the adverse reaction of antibiotics and has certain application value. It is worth popularizing in clinical practice.

Erythema multiforme-like eruption from a slimming drug preparation cutaneous adverse drug reaction

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Linda Tognetti

2011-01-01

Full Text Available We report a case of a 34-year-old woman presenting with an erythema multiforme (EM-like eruption. Lesions developed after a 12-day treatment with a slimming drug preparation (food integrator with thermogenic activity and a herbal remedy (pilosella tincture. Serological investigations excluded viral or bacterial infections. Patch testing with galenic preparations of both drugs demonstrated sensitization to the slimming drug preparation. According to literature reports and immune-chemical properties, those components that are likely to have triggered the skin eruption are clorazepate dipotassium and theobromine. Their interaction with other two constituents such as pseudoephedrine hydrochloride and dehydrocholic acid may have caused the adverse reaction by means of a summation effect. There are no reports specifically about EM caused by a slimming drug preparation and no studies have identified thermogenic pills as cause of EM/EM-like eruption. Weight-loss compounds in slimming preparations should be kept in mind as a possible cause of drug-induced EM-like eruption.

The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety

International Nuclear Information System (INIS)

Boyd, Ian W.

2002-01-01

The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. Australia was a founding member of the WHO International Drug Monitoring Programme which commenced in 1968 and currently there are about 153000 reports in the ADRAC database. Reports from health professionals have uncovered a number of significant safety problems over the years. Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin

Proarrhythmic potential of dronedarone: emerging evidence from spontaneous adverse event reporting.

Science.gov (United States)

Kao, David P; Hiatt, William R; Krantz, Mori J

2012-08-01

To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting. Retrospective analysis. Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between July 1, 2009, and June 30, 2011. All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the Drugs@FDA database, and the Medical Dictionary for Regulatory Activities (MedDRA) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the United States (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone. Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation. © 2012 Pharmacotherapy Publications, Inc. All rights reserved.

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

Science.gov (United States)

Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2013-12-01

Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

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El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

2011-09-01

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

Predicting adverse drug reaction profiles by integrating protein interaction networks with drug structures.

Science.gov (United States)

Huang, Liang-Chin; Wu, Xiaogang; Chen, Jake Y

2013-01-01

The prediction of adverse drug reactions (ADRs) has become increasingly important, due to the rising concern on serious ADRs that can cause drugs to fail to reach or stay in the market. We proposed a framework for predicting ADR profiles by integrating protein-protein interaction (PPI) networks with drug structures. We compared ADR prediction performances over 18 ADR categories through four feature groups-only drug targets, drug targets with PPI networks, drug structures, and drug targets with PPI networks plus drug structures. The results showed that the integration of PPI networks and drug structures can significantly improve the ADR prediction performance. The median AUC values for the four groups were 0.59, 0.61, 0.65, and 0.70. We used the protein features in the best two models, "Cardiac disorders" (median-AUC: 0.82) and "Psychiatric disorders" (median-AUC: 0.76), to build ADR-specific PPI networks with literature supports. For validation, we examined 30 drugs withdrawn from the U.S. market to see if our approach can predict their ADR profiles and explain why they were withdrawn. Except for three drugs having ADRs in the categories we did not predict, 25 out of 27 withdrawn drugs (92.6%) having severe ADRs were successfully predicted by our approach. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose-specific adverse drug reaction identification in electronic patient records: temporal data mining in an inpatient psychiatric population.

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Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl; Brunak, Søren

2014-04-01

Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. We used a psychiatric hospital's EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p patient population, larger doses were prescribed to sedated patients than non-sedated patients; five antipsychotics [corrected] exhibited a significant difference (p<0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection.

[Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

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Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

2012-01-01

Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

Development and Initial Validation of a Patient-Reported Adverse Drug Event Questionnaire

NARCIS (Netherlands)

de Vries, Sieta T.; Mol, Peter G. M.; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M.; Denig, Petra

2013-01-01

Background Direct patient reporting of adverse drug events (ADEs) is relevant for the evaluation of drug safety. To collect such data in clinical trials and postmarketing studies, a valid questionnaire is needed that can measure all possible ADEs experienced by patients. Objective Our aim was to

Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

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LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C

2014-01-01

Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number

Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

Directory of Open Access Journals (Sweden)

Montiago X LaBute

Full Text Available Late-stage or post-market identification of adverse drug reactions (ADRs is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409 of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively. Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

Science.gov (United States)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

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Tinashe Mudzviti

2012-01-01

Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

[Adverse drug reaction reporting in emergency medicine].

Science.gov (United States)

Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves

2004-01-01

A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

Science.gov (United States)

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

Enhancing communication about paediatric medicines: lessons from a qualitative study of parents' experiences of their child's suspected adverse drug reaction.

Science.gov (United States)

Arnott, Janine; Hesselgreaves, Hannah; Nunn, Anthony J; Peak, Matthew; Pirmohamed, Munir; Smyth, Rosalind L; Turner, Mark A; Young, Bridget

2012-01-01

There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children

Enhancing communication about paediatric medicines: lessons from a qualitative study of parents' experiences of their child's suspected adverse drug reaction.

Directory of Open Access Journals (Sweden)

Janine Arnott

Full Text Available There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines.To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction.Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions. Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method.Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction.Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for

Enhancing Communication about Paediatric Medicines: Lessons from a Qualitative Study of Parents' Experiences of Their Child's Suspected Adverse Drug Reaction

Science.gov (United States)

Arnott, Janine; Hesselgreaves, Hannah; Nunn, Anthony J.; Peak, Matthew; Pirmohamed, Munir; Smyth, Rosalind L.

2012-01-01

Background There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and

Consumer adverse drug reaction reporting - A new step in pharmacovigilance?

NARCIS (Netherlands)

van Grootheest, K; de Graaf, L; de Jong-van den Berg, LTW

2003-01-01

The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports. We present an overview of experiences with consumer reporting in various countries of the

Adverse drug reaction reports for cardiometabolic drugs from sub-Saharan Africa: a study in VigiBase.

Science.gov (United States)

Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G M; Dheda, Mukesh; Haaijer-Ruskamp, Flora M; Taxis, Katja; Mol, Peter G M

2015-06-01

Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW). Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI > 0.5. In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44 years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW. 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.' © 2015 John Wiley & Sons Ltd.

Pharmacogenetics of drug-induced arrhythmias : a feasibility study using spontaneous adverse drug reactions reporting data

NARCIS (Netherlands)

De Bruin, Marie L; van Puijenbroek, Eugene P; Bracke, Madelon; Hoes, Arno W; Leufkens, Hubert G M

PURPOSE: The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database of a

[Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

Science.gov (United States)

Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

2009-01-01

With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

Healthcare professionals and pharmacovigilance of pediatric adverse drug reactions: a 5-year analysis of Adverse Events Reporting System database of the Food and Drug Administration.

Science.gov (United States)

Bigi, Caterina; Tuccori, Marco; Bocci, Guido

2017-02-17

To analyze the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (FDA), investigating the characteristics of pediatric adverse drug reactions (ADRs) and describing the effective participation of healthcare professionals in the reporting activity. Reports of ADRs were obtained from the FDA website. Only ADRs in pediatric subjects (divided by age, by country and by professional category) were included into the analysis. The drugs suspected as primary cause of the ADRs in pediatric subjects and their principal anatomic group according to the Anatomical Therapeutic Chemical classification system were considered. To classify the ADRs, the Medical Dictionary for Regularity Activities terminology was adopted. Between 2008 and 2012, FDA collected 113,077 ADRs in pediatric patients. Of the total pediatric ADR reports, those performed by medical doctors were 32%, followed by consumers (26%) and healthcare professionals (25%). Most of the ADR reports were related to the adolescent group (39%). Healthcare professionals resulted the category with the highest rate of ADR reports in neonates and infants. Drugs acting on nervous system and antineoplastic/immunomodulating agents were the most involved the pediatric ADR reports. Pyrexia, convulsion, vomiting and accidental overdose were the reactions more reported both from healthcare professionals and medical doctors. The present study describes the pediatric ADR reports of the FDA database through healthcare professional's perspective, describing the various aspects of pediatric pharmacovigilance.

A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER Database and Association Analysis.

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Masakazu Fujiwara

Full Text Available Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender has not been proposed.We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA. We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male.Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions

Vertigo/dizziness as a Drugs' adverse reaction.

Science.gov (United States)

Chimirri, Serafina; Aiello, Rossana; Mazzitello, Carmela; Mumoli, Laura; Palleria, Caterina; Altomonte, Mariolina; Citraro, Rita; De Sarro, Giovambattista

2013-12-01

Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs' classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly in fragile patients.

[Nursing role in reporting adverse drug reactions].

Science.gov (United States)

Zurita-Garaicoechea, Ana; Reis-Carvalho, Joana; Ripa-Aisa, Irantzu; Jiménez-Mendoza, Ana; Díaz-Balén, Almudena; Oroviogoicoechea, Cristina

2015-01-01

The spontaneous report system, in which suspected adverse drug reaction (ADR) are reported by healthcare workers, is currently one of the primary methods to prevent and discover new and serious ADR to marketed medicinal products. The collaboration of nursing professionals with this task makes it possible to improve patient safety and to reduce ADR costs. Although a total of 781 cases of ADR cases were reported in Navarra in 2011, only 7.33% were reported by nurses. The objectives werw to determine the factors that influence nurses in reporting of ADR, and second, to devise strategies which help to increase reporting. A bibliographic search for articles that included the words: reacciones adversas medicamentosas (adverse drug reactions), notificación (reporting) and enfermería (nursing) was conducted using the PubMed and Cinhal databases. A total of 107 articles were retrieved, of which 27 were selected according to inclusion and exclusion criteria. The conclusion learned by reading and analyzing the selected articles was that the factors that affect the notification depend on the attitude of the notifier, as well as personal and professional factors. The main strategies to encourage notification are education and training, motivation, and the availability of facilitating tools. The main factors that have an influence on under-notification are the lack of knowledge and motivation among professionals. To solve the problem of under-notification, the main actions and strategies to undertake are education, motivation and persistence. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

DEFF Research Database (Denmark)

Eriksson, Robert; Jensen, Peter Bjødstrup; Pletscher-Frankild, Sune

2013-01-01

Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible...... the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location.Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient...

The concept of adverse drug reaction reporting: awareness among pharmacy students in a Nigerian university

Directory of Open Access Journals (Sweden)

Johnson Segun Showande

2013-01-01

Full Text Available Adverse drug reaction (ADR is poorly reported globally but more in developing countries with poor participation by health professionals. Currently, there is no known literature on the Nigerian pharmacy students’ knowledge on ADR reporting. Hence the purpose of this study was to find out the level of knowledge of pharmacy students on the concept of pharmacovigilance and adverse drug reaction reporting and also to evaluate their opinions on the National Pharmacovigilance Centre guidelines on adverse drug reaction reporting. A pretested 34-item semi-structured questionnaire was administered among 69 pharmacy undergraduate students in their penultimate and final years that consented to take part in the study, in one of the universities in Nigeria. The study was carried out strictly adhering to the principles outlined in the Helsinki declaration of 1964, which was revised in 1975. The questionnaire used had four sections which included a section on biographical data, a section which evaluated the students knowledge on the concept of pharmacovigilance and adverse drug reaction reporting, a section on students personal experiences of adverse drug reactions and modes of reporting them and the final section of the questionnaire evaluated the students’ opinions on the National Pharmacovigilance Centre guidelines for reporting adverse drug reactions. Descriptive statistics, Mann-Whitney U and Kruskal Wallis statistical tests were used to analyze the data obtained. None of the participants knew the sequence of reporting ADR. More than half, 40(58.0% had heard about pharmacovigilance at symposiums, 7(10.1% during clinical clerkship program and 18(26.1% from media jingles. Twenty nine (42.0% agreed that pharmacovigilance was in their curriculum, however only 16(23.2% could define the term correctly. None of the participants had seen or used an ADR form prior to the study, but the students could easily identify and describe the type of ADR they had

Children and ADRs (Adverse Drug Reactions

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Napoleone Ettore

2010-01-01

Full Text Available Abstract Many medicines are prescribed to the paediatric population on an unlicensed or 'off-label' basis because they have not been adequately tested and/or formulated and authorized for use in appropriate paediatric age groups. Regulatory authorities also need to remind health professionals about the importance of their contribution towards the process of paediatric pharmacovigilance thanks to their reporting of adverse drug reactions. The lack of reliable data in the paediatric population is associated with specific problems including: limited availability of safety data due to the lack of clinical trials in the paediatric population; under- or over-dosing in some age groups due to the lack of pharmacokinetics data or dose-finding studies; maturation, growth and development of the paediatric population susceptible to drug-induced growth and development disorders as well as to delayed ADRs not findable in adults. Pre-marketing trials are able to provide information about the benefits of drugs but do not manage to establish a safety profile. Spontaneous reporting of suspected ADRs become an important means to promote reasonable warning signs. Therefore some ADRs may be known in their qualitative aspect and quantitative aspect only after successful marketing and use in the population during a "normal" use. When the drug is used in clinical practice in large unselected populations, epidemiological post-marketing studies are useful as they find their major confirmation in recalling all the events that occur during monitoring, with estimates of incidence of ADRs that can not be obtained by spontaneous reports. In these studies a significant role can be played by the Family Pediatricians with the participation to active pharmacovigilance projects.

Study of adverse drug reactions in out-patient departments of a teaching hospital

Directory of Open Access Journals (Sweden)

Zinnat Ara Begum

2012-06-01

Full Text Available The study conducted in the Medicine and Skin outpatient departments of Dhaka Medical College, Dhaka revealed 19 cases (7 males, 12 females of adverse drug reactions (ADR out of 160 patients. 31.58% ADRs were of mild type, 42.1% were of moderate and 26.32% were of severe in nature. Gastrointestinal complications were the most frequent adverse effect (56%. Antimicrobial drugs were the most common cause of ADR (42.86% followed by NSAIDs (33.33%. This study is a preliminary study for getting information on the pattern of ADRs in Bangladesh needing further studies.

Bias in spontaneous reporting of adverse drug reactions in Japan.

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Shinichi Matsuda

Full Text Available Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs in Japan are not well known, and Japan's unique system of surveillance, called early post-marketing phase vigilance (EPPV, may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.A manufacturer's database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.

Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text.

Science.gov (United States)

Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

2013-01-01

Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives.

Information about adverse drug reactions reported in children

DEFF Research Database (Denmark)

Aagaard, Lise; Christensen, Arne; Hansen, Ebba Holme

2010-01-01

AIM: To review the literature on adverse drug reactions (ADRs) in children with respect to occurrence, seriousness, type, therapeutic group, age and gender of the child and category of reporter. METHODS: Medline and Embase databases were searched from origin and updated until February 2010. We...... included empirically based articles on ADRs in populations aged 0 to 17 years. Studies monitoring ADRs in patients with particular conditions or drug exposure were excluded. We extracted information about types and seriousness of ADRs, therapeutic groups, age and gender of the child and category...... of reporter. ADR occurrence was calculated as incidence rate and prevalence. RESULTS: We included 33 studies monitoring ADRs in general paediatric populations. The highest numbers of ADRs were reported in national ADR databases where data were collected over a longer period than in studies monitoring...

Adverse drug reactions of angiotensin converting enzyme inhibitors : towards precision medicine

NARCIS (Netherlands)

Mahmoud Pour, S.H.

2016-01-01

Worldwide, millions of patients with cardiovascular diseases are treated with angiotensin converting enzyme inhibitors (ACEIs) according to the international treatment guidelines. Although this class of medications is generally well tolerated, adverse drug reactions (ADRs) may prevent their use in

[Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

Science.gov (United States)

Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

2011-01-01

Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

Science.gov (United States)

Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

2011-01-01

Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

[Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs].

Science.gov (United States)

Zhang, Xiao-Meng; Li, Fan; Zhang, Bing; Chen, Xiao-Fen; Piao, Jing-Zhu

2018-01-01

The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication

[Drug surveillance and adverse reactions to drugs. The literature and importance of historical data].

Science.gov (United States)

Mariani, L; Minora, T; Ventresca, G P

1996-12-01

The authors highlight the essential role of pharmacovigilance and the need for a simple, efficient and low-cost system of adverse reaction (AR) reporting which could cover the whole population and all marketed drugs, and suggest that the only one presently viable is based on spontaneous reporting. To support their proposal the authors provide a definition of AR and of the different monitoring system, and list as many drugs as possible to find in the literature that have been associated with a specific AR, together with the active molecule, the therapeutic indication, the features of the AR and the regulatory actions (withdrawal from the market, restriction of use). Moreover, by describing the "history" behind some of these drugs the authors highlight the contribution that pharmacovigilance and spontaneous reporting have had to the development of regulations for approval and marketing of new drugs. It is also highlighted how some of these unexpected events (thalidomide, DES) have had a significant and important contribution to pharmacological and toxicological knowledge.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

International Nuclear Information System (INIS)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-01-01

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

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Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

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Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

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Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort.

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Stein, Lauren J; Gunier, Robert B; Harley, Kim; Kogut, Katherine; Bradman, Asa; Eskenazi, Brenda

2016-09-01

Previous studies have observed an adverse association between prenatal exposure to organophosphate pesticide (OPs) and child cognition, but few studies consider the potential role of social stressors in modifying this relationship. We seek to explore the potential role of early social adversities in modifying the relationship between OPs and child IQ in an agricultural Mexican American population. Participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a prospective longitudinal pre-birth cohort study, include 329 singleton infants and their mothers followed from pregnancy through age 7. Dialkyl phosphate metabolite concentrations (DAPs), a biomarker of organophosphate pesticide exposure, were measured in maternal urine collected twice during pregnancy and averaged. Child cognitive ability was assessed at 7 years using the Wechsler Intelligence Scale for Children - Fourth Edition. Demographic characteristics and adversity information were collected during interviews and home visits at numerous time points from pregnancy until age 7. Among low-income Latina mothers and their children in the Salinas Valley, total adversity and specific domains of adversity including poor learning environment and adverse parent-child relationships were negatively associated with child cognition. Adverse associations between DAP concentrations and IQ were stronger in children experiencing greater adversity; these associations varied by child sex. For example, the association between prenatal OP exposure and Full-Scale IQ is potentiated among boys who experienced high adversity in the learning environment (β=-13.3; p-value child IQ differently among male and female children. These findings emphasize the need to consider plausible interactive pathways between social adversities and environmental exposures. Copyright © 2016 Elsevier B.V. All rights reserved.

Consumer reporting of adverse drug reactions

DEFF Research Database (Denmark)

Aagaard, Lise; Nielsen, Lars Hougaard; Hansen, Ebba Holme

2009-01-01

BACKGROUND: Reporting adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. Since 2003 in Denmark, consumers have been able to report ADRs directly to the authorities. The objective of this study was to compare ADRs reported by consumers with ADRs...... medicines on level 1 of the anatomical therapeutic chemical (ATC) classification system. ADR reports from consumers were compared with reports from other sources (physicians, pharmacists, lawyers, pharmaceutical companies and other healthcare professionals). Chi-square and odds ratios (ORs) were calculated...... to investigate the dependence between type of reporter and reported ADRs (classified by ATC or SOC). FINDINGS: We analysed 6319 ADR reports corresponding to 15 531 ADRs. Consumers reported 11% of the ADRs. Consumers' share of 'serious' ADRs was comparable to that of physicians (approximately 45%) but lower than...

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

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Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

2017-05-01

To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. © Copyright: Yonsei University College of Medicine 2017

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

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Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

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Charu Sharma

2015-01-01

Full Text Available The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2 which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.

Adverse drug reactions monitoring of psychotropic drugs: a tertiary care centre study

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Hemendra Singh

2017-06-01

Full Text Available Background: Many new psychotropic drugs/ agents have been developed and found to be effective in the treatment of psychiatric disorders. However, these drugs also exhibit adverse drug reactions (ADRs which may affect compliance in psychiatric patients. Hence the present study was aimed at monitoring and assessing ADRs caused by psychotropic drugs. Methods: A hospital based prospective observational study was carried out in the psychiatry outpatient department of a tertiary care teaching hospital for the duration of six months. Two hundred and two patients were included in the study and ADRs were documented using a predesigned data collection form. The causality assessment was carried out as per the criteria of both the World Health Organization- Uppsala Monitoring Centre (WHO-UMC and Naranjo scale. Severity and predictability assessment of ADRs were also performed. Results: A total of 106 ADRs were observed during the study period with majority of them occurring in 25-35 years of age group (40.56%. Weight gain (18.86% followed by sedation (16.03% and insomnia (11.32% were found to be the commonest ADRs. Risperidone (19.8% and escitalopram (12.3% were the drugs responsible for majority of the ADRs. Causality assessment showed that most of ADRs were possible and probable. 94.33% of ADRs were found to be mild and 89% of them were predictable. Conclusion: A wide range of ADRs affecting central nervous and metabolic systems were reported with psychotropic drugs. The study findings necessitate the need for an active pharmacovigilance programme for the safe and effective use of psychotropics.

Identification of possible adverse drug reactions in clinical notes

DEFF Research Database (Denmark)

Warrer, Pernille; Jensen, Peter Bjødstrup; Aagaard, Lise

2015-01-01

and labeling status. Findings: A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin......Objective: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood....... Methods: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness...

Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review 1

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Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

2016-01-01

ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380

Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review.

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Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2018-01-01

Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. Areas covered: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler's Side Effects of Drugs; Stephens' Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions. Expert opinion: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

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Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

2013-01-01

Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Materials and methods Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. Discussion The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. Conclusions The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives. PMID:23703825

Despite 2007 law requiring FDA hotline to be included in print drug ads, reporting of adverse events by consumers still low.

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Du, Dongyi; Goldsmith, John; Aikin, Kathryn J; Encinosa, William E; Nardinelli, Clark

2012-05-01

In 2007 the federal government began requiring drug makers to include in their print direct-to-consumer advertisements information for consumers on how to contact the Food and Drug Administration directly, either by phone or through the agency's website, to report any adverse events that they experienced after taking a prescription drug. Adverse events can range from minor skin problems like itching to serious injuries or illness that result in hospitalization, permanent disability, or even death. Even so, current rates of adverse event reporting are low. We studied adverse event reports about 123 drugs that came from patients before and after the enactment of the print advertising requirement and estimated that requirement's impact with model simulations. We found that if monthly spending on print direct-to-consumer advertising increased from zero to $7.7 million per drug, the presence of the Food and Drug Administration contact information tripled the increase in patient-reported adverse events, compared to what would have happened in the absence of the law. However, the absolute monthly increase was fewer than 0.24 reports per drug, suggesting that the public health impact of the increase was small and that the adverse event reporting rate would still be low. The study results suggest that additional measures, such as more publicity about the Adverse Event Reporting System or more consumer education, should be considered to promote patient reporting of adverse events.

A PROSPECTIVE, OBSERVATIONAL STUDY OF ADVERSE REACTIONS TO DRUG REGIME FOR MULTI-DRUG RESISTANT PULMONARY TUBERCULOSIS IN CENTRAL INDIA.

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Dr. Rohan C. Hire

2014-09-01

Full Text Available Abstract Objective: 1 To assess the adverse drug reactions of second line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR TB in central India on the basis of causality, severity and avoidability scales. 2 To study the relationship of type of MDR TB (primary or secondary and presence of diabetes mellitus (DM with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug resistant tuberculosis patients enrolled for DOTS‑Plus regimen at TB and Chest Disease Department from January to December 2012. They were followed for 9 months thereafter and encountered adverse drug reactions (ADRs were noted along with the time of sputum conversion. The data were analysed by Chi-square or Fisher’s exact test and unpaired student’s‘t’ test. Results: Total 64 ADRs were reported in 55 patients out of total 110 patients (n = 110. As per the Naranjo causality assessment of ADRs, 7 patients had “definite” causal relation, 45 had “probable” causal relation and 3 had “possible” causal relation with drugs of DOTS Plus regime. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being “Definitely avoidable”, 26 “Possibly avoidable”, 23 “Not avoidable” and 3 “unevaluable”. . Mean sputum smear conversion time is significantly higher in patients with secondary type than that of primary type of MDR TB (p = 0.0001 and in patients with DM than those without DM (p <0.0001. Conclusion: ADRs were common in patients of MDR TB on DOTs-Plus drug regime. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regime compared to DOTS regime in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and

Adverse event management in mass drug administration for neglected tropical diseases.

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Caplan, Arthur; Zink, Amanda

2014-03-01

The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

Adverse Effects of Nutraceuticals and Dietary Supplements.

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Ronis, Martin J J; Pedersen, Kim B; Watt, James

2018-01-06

Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

Adverse drug reaction and toxicity caused by commonly used antimicrobials in canine practice

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K. Arunvikram

2014-05-01

Full Text Available An adverse drug reaction (ADR is a serious concern for practicing veterinarians and other health professionals, and refers to an unintended, undesired and unexpected response to a drug that negatively affects the patient's health. It may be iatrogenic or genetically induced, and may result in death of the affected animal. The ADRs are often complicated and unexpected due to myriad clinical symptoms and multiple mechanisms of drug-host interaction. Toxicity due to commonly used drugs is not uncommon when they are used injudiciously or for a prolonged period. Licosamides, exclusively prescribed against anaerobic pyoderma, often ends with diarrhoea and vomiting in canines. Treatment with Penicillin and β-lactam antibiotics induces onset of pemphigious vulgare, drug allergy or hypersensitivity. Chloroamphenicol and aminoglycosides causes Gray's baby syndrome and ototoxicity in puppies, respectively. Aminoglycosides are very often associated with nephrotoxicity, ototoxicity and neuromuscular blockage. Injudicious use of fluroquinones induces the onset of arthropathy in pups at the weight bearing joints. The most effective therapeutic measure in managing ADR is to treat the causative mediators, followed by supportive and symptomatic treatment. So, in this prospective review, we attempt to bring forth the commonly occurring adverse drug reactions, their classification, underlying mechanism, epidemiology, treatment and management as gleaned from the literature available till date and the different clinical cases observed by the authors.

Exposure to Prescription Drugs Labeled for Risk of Adverse Effects of Suicidal Behavior or Ideation among 100 Air Force Personnel Who Died by Suicide, 2006-2009

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Lavigne, Jill E.; McCarthy, Michael; Chapman, Richard; Petrilla, Allison; Knox, Kerry L.

2012-01-01

Prescription drugs for many indications are labeled with warnings for potential risk of suicidal ideation or behavior. Exposures to prescription drugs labeled for adverse effects of suicidal behavior or ideation among 100 Air Force personnel who died by suicide between 2006 and 2009 are described. Air Force registry data were linked to…

Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
.

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Maeda, Akimitsu; Ando, Hitoshi; Ura, Takashi; Komori, Azusa; Hasegawa, Ayako; Taniguchi, Hiroya; Kadowaki, Shigenori; Muro, Kei; Tajika, Masahiro; Kobara, Makiko; Matsuzaki, Masahide; Hashimoto, Naoya; Maeda, Mieko; Kojima, Yasushi; Aoki, Masahiro; Kondo, Eisaku; Mizutani, Akiyoshi; Fujimura, Akio

2017-05-01

Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings.
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Preventing drug-related adverse events following hospital discharge: the role of the pharmacist

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Nicholls J

2017-02-01

Full Text Available Justine Nicholls,1 Craig MacKenzie,1 Rhiannon Braund2 1Dunedin Hospital Pharmacy, 2School of Pharmacy, University of Otago, Dunedin, New Zealand Abstract: Transition of care (ToC points, and in particular hospital admission and discharge, can be associated with an increased risk of adverse drug events (ADEs and other drug-related problems (DRPs. The growing recognition of the pharmacist as an expert in medication management, patient education and communication makes them well placed to intervene. There is evidence to indicate that the inclusion of pharmacists in the health care team at ToC points reduces ADEs and DRPs and improves patient outcomes. The objectives of this paper are to outline the following using current literature: 1 the increased risk of medication-related problems at ToC points; 2 to highlight some strategies that have been successful in reducing these problems; and 3 to illustrate how the role of the pharmacist across all facets of care can contribute to the reduction of ADEs, particularly for patients at ToC points. Keywords: pharmacist, adverse drug events, drug-related problems, transitions of care, hospital discharge

Adverse drug reactions in older patients during hospitalisation: are they predictable?

LENUS (Irish Health Repository)

O'Connor, Marie N

2012-11-01

adverse drug reactions (ADRs) are a major cause of morbidity and healthcare utilisation in older people. The GerontoNet ADR risk score aims to identify older people at risk of ADRs during hospitalisation. We aimed to assess the clinical applicability of this score and identify other variables that predict ADRs in hospitalised older people.

Adverse drug reactions due to antipsychotics and sedative-hypnotics in the elderly

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Natasha S Kate

2015-01-01

Full Text Available Psychotropic drugs are commonly used to manage mental and behavioral problems in geriatric patients. This is, however, accompanied by the risk of developing adverse drug reactions (ADRs, impacting the safety with which the drug can be used. In this article, we provide an overview of the factors associated with the ADRs due to psychotropic medication in the elderly, and the ADRs associated with the use of antipsychotics and sedative-hypnotics in the geriatric population. For this, literature searches were conducted through MEDLINE, PubMed, and Google Scholar using keyword terms: Geriatric, elderly, safety, adverse events, ADRs, antipsychotic, names of individual antipsychotics, benzodiazepine, sedative, hypnotic, zolpidem, zaleplon, zopiclone. Research data indicate that antipsychotics are associated with an increased risk of metabolic syndrome, thromboembolism, cerebrovascular and cardiac events, pneumonia, fractures, and increased mortality. Among antipsychotics, aripiprazole seems to have fewer ADRs while other antipsychotics (typical and atypicals have reports of troublesome side effect profiles. Sedative-hypnotics are associated with a risk of falls, fractures, cognitive impairment, and may increase the risk of developing dementia with long-term use. The risk of these complications is present with both benzodiazepines and medications such as zolpidem and zopiclone.

81-85 Community Awareness of Adverse Effects of No

African Journals Online (AJOL)

Secretary

- inflammatory drugs. They were also asked if ... seek treatment for the pain. Only 8% of the study participants knew some adverse effects caused by ... (35%) of them did not know of any adverse effects due to NSAIDs but 53% cited potential ...

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database.

Science.gov (United States)

Naganuma, Misa; Motooka, Yumi; Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Fukuda, Akiho; Nakao, Satoshi; Shimada, Kazuyo; Hirade, Koseki; Mori, Takayuki; Yoshimura, Tomoaki; Kato, Takeshi; Nakamura, Mitsuhiro

2018-01-01

Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5-3.0), 0.6 (0.5-0.7), 0.8 (0.7-1.0), and 1.3 (0.8-2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower-upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0-8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient's background prior to treatment.

Information needs for making clinical recommendations about potential drug-drug interactions: a synthesis of literature review and interviews.

Science.gov (United States)

Romagnoli, Katrina M; Nelson, Scott D; Hines, Lisa; Empey, Philip; Boyce, Richard D; Hochheiser, Harry

2017-02-22

Drug information compendia and drug-drug interaction information databases are critical resources for clinicians and pharmacists working to avoid adverse events due to exposure to potential drug-drug interactions (PDDIs). Our goal is to develop information models, annotated data, and search tools that will facilitate the interpretation of PDDI information. To better understand the information needs and work practices of specialists who search and synthesize PDDI evidence for drug information resources, we conducted an inquiry that combined a thematic analysis of published literature with unstructured interviews. Starting from an initial set of relevant articles, we developed search terms and conducted a literature search. Two reviewers conducted a thematic analysis of included articles. Unstructured interviews with drug information experts were conducted and similarly coded. Information needs, work processes, and indicators of potential strengths and weaknesses of information systems were identified. Review of 92 papers and 10 interviews identified 56 categories of information needs related to the interpretation of PDDI information including drug and interaction information; study design; evidence including clinical details, quality and content of reports, and consequences; and potential recommendations. We also identified strengths/weaknesses of PDDI information systems. We identified the kinds of information that might be most effective for summarizing PDDIs. The drug information experts we interviewed had differing goals, suggesting a need for detailed information models and flexible presentations. Several information needs not discussed in previous work were identified, including temporal overlaps in drug administration, biological plausibility of interactions, and assessment of the quality and content of reports. Richly structured depictions of PDDI information may help drug information experts more effectively interpret data and develop recommendations

Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?

Science.gov (United States)

Kanner, Andres M; Barry, John J; Gilliam, Frank; Hermann, Bruce; Meador, Kimford J

2012-06-01

To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)-related adverse events (AEs) in persons with epilepsy (PWE). The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory-II (BDI-II) scores >12 or the Centers of Epidemiologic Studies-Depression (CES-D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED-related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. Depressive and anxiety disorders worsen AED-related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

Science.gov (United States)

Federer, Callie; Yoo, Minjae; Tan, Aik Choon

2016-12-01

Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

Factors Affecting Adverse Drug Reaction Reporting of Healthcare Professionals and Their Knowledge, Attitude, and Practice towards ADR Reporting in Nekemte Town, West Ethiopia

Directory of Open Access Journals (Sweden)

Lense Temesgen Gurmesa

2016-01-01

Full Text Available Background. Adverse drug reactions are global problems of major concern. Adverse drug reaction reporting helps the drug monitoring system to detect the unwanted effects of those drugs which are already in the market. Aims. To assess the knowledge, attitude, and practice of health care professionals working in Nekemte town towards adverse drug reaction reporting. Methods and Materials. A cross-sectional study design was conducted on a total of 133 health care professionals by interview to assess their knowledge, attitude, and practice using structured questionnaire. Results. Of the total respondents, only 64 (48.2%, 56 (42.1%, and 13 (9.8% health care professionals have correctly answered the knowledge, attitude, and practice assessment questions, respectively. Lack of awareness and knowledge on what, when, and to whom to report adverse drug reactions and lack of commitments of health care professionals were identified as the major discouraging factors against adverse drug reaction reporting. Conclusion. This study has revealed that the knowledge, attitude, and practice of the health care professionals working in Nekemte town towards spontaneous adverse drug reaction reporting were low that we would like to recommend the concerned bodies to strive on the improvement of the knowledge, attitude, and practice status of health care professionals.

A study on adverse drug reactions in a tertiary care hospital of ...

African Journals Online (AJOL)

Acne (46) was commonly reported reaction. Topical steroids, betamethasone sodium phosphate and clobetasol were reported to induce maximum number of reactions (59). Skin (227, 66.9%) was commonly affected organ system. Most of the adverse drug reactions were possible (240, 94.1%) and mild (222, 87%) in nature.

Meta-analysis of recent studies on patients admitted to hospital due to adverse drug effects

NARCIS (Netherlands)

Atiqi, R.; Cleophas, T. J.; van Bommel, E.; Zwinderman, A. H.

2009-01-01

The use of drugs has expanded during the previous decade. However, earlier studies oil patients admitted for adverse drugs effects (ADEs) have been heterogeneous. The objectives of this Study were to assess the number of recent admissions to hospital Clue to ADEs and to assess the degree of

Ontology-based knowledge management for personalized adverse drug events detection.

Science.gov (United States)

Cao, Feng; Sun, Xingzhi; Wang, Xiaoyuan; Li, Bo; Li, Jing; Pan, Yue

2011-01-01

Since Adverse Drug Event (ADE) has become a leading cause of death around the world, there arises high demand for helping clinicians or patients to identify possible hazards from drug effects. Motivated by this, we present a personalized ADE detection system, with the focus on applying ontology-based knowledge management techniques to enhance ADE detection services. The development of electronic health records makes it possible to automate the personalized ADE detection, i.e., to take patient clinical conditions into account during ADE detection. Specifically, we define the ADE ontology to uniformly manage the ADE knowledge from multiple sources. We take advantage of the rich semantics from the terminology SNOMED-CT and apply it to ADE detection via the semantic query and reasoning.

Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database.

Science.gov (United States)

Chiappini, Stefania; Schifano, Fabrizio

2018-02-01

A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine. All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed. From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine. Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.

Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

NARCIS (Netherlands)

Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

2012-01-01

textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

OpenAIRE

Castleden, C M; Pickles, H

1988-01-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age grou...

Adverse-drug-event data provided by pharmaceutical companies.

Science.gov (United States)

Cudny, Magdalena E; Graham, Angie S

2008-06-01

Pharmaceutical company drug information center (PCDIC) responses to queries about adverse drug events (ADEs) were studied to determine whether PCDICs search sources other than the prescribing information on the package insert (PI) and whether the PCDICs' approach differs according to whether an ADE is listed in the PI (labeled) or not (unlabeled). Companies were selected from a list of PCDICs in the Physicians' Desk Reference. One oral or injectable prescription drug from each company was selected. For each drug, a labeled ADE and an unlabeled ADE about which to query the PCDICs were randomly selected from the index of an annual publication on ADEs. The investigators telephoned the PCDICs with an open-ended inquiry about the incidence, timing, and management of the ADE as reported in the literature and the company's internal data; they clarified that the request did not concern a specific patient. Whether or not information was provided, the source searched was recorded (PI, literature, internal database), and the percentages of PCDICs that used each source for labeled and for unlabeled ADEs were analyzed. Results were obtained from 100 companies to questions about 100 drugs (200 ADEs). For ADEs overall, 80% used the PI, 50% the medical literature, and 38% internal data. For labeled versus unlabeled ADEs, respectively, the PI was used by 84% and 76%; literature, both 50%; and internal data, 35% and 41%. The PCDIC specialists referencing the PI did not always provide accurate or up-to-date information. Some specialists, when asked to query internal databases, said that was not an option. For both labeled and unlabeled ADEs, the PI was the primary source used by PCDICs to answer safety questions about their products, and internal data were the least-used source. Most resources used by PCDICs are readily available to practicing pharmacists.

Filtering big data from social media--Building an early warning system for adverse drug reactions.

Science.gov (United States)

Yang, Ming; Kiang, Melody; Shang, Wei

2015-04-01

Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides

SSEL-ADE: A semi-supervised ensemble learning framework for extracting adverse drug events from social media.

Science.gov (United States)

Liu, Jing; Zhao, Songzheng; Wang, Gang

2018-01-01

With the development of Web 2.0 technology, social media websites have become lucrative but under-explored data sources for extracting adverse drug events (ADEs), which is a serious health problem. Besides ADE, other semantic relation types (e.g., drug indication and beneficial effect) could hold between the drug and adverse event mentions, making ADE relation extraction - distinguishing ADE relationship from other relation types - necessary. However, conducting ADE relation extraction in social media environment is not a trivial task because of the expertise-dependent, time-consuming and costly annotation process, and the feature space's high-dimensionality attributed to intrinsic characteristics of social media data. This study aims to develop a framework for ADE relation extraction using patient-generated content in social media with better performance than that delivered by previous efforts. To achieve the objective, a general semi-supervised ensemble learning framework, SSEL-ADE, was developed. The framework exploited various lexical, semantic, and syntactic features, and integrated ensemble learning and semi-supervised learning. A series of experiments were conducted to verify the effectiveness of the proposed framework. Empirical results demonstrate the effectiveness of each component of SSEL-ADE and reveal that our proposed framework outperforms most of existing ADE relation extraction methods The SSEL-ADE can facilitate enhanced ADE relation extraction performance, thereby providing more reliable support for pharmacovigilance. Moreover, the proposed semi-supervised ensemble methods have the potential of being applied to effectively deal with other social media-based problems. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidemiology of adverse drug reactions in Europe

DEFF Research Database (Denmark)

Bouvy, Jacoline C; De Bruin, Marie L; Koopmanschap, Marc A

2015-01-01

Adverse drug reactions (ADRs) cause considerable mortality and morbidity but no recent reviews are currently available for the European region. Therefore, we performed a review of all epidemiological studies quantifying ADRs in a European setting that were published between 1 January 2000 and 3...... September 2014. Included studies assessed the number of patients who were admitted to hospital due to an ADR, studies that assessed the number of patients who developed an ADR during hospitalization, and studies that measured ADRs in the outpatient setting. In total, 47 articles were included in the final...... review. The median percentage of hospital admissions due to an ADR was 3.5 %, based on 22 studies, and the median percentage of patients who experienced an ADR during hospitalization was 10.1 %, based on 13 studies. Only five studies were found that assessed ADRs occurring in the outpatient setting...

Inappropriate prescribing and adverse drug events in older people

Directory of Open Access Journals (Sweden)

Gallagher Paul F

2009-01-01

Full Text Available Abstract Inappropriate prescribing (IP in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs, morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training.

Inappropriate prescribing and adverse drug events in older people.

LENUS (Irish Health Repository)

Hamilton, Hilary J

2009-01-01

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training.

Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

Science.gov (United States)

Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

2017-01-01

The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

Directory of Open Access Journals (Sweden)

Herxheimer Andrew

2002-03-01

Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

Global patterns of adverse drug reactions over a decade

DEFF Research Database (Denmark)

Aagaard, Lise; Strandell, Johanna; Melskens, Lars

2012-01-01

Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported......, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1¿359¿067 ADR reports including 3¿013¿074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3...

Pharmacy Student Facilitation of Reporting of Adverse Drug Reactions in a Hospital.

Science.gov (United States)

Wentzell, Jason; Nguyen, Tiffany; Bui, Stephanie; MacDonald, Erika

2017-01-01

Health Canada relies on health professionals to voluntarily report adverse reactions to the Canada Vigilance Program. Current rates of reporting adverse drug reactions (ADRs) are inadequate to detect important safety issues. To assess the impact of pharmacy student facilitation of ADR reporting by pharmacists at a tertiary care teaching hospital in Canada. The intervention of interest, implemented at one campus of the hospital, was facilitation of ADR reporting by pharmacy students. The students received training on how to submit ADR reports and presented information sessions on the topic to hospital pharmacists; the pharmacists were then encouraged to report ADRs to a designated student for formal reporting. Frequency of reporting by pharmacists at the intervention campus was compared with reporting at a control campus of the same hospital. Data were collected prospectively over a 6-month pilot period, starting in April 2015. During the pilot period, 27 ADR reports were submitted at the intervention campus, and 3 reports at the control campus. All student participants strongly agreed that they would recommend that responsibility for submitting ADR reports to the Canada Vigilance Program remain with pharmacy students during future rotations. Availability of a pharmacy student to facilitate reporting of ADRs may increase the frequency of ADR reporting and could alleviate pharmacist workload; this activity is also a potentially valuable learning experience for students.

Consequences of the exclusion of known adverse drug reactions in a spontaneous reporting system on the possibility to detect unknown drug/ADR combinations

NARCIS (Netherlands)

Borgsteede, Sander; Van Puijenbroek, Eugene; Van Grootheest, Kees

Background: The Reporting Odds Ratio (ROR) is one of the expressions to analyse disproportionallity of adverse drug reactions (ADRs) in a spontaneous reporting system. The ROR is defined as the extent to which the association between a suspected drug and ADR stands out against the background

Analysis of the use and adverse effects of non-steroidal anti-inflammatory drugs: A pilot study

Directory of Open Access Journals (Sweden)

Perić Aneta

2006-01-01

Full Text Available Background/Aim. The use and adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs in outpatients with rheumatic diseases has not yet been studied enough. The aim of this study was to evaluate the data about the efficacy and safety of NSAIDs obtained from the questionnaires submitted to the outpatients receiving these drugs. Methods. The patients who had been prescribed any of NSAIDs within the period from June to September, 2004 were included in the study. The answers obtained from the questionnaires were statistically analyzed by means of χ2-test. Results. At the time of the study, 150 patients had been prescribed ibuprofen or some other NSAID. Out of the total number of dispensed questionnaires (n = 150, only 45 (30% were shown to be correctly filled-in. Their analysis showed that 64.4% of the patients had suffered from rheumatic diseases for more than five years, and had regularly used NSAIDs. The average age of these patients was about 70 years, and the number of females was double as high as that of the males. The most frequently used NSAIDs were diclofenac and ibuprofen (46.14%, and 23.24%, respectively. According to the answers given by the patients, the most often adverse reactions were gastric complaints such as nausea (11.1%, and stomach pain (8.9%. Due to this, the majority of the patients (64.4% used some of the antiulcer drugs, most often ranitidine (31.1%. Conclusion. The results of this pilot study revealed that among the outpatients suffering from rheumatic diseases, the number of females was double as high as the number of males, that these patients were of the mean age of 70 years, and that their diseases lasted longer than five years. Gastric complains such as nausea and gastric pain of mild intensity were the most often adverse effects of NSAIDs reported by our patients. It could be the consequence of the predominant use of diclofenac and ibuprofen, NSAIDs with mild to moderate ulcerogenic potential, as well as the

Benzodiazepine Use During Hospitalization: Automated Identification of Potential Medication Errors and Systematic Assessment of Preventable Adverse Events.

Directory of Open Access Journals (Sweden)

David Franklin Niedrig

Full Text Available Benzodiazepines and "Z-drug" GABA-receptor modulators (BDZ are among the most frequently used drugs in hospitals. Adverse drug events (ADE associated with BDZ can be the result of preventable medication errors (ME related to dosing, drug interactions and comorbidities. The present study evaluated inpatient use of BDZ and related ME and ADE.We conducted an observational study within a pharmacoepidemiological database derived from the clinical information system of a tertiary care hospital. We developed algorithms that identified dosing errors and interacting comedication for all administered BDZ. Associated ADE and risk factors were validated in medical records.Among 53,081 patients contributing 495,813 patient-days BDZ were administered to 25,626 patients (48.3% on 115,150 patient-days (23.2%. We identified 3,372 patient-days (2.9% with comedication that inhibits BDZ metabolism, and 1,197 (1.0% with lorazepam administration in severe renal impairment. After validation we classified 134, 56, 12, and 3 cases involving lorazepam, zolpidem, midazolam and triazolam, respectively, as clinically relevant ME. Among those there were 23 cases with associated adverse drug events, including severe CNS-depression, falls with subsequent injuries and severe dyspnea. Causality for BDZ was formally assessed as 'possible' or 'probable' in 20 of those cases. Four cases with ME and associated severe ADE required administration of the BDZ antagonist flumazenil.BDZ use was remarkably high in the studied setting, frequently involved potential ME related to dosing, co-medication and comorbidities, and rarely cases with associated ADE. We propose the implementation of automated ME screening and validation for the prevention of BDZ-related ADE.

Building a knowledge base of severe adverse drug events based on AERS reporting data using semantic web technologies.

Science.gov (United States)

Jiang, Guoqian; Wang, Liwei; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

2013-01-01

A semantically coded knowledge base of adverse drug events (ADEs) with severity information is critical for clinical decision support systems and translational research applications. However it remains challenging to measure and identify the severity information of ADEs. The objective of the study is to develop and evaluate a semantic web based approach for building a knowledge base of severe ADEs based on the FDA Adverse Event Reporting System (AERS) reporting data. We utilized a normalized AERS reporting dataset and extracted putative drug-ADE pairs and their associated outcome codes in the domain of cardiac disorders. We validated the drug-ADE associations using ADE datasets from SIDe Effect Resource (SIDER) and the UMLS. We leveraged the Common Terminology Criteria for Adverse Event (CTCAE) grading system and classified the ADEs into the CTCAE in the Web Ontology Language (OWL). We identified and validated 2,444 unique Drug-ADE pairs in the domain of cardiac disorders, of which 760 pairs are in Grade 5, 775 pairs in Grade 4 and 2,196 pairs in Grade 3.

Suspected adverse reactions to veterinary drugs reported in South Africa (January 1998 - February 2001 : special report

Directory of Open Access Journals (Sweden)

R. Gehring

2001-07-01

Full Text Available The Veterinary Pharmacovigilance Centre received 59 reports of suspected adverse drug reactions during the period January 1998 - February 2001. The number of reports received increased after the establishment of a formal procedure for recording and responding to reports. The number of reports received per species was: dogs 19, cats 15, cattle 7, sheep/ goats 6, chickens 4, pigs 3, horses 2 and giraffe 1. Many different types of adverse reactions were reported, including lack of efficacy, hypersensitivity, inappropriate use of products by non-veterinarians, known adverse effects and adverse effects encountered with extra-label use of products.

Adverse Health Consequences of Performance-Enhancing Drugs: An Endocrine Society Scientific Statement

Science.gov (United States)

Pope, Harrison G.; Wood, Ruth I.; Rogol, Alan; Nyberg, Fred; Bowers, Larry

2014-01-01

Despite the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reality, the vast majority of PED users are not athletes but rather nonathlete weightlifters, and the adverse health effects of PED use are greatly underappreciated. This scientific statement synthesizes available information on the medical consequences of PED use, identifies gaps in knowledge, and aims to focus the attention of the medical community and policymakers on PED use as an important public health problem. PED users frequently consume highly supraphysiologic doses of PEDs, combine them with other PEDs and/or other classical drugs of abuse, and display additional associated risk factors. PED use has been linked to an increased risk of death and a wide variety of cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. Because randomized trials cannot ethically duplicate the large doses of PEDs and the many factors associated with PED use, we need observational studies to collect valid outcome data on the health risks associated with PEDs. In addition, we need studies regarding the prevalence of PED use, the mechanisms by which PEDs exert their adverse health effects, and the interactive effects of PEDs with sports injuries and other high-risk behaviors. We also need randomized trials to assess therapeutic interventions for treating the adverse effects of PEDs, such as the anabolic-androgen steroid withdrawal syndrome. Finally, we need to raise public awareness of the serious health consequences of PEDs. PMID:24423981

Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

Science.gov (United States)

Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

2017-09-01

Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gender differences in the effects of childhood adversity on alcohol, drug, and polysubstance-related disorders.

Science.gov (United States)

Evans, Elizabeth A; Grella, Christine E; Upchurch, Dawn M

2017-07-01

To examine gender differences in the associations between childhood adversity and different types of substance use disorders and whether gender moderates these relationships. We analyzed data from 19,209 women and 13,898 men as provided by Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender moderates the associations between childhood adversity and DSM-IV defined lifetime occurrence of alcohol, drug, and polysubstance-related disorders. We used multinomial logistic regression, weighted to be representative of the US adult civilian, noninstitutionalized population, and we calculated predicted probabilities by gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pair-wise comparisons corrected for multiple comparisons using Bonferroni's method. For each type of substance use disorder, risk was increased by more exposure to childhood adversity, and women had a lower risk than men. However, moderation effects revealed that with more experiences of childhood adversity, the gender gap in predicted probability for a disorder narrowed in relation to alcohol, it converged in relation to drugs such that risk among women surpassed that among men, and it widened in relation to polysubstances. Knowledge regarding substance-specific gender differences associated with childhood adversity exposure can inform evidence-based treatments. It may also be useful for shaping other types of gender-sensitive public health initiatives to ameliorate or prevent different types of substance use disorders.

Use and Perceived Benefits of Mobile Devices by Physicians in Preventing Adverse Drug Events in the Nursing Home

Science.gov (United States)

Handler, Steven M.; Boyce, Richard D.; Ligons, Frank; Perera, Subashan; Nace, David A.; Hochheiser, Harry

2015-01-01

Objective Although mobile devices equipped with drug reference software may help prevent adverse drug events (ADEs) in the nursing home (NH) by providing medication information at the point-of-care, little is known about their use and perceived benefits. The goal of this study was to conduct a survey of a nationally representative sample of NH physicians to quantify the use and perceived benefits of mobile devices in preventing ADEs in the NH setting. Design/Setting/Participants We surveyed physicians who attended the 2010 the AMDA Annual Symposium about their use of mobile devices and beliefs about the effectiveness of drug reference software in preventing ADEs. Results The overall net valid response rate was 70% (558/800) with 42% (236/558) using mobile devices to assist with prescribing in the NH. Physicians with ≤15 years clinical experience were 67% more likely to be mobile device users, compared to those with >15 years of clinical experience (odds ratio=1.68; 95% confidence interval=1.17-2.41; p=0.005). For those who used a mobile device to assist with prescribing, almost all (98%) reported performing an average of one or more drug look-ups per day, performed an average of 1-2 lookups per day for potential drug-drug interactions (DDIs), and most (88%) believed that drug reference software had helped to prevent at least one potential ADE in the preceding four-week period. Conclusions The proportion of NH physicians who use mobile devices with drug reference software, while significant, is lower than in other clinical environments. Our results suggest that NH physicians who use mobile devices equipped with drug reference software believe they are helpful for reducing ADEs. Further research is needed to better characterize the facilitators and barriers to adoption of the technology in the NH and its precise impact on NH ADEs. PMID:24094901

Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

Directory of Open Access Journals (Sweden)

Funda Karbek Akarca

2017-12-01

Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis

High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

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Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

2010-11-13

Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

Potential drug-drug interactions on in-patient medication ...

African Journals Online (AJOL)

Potential drug-drug interactions on in-patient medication prescriptions at Mbarara Regional Referral Hospital (MRRH) in western Uganda: prevalence, clinical importance and associated factors. SJ Lubinga, E Uwiduhaye ...

The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

Science.gov (United States)

Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia

2014-09-01

To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

Detecting potential adverse reactions of sulpiride in schizophrenic patients by prescription sequence symmetry analysis.

Directory of Open Access Journals (Sweden)

Edward Chia-Cheng Lai

Full Text Available PURPOSE: Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects. MATERIALS AND METHODS: Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA was employed to efficiently identify potential causal relationships while controlling for potential selection bias. RESULTS: A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46-2.06 and hyperprolactinemia (12.04; 1.59-91.2. In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment. CONCLUSIONS: We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including

Attitudes and Usage of the Food and Drug Administration Adverse Event Reporting System Among Gastroenterology Nurse Practitioners and Physician Assistants.

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Salk, Allison; Ehrenpreis, Eli D

2016-01-01

The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs.

Predicting drug?drug interactions through drug structural similarities and interaction networks incorporating pharmacokinetics and pharmacodynamics knowledge

OpenAIRE

Takeda, Takako; Hao, Ming; Cheng, Tiejun; Bryant, Stephen H.; Wang, Yanli

2017-01-01

Drug?drug interactions (DDIs) may lead to adverse effects and potentially result in drug withdrawal from the market. Predicting DDIs during drug development would help reduce development costs and time by rigorous evaluation of drug candidates. The primary mechanisms of DDIs are based on pharmacokinetics (PK) and pharmacodynamics (PD). This study examines the effects of 2D structural similarities of drugs on DDI prediction through interaction networks including both PD and PK knowledge. Our a...

[Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward].

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Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge

2006-03-01

Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.

A case of adverse drug reaction induced by dispensing error.

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Gallelli, L; Staltari, O; Palleria, C; Di Mizio, G; De Sarro, G; Caroleo, B

2012-11-01

To report about a case of acute renal failure due to absence of communication between physician and patient. A 78 year old man with human immunodeficiency virus (HIV) accessed our hospital and was brought to our attention in August 2011 for severe renal failure. Clinical history revealed that he had been taking highly active antiretroviral therapy with lamivudine/abacavir and fosamprenavir since 2006. In April 2011 due to an augmentation in creatinine plasma levels, a reduction in lamivudine dosage to 100 mg/day and the prescription of abacavir 300 mg/day became necessary. Unfortunately, the patient took both lamivudine and abacavir therefore the association of the two medications (lamivudine/abacavir) lead to asthenia and acute renal failure within a few days. This case emphasizes the importance about how physicians must pay very careful attention during drug prescription, most particularly, as far as elderly patients are concerned. In fact, communication improvement between physicians and patients can prevent increase of adverse drug reactions related to drug dispensing, with consequential reduction of costs in the healthcare system. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

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Allen, Cheryl A; Ivester, Julius R

2017-12-01

An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf-Hirschhorn syndrome.

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Ho, Karen S; Markham, Leah M; Twede, Hope; Lortz, Amanda; Olson, Lenora M; Sheng, Xiaoming; Weng, Cindy; Wassman, E Robert; Newcomb, Tara; Wassman, E Robert; Carey, John C; Battaglia, Agatino

2018-04-01

Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a psyndromes which may have complex seizure etiologies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

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Sevene, Esperança; Mariano, Alda; Mehta, Ushma; Machai, Maria; Dodoo, Alexander; Vilardell, David; Patel, Sam; Barnes, Karen; Carné, Xavier

2008-01-01

The roll out of various public health programmes involving mass administration of medicines calls for the deployment of responsive pharmacovigilance systems to permit identification of signals of rare or even common adverse reactions. In developing countries in Africa, these systems are mostly absent and their performance under any circumstance is difficult to predict given the known shortage of human, financial and technical resources. Nevertheless, the importance of such systems in all countries is not in doubt, and research to identify problems, with the aim of offering pragmatic solutions, is urgently needed. To examine the impact of training and monitoring of healthcare workers, making supervisory visits and the availability of telecommunication and transport facilities on the implementation of a pharmacovigilance system in Mozambique. This was a descriptive study enumerating the lessons learnt and challenges faced in implementing a spontaneous reporting system in two rural districts of Mozambique - Namaacha and Matutuíne - where remote location, poor telecommunication services and a low level of education of health professionals are ongoing challenges. A 'yellow card' system for spontaneous reporting of adverse drug reactions (ADRs) was instituted following training of health workers in the selected districts. Thirty-five health professionals (3 medical doctors, 2 technicians, 24 nurses, 4 basic healthcare agents and 2 pharmacy agents) in these districts were trained to diagnose, treat and report ADRs to all medicines using a standardized yellow card system. There were routine site visits to identify and clarify any problems in filling in and sending the forms. One focal person was identified in each district to facilitate communication between the health professionals and the National Pharmacovigilance Unit (NPU). The report form was assessed for quality and causality. The availability of telecommunications and transport was assessed. Fourteen months after

Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database.

Science.gov (United States)

Hosoya, Ryuichiro; Uesawa, Yoshihiro; Ishii-Nozawa, Reiko; Kagaya, Hajime

2017-01-01

Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present

Factors Associated with Potential Food-Drug Interaction in Hospitalized Patients: A Cross-Sectional Study in Northeast Iran

Directory of Open Access Journals (Sweden)

Mostafa Abdollahi

2018-04-01

Full Text Available Background: The minimization of adverse food-drug interactions will improve patient care by optimizing the therapeutic effects and maintaining proper nutritional status. Aim: The aim of the present study was to find the main factors that may place the hospitalized patients at risk of potential food-drug interactions. Method: This cross-sectional, descriptive study was conducted on 400 inpatients admitted to the Department of Internal Medicine of a teaching hospital in Mashhad, Northeast Iran, within 20 March 2013 to 20 April 2013. The potential food-drug interactions were evaluated for 19 commonly prescribed medications. The main factors (e.g., age, gender, education level, number of medications, and duration of the disease that may place the patients at risk of potential food-drug interactions were analyzed for each patient. Results: Out of the 19 commonly prescribed medications, 17 drugs (89% were not properly used with respect to meal. Furthermore, 14 commonly prescribed drugs were found to have a high frequency (≥50% of potential food-drug interactions. Most of the patients (n=359, 89.8% consumed their medicines at inappropriate time with respect to meals. The results of a multiple logistic regression after adjustment for confounders revealed that the age [β=0.005, CI: 0.0-0.01; P=033], number of medications [β=0.1, CI: 0.083-0.117; P

Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

Science.gov (United States)

Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

2018-03-01

Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

Use and perceived benefits of mobile devices by physicians in preventing adverse drug events in the nursing home.

Science.gov (United States)

Handler, Steven M; Boyce, Richard D; Ligons, Frank M; Perera, Subashan; Nace, David A; Hochheiser, Harry

2013-12-01

Although mobile devices equipped with drug reference software may help prevent adverse drug events (ADEs) in the nursing home (NH) by providing medication information at the point of care, little is known about their use and perceived benefits. The goal of this study was to conduct a survey of a nationally representative sample of NH physicians to quantify the use and perceived benefits of mobile devices in preventing ADEs in the NH setting. We surveyed physicians who attended the 2010 American Medical Directors Association Annual Symposium about their use of mobile devices, and beliefs about the effectiveness of drug reference software in preventing ADEs. The overall net valid response rate was 70% (558/800) with 42% (236/558) using mobile devices to assist with prescribing in the NH. Physicians with 15 or fewer years of clinical experience were 67% more likely to be mobile device users, compared with those with more than 15 years of clinical experience (odds ratio = 1.68; 95% confidence interval = 1.17-2.41; P = .005). For those who used a mobile device to assist with prescribing, almost all (98%) reported performing an average of 1 or more drug look-ups per day, performed an average of 1 to 2 lookups per day for potential drug-drug interactions (DDIs), and most (88%) believed that drug reference software had helped to prevent at least 1 potential ADE in the preceding 4-week period. The proportion of NH physicians who use mobile devices with drug reference software, although significant, is lower than in other clinical environments. Our results suggest that NH physicians who use mobile devices equipped with drug reference software believe they are helpful for reducing ADEs. Further research is needed to better characterize the facilitators and barriers to adoption of the technology in the NH and its precise impact on NH ADEs. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Indolealkylamines: biotransformations and potential drug-drug interactions.

Science.gov (United States)

Yu, Ai-Ming

2008-06-01

Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

Science.gov (United States)

Carrascosa, J M; Del-Alcazar, E

2018-04-01

Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

Methodological Considerations for Comparison of Brand Versus Generic Versus Authorized Generic Adverse Event Reports in the US Food and Drug Administration Adverse Event Reporting System (FAERS).

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Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, David C; Hansen, Richard A

2017-12-01

The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

Adverse drug reactions of haloperidol used in critically ill children for the treatment of delirium

NARCIS (Netherlands)

Spaans, E.; Slooff, V.; Van Puijenbroek, E.; Jessurun, N.; De Hoog, M.; Tibboel, D.; De Wildt, S.

BACKGROUND: As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol. However, little is known about its safety in this context. The objective of this study was to investigate the incidence and nature of adverse events

Drug-induced urinary incontinence

NARCIS (Netherlands)

Tsakiris, Peter; Oelke, Matthias; Michel, Martin C.

2008-01-01

Physiological urinary continence depends on many factors that are potentially vulnerable to adverse drug effects, which may lead to incontinence. In principle, drugs could cause incontinence by lowering bladder outlet resistance and/or by increasing intravesical pressure, which disrupts the normal

[Adverse effects of oxcarbazepine].

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Fang, Shu; Gong, Zhi-Cheng

2015-04-01

Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

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Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

2016-06-01

In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Adverse health effects of non-medical cannabis use.

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Hall, Wayne; Degenhardt, Louisa

2009-10-17

For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

Number of medications and adverse drug events by unintentional poisoning among older adults in consideration of inappropriate drug use : A Swedish population-based matched case-control study

NARCIS (Netherlands)

Rausch, Christian; Laflamme, L.; Bultmann, U.; Moller, J.

Purpose This national, population-based study aims to determine the association between the number of prescribed medications and adverse drug events (ADE) by unintentional poisoning and examine this risk when known indicators of inappropriate drug use (IDU) are accounted for. Methods We employed a

Pharmacogenetics in drug regulation: promise, potential and pitfalls

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Shah, Rashmi R

2005-01-01

Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic levels—the two components of the dose–response curve of a drug. Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose–response relationship between individuals. For some drugs, although retrospective data from case studies suggests that these polymorphisms are frequently associated with adverse drug reactions or failure of efficacy, the clinical utility of such data remains unproven. There is, therefore, an urgent need for prospective data to determine whether pre-treatment genotyping can improve therapy. Various regulatory guidelines already recommend exploration of the role of genetic factors when investigating a drug for its pharmacokinetics, pharmacodynamics, dose–response relationship and drug interaction potential. Arising from the global heterogeneity in the frequency of variant alleles, regulatory guidelines also require the sponsors to provide additional information, usually pharmacogenetic bridging data, to determine whether data from one ethnic population can be extrapolated to another. At present, sponsors explore pharmacogenetic influences in early clinical pharmacokinetic studies but rarely do they carry the findings forward when designing dose–response studies or pivotal studies. When appropriate, regulatory authorities include genotype-specific recommendations in the prescribing information. Sometimes, this may include the need to adjust a dose in some genotypes under specific circumstances. Detailed references to pharmacogenetics in prescribing information and pharmacogenetically based prescribing in routine therapeutics will require robust prospective data from well-designed studies. With greater integration of pharmacogenetics in drug development, regulatory authorities expect to receive more detailed genetic data. This is likely to complicate the drug evaluation process as well as

Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil

DEFF Research Database (Denmark)

Aagaard, Lise; Hansen, Ebba Holme

2013-01-01

Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs......). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations...... of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted...

Serious adverse events with infliximab: analysis of spontaneously reported adverse events.

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Hansen, Richard A; Gartlehner, Gerald; Powell, Gregory E; Sandler, Robert S

2007-06-01

Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication. The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories. Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction. In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process.

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

NARCIS (Netherlands)

van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

2013-01-01

Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

NARCIS (Netherlands)

R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

2013-01-01

textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

Knowledge, perception, practices and barriers of healthcare professionals in Bosnia and Herzegovina towards adverse drug reaction reporting and pharmacovigilance

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Maša Amrain

2014-09-01

Full Text Available Introduction: Pharmacovigilance is an arm of patient care. No one wants to harm patients, but unfortunately any medicine will sometimes do just this. Underreporting of adverse drug reactions by healthcare professionals is a major problem in many countries. In order to determine whether our pharmacovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of health care professionals in adverse drug reaction (ADR reporting was performed.Methods: A pretested questionnaire comprising of 20 questions was designed for assessment of knowledge, perceptions, practice and barriers toward ADR reporting on a random sample of 1000 healthcare professionals in Bosnia and Herzegovina.Results: Of the 1000 respondents, 870 (87% completed the questionnaire. The survey showed that 62.9% health care professionals would report ADR to the Agency for Medicinal Products and Medical Device of Bosnia and Herzegovina (ALMBIH. Most of surveyed respondents has a positive perception towards ADR reporting, and believes that this is part of their professional and legal obligation, and they also recognize the importance of reporting adverse drug reactions. Only small percent (15.4% of surveyed health care professionals reported adverse drug reaction.Conclusions: The knowledge of ADRs and how to report them is inadequate among health care professionals. Perception toward ADR reporting was positive, but it is not reflected in the actual practice of ADRs, probably because of little experience and knowledge regarding pharmacovigilance. Interventions such as education and training, focusing on the aims of pharmacovigilance, completing the ADR form and clarifying the reporting criteria are strongly recommended.

Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients.

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Forbes, Heather L; Polasek, Thomas M

2017-10-01

To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients. This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs. There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs. Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.

Adverse drug reactions reported by consumers for nervous system medications in Europe 2007 to 2011

DEFF Research Database (Denmark)

Aagaard, Lise; Hansen, Ebba Holme

2013-01-01

Reporting of adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. In the European Union, more countries have allowed consumers to report ADRs directly to the regulatory agencies. The aim of this study was to characterize ADRs reported by European...... consumer for nervous system medications....

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

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Castleden, C M; Pickles, H

1988-10-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

[Prevalence of potentially inappropriate drug prescription in the elderly].

Science.gov (United States)

Fajreldines, A; Insua, J; Schnitzler, E

2016-01-01

One of the causes of preventable adverse drug events (ADES) in older patients constitutes inappropriate prescription of drugs (PIM). The PIM is where risks exceed the clinical benefit. Several instruments can be use to measure this problem, the most used are: a) Beers criteria; b) Screening tool to Older People Potentially inappropriate Prescription (STOPP); c) Screening tool to Alert Doctors to Right Appropriate indicated Treatments (START); d) The Medication Appropriateness Index (MAI). This study aims to assess the prevalence of PIM, in a population of older adults in three clinical scopes of university hospital. cross sectional study of 300 cases from a random sample of fields: hospitalization (n=100), ambulatory (n=100) and emergency (n=100), all patients over 65 years old or more who where treated at our hospital. 1355 prescription drugs were analized, finding patients hospitalized (PIM) of 57.7%, 55%, 26%, and 80% according to Beers, in ambulatory 36%, 36.5%, 5% and 52% with the same tools and in emergency 35%, 35%, 6% y 52% with the same tools. Was found significant association the PIM with polipharmacy with Beers, STOPP and MAI. results can be compare to world literature (26-80% vs 11-73.1%). The STOPP-START used in an integrated manner would be best estimating the problem of PIM. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

A New Zealand platform to enable genetic investigation of adverse drug reactions.

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Maggo, Simran Ds; Chua, Eng Wee; Chin, Paul; Cree, Simone; Pearson, John; Doogue, Matthew; Kennedy, Martin A

2017-12-01

A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.

Oral adverse effects of gastrointestinal drugs and considerations for dental management in patients with gastrointestinal disorders

Directory of Open Access Journals (Sweden)

Ramya Karthik

2012-01-01

Full Text Available Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases.

Adverse drug events associated with vitamin K antagonists: factors of therapeutic imbalance

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El-Helou N

2013-03-01

Full Text Available Nancy El-Helou, Amal Al-Hajje, Rola Ajrouche, Sanaa Awada, Samar Rachidi, Salam Zein, Pascale SalamehClinical and Epidemiological Research Laboratory, Faculty of Pharmacy, Lebanese University, Beirut, LebanonBackground: Adverse drug events (ADE occur frequently during treatment with vitamin K antagonists (AVK and contribute to increase hemorrhagic risks.Methods: A retrospective study was conducted over a period of 2 years. Patients treated with AVK and admitted to the emergency room of a tertiary care hospital in Beirut were included. The aim of the study was to identify ADE characterized by a high international normalized ratio (INR and to determine the predictive factors responsible for these events. Statistical analysis was performed with the SPSS statistical package.Results: We included 148 patients. Sixty-seven patients (47.3% with an INR above the therapeutic range were identified as cases. The control group consisted of 81 patients (54.7% with an INR within the therapeutic range. Hemorrhagic complications were observed in 53.7% of cases versus 6.2% of controls (P < 0.0001. No significant difference was noticed between cases and controls regarding the indication and the dose of AVK. Patients aged over 75 years were more likely to present an INR above the therapeutic range (58.2%, P = 0.049. Recent infection was present in 40.3% of cases versus 6.2% of controls (P < 0.0001 and hypoalbuminemia in 37.3% of cases versus 6.1% of controls (P < 0.0001. Treatment with antibiotics, amiodarone, and anti-inflammatory drugs were also factors of imbalance (P < 0.0001.Conclusion: Many factors may be associated with ADE related to AVK. Monitoring of INR and its stabilization in the therapeutic range are important for preventing these events.Keywords: adverse drug events, vitamin K antagonists, bleeding risks, therapeutic imbalance

Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

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DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

2017-07-01

Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

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Hanlon, J T; Perera, S; Newman, A B; Thorpe, J M; Donohue, J M; Simonsick, E M; Shorr, R I; Bauer, D C; Marcum, Z A

2017-04-01

There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2�

The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure

DEFF Research Database (Denmark)

Krintel, Sophine B; Grunert, Veit Peter; Hetland, Merete L

2013-01-01

To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.......To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure....

Concordance and predictive value of two adverse drug event data sets.

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Cami, Aurel; Reis, Ben Y

2014-08-22

Accurate prediction of adverse drug events (ADEs) is an important means of controlling and reducing drug-related morbidity and mortality. Since no single "gold standard" ADE data set exists, a range of different drug safety data sets are currently used for developing ADE prediction models. There is a critical need to assess the degree of concordance between these various ADE data sets and to validate ADE prediction models against multiple reference standards. We systematically evaluated the concordance of two widely used ADE data sets - Lexi-comp from 2010 and SIDER from 2012. The strength of the association between ADE (drug) counts in Lexi-comp and SIDER was assessed using Spearman rank correlation, while the differences between the two data sets were characterized in terms of drug categories, ADE categories and ADE frequencies. We also performed a comparative validation of the Predictive Pharmacosafety Networks (PPN) model using both ADE data sets. The predictive power of PPN using each of the two validation sets was assessed using the area under Receiver Operating Characteristic curve (AUROC). The correlations between the counts of ADEs and drugs in the two data sets were 0.84 (95% CI: 0.82-0.86) and 0.92 (95% CI: 0.91-0.93), respectively. Relative to an earlier snapshot of Lexi-comp from 2005, Lexi-comp 2010 and SIDER 2012 introduced a mean of 1,973 and 4,810 new drug-ADE associations per year, respectively. The difference between these two data sets was most pronounced for Nervous System and Anti-infective drugs, Gastrointestinal and Nervous System ADEs, and postmarketing ADEs. A minor difference of 1.1% was found in the AUROC of PPN when SIDER 2012 was used for validation instead of Lexi-comp 2010. In conclusion, the ADE and drug counts in Lexi-comp and SIDER data sets were highly correlated and the choice of validation set did not greatly affect the overall prediction performance of PPN. Our results also suggest that it is important to be aware of the

Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

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Jorge Enrique Machado-Alba

2014-12-01

Full Text Available This study describes the adverse drug reactions (ADRs and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART. A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years; these patients were from a cohort of 1 364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9. The cohort was mostly female (366, 87.4% and had a mean age of 52.7 years (± 13.1. The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively. The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

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Francesca Scicchitano

2012-01-01

Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

Science.gov (United States)

Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2012-09-01

Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

STUDIES OF ADVERSE DRUG REACTION PROFILE OF ANTISNAKE VENOM AT DISTRICT GENERAL HOSPITAL

OpenAIRE

Mulchand Shende *, Sneha Gawali , Kanchan Bhongade , Vivek Bhuskade , Abhijit Nandgaonkar

2017-01-01

Snake bite is a common predominant problem of the rural and periurban areas, neglected and frequently devastating environmental and occupational disease, especially in rural areas of tropical developing countries. This study aimed to investigate of the adverse drug reaction profile of anti-snake venom (ASV) in a district general hospital. An observational study was conducted in hospital for six months. A total number of 142 indoor case papers of snake bite from October 2016 to April 2017 were...

Adverse Reactions to Antituberculosis Drugs in Iranian Tuberculosis Patients

Directory of Open Access Journals (Sweden)

Aliasghar Farazi

2014-01-01

Full Text Available Background. Antituberculosis multidrug regimens have been associated with increased incidence of adverse drug reactions (ADRs. This study aimed to determine the incidence and associated factors of ADRs due to antituberculosis therapy. Methods. This is a retrospective cross-sectional study on tuberculosis patients who were treated in tuberculosis clinics in Markazi province in Iran. The information contained in the medical files was extracted and entered into the questionnaire. Data was descriptively analyzed by using statistical package for social sciences (SPSS 18. Results. A total of 940 TB patients of 1240 patients’ medical records available in 10 medical offices were included in this study. Of the 563 ADRs found in this study, 82.4% were considered minor reactions and 17.6% were major reactions. No death from antituberculosis ADR was observed. We found that the risk of major ADRs was higher in females (P  value=0.0241, age >50 y (P  value=0.0223, coinfection with HIV (P  value=0.0323, smoking (P  value=0.002, retreatment TB (P  value=0.0203, and comorbidities (P  value=0.0005. Conclusions. This study showed that severe side effects of anti-TB drugs are common in patients who have risk factors of ADRs and they should be followed up by close monitoring.

A web-based quantitative signal detection system on adverse drug reaction in China.

Science.gov (United States)

Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan

2009-07-01

To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.

Effect of a ward-based pharmacy team on preventable adverse drug events in surgical patients (SUREPILL study)

NARCIS (Netherlands)

de Boer, M.; Boeker, E. B.; Ramrattan, M. A.; Kiewiet, J. J. S.; Ram, K.; Gombert-Handoko, K. B.; van Lent-Evers, N. A. E. M.; Kuks, P. F. M.; Mulder, W. M. C.; Breslau, P. J.; Oostenbroek, R. J.; Dijkgraaf, M. G. W.; Lie-A-Huen, L.; Boermeester, M. A.

2015-01-01

Surgical patients are at risk of adverse drug events (ADEs) causing morbidity and mortality. Much harm is preventable. Ward-based pharmacy interventions to reduce medication-related harm have not been evaluated in surgical patients. This multicentre prospective clinical trial evaluated a

Drug Utilisation Pattern and Adverse Events in Patients with Chronic Kidney Disease Undergoing Maintenance Haemodialysis at a Tertiary Care Hospital of Odisha

Directory of Open Access Journals (Sweden)

P. Ansuman Abhisek

2017-10-01

>45 years (p<0.001. Conclusion: This study provides an insight regarding utilisation pattern of a wide variety of drug classes in CKD patients undergoing maintenance haemodialysis in a tertiary care teaching hospital setting and suggests a possible improvement in medicine practices among patients suffering from CKD which may probably affect adherence patterns positively. Certain areas like potential drug interactions, adverse drug reactions and adherence are required to be explored further.

21 CFR 314.104 - Drugs with potential for abuse.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drugs with potential for abuse. 314.104 Section 314.104 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and Abbreviated Applications § 314.104 Drugs with potential for abuse. The Food and Drug...

A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs).

Science.gov (United States)

Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

2014-01-01

Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

Energy Technology Data Exchange (ETDEWEB)

Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: appo@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)

2014-01-01

Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

International Nuclear Information System (INIS)

Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

2014-01-01

Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified

Experiences from consumer reports on psychiatric adverse drug reactions with antidepressant medication: a qualitative study of reports to a consumer association.

Science.gov (United States)

Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders

2012-12-23

The new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication. All reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN's Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments. Three main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them attempt to discontinue their

Potential intravenous drug interactions in intensive care

Directory of Open Access Journals (Sweden)

Maiara Benevides Moreira

Full Text Available Abstract OBJECTIVE To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. METHOD Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. RESULTS The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole, increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. CONCLUSION A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences.

Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting

Directory of Open Access Journals (Sweden)

Protić D

2016-02-01

between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts. Conclusion: We may draw a profile of rheumatological patients willing to report ADRs: 1 The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2 They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3 They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients’ reporting of potential ADRs. Keywords: adverse drug reactions, patient reporting system, rheumatology, bias

Contraceptives as possible risk factors for postpartum depression: A retrospective study of the food and drug administration adverse event reporting system, 2004-2015.

Science.gov (United States)

Horibe, Megumi; Hane, Yuuki; Abe, Junko; Matsui, Toshinobu; Kato, Yamato; Ueda, Natsumi; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Hasegawa, Shiori; Kinosada, Yasutomi; Hara, Hideaki; Nakamura, Mitsuhiro

2018-04-01

Postpartum depression is a mood disorder that commonly affects women during the early postpartum period. The objective of this study was to analyse the association of postpartum depression with drugs (including contraceptive devices and implants) with spontaneously reported adverse events reported in the US Food and Drug Administration Adverse Event Reporting System database. Retrospective study. Reports of postpartum depression events between 2004-2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical Dictionary for Regulatory Activities was used to identify postpartum depression. The reporting odds ratios (95% confidence intervals, CI) of levonorgestrel (an intrauterine device with progestogen), etonogestrel (a hormonal contraceptive implant), sertraline and drospirenone (an oral contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4 (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration Adverse Event Reporting System database, the use of contraceptives or an intrauterine device with progestogen might convey risk for postpartum depression.

Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS).

Science.gov (United States)

Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon

2018-03-28

General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.

Risk factors for potential drug interactions in general practice

DEFF Research Database (Denmark)

Bjerrum, Lars; Gonzalez Lopez-Valcarcel, Beatriz; Petersen, Gert

2008-01-01

interactions during 1 year. Patient factors associated with increased risk of potential drug interactions were high age, a high number of concurrently used drugs, and a high number of prescribers. Practice factors associated with potential drug interactions were a high percentage of elderly patients and a low......Objective: To identify patient- and practice-related factors associated with potential drug interactions. Methods: A register analysis study in general practices in the county of Funen, Denmark. Prescription data were retrieved from a population-based prescription database (Odense University......, depending on the severity of outcome and the quality of documentation. A two-level random coefficient logistic regression model was used to investigate factors related to potential drug interactions. Results: One-third of the population was exposed to polypharmacy, and 6% were exposed to potential drug...

Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

Science.gov (United States)

Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

2012-08-01

Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs.

Directory of Open Access Journals (Sweden)

Qifan Kuang

Full Text Available Early and accurate identification of adverse drug reactions (ADRs is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs.In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper.Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

Science.gov (United States)

Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

Science.gov (United States)

Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

2008-01-01

Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

[MT-45--a dangerous and potentially ototoxic internet drug].

Science.gov (United States)

Lindeman, Erik; Bäckberg, Matilda; Personne, Mark; Helander, Anders

2014-09-11

During the last years several synthetic opioids have been introduced on Internet sites selling new psychoactive substances (NPS). One of these, called MT-45, a piperazine derivative originally synthesized as a therapeutic drug candidate in the 1970s, has recently been detected in 21 deaths, according to unpublished data from the Swedish National Board of Forensic Medicine. We present clinical data from 12 analytically confirmed hospital cases of MT-45 poisoning. The cases demonstrate that MT-45, like other opioids, can induce potentially life threatening respiratory depression and loss of consciousness in users and that symptoms are usually reversed by standard doses of the opioid receptor antagonist naloxone. Significant auditory symptoms with transient tinnitus and hearing loss occurred in two cases and a pronounced sensorineural hearing loss still present at two weeks follow-up in one case. This indicates that MT-45 may be an ototoxic substance, illustrating the ubiquitous risk of unintended adverse effects NPSs pose to users.

Rare and very rare adverse effects of clozapine

Directory of Open Access Journals (Sweden)

De Fazio P

2015-08-01

Full Text Available Pasquale De Fazio,1 Raffaele Gaetano,1 Mariarita Caroleo,1 Gregorio Cerminara,1 Francesca Maida,2 Antonio Bruno,3 Maria Rosaria Muscatello,3 Maria Jose Jaén Moreno,4 Emilio Russo,2 Cristina Segura-García1 1Department of Health Sciences, School of Specialization in Psychiatry, 2Department of Health Sciences, School of Specialization in Pharmacology, University “Magna Graecia”, Catanzaro, 3Department of Neurosciences, School of Specialization in Psychiatry, University of Messina, Messina, Italy; 4Department of Social Health Sciences, Radiology and Physical Medicine, University of Cordoba, Cordoba, Spain Abstract: Clozapine (CLZ is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

DEFF Research Database (Denmark)

Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl

2014-01-01

patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength.When applying the method to the 3,394 patients...... all indication areas.The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner.We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified...

Cutaneous adverse drug reactions: clinical pattern and causative agents--a 6 year series from Chandigarh, India.

Directory of Open Access Journals (Sweden)

Sharma V

2001-04-01

Full Text Available AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR and to determine the causative drugs. MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study. The most common types of cutaneous ADR patterns were maculopapular rash (34.6%, fixed drug eruption (FDE (30% and urticaria (14%. The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%, anticonvulsants (22.2% and NSAIDs (18%. Anticonvulsants were implicated in 41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3% and penicillins(20%. Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations. Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.

Adverse event reporting patterns of newly approved drugs in the USA in 2006: an analysis of FDA Adverse Event Reporting System data.

Science.gov (United States)

Chhabra, Pankdeep; Chen, Xing; Weiss, Sheila R

2013-11-01

The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. To determine the AE reporting patterns for new molecular entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-year period from the drug’s approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed

Patch testing in non-immediate cutaneous adverse drug reactions: value of extemporaneous patch tests.

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Assier, Haudrey; Valeyrie-Allanore, Laurence; Gener, Gwendeline; Verlinde Carvalh, Muriel; Chosidow, Olivier; Wolkenstein, Pierre

2017-11-01

Patch testing following a standardized protocol is reliable for identifying the culprit drug in cutaneous adverse drug reactions (CADRs). However, these patch tests (PTs) require pharmaceutical material and staff, which are not always easily available. To evaluate an extemporaneous PT method in CADRs. We retrospectively analysed data for all patients referred to our department between March 2009 and June 2013 for patch testing after a non-immediate CADR. The patients who supplied their own suspected drugs were tested both with extemporaneous PTs and with conventional PTs. Extemporaneous PTs involved a nurse crushing and diluting the drug in pet. in a ratio of approximately one-third to two-thirds. Standardized PTs were performed according to guidelines, with commercial drugs diluted to 30% or with active ingredients diluted to 10%. We analysed the data for the two PT methods in terms of the number of positive test reactions, drugs tested, and type of CADR for patients in whom the two PT methods were used. In total, 75 of 156 patients underwent the two PT procedures, including 91 double tests. Overall, 21 tests gave positive reactions with the two methods, and 69 other tests gave negative results with the two methods. Our series yielded results similar to those of published series concerning the types of CADR and the drugs responsible. Our results suggest that, for CADRs, if a patient supplies a suspected drug but if the pharmaceutical material and staff are not available for conventional PTs, extemporaneous PTs performed by the nurse with the commercial drug used by the patient can be useful and reliable. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pattern of adverse drug reactions reported by the community pharmacists in Nepal

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Palaian S

2010-09-01

Full Text Available The pharmacovigilance program in Nepal is less than a decade old, and is hospital centered. This study highlights the findings of a community based pharmacovigilance program involving the community pharmacists. Objectives: To collect the demographic details of the patients experiencing adverse drug reactions (ADR reported by the community pharmacists; to identify the common drugs causing the ADRs, the common types of ADRs; and to carry out the causality, severity and preventability assessments of the reported ADRs. Methods: The baseline Knowledge-Attitude-Practices (KAP of 116 community pharmacists from Pokhara valley towards drug safety was evaluated using a validated (Cronbach alpha=0.61 KAP questionnaire having 20 questions [(knowledge 11, attitude 5 and practice 4 maximum possible score 40]. Thirty community pharmacists with high scores were selected for three training sessions, each session lasting for one to two hours, covering the basic knowledge required for the community pharmacists for ADR reporting. Pharmacist from the regional pharmacovigilance center visited the trained community pharmacists every alternate day and collected the filled ADR reporting forms. Results: Altogether 71 ADRs, from 71 patients (37 males were reported. Antibiotics/ antibacterials caused 42% (n=37 of the total ADRs followed by non steroidal anti-inflammatory drugs [25% (n=22]. Ibuprofen/paracetamol combination accounted for ten ADRs. The most common type of ADR was itching [17.2 % (n=20, followed by generalized edema [8.6 % (n=10]. In order to manage the ADRs, the patients needed medical treatment in 69% (n=49 of the cases. Over two third (69% of the ADRs had a ‘possible’ association with the suspected drugs and a high percentage (70.4% were of ‘mild (level 2’ type. Nearly two third [64.7 % (n=46] of the ADRs were ‘definitely preventable’. Conclusion: The common class of drugs known to cause ADRs was antibacterial/ antibiotics. Ibuprofen

Coping with adverse drug events in patients with heart failure : Exploring the role of medication beliefs and perceptions

NARCIS (Netherlands)

De Smedt, R. H.; Jaarsma, T.; Ranchor, A. V.; van der Meer, K.; Groenier, K. H.; Haaijer-Ruskamp, F. M.; Denig, P.

2012-01-01

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE

Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

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Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

2016-08-01

Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

The effect of an active on-ward participation of hospital pharmacists in Internal Medicine teams on preventable Adverse Drug Events in elderly inpatients: protocol of the WINGS study (Ward-oriented pharmacy in newly admitted geriatric seniors)

NARCIS (Netherlands)

Klopotowska, J.E.; Wierenga, P.C.; de Rooij, S.E.; Stuijt, C.C.; Arisz, L.; Kuks, P.F.; Dijkgraaf, M.G.; Lie-A-Huen, L.; Smorenburg, S.M.

2011-01-01

The potential of clinical interventions, aiming at reduction of preventable Adverse Drug Events (preventable ADEs) during hospital stay, have been studied extensively. Clinical Pharmacy is a well-established and effective service, usually consisting of full-time on-ward participation of clinical

Adverse childhood experiences and prescription drug use in a cohort study of adult HMO patients

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Dube Shanta R

2008-06-01

Full Text Available Abstract Background Prescription drugs account for approximately 11% of national health expenditures. Prior research on adverse childhood experiences (ACEs, which include common forms of child maltreatment and related traumatic stressors, has linked them to numerous health problems. However, data about the relationship of these experiences to prescription drug use are scarce. Method We used the ACE Score (an integer count of 8 different categories of ACEs as a measure of cumulative exposure to traumatic stress during childhood. We prospectively assessed the relationship of the Score to prescription drug use in a cohort of 15,033 adult HMO patients (mean follow-up: 6.1 years and assessed mediation of this relationship by documented ACE-related health and social problems. Results Nearly 1.2 million prescriptions were recorded; prescriptions rates increased in a graded fashion as the ACE Score increased (p for trend Conclusion ACEs substantially increase the number of prescriptions and classes of drugs used for as long as 7 or 8 decades after their occurrence. The increases in prescription drug use were largely mediated by documented ACE-related health and social problems.

A systematic review of adverse drug events associated with administration of common asthma medications in children.

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James S Leung

Full Text Available To systematically review the literature and determine frequencies of adverse drug events (ADE associated with pediatric asthma medications.Following PRISMA guidelines, we systematically searched six bibliographic databases between January 1991 and January 2017. Study eligibility, data extraction and quality assessment were independently completed and verified by two reviewers. We included randomized control trials (RCT, case-control, cohort, or quasi-experimental studies where the primary objective was identifying ADE in children 1 month- 18 years old exposed to commercial asthma medications. The primary outcome was ADE frequency.Our search identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS (n = 24, short-acting beta-agonists (n = 10, long-acting beta-agonists (LABA (n = 3, ICS + LABA (n = 3, Leukotriene Receptor Antagonists (n = 3 and others (n = 3. 29 studies occurred in North America, and 29 were industry funded. We report a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data focuses on ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. We observed serious ADE, although they were rare, with frequency ranging between 0.9-6% per drug. There were no confirmed deaths, except for 13 potential deaths in a LABA study including combined adult and pediatric participants. We identified substantial methodological concerns, particularly with identifying ADE and determining severity. No studies utilized available standardized causality, severity or preventability assessments.The majority of studies focus on ICS, with adrenal and growth suppression described. Serious ADE are relatively uncommon, with no confirmed pediatric deaths. We identify substantial methodological concerns

Adverse childhood experiences among women prisoners: relationships to suicide attempts and drug abuse.

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Friestad, Christine; Åse-Bente, Rustad; Kjelsberg, Ellen

2014-02-01

Women prisoners are known to suffer from an accumulation of factors known to increase the risk for several major health problems. This study examines the prevalence of adverse childhood experiences (ACE) and the relationship between such experiences and suicide attempts and drug use among incarcerated women in Norway. A total of 141 women inmates (75% of all eligible) were interviewed using a structured interview guide covering information on demographics and a range of ACE related to abuse and neglect, and household dysfunction. The main outcome variables were attempted suicide and adult drug abuse. Emotional, physical and sexual abuse during childhood was experienced by 39%, 36% and 19%, respectively, and emotional and physical neglect by 31% and 33%, respectively. Looking at the full range of ACE, 17% reported having experienced none, while 34% reported having experienced more than five ACEs. After controlling for age, immigrant background and marital status, the number of ACEs significantly increased the risk of attempted suicide and current drug abuse. The associations observed between early life trauma and later health risk behaviour indicate the need for early prevention. The findings also emphasize the important role of prison health services in secondary prevention among women inmates.

Statin drug-drug interactions in a Romanian community pharmacy.

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Badiu, Raluca; Bucsa, Camelia; Mogosan, Cristina; Dumitrascu, Dan

2016-01-01

Statins are frequently prescribed for patients with dyslipidemia and have a well-established safety profile. However, when associated with interacting dugs, the risk of adverse effects, especially muscular toxicity, is increased. The objective of this study was to identify, characterize and quantify the prevalence of the potential drug-drug interactions (pDDIs) of statins in reimbursed prescriptions from a community pharmacy in Bucharest. We analyzed the reimbursed prescriptions including statins collected during one month in a community pharmacy. The online program Medscape Drug Interaction Checker was used for checking the drug interactions and their classification based on severity: Serious - Use alternative, Significant - Monitor closely and Minor. 132 prescriptions pertaining to 125 patients were included in the analysis. Our study showed that 25% of the patients who were prescribed statins were exposed to pDDIs: 37 Serious and Significant interactions in 31 of the statins prescriptions. The statins involved were atorvastatin, simvastatin and rosuvastatin. Statin pDDIs have a high prevalence and patients should be monitored closely in order to prevent the development of adverse effects that result from statin interactions.

Serious Adverse Events Associated With Using Biological Agents To Treat Rheumatic Diseases

DEFF Research Database (Denmark)

Tarp, Simon; Tarp, Ulrik; Andersen, Lis S

Background/Purpose: Clinical guidelines are needed to help clinicians provide optimal medical treatment and advise patients about the potential hazards associated with certain drugs. Our objective was to compare the number of serious adverse events (SAEs) for the biologics available for inflammat...

A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

Science.gov (United States)

Scholl, Joep H G; van Hunsel, Florence P A M; Hak, Eelko; van Puijenbroek, Eugène P

2018-02-01

The statistical screening of pharmacovigilance databases containing spontaneously reported adverse drug reactions (ADRs) is mainly based on disproportionality analysis. The aim of this study was to improve the efficiency of full database screening using a prediction model-based approach. A logistic regression-based prediction model containing 5 candidate predictors was developed and internally validated using the Summary of Product Characteristics as the gold standard for the outcome. All drug-ADR associations, with the exception of those related to vaccines, with a minimum of 3 reports formed the training data for the model. Performance was based on the area under the receiver operating characteristic curve (AUC). Results were compared with the current method of database screening based on the number of previously analyzed associations. A total of 25 026 unique drug-ADR associations formed the training data for the model. The final model contained all 5 candidate predictors (number of reports, disproportionality, reports from healthcare professionals, reports from marketing authorization holders, Naranjo score). The AUC for the full model was 0.740 (95% CI; 0.734-0.747). The internal validity was good based on the calibration curve and bootstrapping analysis (AUC after bootstrapping = 0.739). Compared with the old method, the AUC increased from 0.649 to 0.740, and the proportion of potential signals increased by approximately 50% (from 12.3% to 19.4%). A prediction model-based approach can be a useful tool to create priority-based listings for signal detection in databases consisting of spontaneous ADRs. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Intracranial self-stimulation to evaluate abuse potential of drugs.

Science.gov (United States)

Negus, S Stevens; Miller, Laurence L

2014-07-01

Intracranial self-stimulation (ICSS) is a behavioral procedure in which operant responding is maintained by pulses of electrical brain stimulation. In research to study abuse-related drug effects, ICSS relies on electrode placements that target the medial forebrain bundle at the level of the lateral hypothalamus, and experimental sessions manipulate frequency or amplitude of stimulation to engender a wide range of baseline response rates or response probabilities. Under these conditions, drug-induced increases in low rates/probabilities of responding maintained by low frequencies/amplitudes of stimulation are interpreted as an abuse-related effect. Conversely, drug-induced decreases in high rates/probabilities of responding maintained by high frequencies/amplitudes of stimulation can be interpreted as an abuse-limiting effect. Overall abuse potential can be inferred from the relative expression of abuse-related and abuse-limiting effects. The sensitivity and selectivity of ICSS to detect abuse potential of many classes of abused drugs is similar to the sensitivity and selectivity of drug self-administration procedures. Moreover, similar to progressive-ratio drug self-administration procedures, ICSS data can be used to rank the relative abuse potential of different drugs. Strengths of ICSS in comparison with drug self-administration include 1) potential for simultaneous evaluation of both abuse-related and abuse-limiting effects, 2) flexibility for use with various routes of drug administration or drug vehicles, 3) utility for studies in drug-naive subjects as well as in subjects with controlled levels of prior drug exposure, and 4) utility for studies of drug time course. Taken together, these considerations suggest that ICSS can make significant contributions to the practice of abuse potential testing. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Analysis of Adverse Reaction of Analgesics, Antipyretics and Non-Steroidal Anti-Inflammatory Drugs Prescribed by Physicians of Health Care Facilities in Podilskyi Region during 2015

OpenAIRE

Stepaniuk, N. H.; Hladkykh, F. V.; Basarab, O. V.

2016-01-01

The problem of medicines rational use exists all over the world. It concerns particularly analgesics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs). In Ukraine the side effects caused by non-steroidal antiphlogistics rank the second place according to the prevalence among all registered cases.The objective of the research was to analyze adverse drug reaction report forms concerning adverse reactions caused by the use of NSAIDs, analgesics, antipyretics, and were submitted du...

[Active surveillance of adverse drug reaction in the era of big data: challenge and opportunity for control selection].

Science.gov (United States)

Wang, S F; Zhan, S Y

2016-07-01

Electronic healthcare databases have become an important source for active surveillance of drug safety in the era of big data. The traditional epidemiology research designs are needed to confirm the association between drug use and adverse events based on these datasets, and the selection of the comparative control is essential to each design. This article aims to explain the principle and application of each type of control selection, introduce the methods and parameters for method comparison, and describe the latest achievements in the batch processing of control selection, which would provide important methodological reference for the use of electronic healthcare databases to conduct post-marketing drug safety surveillance in China.

Willingness to pay for adverse drug event regulatory actions.

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Bouvy, Jacoline; Weemers, Just; Schellekens, Huub; Koopmanschap, Marc

2011-11-01

. This study is, as far as we know, one of the first attempts to analyse the WTP for drug regulation and should in future be used in studies of the societal costs of drug regulation for epoetin alpha use. Our results indicate that the Dutch general public, especially Dutch dialysis patients, are willing to pay limited amounts to reduce the risk of serious adverse events associated with drug use.

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review.

Science.gov (United States)

Pisano, Umberto; Deosaran, Jordanna; Leslie, Stephen J; Rushworth, Gordon F; Stewart, Derek; Ford, Ian; Watson, Angus J M

2016-03-01

Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

Science.gov (United States)

Mula, Marco; von Oertzen, Tim J; Cock, Hannah R; Yogarajah, Mahinda; Lozsadi, Dora A; Agrawal, Niruj

2017-07-01

To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood. Copyright © 2017 Elsevier Inc. All rights reserved.

Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

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Swedberg, Michael D B

2016-01-01

Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

Teledermatologist expert skin advice: A unique model of care for managing skin disorders and adverse drug reactions in hepatitis C patients.

Science.gov (United States)

Charlston, Samuel; Siller, Gregory

2018-03-23

To conduct an audit of teledermatologist expert skin advice, a store and forward tele-dermatological service, to determine its effectiveness and user satisfaction in managing cutaneous adverse drug reactions in patients with hepatitis C, and to demonstrate a unique collaborative model of care for patients receiving specialised drug therapy. A retrospective analysis of data on teledermatologist expert skin advice referrals from January 2014 to December 2015 was performed. The primary outcomes assessed included number of referrals, referral locations, diagnoses, response times, quality of clinical information provided and user satisfaction ratings. Altogether 43 consultations from 29 referring sites were received from Australian metropolitan and rural settings. Of the patients, 43 were diagnosed with an adverse drug reaction related to the use of either telaprevir or simeprevir. The average time taken for the dermatologist to reply electronically with a final diagnosis and management plan was 1 h 57 min. As many as 26% of referrals required additional photos to establish a diagnosis due to poor-quality images or insufficient detail. Altogether 18 clinicians completed the customer satisfaction survey, all of whom rated teledermatologist expert skin advice nine or above on a scale of one to 10. Teledermatologist expert skin advice was regarded by clinicians as a valuable patient care service. The platform is a novel modality that supports patients undergoing specialised treatments at risk of cutaneous adverse drug reaction. © 2018 The Australasian College of Dermatologists.

Stimulated reporting: the impact of US food and drug administration-issued alerts on the adverse event reporting system (FAERS).

Science.gov (United States)

Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B

2014-11-01

The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.

Adverse drug reactions from psychotropic medicines in the paediatric population

DEFF Research Database (Denmark)

Aagaard, Lise; Hansen, Ebba H

2010-01-01

of these products in childhood. Little evidence has been reported about the adverse drug reactions (ADRs) of these medicines in practice. As spontaneous reports are the main source for information about previously unknown ADRs, we analysed data submitted to a national ADR database. The objective was to characterise...... ADRs reported for psychotropic medicines in the Danish paediatric population over a decade. FINDINGS: All spontaneous ADR reports from 1998 to 2007 for children from birth to 17 years of age were included. The unit of analysis was one ADR. We analysed the distribution of ADRs per year, seriousness, age...... and gender of the child, suspected medicine and type of reported ADR. A total of 429 ADRs were reported for psychotropic medicines and 56% of these were classified as serious. Almost 20% of psychotropic ADRs were reported for children from birth up to 2 years of age and one half of ADRs were reported...

AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

Science.gov (United States)

Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

Prediction of potential drug targets based on simple sequence properties

Directory of Open Access Journals (Sweden)

Lai Luhua

2007-09-01

Full Text Available Abstract Background During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets. Results Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research. Conclusion We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.

Epidemiology and risk factors for drug allergy.

Science.gov (United States)

Thong, Bernard Y-H; Tan, Teck-Choon

2011-05-01

The aim of this review was to describe the current evidence-based knowledge of the epidemiology, prevalence, incidence, risk factors and genetic associations of drug allergy. Articles published between 1966 and 2010 were identified in MEDLINE using the key words adult, adverse drug reaction reporting systems, age factors, anaphylactoid, anaphylaxis, anaesthetics, antibiotics, child, drug allergy, drug eruptions, ethnic groups, hypersensitivity, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, sex factors, Stevens Johnson syndrome and toxic epidermal necrolysis. Additional studies were identified from article reference lists. Relevant, peer-reviewed original research articles, case series and reviews were considered for review. Current epidemiological studies on adverse drug reactions (ADRs) have used different definitions for ADR-related terminology, often do not differentiate immunologically and non-immunologically mediated drug hypersensitivity, study different study populations (different ethnicities, inpatients or outpatients, adults or children), utilize different methodologies (spontaneous vs. non-spontaneous reporting, cohort vs. case-control studies), different methods of assessing drug imputability and different methods of data analyses. Potentially life-threatening severe cutaneous adverse reactions (SCAR) are associated with a high risk of morbidity and mortality. HLA associations for SCAR associated with allopurinol, carbamazepine and abacavir have been reported with the potential for clinical use in screening prior to prescription. Identification of risk factors for drug allergy and appropriate genetic screening of at-risk ethnic groups may improve the outcomes of drug-specific SCAR. Research and collaboration are necessary for the generation of clinically-relevant, translational pharmacoepidemiological and pharmacogenomic knowledge, and success of health outcomes research and policies on drug allergies. © 2011 The Authors

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

Science.gov (United States)

Besi, E; Boniface, D R; Cregg, R; Zakrzewska, J M

2015-01-01

Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study.

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Lun Yang

2011-03-01

Full Text Available In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI, which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs.

Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews.

Science.gov (United States)

Tutubalina, Elena; Nikolenko, Sergey

2017-01-01

Adverse drug reactions (ADRs) are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.

Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews

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Elena Tutubalina

2017-01-01

Full Text Available Adverse drug reactions (ADRs are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

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David Smith

2013-03-01

Full Text Available Background: Drug adverse event (AE signal detection using the Gamma Poisson Shrinker (GPS is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan. Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds.

Nanomaterials potentiating standard chemotherapy drugs' effect

Science.gov (United States)

Kazantsev, S. O.; Korovin, M. S.

2017-09-01

Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

Causes for the underreporting of adverse drug events by health professionals: a systematic review

Directory of Open Access Journals (Sweden)

Fabiana Rossi Varallo

2014-08-01

Full Text Available Objective: Identifying the main causes for underreporting of Adverse Drug Reaction (ADR by health professionals. Method: A systematic review carried out in the following databases: LILACS, PAHO, SciELO, EMBASE and PubMed in the period between 1992 and 2012. Descriptors were used in the search for articles, and the identified causes of underreporting were analyzed according to the classification of Inman. Results: In total, were identified 149 articles, among which 29 were selected. Most studies were carried out in hospitals (24/29 for physicians (22/29, and pharmacists (10/29. The main causes related to underreporting were ignorance (24/29, insecurity (24/29 and indifference (23/29. Conclusion: The data show the eighth sin in underreporting, which is the lack of training in pharmacovigilance. Therefore, continuing education can increase adherence of professionals to the service and improve knowledge and communication of risks due to drug use.

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

International Nuclear Information System (INIS)

Vedani, Angelo; Dobler, Max; Smieško, Martin

2012-01-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

Energy Technology Data Exchange (ETDEWEB)

Vedani, Angelo, E-mail: angelo.vedani@unibas.ch [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland); Dobler, Max [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Smieško, Martin [Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland)

2012-06-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

Science.gov (United States)

Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

2017-09-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

Adverse and Advantageous Selection in the Medicare Supplemental Market: A Bayesian Analysis of Prescription drug Expenditure.

Science.gov (United States)

Li, Qian; Trivedi, Pravin K

2016-02-01

This paper develops an extended specification of the two-part model, which controls for unobservable self-selection and heterogeneity of health insurance, and analyzes the impact of Medicare supplemental plans on the prescription drug expenditure of the elderly, using a linked data set based on the Medicare Current Beneficiary Survey data for 2003-2004. The econometric analysis is conducted using a Bayesian econometric framework. We estimate the treatment effects for different counterfactuals and find significant evidence of endogeneity in plan choice and the presence of both adverse and advantageous selections in the supplemental insurance market. The average incentive effect is estimated to be $757 (2004 value) or 41% increase per person per year for the elderly enrolled in supplemental plans with drug coverage against the Medicare fee-for-service counterfactual and is $350 or 21% against the supplemental plans without drug coverage counterfactual. The incentive effect varies by different sources of drug coverage: highest for employer-sponsored insurance plans, followed by Medigap and managed medicare plans. Copyright © 2014 John Wiley & Sons, Ltd.

Carbon nanotubes buckypapers for potential transdermal drug delivery

International Nuclear Information System (INIS)

Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

2015-01-01

Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

Carbon nanotubes buckypapers for potential transdermal drug delivery

Energy Technology Data Exchange (ETDEWEB)

Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

2015-12-01

Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

Intimate partner violence and prescription of potentially addictive drugs: prospective cohort study of women in the Oslo Health Study

Science.gov (United States)

Dyb, Grete; Tverdal, Aage; Jacobsen, Geir Wenberg; Schei, Berit

2012-01-01

Objectives To investigate the prescription of potentially addictive drugs, including analgesics and central nervous system depressants, to women who had experienced intimate partner violence (IPV). Design Prospective population-based cohort study. Setting Information about IPV from the Oslo Health Study 2000/2001 was linked with prescription data from the Norwegian Prescription Database from 1 January 2004 through 31 December 2009. Participants The study included 6081 women aged 30–60 years. Main outcome measures Prescription rate ratios (RRs) for potentially addictive drugs derived from negative binomial models, adjusted for age, education, paid employment, marital status, chronic musculoskeletal pain, mental distress and sleep problems. Results Altogether 819 (13.5%) of 6081 women reported ever experiencing IPV: 454 (7.5%) comprised physical and/or sexual IPV and 365 (6.0%) psychological IPV alone. Prescription rates for potentially addictive drugs were clearly higher among women who had experienced IPV: crude RRs were 3.57 (95% CI 2.89 to 4.40) for physical/sexual IPV and 2.13 (95% CI 1.69 to 2.69) for psychological IPV alone. After full adjustment RRs were 1.83 (1.50 to 2.22) for physical/sexual IPV, and 1.97 (1.59 to 2.45) for psychological IPV alone. Prescription rates were increased both for potentially addictive analgesics and central nervous system depressants. Furthermore, women who reported IPV were more likely to receive potentially addictive drugs from multiple physicians. Conclusions Women who had experienced IPV, including psychological violence alone, more often received prescriptions for potentially addictive drugs. Researchers and clinicians should address the possible adverse health and psychosocial impact of such prescription and focus on developing evidence-based healthcare for women who have experienced IPV. PMID:22492384

Reporting of adverse drug reactions: predictors of under-reporting in Malaysia.

Science.gov (United States)

Aziz, Zoriah; Siang, Tan Ching; Badarudin, Nurul Suhaida

2007-02-01

Malaysia like many other countries worldwide uses spontaneous reporting systems as a mean of collecting data on suspected adverse drug reaction (ADR). However, compared to other countries, which use the system, the reporting rate in Malaysia is very low. Why some physicians do not report ADRs is not well understood. To identify factors, which would predict physicians' failure to send ADR reports. Face-to-face interview using a structured questionnaire involving physicians working at the University of Malaya Medical Centre, Malaysia. About a third of the physicians in the Centre participated. Sixty-five of the 415 approached refused to participate. A high proportion of the respondents (81.4%) indicated that they had suspected an ADR but did not report it, while about 40% of the respondents were not aware of the existence of the national reporting system in Malaysia. Logistic regression modelling identified the variable 'ADR considered to be too trivial or too well known to report' as the strongest predictor of not reporting, followed by physicians' category and uncertainty that the reaction had been definitely caused by a drug. Important predictor variables, which limit physicians from reporting ADR in Malaysia, were related to uncertainty of types of reaction to report, lack of awareness about the existence, function and purpose of national ADR reporting. The findings could be useful for planning strategies to improve the reporting rate.

The role of Clinical Pharmacists in the improvement of a pharmacovigilance system: A review of the reported adverse drug reactions during 2004-2010 in Mazandaran Province of Iran

Directory of Open Access Journals (Sweden)

Elham Azhdari

2013-02-01

Full Text Available Background: Following establishment of Iranian Adverse Drug Reaction (ADR Monitoring Center in 1997, ADR committees were established in all hospitals of Mazandaran Province of Iran. Clinical pharmacists from Mazandaran University of Medical Sciences have been involved with these committees since 2007. The aim of this study was to compare the results of the pharmacovigilance system before and after active involvement of clinical pharmacists. Methods: This study included Yellow Cards filled out by healthcare providers in Mazandaran Province during 2004-2010. Frequency of Adverse Drug Reactions (ADRs, route of administration, reporters, number of reports in each years and damaged organs were focuses. Statistical analysis was performed by SPSS 16 software. P Results: A total of 793 yellow cards were completed during 2004 – 2010. Only 38 ADRs (4.8% were related to 2004-2007. Most of the reports generated by Nurses (49.3% followed by Pharmacists and Physicians (P Conclusion: Clinical pharmacists’ intervention regarding establishing ADR committees in the hospitals improved the output of the pharmacovigilance system, although under-reporting is still a major drawback of spontaneous reporting. Keywords: Pharmacovigilance, Adverse Drug Reaction, Mazandaran, Adverse Drug Reaction Reporting Systems

Adverse Drug Reactions Reported With Cholinesterase Inhibitors : An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

NARCIS (Netherlands)

Kroeger, Edeltraut; Mouls, Marie; Wilchesky, Machelle; Berkers, Mieke; Carmichael, Pierre-Hugues; van Marum, Rob; Souverein, Patrick; Egberts, Toine; Laroche, Marie-Laure

2015-01-01

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer's disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer's disease

Filtering Entities to Optimize Identification of Adverse Drug Reaction From Social Media: How Can the Number of Words Between Entities in the Messages Help?

Science.gov (United States)

Abdellaoui, Redhouane; Schück, Stéphane; Texier, Nathalie; Burgun, Anita

2017-06-22

With the increasing popularity of Web 2.0 applications, social media has made it possible for individuals to post messages on adverse drug reactions. In such online conversations, patients discuss their symptoms, medical history, and diseases. These disorders may correspond to adverse drug reactions (ADRs) or any other medical condition. Therefore, methods must be developed to distinguish between false positives and true ADR declarations. The aim of this study was to investigate a method for filtering out disorder terms that did not correspond to adverse events by using the distance (as number of words) between the drug term and the disorder or symptom term in the post. We hypothesized that the shorter the distance between the disorder name and the drug, the higher the probability to be an ADR. We analyzed a corpus of 648 messages corresponding to a total of 1654 (drug and disorder) pairs from 5 French forums using Gaussian mixture models and an expectation-maximization (EM) algorithm . The distribution of the distances between the drug term and the disorder term enabled the filtering of 50.03% (733/1465) of the disorders that were not ADRs. Our filtering strategy achieved a precision of 95.8% and a recall of 50.0%. This study suggests that such distance between terms can be used for identifying false positives, thereby improving ADR detection in social media. ©Redhouane Abdellaoui, Stéphane Schück, Nathalie Texier, Anita Burgun. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 22.06.2017.

Cutaneous adverse reactions of chemotherapy in cancer patients: A clinicoepidemiological study

Directory of Open Access Journals (Sweden)

Saumita Ghosh Biswal

2018-01-01

Full Text Available Background: The diagnosis of cutaneous adversities in the cancer patient is especially difficult, given the complexity of their illness and combination protocols used for the treatment. The present study was undertaken to know the spectrum of cutaneous adversities in patients undergoing chemotherapy and the drug(s most commonly associated with it. Materials and Methods: A total of 1000 patients with malignancies under chemotherapy in the oncology ward and outpatient department were screened in this observational study from January 2013 to February 2015. Relevant investigations for diagnosis of malignancies under chemotherapy and dermatological disorders were carried out. Results: Three hundred and eighty-four patients presented with cutaneous adversities of chemotherapy. The most common was anagen effluvium (78.6%, followed by xerosis (4.4%, thrombophlebitis (3.1%, generalised pruritus (2.9%, melanonychia (2.9%, hand-foot syndrome (2.6%, extravasation reactions (1.8%, flagellate dermatosis (1.3%, prurigo nodularis (0.8%, exfoliation (0.5%, ichthyosis (0.5%, papulopustular rash (0.3%, bullous photodermatitis (0.3%, and Sweet's syndrome (0.3%. Chemotherapeutic drugs were mostly given in combinations. Most common drugs to cause anagen effluvium were alkylating agents in combinations, hand-foot syndrome by taxanes (docetaxel, flagellate dermatoses by antitumour antibiotics (bleomycin, and exfoliation by antimetabolites (methotrexate. The limitation of this study was to imply a specific drug as the causation of the cutaneous adversities since the chemotherapy mostly consisted of combination protocols. Therefore, we have tried to associate the drug combination itself. Conclusion: Chemotherapeutic drugs produce a range of cutaneous adversities, certain specific adversities pertaining to drugs, and their combinations have been implicated which should be looked for and managed accordingly. Knowledge of the adverse effects of anticancer drugs will help

Adverse Events During Immunotherapy Against Grass Pollen-Induced Allergic Rhinitis

DEFF Research Database (Denmark)

Aasbjerg, Kristian; Dalhoff, Kim Peder; Backer, Vibeke

2015-01-01

Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual...... and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy (SLIT) against grass pollen-induced AR. A thorough literature search was performed with PubMed and EMBASE. The findings were compared...

An analysis of serious adverse drug reactions at a tertiary care teaching hospital

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Kinjal Prajapati

2016-01-01

Full Text Available Objective: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. Materials and Methods: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo′s algorithm, severity (Hartwig and Siegel scale, and preventability (Schumock and Thornton criteria. Results: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%. The common causal drug group was antitubercular (129, 34.4% followed by antiretroviral (76, 20.3% agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7% followed by hospitalization (158, 42.1%. Majority of the serious ADRs were continuing (191, 50.9% at the time of reporting, few recovered (101, 26.9%, and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8% followed by probable (173, 46.1% in nature. Conclusion: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.

Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

Science.gov (United States)

Krentz, A J; Fujioka, K; Hompesch, M

2016-06-01

Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. © 2016 John Wiley & Sons Ltd.

Adverse Drug Reactions Reported With Cholinesterase Inhibitors: An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

NARCIS (Netherlands)

Kroger, E.; Mouls, M.; Wilchesky, M.; Berkers, M.; Carmichael, P.H.; van Marum, R.J.; Souverein, P.; Egberts, T.; Laroche, M.L.

2015-01-01

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer’s disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer’s disease

Detection of Adverse Reaction to Drugs in Elderly Patients through Predictive Modeling

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Rafael San-Miguel Carrasco

2016-03-01

Full Text Available Geriatrics Medicine constitutes a clinical research field in which data analytics, particularly predictive modeling, can deliver compelling, reliable and long-lasting benefits, as well as non-intuitive clinical insights and net new knowledge. The research work described in this paper leverages predictive modeling to uncover new insights related to adverse reaction to drugs in elderly patients. The differentiation factor that sets this research exercise apart from traditional clinical research is the fact that it was not designed by formulating a particular hypothesis to be validated. Instead, it was data-centric, with data being mined to discover relationships or correlations among variables. Regression techniques were systematically applied to data through multiple iterations and under different configurations. The obtained results after the process was completed are explained and discussed next.

Understanding the nature of errors in nursing: using a model to analyse critical incident reports of errors which had resulted in an adverse or potentially adverse event.

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Meurier, C E

2000-07-01

Human errors are common in clinical practice, but they are under-reported. As a result, very little is known of the types, antecedents and consequences of errors in nursing practice. This limits the potential to learn from errors and to make improvement in the quality and safety of nursing care. The aim of this study was to use an Organizational Accident Model to analyse critical incidents of errors in nursing. Twenty registered nurses were invited to produce a critical incident report of an error (which had led to an adverse event or potentially could have led to an adverse event) they had made in their professional practice and to write down their responses to the error using a structured format. Using Reason's Organizational Accident Model, supplemental information was then collected from five of the participants by means of an individual in-depth interview to explore further issues relating to the incidents they had reported. The detailed analysis of one of the incidents is discussed in this paper, demonstrating the effectiveness of this approach in providing insight into the chain of events which may lead to an adverse event. The case study approach using critical incidents of clinical errors was shown to provide relevant information regarding the interaction of organizational factors, local circumstances and active failures (errors) in producing an adverse or potentially adverse event. It is suggested that more use should be made of this approach to understand how errors are made in practice and to take appropriate preventative measures.

[PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT].

Science.gov (United States)

Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia

2015-01-01

To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm

OAE: The Ontology of Adverse Events.

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He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

2014-01-01

A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e

Differences by Veteran/civilian status and gender in associations between childhood adversity and alcohol and drug use disorders.

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Evans, Elizabeth A; Upchurch, Dawn M; Simpson, Tracy; Hamilton, Alison B; Hoggatt, Katherine J

2018-04-01

To examine differences by US military Veteran status and gender in associations between childhood adversity and DSM-5 lifetime alcohol and drug use disorders (AUD/DUD). We analyzed nationally representative data from 3119 Veterans (n = 379 women; n = 2740 men) and 33,182 civilians (n = 20,066 women; n = 13,116 men) as provided by the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). We used weighted multinomial logistic regression, tested interaction terms, and calculated predicted probabilities by Veteran status and gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pairwise comparisons. Among civilians, women had lower AUD and DUD prevalence than men; however, with more childhood adversity, this gender gap narrowed for AUD and widened for DUD. Among Veterans, in contrast, similar proportions of women and men had AUD and DUD; with more childhood adversity, AUD-predicted probability among men surpassed that of women. Childhood adversity elevated AUD probability among civilian women to levels exhibited by Veteran women. Among men, Veterans with more childhood adversity were more likely than civilians to have AUD, and less likely to have DUD. Childhood adversity alters the gender gap in AUD and DUD risk, and in ways that are different for Veterans compared with civilians. Department of Defense, Veterans Affairs, and community health centers can prevent and ameliorate the harmful effects of childhood adversity by adapting existing behavioral health efforts to be trauma informed, Veteran sensitive, and gender tailored.

Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

DEFF Research Database (Denmark)

Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

2010-01-01

BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...

A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients.

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Rosliana Rosli

Full Text Available Spontaneous reporting on adverse drug reactions (ADR has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups.Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification, category of ADR (according to system organ class as well as the severity of the ADR.In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%. The most common ADRs reported were from the following system organ classes: application site disorders (32.2%, skin and appendages disorders (20.6%, body as a whole general disorders (12.8% and central and peripheral nervous system disorders (11.2%. Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0% were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%. Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities.ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of

The in vitro diagnosis of drug allergy: status and perspectives

NARCIS (Netherlands)

Ebo, D. G.; Leysen, J.; Mayorga, C.; Rozieres, A.; Knol, E. F.; Terreehorst, I.

2011-01-01

Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the

Drug affordability-potential tool for comparing illicit drug markets.

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Groshkova, Teodora; Cunningham, Andrew; Royuela, Luis; Singleton, Nicola; Saggers, Tony; Sedefov, Roumen

2018-06-01

-national comparisons of retail drug markets in Europe. Future work will need to examine other potential uses of the drug affordability tool. The limitations of this measure reflect primarily the limitations of the constituent data; in addition to issues inherent in collecting accurate data on illicit markets, analysis that relies on data collected from multiple countries is susceptible to discrepancies in data collection practices from country to country. Copyright © 2018 Elsevier B.V. All rights reserved.

Adverse effects of concentrated green tea extracts.

Science.gov (United States)

Schönthal, Axel H

2011-06-01

A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Campania preventability assessment committee: a focus on the preventability of the contrast media adverse drug reactions.

Science.gov (United States)

Sessa, Maurizio; Rossi, Claudia; Rafaniello, Concetta; Mascolo, Annamaria; Cimmaruta, Daniela; Scavone, Cristina; Fiorentino, Sonia; Grassi, Enrico; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

2016-12-01

The current study aims to assess the preventability of the contrast media adverse drug reactions reported through the Campania spontaneous reporting system, identifying the possible limitations emerged in this type of evaluation. All the individual case safety reports validated by the Campania Pharmacovigilance Regional Centre from July 2012 to September 2015 were screened to select those that reported contrast media as suspected drug. Campania Preventability Assessment Committee, in collaboration with clinicians specialized in Radiology, assessed the preventability according to the P-Method, through a case-by-case approach. From July 2012 to September 2015, 13798 cases were inserted by pharmacovigilance managers in the Italian Pharmacovigilance Network database (in the geographical contest of the Campania Region), of which 67 reported contrast media as suspected drug. Five preventable cases were found. The most reported causes for preventability were the inappropriate drug use for the case clinical conditions and the absence of the preventive measure administrated prior to the contrast media administration. Several limitations were found in the evaluation of the critical criteria for the preventability assessment. Educational initiatives will be organized directly to the healthcare professionals involved in the contrast media administration, to promote an appropriate use of the contrast media.

MONITORING POTENTIAL DRUG INTERACTIONS AND REACTIONS VIA NETWORK ANALYSIS OF INSTAGRAM USER TIMELINES.

Science.gov (United States)

Correia, Rion Brattig; Li, Lang; Rocha, Luis M

2016-01-01

Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this "Bibliome", the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products-including cannabis-which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015.We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that Instagram

Adverse drug reactions to CT contrast media in south Korea: Incidence and risk factors

International Nuclear Information System (INIS)

Bae, Kyung Soo; Jeon, Kyung Nyeo; Moon, Jin Il; Choi, Bo Hwa; Baek, Hye Jin; Cho, Soo Buem; Lee, Sang Min; Ha, Ji Young; Choi, Dae Seob; Cho, Jae Min; Na, Jae Beom

2016-01-01

To evaluate the incidence, severity, and risk factors of adverse drug reactions (ADR) to intravenous administration of nonionic iodinated contrast media in computed tomography (CT), and to determine the recurrence rate after premedication in patients with a previous history of ADR. We prospectively recorded all ADR to intravenous CT contrast media in 32313 consecutive outpatients (54572 cases) who underwent contrast enhanced CT examinations. Clinical report forms and electronic medical records were reviewed to search for the incidence of ADR, treatment, and clinical outcome of patients. The risk factors of ADR to CT contrast media (age, sex, history of previous ADR, season) were evaluated using statistical analysis. Of the 54572 cases, a total of 191 (0.35%) had adverse reactions. Of the 191 cases, 157 (82%) were categorized as mild reactions, 29 (15%) were moderate, and 5 (3%) were severe. A total of 165 (86.4%) cases had acute adverse reactions (which occurred within 1 hour after administration), while 26 (13.6%) had delayed adverse reactions (occurred 1 hour after the administration). The rate of ADR was significantly higher in females [relative risk (RR) = 2.05, 95% confidence interval (CI) 1.53-2.75], patients under the age of 60 years (RR = 1.45, 95% CI 1.07-1.98), patients with a history of previous ADR (RR = 6.51, 95% CI 3.13-13.57), and in the spring season (RR = 1.44, 95% CI 1.07-1.95). The recurrence rate after premedication in patients with previous ADR to CT contrast media was 3.2% (8/247). No deaths occurred that were attributed to the contrast media. The incidence of ADR to nonionic CT contrast media was 0.35%; most of which were mild reactions. Risk factors for ADR included female gender, an age of under 60 years, a history of previous ADR, and spring season

Adverse drug reactions to CT contrast media in south Korea: Incidence and risk factors

Energy Technology Data Exchange (ETDEWEB)

Bae, Kyung Soo; Jeon, Kyung Nyeo; Moon, Jin Il; Choi, Bo Hwa; Baek, Hye Jin; Cho, Soo Buem [Dept. of Radiology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon (Korea, Republic of); Lee, Sang Min; Ha, Ji Young; Choi, Dae Seob; Cho, Jae Min; Na, Jae Beom [Dept. of Radiology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)

2016-07-15

To evaluate the incidence, severity, and risk factors of adverse drug reactions (ADR) to intravenous administration of nonionic iodinated contrast media in computed tomography (CT), and to determine the recurrence rate after premedication in patients with a previous history of ADR. We prospectively recorded all ADR to intravenous CT contrast media in 32313 consecutive outpatients (54572 cases) who underwent contrast enhanced CT examinations. Clinical report forms and electronic medical records were reviewed to search for the incidence of ADR, treatment, and clinical outcome of patients. The risk factors of ADR to CT contrast media (age, sex, history of previous ADR, season) were evaluated using statistical analysis. Of the 54572 cases, a total of 191 (0.35%) had adverse reactions. Of the 191 cases, 157 (82%) were categorized as mild reactions, 29 (15%) were moderate, and 5 (3%) were severe. A total of 165 (86.4%) cases had acute adverse reactions (which occurred within 1 hour after administration), while 26 (13.6%) had delayed adverse reactions (occurred 1 hour after the administration). The rate of ADR was significantly higher in females [relative risk (RR) = 2.05, 95% confidence interval (CI) 1.53-2.75], patients under the age of 60 years (RR = 1.45, 95% CI 1.07-1.98), patients with a history of previous ADR (RR = 6.51, 95% CI 3.13-13.57), and in the spring season (RR = 1.44, 95% CI 1.07-1.95). The recurrence rate after premedication in patients with previous ADR to CT contrast media was 3.2% (8/247). No deaths occurred that were attributed to the contrast media. The incidence of ADR to nonionic CT contrast media was 0.35%; most of which were mild reactions. Risk factors for ADR included female gender, an age of under 60 years, a history of previous ADR, and spring season.

Modelling the adverse effects associated with ecstasy use.

Science.gov (United States)

Fisk, John E; Murphy, Philip N; Montgomery, Catharine; Hadjiefthyvoulou, Florentia

2011-04-01

Ecstasy, the street name for 3,4-meththylenedioxymethamphetamine, has been associated with a range of psychiatric symptoms and impaired psychological health in both problem and recreational users. The purpose of the present paper is to determine how these impairments are related to the history of polydrug use, and the conditions under which individuals ingest ecstasy. Associations between the variables of interest were investigated utilizing negative binomial regression. Liverpool and Preston in the North West of England. A convenience sample of 159 recreational ecstasy/polydrug users (80 males, 79 females). The sample was composed primarily of undergraduates. The dependent variable was the number of reported ecstasy-related adverse effects. Independent variables included quantitative aspects of ecstasy and other drug use, and the various beliefs and behaviours associated with ecstasy use. The number of adverse effects was associated positively with life-time exposure to ecstasy and negatively with period of abstinence from the drug. Adverse effects were more common among those who consumed ecstasy and alcohol concurrently, but were unrelated to other aspects of polydrug use. They were unaffected by whether the user took precautions when using the drug, and only weakly related to prior beliefs concerning the effects of ecstasy. Greater life-time exposure to ecstasy and consuming the drug concurrently with alcohol increase the likelihood of experiencing adverse effects, including paranoia, poor general health, irritability, confusion and moodiness. Adverse effects decrease with the period of abstinence from the drug. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Investigating drug repositioning opportunities in FDA drug labels through topic modeling.

Science.gov (United States)

Bisgin, Halil; Liu, Zhichao; Kelly, Reagan; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-01-01

addition, we identified two therapeutic groups of drugs (Musculo-skeletal system and Anti-infective for systemic use) where over 80% of the drugs have a potential replacement with high significance. Topic modeling can be a powerful tool for the identification of repositioning opportunities by examining the adverse event terms in FDA approved drug labels. The proposed framework not only suggests drugs that can be repurposed, but also provides insight into the safety of repositioned drugs.

Nurses' reporting of suspect adverse drug reactions: a mixed-methods study

Directory of Open Access Journals (Sweden)

Alessia De Angelis

2015-12-01

Full Text Available OBJECTIVE: To assess nurses' knowledge, attitudes and practices (KAP towards spontaneous adverse drug reactions (ADRs reporting. METHODS: The mixed-method study was conducted following a quanti-qualitative sequential approach: a survey (using a KAP questionnaire followed by a focus group was performed. RESULTS: In the quantitative findings, responders (570 hospital nurses declared that they were unaware of the pharmacovigilance system (58.1%, n = 331; where to find the reporting form (63.5%, n = 362; how fill it in (71.6%, n = 408; to whom and how to send it (65.8%, n = 375. Only 11.1% (n = 63 reported ADRs. The qualitative phase supported the quantitative findings and provided new information about other factors that condition ADR reporting: misinterpretation of the meaning of "reporting", unawareness of nurses' autonomy in ADR reporting and fear of consequences after ADR reporting. CONCLUSION: Nurses are not fully aware of their role in ADR reporting. We recommend educational interventions and management changes.

Potential drug interactions in patients given antiretroviral therapy.

Science.gov (United States)

Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-11-21

to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga

Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.

Science.gov (United States)

Muhič, Neža; Mrhar, Ales; Brvar, Miran

2017-07-01

Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.

The innovative use of a large-scale industry biomedical consortium to research the genetic basis of drug induced serious adverse events.

Science.gov (United States)

Holden, Arthur L

2007-01-01

The International Serious Adverse Event Consortium (SAEC) is a pharmaceutical industry and FDA led international (501 c3 non-profit) consortium, focused on identifying and validating DNA-variants useful in predicting the risk of drug induced, rare serious adverse events (SAEs). As such, it functions with the explicit purpose of enhancing the 'public good'. Its members are (i) organizations engaged principally in the business of discovering, developing and marketing pharmaceutical products, or (ii) a charitable, governmental, or other non-profit organization with an interest in researching the molecular basis of drug response.Drug-induced, rare SAEs present significant health issues for patients; and pose challenges for the safe use of approved drugs and the development of new drugs. Examples of drug-induced, rare SAEs include hepatotoxicity, QT prolongation, rhabdomyolosis, serious skin rashes (e.g. SJS), edema, acute renal failure, acute hypersensitivity, anemias/neutropenias, excessive weigh gain, retinopathy, vasculitis, among others. The rarity of such drug induced SAEs and the absence of effective government surveillance/research networks, makes it extremely difficult for any one company or research entity to accrue enough SAE cases and controls to conduct effective whole genome studies. Central to the notion of the SAEC is industry, government and health care providers can join forces to make use of a variety of sample and data resources in researching the genetic basis of these events.The purpose of the SAEC is threefold:•To carry out research directed toward the discovery of DNA-variants clinically useful in understanding and predicting the risk of drug induced serious adverse events and similar scientific research.•To ensure the widespread availability of the results of such research to the scientific research community and the public at large for no charge through publication and web-based methods; and•To educate the scientific research and medical

The Impact of Experiencing Adverse Drug Reactions on the Patient's Quality of Life : A Retrospective Cross-Sectional Study in the Netherlands

NARCIS (Netherlands)

Rolfes, Leàn; van Hunsel, Florence; Taxis, Katja; van Puijenbroek, Eugène

INTRODUCTION: There is little information as to what extent adverse drug reactions (ADRs) influence patients' health-related quality of life (HR-QOL). From a pharmacovigilance perspective, capturing and making the best use of this information remains a challenge. The Netherlands Pharmacovigilance

Human abuse liability evaluation of CNS stimulant drugs.

Science.gov (United States)

Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

2014-12-01

Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adverse childhood experiences and consumption of alcohol, tobacco and illicit drugs among adolescents of a Brazilian birth cohort.

Science.gov (United States)

Gonçalves, Helen; Soares, Ana Luiza Gonçalves; Santos, Ana Paula Gomes Dos; Ribeiro, Camila Garcez; Bierhals, Isabel Oliveira; Vieira, Luna Strieder; Hellwig, Natália Limões; Wehrmeister, Fernando C; Menezes, Ana M B

2016-11-03

The objective of this study was to investigate the association between adverse childhood experiences (ACEs) and the use of alcohol, tobacco and illicit drugs among adolescents from a Brazilian cohort. The occurrence of five ACEs, the use of alcohol and tobacco and trying illicit drugs were investigated in the 1993 Pelotas birth cohort at the age of 15 (n = 4,230). A score was created for the ACEs and their association with the use of substances was evaluated. Around 25% of adolescents consumed alcohol, 6% smoked and 2.1% reported having used drugs at least once in their lives. The ACEs were associated with the use of alcohol, tobacco and illicit drugs. A dose-response relation between the number of ACEs and the substance use was found, particularly with regard to illicit drugs. The occurrence of ACEs was positively associated with the use of alcohol, tobacco and illicit drugs among adolescents and the risk may be different for men and women. These results point to the fact that strategies for preventing the use of substances should include interventions both among adolescents and within the family environment.

Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration Adverse Event database: a systematic Bayesian signal detection analysis.

Science.gov (United States)

Baker, Ross A; Pikalov, Andrei; Tran, Quynh-Van; Kremenets, Tatyana; Arani, Ramin B; Doraiswamy, P Murali

2009-01-01

Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database. Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05-EB95) were calculated to estimate the degree of drug-event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05-LR95) were calculated for diabetes mellitus events. All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios. In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

Potential drug therapies for the treatment of fibromyalgia.

Science.gov (United States)

Lawson, Kim

2016-09-01

Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

Clinical relevance of cimetidine drug interactions.

Science.gov (United States)

Shinn, A F

1992-01-01

The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

Science.gov (United States)

Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

2011-11-01

We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups. Copyright © 2011 Elsevier Inc. All rights reserved.

Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

International Nuclear Information System (INIS)

Connor, Michael J.; Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd; Recht, Abram; Hattangadi-Gluth, Jona A.

2017-01-01

Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ"2 test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance, improved

Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

Energy Technology Data Exchange (ETDEWEB)

Connor, Michael J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California (United States); Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

2017-01-01

Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

Directory of Open Access Journals (Sweden)

Toshiyuki Sakaeda

Full Text Available OBJECTIVE: Adverse event reports (AERs submitted to the US Food and Drug Administration (FDA were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors (statins and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

Science.gov (United States)

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

Science.gov (United States)

Andrade, Paulo Henrique Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros

2017-01-01

The present study aims to identify the risk factors for adverse drug reactions (ADR) in pediatric inpatients. A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used. A total of 173 children (208 admissions) and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%). In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56) were identified risk factors for ADR. We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

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Paulo Henrique Santos Andrade

Full Text Available The present study aims to identify the risk factors for adverse drug reactions (ADR in pediatric inpatients.A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used.A total of 173 children (208 admissions and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%. In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR 2.44; 95% confidence interval (CI 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54, antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98 and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56 were identified risk factors for ADR.We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

Severe adverse drug reaction following Crotalidae Polyvalent Immune Fab (Ovine) administration for copperhead snakebite.

Science.gov (United States)

Lepak, Maryjoy R; Bochenek, Samantha H; Bush, Sean P

2015-01-01

To present the case of a severe anaphylactic/anaphylactoid reaction to Crotalidae Polyvalent Immune Fab (Ovine) in a patient bitten by a copperhead snake. A 68-year-old man presented with progressive envenomation after receiving a copperhead snakebite on each hand. Crotalinae Fab antivenom was administered. While the initial and only dose was partially infusing, the patient developed an adverse drug reaction (ADR) of urticaria and hypotension, which resolved with cessation of the infusion, recurred with resumption of the infusion, and ultimately was completed with supportive care. An additional episode of hypotension, urticaria, and angioedema occurred shortly after antivenom therapy completion. Epinephrine was administered, resolving the reaction with complete patient recovery. The event received a Naranjo score of 10, indicating a definite ADR. Treating copperhead snakebites with antivenom is a matter of debate. Concern over adverse events and cost induce some physicians to manage copperhead bites without antivenom because they are generally milder in severity. As demonstrated in this case, severe ADR can occur with Crotalinae Fab antivenom, and its efficacy for copperhead envenoming needs to be better established via placebo-controlled, randomized trials. © The Author(s) 2014.

Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole

DEFF Research Database (Denmark)

Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine

2016-01-01

Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study...... with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic...

A STUDY ON ADVERSE DRUG REACTIONS INVOLVING CENTRAL NERVOUS SYSTEM, ITS SEVERITY AND CAUSALITY ASSESSMENT IN PEDIATRIC PATIENTS ADMITTED TO A TERTIARY CARE HOSPITAL

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Arati

2015-09-01

Full Text Available A retrospective study was conducted in Department of pediatrics SCB Medical College and SVPPGIP for a period of 2 years i.e. September 2012 to August 2014 . All the patients from birth to 14 years admitted to the pediatric ward in this study were under ADR surveillance. Patients admitted to our hospital with adverse drug reaction o r patients developing adverse drug reaction in our hospital were studied; only those cases where the central nervous system was involved were taken in our study. The cases were compiled and the causality of offending drugs was found using WHO - UMC causality assessment score. The severity of drug reaction in every case was determined by using HARTWIG’s severity scoring scale. Total 350 Adverse reactions were reported in this period with prevalence rate of 2.04% i.e. 20 out of 1000 children faced ADR due to dr ugs, with annual incidence rate of 0.9% and 1.14% over two years. Out of total 350 cases dermatological system was most commonly involved i.e. 207 cases (59.14%. This is followed by involvement of central nervous system 46 number of cases (13.14%. The GI system was involved in 34 cases i.e. (9.71%. Life threatening reactions like anaphylaxis, angioedema and shock like immediate life threatening ADRs were reported in 16 cases. Our study group was the patient in whom the ADR involved the CNS. Out of 46 suc h cases, there were 25 female and 21 male. Various reaction due to drug were encephalopathy , eps, febrile seizure, tremor, head reeling, ototoxicity, persistant cry, pseudotumor cerebri, psychosis, seizure, status epilepticus, toxic amblyopia, tremor, atax ia etc. The most common CNS manifestation was Extra pyramidal side effects (EPS involving 21% of cases. The most common Drug causing CNS manifestation was ATT (HRZE causing blindness, Eps, psychosis , toxic amblyopia blindness etc.

Prediction of drug-related cardiac adverse effects in humans--B: use of QSAR programs for early detection of drug-induced cardiac toxicities.

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Frid, Anna A; Matthews, Edwin J

2010-04-01

This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme, MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs. Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs. Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows, respectively: 70.7%, 91.7%, and 98.0% specificity; 74.7%, 47.2%, and 21.0% sensitivity; and 138.2, 206.3, and 144.2 chi(2). In addition, a prospective study using AE data from the U.S. Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity. Published by Elsevier Inc.

Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

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Yuri Pevzner

2014-05-01

Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

Directory of Open Access Journals (Sweden)

Yuri Pevzner

2015-08-01

Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

Caracterización de las reacciones adversas medicamentosas en ancianos: Cuba, 2003-2005 Characterization of the adverse reactions to drugs in the elderly: Cuba, 2003-2005

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Raisa Rodriguez Duque

2007-12-01

Full Text Available El seguimiento de las reacciones adversas en poblaciones de riesgo como los ancianos es prioridad del sistema cubano de farmacovigilancia. Por lo que se realizó una investigación descriptiva y prospectiva, para caracterizar las notificaciones de sospechas de reacciones adversas medicamentosas en ancianos mayores de 60 años de edad, recibidas en la Unidad Coordinadora Nacional de Farmacovigilancia desde el 1ro de enero de 2003 al 31 de diciembre de 2005. Constituyeron objetivos del trabajo la identificación de los grupos farmacológicos que produjeron las reacciones adversas medicamentosas así como los fármacos más comprometidos, la clasificación de las reacciones adversas según la severidad, el mecanismo de producción, el sistema de órgano afectado y el grado de imputabilidad. De igual manera, se analizó si la presencia de factores como la polifarmacia y los antecedentes patológicos personales predisponen la aparición de la reacción adversa medicamentosa y su posible prevención. Los resultados más importantes muestran que los grupos farmacológicos con mayor representatividad resultaron los antibacterianos, los antihipertensivos y los antiinflamatorios y analgésicos no opioides; los fármacos más frecuentes fueron el captopril, la penicilina procaínica y la nifedipina; las reacciones leves ocuparon el mayor porcentaje así como las reacciones probables. Predominó el mecanismo de producción tipo A; el sistema de órgano más afectado fue la piel y anejos, y la presencia de antecedentes patológicos personales propició en gran medida la aparición de las reacciones adversas medicamentosas, lo que no ocurrió con la polifarmacia. Se pudieron haber evitado el 82,3 % del total de reacciones adversas medicamentosas estudiadasThe follow-up of adverse reactions in risk populations as the elderly is a priority of the Cuban drug surveillance system. A descriptive and prospective research was conducted to characterize the

Arabic translation and cultural adaptation of Liverpool Adverse ...

African Journals Online (AJOL)

Keywords: Adverse drug event, Epilepsy, Older adults, Cronbach's alpha, Liverpool Adverse Events. Profile, Seizure ... uncommon symptoms such as memory loss [5]. Age is a known .... to control seizures and minimize their side effects. [22].

ADEpedia: a scalable and standardized knowledge base of Adverse Drug Events using semantic web technology.

Science.gov (United States)

Jiang, Guoqian; Solbrig, Harold R; Chute, Christopher G

2011-01-01

A source of semantically coded Adverse Drug Event (ADE) data can be useful for identifying common phenotypes related to ADEs. We proposed a comprehensive framework for building a standardized ADE knowledge base (called ADEpedia) through combining ontology-based approach with semantic web technology. The framework comprises four primary modules: 1) an XML2RDF transformation module; 2) a data normalization module based on NCBO Open Biomedical Annotator; 3) a RDF store based persistence module; and 4) a front-end module based on a Semantic Wiki for the review and curation. A prototype is successfully implemented to demonstrate the capability of the system to integrate multiple drug data and ontology resources and open web services for the ADE data standardization. A preliminary evaluation is performed to demonstrate the usefulness of the system, including the performance of the NCBO annotator. In conclusion, the semantic web technology provides a highly scalable framework for ADE data source integration and standard query service.

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

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Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

Directory of Open Access Journals (Sweden)

Mugoša S

2016-08-01

Full Text Available Snežana Mugoša,1,2 Nataša Djordjević,3 Nina Djukanović,4 Dragana Protić,5 Zoran Bukumirić,6 Ivan Radosavljević,7 Aneta Bošković,8 Zoran Todorović5,9 1Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro, 2Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro; 3Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 4High Medical School “Milutin Milanković”, Belgrade, 5Department of Pharmacology, Clinical Pharmacology and Toxicology, 6Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, 7Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 8Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro; 9Department of Clinical Immunology and Allergy, Medical Center “Bežanijska kosa”, Belgrade, Serbia Abstract: The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6 poor metabolizer alleles (*3, *4, *5, and *6 on a Montenegrin population and its impact on developing adverse drug reactions (ADRs of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9% patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001, with ADRs’ occurrence significantly

Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

Science.gov (United States)

Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

2013-01-01

Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence.

Science.gov (United States)

Matthews, Edwin J; Frid, Anna A

2010-04-01

This is the first of two reports that describes the compilation of a database of drug-related cardiac adverse effects (AEs) that was used to construct quantitative structure-activity relationship (QSAR) models to predict these AEs, to identify properties of pharmaceuticals correlated with the AEs, and to identify plausible mechanisms of action (MOAs) causing the AEs. This database of 396,985 cardiac AE reports was linked to 1632 approved drugs and their chemical structures, 1851 clinical indications (CIs), 997 therapeutic targets (TTs), 432 pharmacological MOAs, and 21,180 affinity coefficients (ACs) for the MOA receptors. AEs were obtained from the Food and Drug Administration's (FDA's) Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) and publicly available medical literature. Drug TTs were obtained from Integrity; drug MOAs and ACs were predicted by BioEpisteme. Significant cardiac AEs and patient exposures were estimated based on the proportional reporting ratios (PRRs) for each drug and each AE endpoint as a percentage of the total AEs. Cardiac AE endpoints were bundled based on toxicological mechanism and concordance of drug-related findings. Results revealed that significant cardiac AEs formed 9 clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes), and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). Based on the observation that each drug had one TT and up to 9 off-target MOAs, cardiac AEs were highly correlated with drugs affecting cardiovascular and cardioneurological functions and certain MOAs (e.g., alpha- and beta-adeno, dopamine, and hydroxytryptomine receptors). Copyright 2010. Published by Elsevier Inc.

Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

Science.gov (United States)

Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

2017-07-01

We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation. © The Author 2017. Published by Oxford University Press on behalf of the American

Retrieval of Enterobacteriaceae drug targets using singular value decomposition.

Science.gov (United States)

Silvério-Machado, Rita; Couto, Bráulio R G M; Dos Santos, Marcos A

2015-04-15

The identification of potential drug target proteins in bacteria is important in pharmaceutical research for the development of new antibiotics to combat bacterial agents that cause diseases. A new model that combines the singular value decomposition (SVD) technique with biological filters composed of a set of protein properties associated with bacterial drug targets and similarity to protein-coding essential genes of Escherichia coli (strain K12) has been created to predict potential antibiotic drug targets in the Enterobacteriaceae family. This model identified 99 potential drug target proteins in the studied family, which exhibit eight different functions and are protein-coding essential genes or similar to protein-coding essential genes of E.coli (strain K12), indicating that the disruption of the activities of these proteins is critical for cells. Proteins from bacteria with described drug resistance were found among the retrieved candidates. These candidates have no similarity to the human proteome, therefore exhibiting the advantage of causing no adverse effects or at least no known adverse effects on humans. rita_silverio@hotmail.com. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of membrane diffusion potential change on anionic drugs ...

African Journals Online (AJOL)

The effect of membrane potential change on anionic drugs Indomethacin and barbitone induced human erythrocyte shape change and red cell uptake of drug has been studied using microscopy and spectrophotometry techniques respectively. The membrane potential was changed by reducing the extracellular chloride ...

[Drugs and light].

Science.gov (United States)

Tønnesen, H H

1997-06-30

The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

Science.gov (United States)

Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

2017-07-01

Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Perfluorocarbon (PFC) emulsions as potential drug carriers

International Nuclear Information System (INIS)

Yuhas, J.M.; Goodman, R.L.; Moore, R.E.

1984-01-01

PFC emulsions have excellent oxygen transporting properties and have been reported to enhance the response of murine tumors to both radiation and BCNU. While the presently available emulsions are far too toxic to the immune system to be used in cancer therapy, they can be used to investigate the overall potential of this approach. As an example, the authors have found that these emulsions can alter drug availability. The lipophilicity of both the PFC and the drug in question determine the partitioning of the drug between the organic and aqueous phases of an emulsion. In vitro, this can reduce drug effectiveness by reducing the amount of drug available to the cells. In vivo, however, this partitioning may produce sustained drug exposure, which could be of benefit in cancer therapy and other applications. In brief, as the drug is absorbed from the circulating aqueous phase, additional drug would leach from the PFC, thereby providing a sustained drug exposure similar to that obtained with liposomes. While a great deal more work will be required to evaluate the practicality of this approach, the existence of this phenomenon must be taken into account in both the design and interpretation of efficacy studies in which anesthetics, chemotherapeutics, etc are employed

Safe Handling of Cytotoxic Drugs and Risks of Occupational Exposure to Nursing Staffs

Directory of Open Access Journals (Sweden)

Somayeh Hanafi

2016-05-01

Full Text Available Background: Inherent toxicity of cytotoxic drugs is the basis for their potential adverse risks from occupational exposure to the nursing staff. In Iran, chemotherapy regimens are prescribed and administered according to the world updated protocols. But little is done regarding the protective standards in this field.Methods: An observational cross-sectional survey was conducted among nurses who work in three tertiary care teaching hospitals in Tehran, Iran in 2012. All participants worked in one of the hospital wards handling cytotoxic drugs (preparation and administration. A questionnaire was used for interviewing all subjects, and observing them preparing and administering the drugs. We examined all adverse effects associated with handling of antineoplastic drugs.Results: Totally 270 adverse reactions were reported. The most frequently reported adverse effects included headache and vertigo (40 cases, hair loss (36 cases, skin rashes and itching (31 cases, and burning sensation in eyes (31 cases. In all hospital wards, the standards were met in not more than 50% of the items.Conclusion: Monitoring the personnel who are directly involved in handling of cytotoxic drugs is of great importance. Furthermore, educating the personnel in the field of standards of cytotoxic drugs handling could increase the nursing staff’s knowledge regarding these drugs’ adverse reactions.

Prospective observational study of adverse drug reactions to diclofenac in children

Science.gov (United States)

Standing, Joseph F; Ooi, Kuan; Keady, Simon; Howard, Richard F; Savage, Imogen; Wong, Ian C K

2009-01-01

AIM The aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODS A prospective observational study was undertaken on paediatric surgical patents aged ≤12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTS Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%. PMID:19694745

Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

International Nuclear Information System (INIS)

Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

2017-01-01

Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

Dithranol-loaded lipid-core nanocapsules improve the photostability and reduce the in vitro irritation potential of this drug

Energy Technology Data Exchange (ETDEWEB)

Savian, Ana L. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Rodrigues, Daiane [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Weber, Julia; Ribeiro, Roseane F. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Motta, Mariana H. [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Schaffazick, Scheila R.; Adams, Andréa I.H. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105-900 (Brazil); Andrade, Diego F. de; Beck, Ruy C.R. [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS 90610-000 (Brazil); and others

2015-01-01

Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230–250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1 h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7 h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug. - Highlights: • Strategy to prepare lipid-core nanocapsules containing dithranol • Evaluation of the nanoencapsulation effect on the photostability and irritation • Evaluation of the in vitro release of dithranol-loaded lipid-core nanocapsules.

Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999

DEFF Research Database (Denmark)

Andersen, V; Sonne, J; Andersen, M

2001-01-01

valproate (two cases), clomipramine (one case) and azathioprine (one case). Definite relationship was stated for mesalazine (three cases), azathioprine (two cases) and simvastatin (one case) on the basis of re-challenge. A possible or probable causality was considered for a further 30 drugs including 5...... (measles" mumps/rubella) vaccination. CONCLUSION: Drug-induced pancreatitis is rarely reported. The incidence may be increasing and the course is often serious. This is the first report on definite simvastatin-induced pancreatitis. Further studies on the pancreotoxic potential of drugs are warranted.......OBJECTIVES: To present an update on drug-induced pancreatitis reported to the Danish Committee on Adverse Drug Reactions. DESIGN: Retrospective study of spontaneous case reports to the Danish reporting system on adverse drug reactions. METHODS: All cases of suspected drug-induced pancreatitis...

Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period.

Science.gov (United States)

Shimada, Yutaka; Fujimoto, Makoto; Nogami, Tatsuya; Watari, Hidetoshi; Kitahara, Hideyuki; Misawa, Hiroki; Kimbara, Yoshiyuki

2017-12-21

Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety. We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events. Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was