Interferon-gamma (INF-gamma) release test can detect cutaneous adverse effects to statins.

PubMed

Goldberg, Ilan; Isman, Gila; Shirazi, Idit; Brenner, Sarah

2009-12-01

An increasing number of cutaneous adverse effects are being reported as use of statins becomes more widespread. A study was undertaken to establish the relationship between statin and a cutaneous reaction by the in vitro interferon-gamma (INF-gamma) release test. The lymphocytes of 20 patients with suspected drug-induced skin reaction were incubated with and without the drug. The level of INF-gamma from the supernatant was measured by enzyme-linked immunosorbent assay (ELISA), and the increase calculated. Response was positive in 27 (21.43%) of the 126 drugs. Statin was the only drug with a positive response in 80% of those cases. Nine of 20 patients (45.0%) had complete resolution after discontinuation of the drug; 6 (30.0%) who replaced one drug by another statin had partial or no resolution; and 5 (20.0%) had no resolution despite cessation of statins of all kinds. A positive INF-gamma release test was found in patients who developed skin reactions while taking statins; the test's reliability was strengthened by prompt improvement following elimination of the suspected drug in the majority of patients.

Causality or Relatedness Assessment in Adverse Drug Reaction and Its Relevance in Dermatology.

PubMed

Pande, Sushil

2018-01-01

Causality assessment essentially means finding a causal association or relationship between a drug and drug reaction. Identifying the culprit drug or drugs can be lifesaving or helpful in preventing the further damage caused by the drug to our body systems. In dermatology practice, when it comes to cutaneous adverse drug reaction, this is much more important and relevant because many aetiologies can produce a similar cutaneous manifestation. There are multiple criteria or algorithms available as of now for establishing a causal relationship in cases of adverse drug reaction (ADR), indicating that none of them is specific or complete. Most of these causality assessment tools (CATs) use four cardinal principles of diagnosis of ADR such as temporal relationship of drug with the drug reaction, biological plausibility of the drug causing a reaction, dechallenge, and rechallenge. The present study reviews some of the established or commonly used CATs and its implications or relevance to dermatology in clinical practice.

Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation

PubMed Central

Su, Shih-Chi; Hung, Shuen-Iu; Fan, Wen-Lang; Dao, Ro-Lan; Chung, Wen-Hung

2016-01-01

Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine. PMID:27854302

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

Musette, Philippe; Kaufman, Jean-Marc; Rizzoli, René; Cacoub, Patrice; Brandi, Maria Louisa; Reginster, Jean-Yves

2011-01-01

Cutaneous adverse reactions are reported for many therapeutic agents and, in general, are observed in between 0% and 8% of treated patients depending on the drug. Antiosteoporotic agents are considered to be safe in terms of cutaneous effects, however there have been a number of case reports of cutaneous adverse reactions which warrant consideration. This was the subject of a working group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, which focused on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. This position paper was drafted following these discussions and includes a flowchart for their recognition. Cutaneous adverse reactions observed with antiosteoporotic agents were reviewed and included information from case reports, regulatory documents and pharmacovigilance. These reactions ranged from benign effects including exanthematous or maculopapular eruption (drug rash), photosensitivity and urticaria, to the severe and potentially life-threatening reactions of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome and toxic epidermal necrolysis. A review of the available evidence demonstrates that cutaneous adverse reactions occur with all commonly used antiosteoporotic treatments. Notably, there are reports of Stevens Johnson syndrome and toxic epidermal necrolysis for bisphosphonates, and of DRESS and toxic epidermal necrolysis for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases). In general, with proper management and early recognition, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration and systemic corticosteroids if necessary, the prognosis is positive. PMID:22870464

Cutaneous reactions to proton pump inhibitors: a case-control study.

PubMed

Chularojanamontri, Leena; Jiamton, Sukhum; Manapajon, Araya; Suvanasuthi, Saroj; Kulthanan, Kanokvalai; Dhana, Naruemon; Jongjarearnprasert, Kowit

2012-10-01

Even though proton pump inhibitors (PPIs) are commonly used in clinical practice, a limited number of studies are available about cutaneous adverse reactions from PPIs, and most of these are case reports. To demonstrate the pattern of cutaneous reactions related to PPI usage and to evaluate the risk of developing PPI drug eruptions among adult patients. We reviewed the spontaneous reports of any adverse events associated with PPI use, as reported from January 2005 through May 2010 to the Adverse Drug Reaction Center at Siriraj Hospital in Thailand. Each control was sampled from 15 patients who had consecutive hospital numbers from each study case. The prevalence of cutaneous reactions to PPIs varied, ranging from three to 20 per 100,000 of the treated population. Sixty-four patients with a history of reaction to PPIs, and 65 controls were enrolled. Most cutaneous reactions were attributed to omeprazole (n=50; 78.1%), and the most frequently observed cutaneous reaction was maculopapular rash (43.8%). None of the patients experienced a cross-reaction between individual PPIs. Cutaneous adverse reactions to PPIs range from minor drug rashes to a severe, life-threatening reaction. Individuals with a history of adverse drug reaction have an increased risk of cutaneous reaction to PPIs.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report.

PubMed

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-03-26

To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

PubMed Central

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-01-01

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically. PMID:28396847

A patient case highlighting the myriad of cutaneous adverse effects of prolonged use of hydroxyurea.

PubMed

Neill, Brett; Ryser, Ted; Neill, John; Aires, Daniel; Rajpara, Anand

2017-11-15

Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer. We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up. We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Drug skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of cross-reactions between synergistins.

PubMed

Barbaud, A; Trechot, P; Weber-Muller, F; Ulrich, G; Commun, N; Schmutz, J L

2004-01-01

The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens-Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin-quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin.

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

2017-01-01

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. PMID:29333460

Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population

PubMed Central

Koomdee, Napatrupron; Pratoomwun, Jirawat; Jantararoungtong, Thawinee; Theeramoke, Voralaksana; Tassaneeyakul, Wichittra; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha; Santon, Siwalee; Puangpetch, Apichaya; Intusoma, Utcharee; Tempark, Therdpong; Deesudchit, Tayard; Satapornpong, Patompong; Visudtibhan, Anannit; Sukasem, Chonlaphat

2017-01-01

Background: Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA) alleles in Thai patients. Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens–Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60–38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28–18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83–37.41; P = 0.005, OR: 7.33; 95% CI: 1.63–33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45–72.81; P = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group. Conclusion: HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed. PMID:29238301

Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

PubMed

Greenspoon, Jill; Herrmann, Nathan; Adam, David N

2011-07-01

Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals.

PubMed

Fang, Wendy C; Adler, Nikki R; Graudins, Linda V; Goldblatt, Caitlin; Goh, Michelle S Y; Roberts, Stuart K; Trubiano, Jason A; Aung, Ar Kar

2018-05-01

Drug-induced liver injury (DILI) can be associated with certain cutaneous adverse drug reaction (cADR). To demonstrate the prevalence of DILI in patients with cADRs. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. A retrospective cohort study of patients with cADRs was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. One hundred and four patients with cADRs were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with SJS (odds ratio, OR = 6.0, 95% confidence interval, CI: 1.8-19.7, P = 0.003). Antimicrobials were the most common class to be implicated in DILI. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs 11 days, P = 0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. DILI commonly occurs in patients with cADRs and is associated with longer inpatient stay. Patients with SJS/TEN and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury. © 2018 Royal Australasian College of Physicians.

Recent advances in the understanding of severe cutaneous adverse reactions.

PubMed

Adler, N R; Aung, A K; Ergen, E N; Trubiano, J; Goh, M S Y; Phillips, E J

2017-11-01

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients. © 2017 British Association of Dermatologists.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

PubMed Central

Chen, Chun-Bing; Wu, Ming-Ying; Ng, Chau Yee; Lu, Chun-Wei; Wu, Jennifer; Kao, Pei-Han; Yang, Chan-Keng; Peng, Meng-Ting; Huang, Chen-Yang; Chang, Wen-Cheng; Hui, Rosaline Chung-Yee; Yang, Chih-Hsun; Yang, Shun-Fa; Chung, Wen-Hung; Su, Shih-Chi

2018-01-01

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate

Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects

PubMed Central

2017-01-01

BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that typically presents as an annular or oval erythematous patch or blister and subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo biloba leaf extract and vinpocetine are nutritional supplements used to enhance memory in patients with dementia and age-related memory impairment conditions such as Alzheimer’s disease. PURPOSE: To describe a fixed drug eruption in a man who repeatedly developed pruritus and macular erythema on his distal penile shaft after ingesting a natural product containing Ginkgo biloba and vinpocetine. METHODS: The medical literature was retrospectively reviewed using PubMed, searching specifically for the terms cutaneous/skin adverse/side effects, fixed drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous reviews of the subject were critically assessed, and the salient features of cutaneous adverse effects in patients receiving either Ginkgo biloba or vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact dermatitis (following topical exposure) and mucosal symptoms of the mouth and anus (following oral exposure); in addition, an erythematous maculopapular generalized eruption or possibly Steven-Johnson syndrome can occur after oral ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated with vinpocetine ingestion. Pruritus and an annular erythema localized to the distal penile shaft developed after initial and repeat ingestion of a Ginkgo biloba/vinpocetine product. CONCLUSION: Ginkgo biloba and vinpocetine should be added to the agents that can potentially cause a fixed drug eruption. PMID:29344321

Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects.

PubMed

Cohen, Philip R

2017-10-01

BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that typically presents as an annular or oval erythematous patch or blister and subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo biloba leaf extract and vinpocetine are nutritional supplements used to enhance memory in patients with dementia and age-related memory impairment conditions such as Alzheimer's disease. PURPOSE: To describe a fixed drug eruption in a man who repeatedly developed pruritus and macular erythema on his distal penile shaft after ingesting a natural product containing Ginkgo biloba and vinpocetine. METHODS: The medical literature was retrospectively reviewed using PubMed, searching specifically for the terms cutaneous/skin adverse/side effects, fixed drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous reviews of the subject were critically assessed, and the salient features of cutaneous adverse effects in patients receiving either Ginkgo biloba or vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact dermatitis (following topical exposure) and mucosal symptoms of the mouth and anus (following oral exposure); in addition, an erythematous maculopapular generalized eruption or possibly Steven-Johnson syndrome can occur after oral ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated with vinpocetine ingestion. Pruritus and an annular erythema localized to the distal penile shaft developed after initial and repeat ingestion of a Ginkgo biloba/vinpocetine product. CONCLUSION: Ginkgo biloba and vinpocetine should be added to the agents that can potentially cause a fixed drug eruption.

Genetic susceptibility to the cross-reactivity of aromatic antiepileptic drugs-induced cutaneous adverse reactions.

PubMed

Wang, Wei; Hu, Fa-Yun; Wu, Xin-Tong; An, Dong-Mei; Yan, Bo; Zhou, Dong

2014-08-01

The cross-allergic reactions among aromatic antiepileptic drugs (AEDs) are common, but little is known about the genetic mechanisms. The aim of this study was to investigate the genetic associations of the human leukocyte antigen (HLA) genes with the cross-reactivity of cutaneous adverse drug reactions (cADRs) induced by different aromatic AEDs. We reviewed 60 Chinese patients with a history of cADRs induced by an aromatic AED, and which re-challenged other aromatic AEDs as an alternative to the causative AED owing to some particular reasons. According to whether developing another episode of cADRs, these patients were automatically divided into the cross-reactivity group and tolerant control group. High-resolution HLA-A, -B, -DRB1 genotyping were performed for each patient. One out of 10 patients (10%, 1/10) carried the HLA-A*2402 allele in the cross-reactivity group. However, 23 patients (46%, 23/50) carried this allele in the tolerant control group. The difference of the HLA-A*2402 allele between the two groups is statistically significant (P=0.040, OR=0.130, 95% CI: 0.015-1.108). In addition, the frequency differences of other HLA alleles between the two groups, including the HLA-B*1502 allele, did not reach statistical significance (P>0.05). The HLA genes contribute to the genetic susceptibility of the cross-reactivity of cADRs among aromatic AEDs. Our results suggest that HLA-B*1502 is not a major responsible allele for the cross-reactivity of cADRs to aromatic AEDs, but the HLA-A*2402 allele may be a protective marker for the cross-allergic reactions among aromatic AEDs in Han Chinese. Further studies are warranted to test the potential predictive value of the HLA-A*2402 allele in future. Copyright © 2014. Published by Elsevier B.V.

More than skin deep. Ten year follow‐up of delayed cutaneous adverse drug reactions (CADR)

PubMed Central

Ly, Jenny; Trubiano, Jason; Aung, Ar Kar

2016-01-01

Abstract Aims To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). Methods This was a retrospective observational cohort study conducted using hospital coding and databases to identify inpatients diagnosed with CADR from January 2004 to August 2014. Hospital discharge summaries, ADR reports and pharmacy dispensing records were reviewed for ADR documentation. Patients still living in Australia and who did not opt out of being contacted were invited to be surveyed by telephone to determine their understanding of recommendations, re‐exposure rates and long‐term effects. Results Of 85 patients identified, median age was 59 (IQR 44–72) years and 47.1% were male. The most common diagnosis was TENS (49.4%). Ten patients (11.8%) died as inpatients. Of the 81 patients with a drug‐related causality, 47 (58%) had appropriate documentation in all three required medical record platforms. Of the 56 eligible patients, 38 (67.9%) were surveyed; 13% had no information provided upon discharge and 26.3% patients had a mismatch in knowledge of implicated medications. No surveyed patient had a relapse of CADR, but 23.7% had a subsequent unrelated allergic reaction. Thirteen patients (34.2%) reported long‐term effects. Conclusions We found gaps in the accuracy of ADR documentation and communication of risk at discharge, which indicated risks to patient safety. Electronic systems are being developed to improve documentation. Written information about CADR is being provided at discharge to improve patient understanding and knowledge. PMID:27265387

Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

PubMed

Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

2017-09-01

The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug Discovery Algorithm for Cutaneous Leishmaniasis

PubMed Central

Grogl, Max; Hickman, Mark; Ellis, William; Hudson, Thomas; Lazo, John S.; Sharlow, Elizabeth R.; Johnson, Jacob; Berman, Jonathan; Sciotti, Richard J.

2013-01-01

Cutaneous leishmaniasis is clinically widespread but lacks treatments that are effective and well tolerated. Because all present drugs have been grandfathered into clinical use, there are no examples of a pre-clinical product evaluation scheme that lead to new candidates for formal development. To provide oral agents for development targeting cutaneous leishmaniasis, we have implemented a discovery scheme that incorporates in vitro and in vivo testing of efficacy, toxicity, and pharmacokinetics/metabolism. Particular emphasis is placed on in vivo testing, progression from higher-throughput models to those with most clinical relevance, and efficient use of resources. PMID:23390221

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

PubMed

Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

2015-01-01

We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions

PubMed Central

Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

2015-01-01

Objective We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Methods Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Results Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). Conclusions We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse

Pharmacogenetics of adverse reactions to antiepileptic drugs.

PubMed

Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M

2018-04-01

Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Treatment of cutaneous injuries of neonates induced by drug extravasation with hyaluronidase and hirudoid.

PubMed

Yan, Ya-Min; Fan, Qiao-Ling; Li, Ai-Qiu; Chen, Jia-Ling; Dong, Fei-Fei; Gong, Mei

2014-08-01

To analyze the effects of hyaluronidase and hirudoid treatment on drug extravasation in neonates. The medical records of 13 neonates with drug extravasation treated with hyaluronidase and hirudoid between August 1(st), 2010 and May 1(st), 2012 were analyzed retrospectively. The treatment procedure for drug extravasation adhered to the protocol in neonatal department. The information including age, sex, weight, diagnosis, size of affected area, site of extravasation and treatment was collected. Findings : The extravasation injuries alleviated and the symptoms improved after treatment, no adverse drug effects were reported with use of hyaluronidase and hirudoid. The treatment appeared to be beneficial in the management of extravasations of various medications in neonates and may be useful in reducing the severity of cutaneous toxicosis. However, further studies with large samples are still needed to assess the effectiveness and safety of hyaluronidase and hirudoid.

Treatment of Cutaneous Injuries of Neonates Induced by Drug Extravasation with Hyaluronidase and Hirudoid

PubMed Central

Yan, Ya-Min; Fan, Qiao-Ling; Li, Ai-Qiu; Chen, Jia-Ling; Dong, Fei-Fei; Gong, Mei

2014-01-01

Objective: To analyze the effects of hyaluronidase and hirudoid treatment on drug extravasation in neonates. Methods: The medical records of 13 neonates with drug extravasation treated with hyaluronidase and hirudoid between August 1st, 2010 and May 1st, 2012 were analyzed retrospectively. The treatment procedure for drug extravasation adhered to the protocol in neonatal department. The information including age, sex, weight, diagnosis, size of affected area, site of extravasation and treatment was collected. Findings : The extravasation injuries alleviated and the symptoms improved after treatment, no adverse drug effects were reported with use of hyaluronidase and hirudoid. Conclusion: The treatment appeared to be beneficial in the management of extravasations of various medications in neonates and may be useful in reducing the severity of cutaneous toxicosis. However, further studies with large samples are still needed to assess the effectiveness and safety of hyaluronidase and hirudoid. PMID:25755854

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

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

PubMed

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.

[High frequency of cutaneous adverse effects under infliximab. Geneva experience, 1999-2008].

PubMed

Seydtaghia, Floriane; De Saussure, Philippe; Hadengue, Antoine

2011-03-16

Geneva experience, 1999-2008 Infliximab has been used for 10 years in the treatment of chronic inflammatory bowel diseases in the gastroenterology and hepatology department at the University Hospitals of Geneva. This retrospective study shows the follow-up of these patients treated with infliximab and reveals a high rate of cutaneous adverse events, which, although often mild, can sign a definitive intolerance to treatment.

Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.

PubMed

Vinay, Keshavamurthy; Yanamandra, Uday; Dogra, Sunil; Handa, Sanjeev; Suri, Vikas; Kumari, Savita; Khadwal, Alka; Prakash, Gaurav; Lad, Deepesh; Varma, Subhash; Malhotra, Pankaj

2018-03-01

Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. © 2017 The International Society of Dermatology.

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

Adverse Drug Reactions to Antiretroviral Therapy: Prospective Study in Children in Sikasso (Mali)

PubMed Central

Oumar, Aboubacar A.; Diallo, Korotoumou; Dembélé, Jean P.; Samaké, Lassana; Sidibé, Issa; Togo, Boubacar; Sylla, Mariam; Tounkara, Anatole; Dao, Sounkalo; Tulkens, Paul M.

2012-01-01

OBJECTIVES Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS Ninety-two human immunodeficiency virus–infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali. PMID:23411444

Adverse drug reactions in hospitalized Colombian children.

PubMed

de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

2016-09-30

The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p = 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p = 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

Immune responses in dogs with cutaneous adverse food reactions.

PubMed

Veenhof, E Z; Knol, E F; Willemse, T; Rutten, V P M G

2012-06-01

Adverse food reactions (AFR) in dogs are reactions due to apparently harmless food antigens, with an unknown aetiology, i.e. immunopathogenesis. Despite the entry of food allergens via the intestinal tract, in the majority of dogs with AFR, clinical symptoms are only associated with the skin (CAFR). In the present review, factors are presented of relevance in triggering the differentiation of naive T cells into effector T cell types and the role of these T cell types in allergy. More specifically, the allergic immune responses in intestine and skin are discussed in this article as well as the potential pathways, e.g. homing of antigen presenting cells or allergen-induced T cells to the skin, of induction of cutaneous symptoms.

Identification of allergens responsible for canine cutaneous adverse food reactions to lamb, beef and cow's milk.

PubMed

Martín, Aurea; Sierra, María-Paz; González, José L; Arévalo, María-Angeles

2004-12-01

Lamb, beef and cow's milk are common causes of cutaneous adverse food reactions in dogs. The aim of this study was to identify the proteins responsible for cutaneous adverse reactions to these foods. Ten dogs with allergen-specific serum immunoglobulin (Ig)E to lamb, beef and cow's milk were included in the study. These dogs had been diagnosed with cutaneous adverse food reactions by convincing clinical history and food-elimination diet trials followed by challenge exposure. Sera were analysed by enzyme-linked immunosorbent assay with bovine proteins and SDS-PAGE immunoblots with lamb, beef and cow's milk extracts. All the dogs had specific IgE against bovine IgG, and it was the only protein in the cow's milk extract that bound IgE from the sera studied. In the lamb and beef extracts, the major allergens recognized by the specific IgE of most sera had molecular masses between 51 and 58 kDa, which were identified as phosphoglucomutase and the IgG heavy chain. Other IgE-binding proteins with molecular masses of 27, 31, 33, 37 and 42 kDa were also detected with some sera. Our results indicate that bovine IgG is a major allergen in cow's milk and hence it appears to be a source of cross-reactivity with beef and probably with lamb because of the high homology with ovine immunoglobulins. These results are similar to those found for meat allergy in humans. However, this is the first time that phosphoglucomutase has been identified as an important allergen involved in allergic reactions to lamb and beef.

Adverse Drug Reactions in Dental Practice

PubMed Central

Becker, Daniel E.

2014-01-01

Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

Adverse drug reactions induced by valproic acid.

PubMed

Nanau, Radu M; Neuman, Manuela G

2013-10-01

Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Adverse drug reactions and off-label drug use in paediatric outpatients

PubMed Central

Horen, Benjamin; Montastruc, Jean-Louis; Lapeyre-mestre, Maryse

2002-01-01

Aims To investigate the potential relationship between off-label drug use and increased risk of adverse drug reactions in paediatric outpatients. Methods A prospective pharmacovigilance survey of drug prescribing in office based paediatricians was carried out in Haute-Garonne County (south west of France). Results The study involved a sample of 1419 children under 16 years old. Forty-two percent of patients were exposed to at least one off-label prescription. The incidence of adverse drug reactions was 1.41% (95% CI 0.79, 2.11). Off-label drug use was significantly associated with adverse drug reactions (relative risk 3.44; 95% CI 1.26, 9.38), particularly when it was due to an indication different than that defined in the Summary Product Characteristics (relative risk 4.42; 95% CI 1.60, 12.25). Conclusions Our data suggest an increasing risk of adverse drug reactions related to off-label drug use. This risk would be acceptable if further studies prove the potential benefit of such a drug use. PMID:12492616

Adverse drug event monitoring at the Food and Drug Administration.

PubMed

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 treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk.

Adverse Drug Event Monitoring at the Food and Drug Administration

PubMed Central

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 treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. PMID:12534765

Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

PubMed

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

2016-03-01

Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Adverse effects of oral amiodarone therapy.

PubMed

Sinha, P R; Dube, S; Sujata; Gupta, P R; Avasthey, P; Somani, P N

1992-04-01

Oral amiodarone was administered to 38 patients (25 males, 13 females) with mean age of 43.6 years. Ventricular and supraventricular arrhythmias were present in 30 and 8 patients respectively. Amiodarone was given as 400-1200 mg/day for 1-2 weeks as loading dose and then it was maintained as 100-600 mg/day. The mean duration of therapy was 12.4 months. Adverse effects were noted in 21 (55.3%) cases. The commonest adverse effects observed were asymptomatic corneal microdeposits followed by gastrointestinal, cardiac, neurological and cutaneous disturbances. The drug was withdrawn in 2 (5.3%) patients because of nausea and vomiting. One patient died of pulmonary infiltrations. It is concluded that adverse effects are common with amiodarone but are tolerated well, making this drug an excellent choice for treatment of cardiac arrhythmias.

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

Dinotefuran/pyriproxyfen/permethrin pemphigus-like drug reaction in three dogs.

PubMed

Bizikova, Petra; Moriello, Karen A; Linder, Keith E; Sauber, Leslie

2015-06-01

Pemphigus foliaceus (PF) can occur spontaneously or as a reaction pattern associated with cutaneous adverse drug reactions. To provide clinical, histological and immunological assessments of three dogs that developed cutaneous adverse drug reactions following application of a topical flea and tick control product, which contained dinotefuran, pyriproxyfen and permethrin. Three client-owned dogs. The dogs exhibited rapid onset of papules, pustules and crusts at the site of application of the flea control product. In two dogs, the lesions became generalized, while the third exhibited a localized phenotype. Both dogs with generalized lesions required immunosuppressive treatment; one achieved remission after 1 year of treatment and one was euthanized due to adverse effects of glucocorticoids. The dog with a localized phenotype was treated with topical glucocorticoids exclusively and achieved remission after 10 months. Histology revealed subcorneal pustular dermatitis, with acantholysis of keratinocytes and focal to multifocal full-thickness epidermal necrosis. These features are similar to those previously reported for pesticide-triggered and spontaneous PF. Tissue-bound IgG was detected in two of three dogs, and autoantibodies targeting canine desmocollin-1 were identified in the serum of the one dog from which a sample was available. Cutaneous adverse drug reaction caused by a flea control product containing dinotefuran, pyriproxyfen and permethrin closely resembled those reported for other pesticide-associated PF-like cutaneous adverse drug reactions. Although it appears to be a rare entity, clinicians and pathologists should be aware of the potential for flea and tick control products to trigger PF-like reactions. © 2015 ESVD and ACVD.

Severe Delayed Cutaneous and Systemic Reactions to Drugs: A Global Perspective on the Science and Art of Current Practice.

PubMed

Peter, Jonathan Grant; Lehloenya, Rannakoe; Dlamini, Sipho; Risma, Kimberly; White, Katie D; Konvinse, Katherine C; Phillips, Elizabeth J

Most immune-mediated adverse drug reactions (IM-ADRs) involve the skin, and many have additional systemic features. Severe cutaneous adverse drug reactions (SCARs) are an uncommon, potentially life-threatening, and challenging subgroup of IM-ADRs with diverse clinical phenotypes, mechanisms, and offending drugs. T-cell-mediated immunopathology is central to these severe delayed reactions, but effector cells and cytokines differ by clinical phenotype. Strong HLA-gene associations have been elucidated for specific drug-SCAR IM-ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis, although the mechanisms by which carriage of a specific HLA allele is necessary but not sufficient for the development of many IM-ADRs is still being defined. SCAR management is complicated by substantial short- and long-term morbidity/mortality and the potential need to treat ongoing comorbid disease with related medications. Multidisciplinary specialist teams at experienced units should care for patients. In the setting of SCAR, patient outcomes as well as preventive, diagnostic, treatment, and management approaches are often not generalizable, but rather context specific, driven by population HLA-genetics, the pharmacology and genetic risk factors of the implicated drug, severity of underlying comorbid disease necessitating ongoing treatments, and cost considerations. In this review, we update the basic and clinical science of SCAR diagnosis and management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice

PubMed Central

Peter, Jonathan Grant; Lehloenya, Rannakoe; Dlamini, Sipho; Risma, Kimberly; White, Katie D.; Konvinse, Katherine C.; Phillips, Elizabeth J.

2017-01-01

The majority of immune-mediated adverse drug reactions (IM-ADRs) involve the skin, and many have additional systemic features. Severe cutaneous adverse drug reactions (SCAR) are an uncommon, potentially life-threatening and challenging sub-group of IM-ADRs with diverse clinical phenotypes, mechanisms and offending drugs. T-cell mediated immunopathology is central to these severe delayed reactions, but effector cells and cytokines differ by clinical phenotype. Strong HLA-gene associations have been elucidated for specific drug-SCAR IM-ADRs such as Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN); although the mechanisms by which carriage of a specific HLA allele is necessary but not sufficient for the development of many IM-ADRs is still being defined. SCAR management is complicated by substantial short and long-term morbidity/ mortality and the potential need to treat ongoing co-morbid disease with related medications. Multidisciplinary specialist teams at experienced units should care for patients. In the setting of SCAR, patient outcomes as well as preventive,diagnostic, treatment and management approaches are often not generalizable, but rather context specific, driven by population HLA-genetics, the pharmacology and genetic risk factors of the implicated drug, severity of underlying co-morbid disease necessitating ongoing treatments, and cost considerations. In this review, we update the basic and clinical science of SCAR diagnosis and management. PMID:28483310

Bioactivation of drugs in the skin: relationship to cutaneous adverse drug reactions.

PubMed

Sharma, Amy M; Uetrecht, Jack

2014-02-01

Drug-induced skin rashes are poorly understood idiosyncratic reactions, and current methods cannot predict their occurrence. Most idiosyncratic drug reactions are thought to be caused by chemically reactive metabolites, and the skin is a frequent site of idiosyncratic reactions; however, the skin has a very limited capacity to metabolize drugs. To balance this, the skin represents a protective barrier with a very active immune response against pathogens and other types of skin injury. Therefore its response to reactive metabolites is quite different from that of the liver. The purpose of this review is to integrate emerging findings into proposed mechanisms of drug and carcinogen metabolism in the skin that are likely responsible for rashes and other immune responses of the skin. Current evidence suggests the skin possesses significant sulfotransferase and flavin monooxygenases activities, but very low cytochromes P450 activity. However, there are skin-specific P450s that are not present in the liver. The manner in which the skin responds to neoantigens through local antigen presentation and innate immune sensing is reviewed with a focus on insights gained from the contact hypersensitivity (CHS) field. The roles of keratinocytes and Langerhans cells, and the emerging function of NOD-like receptors, are highlighted.

Promoting adverse drug reaction reporting: comparison of different approaches

PubMed Central

Ribeiro-Vaz, Inês; Santos, Cristina Costa; Cruz-Correia, Ricardo

2016-01-01

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report. PMID:27143614

Promoting adverse drug reaction reporting: comparison of different approaches.

PubMed

Ribeiro-Vaz, Inês; Santos, Cristina Costa; Cruz-Correia, Ricardo

2016-01-01

To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

Adverse Effects of Common Drugs: Dietary Supplements.

PubMed

Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

2015-09-01

Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Adverse drug events and medication problems in "Hospital at Home" patients.

PubMed

Mann, Elizabeth; Zepeda, Orlando; Soones, Tacara; Federman, Alex; Leff, Bruce; Siu, Albert; Boockvar, Kenneth

2018-03-26

"Hospital at Home(HaH)" programs provide an alternative to traditional hospitalization. However, the incidence of adverse drug events in these programs is unknown. This study describes adverse drug events and potential adverse drug events in a new HaH program. We examined the charts of the first 50 patients admitted. We found 45 potential adverse drug events and 14 adverse drug events from admission to 30 days after HaH discharge. None of the adverse drug events were severe. Some events, like problems with medication administration, may be unique to the hospital at home setting. Monitoring for adverse drug events is feasible and important for hospital at home programs.

Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia.

PubMed

Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd; Ming, Long Chiau; Manan, Mohamed Mansor

2017-01-01

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% ( n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash ( n = 215), maculopapular rash ( n = 206), urticaria ( n = 169), erythematous rash ( n = 76), and pruritus ( n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial

Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia

PubMed Central

Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd.; Ming, Long Chiau; Manan, Mohamed Mansor

2017-01-01

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia’s national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia’s National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens–Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

PubMed

Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

2018-02-01

Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

iADRs: towards online adverse drug reaction analysis.

PubMed

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.

Recent Advances and Perspectives in Liposomes for Cutaneous Drug Delivery.

PubMed

Carita, Amanda C; Eloy, Josimar O; Chorilli, Marlus; Lee, Robert J; Leonardi, Gislaine Ricci

2018-02-13

The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cutaneous ulcers associated with hydroxyurea therapy.

PubMed

Quattrone, Filippo; Dini, Valentina; Barbanera, Sabrina; Zerbinati, Nicola; Romanelli, Marco

2013-11-01

Hydroxyurea is an antitumoral drug mainly used in the treatment of Philadelphia chromosome-negative myeloproliferative syndromes and sickle-cell disease. Ulcers represent a rare but severe long-term adverse effect of hydroxyurea therapy. Hydroxyurea-induced ulcers are often multiple and bilateral, typically developing in the perimalleolar region, although any cutaneous district is potentially affected. They generally look small, well-defined, shallow with an adherent, yellow, fibrinous necrotic base. A constant finding is also an extremely intense, treatment-resistant pain accompanying these ulcerations. Withdrawal of the drug generally leads to spontaneous healing of these lesions. Care providers tend to show insufficient awareness of this highly debilitating cutaneous side effect, and late or missed diagnoses are frequent. Instead, regular dermatologic screening should be performed on hydroxyurea-treated patients. This article will present a comprehensive review of indexed case reports and clinical studies, followed by a discussion about treatment options aiming at increasing knowledge about this specific topic. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Data-driven prediction of adverse drug reactions induced by drug drug interactions

DTIC Science & Technology

2017-06-08

currently on the market and for which drug-protein interaction information is available . These predictions are publicly accessible at http://avoid...associated with these ADRs via DDIs. We made the predictions publicly available via internet access. Keywords: Drug-drug interactions, Adverse drug reactions...ˆDeceased Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

PubMed

Wang, Chuang-Wei; Yang, Lan-Yan; Chen, Chun-Bing; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chang, Ya-Ching; Lu, Chun-Wei; Chung, Wen-Hung

2018-03-01

Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. ClinicalTrials.gov NCT01276314. Ministry of Science and Technology of Taiwan.

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.

PubMed

Shehab, Nadine; Lovegrove, Maribeth C; Geller, Andrew I; Rose, Kathleen O; Weidle, Nina J; Budnitz, Daniel S

2016-11-22

The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Drugs implicated in ED visits. National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated

Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management.

PubMed

Shen, John; Chang, Jason; Mendenhall, Melody; Cherry, Grace; Goldman, Jonathan W; Kulkarni, Rajan P

2018-01-01

The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with

An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions.

PubMed

Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne; Darsø, Perle; Christophersen, Anette Kvindebjerg; Borck, Bille; Christensen, Catrine; Hansen, Melissa Voigt; Halladin, Natalie Monica Løvland; Christensen, Mikkel Bring; Harboe, Kirstine Moll; Lund, Marie; Jimenez-Solem, Espen

2017-01-01

Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region of Denmark. The ADEM assists healthcare professionals in reporting suspected ADRs to the Danish Health Authority. The aim of this retrospective observational study was to quantify and describe ADRs reported via the ADEM in 2014. All ADR reports handled by the ADEM in 2014 were recorded anonymously and analysed descriptively. A total of 484 ADRs were reported through the ADEM in 2014 (the median number of reports per month was 37; range: 17-78). The majority of the reports came from departments of internal medicine (61%), psychiatry (14%) and dermatology, ophthalmology or otorhinolaryngology (11%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR reporting and helps raise awareness about ADRs, including how and why they should be reported. Hopefully, this will assist national and European spontaneous reporting systems in their work to increase patient safety nationally and abroad. none. not relevant. .

Adverse Drug Reactions (ADR) and Emergencies.

PubMed

Schurig, A Marlen; Böhme, Miriam; Just, Katja S; Scholl, Catharina; Dormann, Harald; Plank-Kiegele, Bettina; Seufferlein, Thomas; Gräff, Ingo; Schwab, Matthias; Stingl, Julia C

2018-04-13

Adverse drug reactions (ADR) are a common reason for emergency room visits and for hospitalization. An ADR is said to have occurred when the patient's symptoms and signs are considered to be possibly, probably, or definitely related to the intake of a drug. In four large hospital emergency departments, one in each of four German cities ( Ulm, Fürth, Bonn, and Stuttgart), the percentage of suspected ADR cases among all patients presenting to the emergency room was determined during a 30-day period of observation. ADRs were ascertained by screening the digital records of all patients seen in the emergency room; causality was assessed as specified by the WHO-UMC (Uppsala Monitoring Center). ADR were sought in a total of 10 174 emergency department visits. 665 cases of suspected ADR were found, yielding a prevalence of 6.5%. The prevalence of ADR among patients with documented drug intake was 11.6%. Among the patients with documented suspected ADRs, 89% were hospitalized (in contrast to the 43.7% hospitalization rate in the entire group of 10 174 emergency department visits). A possible causal relationship between the patient's symptoms and signs and the intake of a drug was found in 74-84% of cases. Patients with ADR were found to be taking a median of 7 different drugs simultaneously. Adverse drug reactions are a relevant cause of emergency department visits, accounting for 6.5% of the total visits in this study, and often lead to hospital admission. The ADRED (Adverse Drug Reactions in Emergency Departments) study, which is now being conducted, is intended to shed further light on their causes, patient risk factors, and potential avoidability.

Cutaneous drug reaction case reports: from the world literature.

PubMed

2003-01-01

Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. Reactions Weekly is the complete drug safety alerting service and summarizes information selected from over 1600 biomedical journals. This newsletter is produced by Adis International and is available in a variety of formats. Please contact your nearest Adis office for subscription details. The use of tradenames, identified by ['~'] or the use of a registered ((R)) or trade mark ( trade mark ), is for product identification purposes only and does not imply endorsement. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reactions database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from National Centers of 65 affiliate countries. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage).

Severe Cutaneous Drug Reactions: Do Overlapping Forms Exist?

PubMed

Horcajada-Reales, C; Pulido-Pérez, A; Suárez-Fernández, R

2016-01-01

Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Adverse Effects of Nonsystemic Steroids (Inhaled, Intranasal, and Cutaneous): a Review of the Literature and Suggested Monitoring Tool.

PubMed

Gupta, Ratika; Fonacier, Luz S

2016-06-01

Inhaled, intranasal, and cutaneous steroids are prescribed by physicians for a plethora of disease processes including asthma and rhinitis. While the high efficacy of this class of medication is well known, the wide range of adverse effects, both local and systemic, is not well elucidated. It is imperative to monitor total steroid burden in its varied forms as well as tracking for possible side effects that may be caused by a high cumulative dose of steroids. This review article highlights the adverse effects of different steroid modalities as well as suggests a monitoring tool to determine steroid totality and side effects.

Cutaneous Squamous Cell Carcinoma in Lupus Vulgaris Caused by Drug Resistant Mycobacterium Tuberculosis

PubMed Central

Kumaran, Muthu S.; Narang, Tarun; Jitendriya, Madhukara; Tirumale, Rajalakshmi; Manjunath, Suraj; Savio, Jayanthi

2017-01-01

Tuberculosis (TB) is still a major public health problem in the world, with many factors contributing to this burden, including poor living conditions, overcrowding, poverty, malnutrition, illiteracy, and rapid spread of human immunodeficiency virus infection. Cutaneous tuberculosis is a less common form of extrapulmonary tuberculosis, and in this paucibacillary form the diagnosis depends on histopathology, tuberculin positivity, and response to treatment. The diagnosis is even more difficult in cases with drug resistant Mycobacterium tuberculosis due to lack of awareness and lack of facilities to diagnose drug resistant tuberculosis. In this article, we describe an unusual case of multidrug resistant lupus vulgaris (LV), in a 34-year-old male who responded to anti-tubercular treatment (ATT) initially, but developed recurrent disease which failed to respond to standard four-drug ATT; subsequently, tissue culture showed growth of multidrug resistant M. tuberculosis. Subsequently, he also developed cutaneous squamous cell carcinoma. This article aims to exemplify a grave complication that can occur in long-standing case of LV, the limitations faced by clinicians in developing countries where tuberculosis is endemic, and classical methods of proving drug resistance are generally unavailable or fail. PMID:28761842

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

PubMed

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.

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

PubMed Central

Wang, Chuang-Wei; Yang, Lan-Yan; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chung, Wen-Hung

2018-01-01

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan. PMID:29400697

21 CFR 882.1320 - Cutaneous electrode.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous electrode. 882.1320 Section 882.1320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1320 Cutaneous electrode. (a...

21 CFR 882.1320 - Cutaneous electrode.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cutaneous electrode. 882.1320 Section 882.1320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1320 Cutaneous electrode. (a...

Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy.

PubMed Central

Mir, L. M.; Glass, L. F.; Sersa, G.; Teissié, J.; Domenge, C.; Miklavcic, D.; Jaroszeski, M. J.; Orlowski, S.; Reintgen, D. S.; Rudolf, Z.; Belehradek, M.; Gilbert, R.; Rols, M. P.; Belehradek, J.; Bachaud, J. M.; DeConti, R.; Stabuc, B.; Cemazar, M.; Coninx, P.; Heller, R.

1998-01-01

Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate. PMID:9649155

Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

PubMed

McNulty, Caitlin M G; Park, Miguel A

2017-11-01

Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

[Use of Nadis(®) software to improve adverse drug reaction reporting of antiretroviral drugs: experience in south west of France (midi-pyrénées)].

PubMed

Pochard, Liselotte; Hauviller, Laurent; Cuzin, Lise; Eyvrard, Fréderic; Sommet, Agnès; Montastruc, Jean-Louis; Bagheri, Haleh

2014-01-01

To study the value of the module of pharmacovigilance in Nadis® to improve the antiretroviral (ARV) drugs-induced adverse drug reactions (ADRs) reporting. We collected the ADRs reported for 17 months from November 2010 until April 2012. Following data were recorded: characteristics of patients, ADRs, ARV drugs. The number of ADRs was compared to those collected in the same period (17 months) before use of Nadis®. The 119 ADRs reported (an increase of 183%) for 109 patients ADRs were mainly gastrointestinal (21.8%) followed by renal (20.2%), neuro-psychiatric (16.8%), hepatic (13.5%), cutaneous (8.4%), metabolic (6.7%) and others (12.6%). The repartition of ARV drugs was: nucleoside (31.8%), nucleotide (13.6%) reverse transcriptase inhibitors respectively, non-nucleoside reverse transcriptase inhibitors (13.1%), protease inhibitors (36.4%), and integrase inhibitors (5.1%). Our results show the improvement of ARV-induced ADRs reporting by Nadis® which could be used to reduce the rate of under-reporting in patients exposed to these drugs. © 2014 Société Française de Pharmacologie et de Thérapeutique.

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

PubMed Central

Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

2013-01-01

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. PMID:23644852

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

PubMed

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

Phenytoin Induced Cutaneous B Cell Pseudolymphoma

PubMed Central

Riyaz, Najeeba; Sasidharanpillai, Sarita; Aravindan, Karumathil P; Nobin, Babu K; Raghavan, Nisha T; Nikhila, Pappinissery K

2015-01-01

Cutaneous pseudolymphomas are benign lymphoproliferative processes mimicking lymphomas clinically and histologically. One of the precipitating factors for pseudolymphoma is drugs like anticonvulsants, antidepressants and angiotensin-converting enzyme inhibitors. According to existing literature phenytoin-induced cutaneous pseudolymphomas are usually T-cell predominant. Most often withdrawal of the drug with or without short-course systemic steroids can attain a cure. Rarely malignant transformation has been reported years later despite withdrawal of the offending drug, which necessitates a long-term follow up of the affected. We report an 80-year-old male patient who was receiving phenytoin sodium and who presented with diffuse erythema and infiltrated skin lesions which histologically resembled cutaneous B-cell lymphoma. Substituting phenytoin with levetiracetam achieved resolution of symptoms. Further evaluation was suggestive of a reactive process. A detailed drug history is of paramount importance in differentiating drug-induced pseudolymphoma from lymphoma. Searching literature we could not find any previous reports of phenytoin-induced cutaneous B-cell pseudolymphoma. PMID:26538730

The pharmacist and adverse drug reaction reporting.

PubMed

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.

Risk of cutaneous adverse events with febuxostat treatment in patients with skin reaction to allopurinol. A retrospective, hospital-based study of 101 patients with consecutive allopurinol and febuxostat treatment.

PubMed

Bardin, Thomas; Chalès, Gérard; Pascart, Tristan; Flipo, René-Marc; Korng Ea, Hang; Roujeau, Jean-Claude; Delayen, Aurélie; Clerson, Pierre

2016-05-01

To investigate the cutaneous tolerance of febuxostat in gouty patients with skin intolerance to allopurinol. We identified all gouty patients who had sequentially received allopurinol and febuxostat in the rheumatology departments of 4 university hospitals in France and collected data from hospital files using a predefined protocol. Patients who had not visited the prescribing physician during at least 2 months after febuxostat prescription were excluded. The odds ratio (OR) for skin reaction to febuxostat in patients with a cutaneous reaction to allopurinol versus no reaction was calculated. For estimating the 95% confidence interval (95% CI), we used the usual Wald method and a bootstrap method. In total, 113 gouty patients had sequentially received allopurinol and febuxostat; 12 did not visit the prescribing physician after febuxostat prescription and were excluded. Among 101 patients (86 males, mean age 61±13.9 years), 2/22 (9.1%) with a history of cutaneous reactions to allopurinol showed skin reactions to febuxostat. Two of 79 patients (2.5%) without a skin reaction to allopurinol showed skin intolerance to febuxostat. The ORs were not statistically significant with the usual Wald method (3.85 [95% CI 0.51-29.04]) or bootstrap method (3.86 [95% CI 0.80-18.74]). The risk of skin reaction with febuxostat seems moderately increased in patients with a history of cutaneous adverse events with allopurinol. This moderate increase does not support the cross-reactivity of the two drugs. Copyright © 2015. Published by Elsevier SAS.

Skin manifestations of drug allergy

PubMed Central

Ardern-Jones, Michael R; Friedmann, Peter S

2011-01-01

Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell-mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti-tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients. PMID:21480947

Adverse drug reactions and outcome of short course anti-tuberculosis drugs between single daily dose and split drug dose (BID) in pulmonary tuberculosis.

PubMed

Chuchottaworn, Charoen; Saipan, Benjawan; Kittisup, Chomnapa; Cheewakul, Krisana

2012-08-01

Standard six months short course regimen for treatment of pulmonary tuberculosis is very effective and is recommended as standard treatment. But this regimen composes of many drugs and causes high adverse drug reactions especially gastrointestinal irritation. Spitted administration of drugs to two times a day may reduce adverse drug reactions. To study adverse drug reactions and outcome of single daily versus split drug (two times a day) administration of standard six month short course regimen in newly diagnosed pulmonary tuberculosis. Newly diagnosed pulmonary tuberculosis patients of the Central Chest Institute of Thailand were randomized to receive standard six months regimen once daily or two times a day (split drug). Patients were followed-up every two weeks and a questionnaire was used to detect adverse drug reactions. Outcome of treatment was evaluated according to national tuberculosis treatment guideline. 122 pulmonary tuberculosis were eligible for the present study and 61 patients were enrolled to each group of once daily or split drug regimen. Pulmonary tuberculosis patients who received split drug regimen had a higher cure rate but not statistical significance because of lower transfer out rate. Adverse drug reactions were similar in both groups of patients who received once daily and split drug regimen. Although split drug group had lower gastrointestinal adverse drug reactions. Split drug regimen has the same cure rate of treatment as single daily regimen and same adverse drug reactions.

Adverse drug events in hospital: pilot study with trigger tool

PubMed Central

Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

2013-01-01

OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for

Role of dermatology in pharmacogenomics: drug-induced skin injury.

PubMed

Borroni, Riccardo G

2015-01-01

Different individuals may respond diversely to the same drug, in terms of efficacy and toxicity. Adverse drug reactions cause about 6% of all hospital admissions and account for up to 9% of hospitalization costs. Drug-induced skin injury (DISI) is the most common presentation of adverse drug reactions, ranging from maculopapular eruptions to severe adverse cutaneous drug reactions (SCARs) with mortality of up to 40%. Specific genetic polymorphisms confer susceptibility to different types of DISI. Identifying patients genetically at risk for SCARs is one of the goals of pharmacogenomics. In this article, the aspects of clinical dermatology relevant to the pharmacogenetics of DISI are reviewed. Many SCARs are now preventable, with consequent reduction of morbidity, mortality and healthcare costs.

Adverse drug reactions induced by cardiovascular drugs in outpatients.

PubMed

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, 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). 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.

Towards Large-scale Twitter Mining for Drug-related Adverse Events.

PubMed

Bian, Jiang; Topaloglu, Umit; Yu, Fan

2012-10-29

Drug-related adverse events pose substantial risks to patients who consume post-market or Drug-related adverse events pose substantial risks to patients who consume post-market or investigational drugs. Early detection of adverse events benefits not only the drug regulators, but also the manufacturers for pharmacovigilance. Existing methods rely on patients' "spontaneous" self-reports that attest problems. The increasing popularity of social media platforms like the Twitter presents us a new information source for finding potential adverse events. Given the high frequency of user updates, mining Twitter messages can lead us to real-time pharmacovigilance. In this paper, we describe an approach to find drug users and potential adverse events by analyzing the content of twitter messages utilizing Natural Language Processing (NLP) and to build Support Vector Machine (SVM) classifiers. Due to the size nature of the dataset (i.e., 2 billion Tweets), the experiments were conducted on a High Performance Computing (HPC) platform using MapReduce, which exhibits the trend of big data analytics. The results suggest that daily-life social networking data could help early detection of important patient safety issues.

Cutaneous Manifestation of Food Allergy.

PubMed

Tam, Jonathan S

2017-02-01

Hypersensitivity reactions to foods can have diverse and highly variable manifestations. Cutaneous reactions, such as acute urticaria and angioedema, are among the most common manifestations of food allergy. However, cutaneous manifestations of food allergy encompass more than just IgE-mediated processes and include atopic dermatitis, contact dermatitis, and even dermatitis herpetiformis. These cutaneous manifestations provide an opportunity to better understand the diversity of adverse immunologic responses to food and the interconnected pathways that produce them. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition.

PubMed

Giacone, Daniela V; Carvalho, Vanessa F M; Costa, Soraia K P; Lopes, Luciana B

2018-02-01

Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) coencapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2 ± 4.0 nm) and negative zeta potential (-4.2 ± 0.8 mV). Elacridar improved NE ability to inhibit verapamil-induced ATPase activity of P-gp; unloaded NE-inhibited P-gp when used at a concentration of 1500 μM, while elacridar encapsulation decreased this concentration by 3-fold (p <0.05). Elacridar-loaded NE reduced paclitaxel penetration into the dermis of freshly excised mice skin and its percutaneous permeation by 1.5- and 1.7-fold (p <0.05), respectively at 6 h, whereas larger drug amounts (1.4-fold, p <0.05) were obtained in viable epidermis. Assessment of cutaneous distribution of a fluorescent paclitaxel derivative confirmed the smaller delivery into the dermis at elacridar presence. In conclusion, we have provided novel evidence that NE containing elacridar exhibited a clear potential for P-gp inhibition and enabled epidermal targeting of paclitaxel, which in turn, can potentially reduce adverse effects associated with systemic exposure to anticancer therapy. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

PubMed

Chen, Chun-Bing; Hsiao, Yi-Hsin; Wu, Tony; Hsih, Mo-Song; Tassaneeyakul, Wichittra; Jorns, Teekayu P; Sukasem, Chonlaphat; Hsu, Chien-Ning; Su, Shih-Chi; Chang, Wan-Chun; Hui, Rosaline Chung-Yee; Chu, Chia-Yu; Chen, Yi-Ju; Wu, Ching-Ying; Hsu, Chao-Kai; Chiu, Tsu-Man; Sun, Pei-Lun; Lee, Hua-En; Yang, Chin-Yi; Kao, Pei-Han; Yang, Chih-Hsun; Ho, Hsin-Chun; Lin, Jing-Yi; Chang, Ya-Ching; Chen, Ming-Jing; Lu, Chun-Wei; Ng, Chau Yee; Kuo, Kang-Ling; Lin, Chien-Yio; Yang, Ching-Sheng; Chen, Ding-Ping; Chang, Pi-Yueh; Wu, Tsu-Lan; Lin, Yu-Jr; Weng, Yi-Ching; Kuo, Tseng-Tong; Hung, Shuen-Iu; Chung, Wen-Hung

2017-01-03

To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6  drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10 -10 ; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further. © 2016 American Academy of Neurology.

Cutaneous Side-effects of Immunomodulators in MS.

PubMed

Lebrun, C; Bertagna, M; Cohen, M

2011-09-01

Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.

Mining adverse drug reactions from online healthcare forums using hidden Markov model.

PubMed

Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

2014-10-23

Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also

[Application analysis of adverse drug reaction terminology WHOART and MedDRA].

PubMed

Liu, Jing; Xie, Yan-ming; Gai, Guo-zhong; Liao, Xing

2015-12-01

Drug safety has always been a global focus. Discovery and accurate information acquisition of adverse drug reaction have been the most crucial concern. Terminology of adverse drug reaction makes adverse reaction medical report meaningful, standardized and accurate. This paper discussed the domestic use of the terminology WHOART and MedDRA in terms of content, structure, and application situation. It also analysed the differences between the two terminologies and discusses the future trend of application in our country

Terbinafine-induced lichenoid drug eruption.

PubMed

Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

2017-03-01

Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

Adverse drug events and the Freedom of Information Act: an apple in Eden.

PubMed

Stang, P E; Fox, J L

1992-02-01

To review some of the abuses and proper uses of the Food and Drug Administration's (FDA's) spontaneous adverse-reaction reporting system, as a way of educating the reader to its strengths and limitations. Published literature and reports based on information obtained from the FDA's database of spontaneous adverse drug-event reports. The Freedom of Information Act has increased public access to the FDA's database of spontaneous adverse drug reaction reports. As these reports are voluntarily received and reported to the FDA, their use for comparisons of drug safety is severely limited. Despite these limitations and the FDA's caveats for use of these data, consumer advocacy groups, researchers, and various pharmaceutical marketing groups have used this source to project the incidence of adverse drug reactions. The FDA's spontaneous adverse-event reporting system is designed to generate signals of unexpected adverse drug events. Use of the data gathered by this system to make drug safety comparisons is beyond their credible scope because many factors influence the reporting of adverse events. Researchers and peer reviewers should place these data in the proper perspective and support sound research into questions of drug safety.

Cutaneous toxicity from epidermal growth factor receptor inhibitors: would a subcutaneous desensitization be helpful? Case report.

PubMed

D'Alessio, Andrea; Cecchini, Sara; Di Mauro, Daniela; Geroli, Luca; Villa, Simonetta; Quadri, Antonello; Resta, Davide; Fortugno, Carmelo

2016-11-11

Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity. Subcutaneous desensitization with increasing concentrations of monoclonal antibodies can induce a tolerance to drug administration and reduce cutaneous adverse effects. To our knowledge, this is the first case in which a reduction or a disappearance of skin toxicity caused by EGFR-Is through subcutaneous desensitization has been achieved. We present cases of 2 Caucasian patients with adenocarcinoma of the colon treated with EGFR-Is who developed severe cutaneous toxicity. A 73-year-old man presented grade 4 skin toxicity of the face and grade 3 skin toxicity of the trunk during treatment with cetuximab. A 68-year-old woman developed G2 rash on the face after the first administration of cetuximab. These patients underwent subcutaneous desensitization with increasing concentrations of EGFR-Is. After this procedure, patients restarted therapy at the optimal dosage with reduction or disappearance of skin toxicity. These cases suggest that by giving rising doses of antibody it is possible to obtain desensitization able to prevent severe cutaneous adverse events in patients treated with EGFR-Is.

Pharmacogenetics of drug hypersensitivity

PubMed Central

Phillips, Elizabeth J; Mallal, Simon A

2010-01-01

Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

Postmarket Drug Surveillance Without Trial Costs: Discovery of Adverse Drug Reactions Through Large-Scale Analysis of Web Search Queries

PubMed Central

Gabrilovich, Evgeniy

2013-01-01

Background Postmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; hence, less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery. Objective Here we propose a low cost, fully automated method for continuous monitoring of adverse drug reactions in single drugs and in combinations thereof, and demonstrate the discovery of heretofore-unknown ones. Methods We used aggregated search data of large populations of Internet users to extract information related to drugs and adverse reactions to them, and correlated these data over time. We further extended our method to identify adverse reactions to combinations of drugs. Results We validated our method by showing high correlations of our findings with known adverse drug reactions (ADRs). However, although acute early-onset drug reactions are more likely to be reported to regulatory agencies, we show that less acute later-onset ones are better captured in Web search queries. Conclusions Our method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials. PMID:23778053

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

PubMed

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

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

PubMed

Helfenstein, M; Zweifel, S; Barthelmes, D; Meier, F; Fehr, J; Böni, C

2017-04-01

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management. Georg Thieme Verlag KG Stuttgart · New York.

National differences in publishing papers on adverse drug reactions

PubMed Central

Ferner, R E; Aronson, J K

2005-01-01

Aims To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers. Methods We searched Ovid EMBASE for publications indexed by the category ′therapeutic agents′, and the subcategory ′adverse effects′, by country for 43 countries. Results We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies. Conclusions Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts. PMID:15606448

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

PubMed

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.

PubMed

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.

Testing an explanatory model of nurses' intention to report adverse drug reactions in hospital settings.

PubMed

Angelis, Alessia De; Pancani, Luca; Steca, Patrizia; Colaceci, Sofia; Giusti, Angela; Tibaldi, Laura; Alvaro, Rosaria; Ausili, Davide; Vellone, Ercole

2017-05-01

To test an explanatory model of nurses' intention to report adverse drug reactions in hospital settings, based on the theory of planned behaviour. Under-reporting of adverse drug reactions is an important problem among nurses. A cross-sectional design was used. Data were collected with the adverse drug reporting nurses' questionnaire. Confirmatory factor analysis was performed to test the factor validity of the adverse drug reporting nurses' questionnaire, and structural equation modelling was used to test the explanatory model. The convenience sample comprised 500 Italian hospital nurses (mean age = 43.52). Confirmatory factor analysis supported the factor validity of the adverse drug reporting nurses' questionnaire. The structural equation modelling showed a good fit with the data. Nurses' intention to report adverse drug reactions was significantly predicted by attitudes, subjective norms and perceived behavioural control (R² = 0.16). The theory of planned behaviour effectively explained the mechanisms behind nurses' intention to report adverse drug reactions, showing how several factors come into play. In a scenario of organisational empowerment towards adverse drug reaction reporting, the major predictors of the intention to report are support for the decision to report adverse drug reactions from other health care practitioners, perceptions about the value of adverse drug reaction reporting and nurses' favourable self-assessment of their adverse drug reaction reporting skills. © 2017 John Wiley & Sons Ltd.

Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

PubMed

Böhm, Ruwen; Cascorbi, Ingolf

2016-01-01

Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

Prediction of adverse drug reactions using decision tree modeling.

PubMed

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.

Can the frequency and risks of fatal adverse drug events be determined?

PubMed

Kelly, W N

2001-05-01

Death is the ultimate adverse drug event. Despite its importance, the frequency of fatal adverse drug events is unknown. Estimates in the United States are as high as 140,000/year, although this number is heavily disputed. Potential reasons and risks for fatal adverse drug events, as well as epidemiologic designs for studying this important public health issue, are discussed and issues are raised to promote further thought.

Epidemiology of adverse drug reactions to phenformin and metformin.

PubMed Central

Bergman, U; Boman, G; Wiholm, B E

1978-01-01

Adverse drug reactions (ADRs) to phenformin and metformin reported to the Swedish Adverse Drug Reaction Committee during 1965--77 were analysed in relation to sales and prescription data. The biguanides accounted for 0.6% of all reported adverse drug reactions but for 6% of the fatal cases (all phenformin). Sixty-four ADRs to phenformin and eight to metformin were classified as causal relation "probable" or "not excluded." Fifty-one of these reactions (71%) were lactic acidosis, all but one being reactions to phenformin. After 1973 phenformin was prescribed less in Sweden and metformin became predominant. A nationwide prescription survey during 1975--6 disclosed no differences in age and sex between patients receiving phenformin and metformin. The mean daily doses prescribed in 1976 were 74 mg of phenformin and 1.5 g of metformin. The numbers of ADRs to the two drugs reported during 1975--7 were related to use. The relative incidences of ADRs reported for phenformin and metformin did not differ. Significantly more cases of lactic acidosis and deaths were reported for phenformin. PMID:678924

Ophthalmic adverse drug reactions to systemic drugs: a systematic review.

PubMed

Miguel, Ana; Henriques, Filipe; Azevedo, Luís Filipe; Pereira, Altamiro Costa

2014-03-01

To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis). Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias. From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy. To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future. Copyright © 2014 John Wiley & Sons, Ltd.

Evaluation of adverse drug event information in US manufacturer labels.

PubMed

Harrington, Catherine A; Garcia, Angela S; Sircar-Ramsewak, Feroza

2011-02-01

Pharmaceutical manufacturer labels are an important source of adverse drug event (ADE) information. The study objective was to determine the sufficiency of ADE reporting in US drug labels. A sample of 50 labels was evaluated from the top 200 drugs dispensed in the US. Electronic copies of labels were obtained and reviewed by 2 pharmacists for ADE incidence and discontinuation data. ADE incidence data were provided in 86% of labels. However, discontinuation rates due to ADEs and ADE incidence by dose were only reported in 60%. ADE incidence reporting by age (46%) or gender (18%) was also low. ADEs that occurred in less than 2% of the population were rarely reported. Incidence rates were based on small populations (median of 794) and short term studies (median of 84 days for chronic conditions). Labels for 19 drugs used chronically had no long term study data. Methods for collecting ADE data were stated in only 12% of labels. Adverse drug event and drug discontinuation data is under-reported in US labels. More information on adverse events causing discontinuation (especially serious events) and those related to dose, age, and gender is needed in labels to ensure safe prescribing and dispensing of drugs.

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

PubMed Central

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

2014-01-01

Background 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. Objective 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. Methods 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. Results 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. Conclusions 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. PMID:25600332

[Local adverse reactions associated with parenteral administration of drugs].

PubMed

Bjånes, Tormod Karlsen

2011-03-04

Parenteral administration of drugs may cause adverse reactions which in severe cases outweigh the intended therapeutic effects. This paper outlines local adverse reactions associated with various routes of parenteral administration. Different measures for prevention and management of such reactions are presented.

Reporting of adverse drug reactions in randomised controlled trials – a systematic survey

PubMed Central

Loke, Yoon Kong; Derry, Sheena

2001-01-01

Background Decisions on treatment are guided, not only by the potential for benefit, but also by the nature and severity of adverse drug reactions. However, some researchers have found numerous deficiencies in trial reports of adverse effects. We sought to confirm these findings by evaluating trials of drug therapy published in seven eminent medical journals in 1997. Methods Literature review to determine whether the definition, recording and reporting of adverse drug reactions in clinical trials were in accordance with published recommendations on structured reporting. Results Of the 185 trials reviewed, 25 (14%) made no mention of adverse drug reactions. Data in a further 60 (32%) could not be fully evaluated, either because numbers were not given for each treatment arm (31 trials), or because a generic statement was made without full details (29 trials). When adverse drug reactions such as clinical events or patient symptoms were mentioned in the reports, details on how they had been recorded were given in only 14/95 (15%) and 18/104 (17%) trials respectively. Of the 86 trials that mentioned severity of adverse drug reactions, only 42 (49%) stated how severity had been defined. The median amount of space used for safety data in the Results and Discussion sections was 5.8%. Conclusions Trial reports often failed to provide details on how adverse drug reactions were defined or recorded. The absence of such methodological information makes comparative evaluation of adverse reaction rates potentially unreliable. Authors and journals should adopt recommendations on the structured reporting of adverse effects. PMID:11591227

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed. PMID:21121777

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study

PubMed Central

Ko, Tai-Ming; Tsai, Chang-Youh; Chen, Shih-Yang; Chen, Kuo-Shu; Yu, Kuang-Hui; Chu, Chih-Sheng; Huang, Chung-Ming; Wang, Chrong-Reen; Weng, Chia-Tse; Yu, Chia-Li; Hsieh, Song-Chou; Tsai, Jer-Chia; Lai, Wen-Ter; Tsai, Wen-Chan; Yin, Guang-Dar; Ou, Tsan-Teng; Cheng, Kai-Hung; Yen, Jeng-Hsien; Liou, Teh-Ling; Lin, Tsung-Hsien; Chen, Der-Yuan; Hsiao, Pi-Jung; Weng, Meng-Yu; Chen, Yi-Ming; Chen, Chen-Hung; Liu, Ming-Fei; Yen, Hsueh-Wei; Lee, Jia-Jung; Kuo, Mei-Chuan; Wu, Chen-Ching; Hung, Shih-Yuan; Luo, Shue-Fen; Yang, Ya-Hui; Chuang, Hui-Ping; Chou, Yi-Chun; Liao, Hung-Ting; Wang, Chia-Wen; Huang, Chun-Lin; Chang, Chia-Shuo; Lee, Ming-Ta Michael; Chen, Pei; Wong, Chih-Shung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Chen, Yuan-Tsong

2015-01-01

Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence

Quality of life in children with adverse drug reactions: a narrative and systematic review.

PubMed

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-10-01

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

Quality of life in children with adverse drug reactions: a narrative and systematic review

PubMed Central

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-01-01

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

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

Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children.

PubMed

Suvichapanich, Supharat; Jittikoon, Jiraphun; Wichukchinda, Nuanjun; Kamchaisatian, Wasu; Visudtibhan, Anannit; Benjapopitak, Suwat; Nakornchai, Somjai; Manuyakorn, Wiparat; Mahasirimongkol, Surakameth

2015-08-01

CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9*3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9*3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19 phenobarbital and 16 phenytoin) were enrolled. CYP2C9*3 was genotyped by allele-specific PCRs. The association between CYP2C9*3 with phenytoin-induced SCARs and phenobarbital-induced SCARs were analyzed in comparison with tolerances and healthy samples. Significant association between phenytoin-induced SCARs and CYP2C9*3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18-∞, P-value=0.044). CYP2C9*3 was not associated with phenobarbital-induced SCARs. This study is the first report of CYP2C9*3 association to phenytoin-induced SCARs in Thai epileptic children. The CYP2C9*3 is a reasonable predictive genetic marker to anticipate SCARs from phenytoin.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.

2007-11-05

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.

Acute cutaneous graft-vs.-host disease compared to drug hypersensitivity reaction with vacuolar interface changes: a blinded study of microscopic and immunohistochemical features.

PubMed

Lehman, Julia S; Gibson, Lawrence E; el-Azhary, Rokea A; Chavan, Rahul N; Hashmi, Shahrukh K; Lohse, Christine M; Flotte, Thomas J

2015-01-01

Complications from graft-vs.-host disease (GVHD), a major contributor to morbidity and mortality following hematopoietic cell transplantation, may be mitigated by early diagnosis and intervention. However, differentiation between acute cutaneous GVHD and other common skin eruptions that develop in the post-transplantation period, such as drug hypersensitivity reaction, can be challenging clinically and microscopically. Because recent evidence indicates that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis, we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous GVHD. We studied 12 skin specimens of patients with grades I-II cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with vacuolar interface changes on biopsy. No differences were seen between the two groups with regards to density or distribution of CD123 expression. Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and fewer dermal eosinophils (P = 0.03) compared to those representing drug hypersensitivity reaction. We conclude that CD123 does not appear to be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful correlation between clinical findings and features with microscopy remains the cornerstone of accurate diagnosis of acute cutaneous GVHD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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.

The knowledge, attitude and behaviours of nurses about pharmacovigilance, adverse drug reaction and adverse event reporting in a state hospital

PubMed Central

Vural, Fisun; Ciftci, Seval; Vural, Birol

2015-01-01

OBJECTIVE: With the use of any drug comes the possibility of unintended consequences which when harmful are referred to as adverse drug reactions (ADRs). The development of national pharmacovigilance systems is the responsibility of all health workers. The aim of this study was to investigate the knowledge of nurses about pharmacovigilance and attitudes about ADR and adverse event reporting. METHODS: This descriptive-cross sectional study was performed in 112 nurses working in a public hospital. The questionnaire was applied about pharmacovigilance and adverse drug reactions. The knowledge, attitudes and practices about adverse drug reactions were asked. RESULTS: The 74.1% of the nurses definition of “severe adverse effect” of drug therapy. The ratio of participants who knew that ADRs are reported to contact person responsible from pharmacovigilance was 34.9%. Although 70.5% of nurses knew the necessity of ADR reporting, the 8% of the nurses knew Turkish Pharmacovigilance Center (TÜFAM). Only 8% of nurses reported ADRs in their professionality. CONCLUSION: Although most of the participants knew the importance of ADR event reporting, event reporting was low. Thiese results showed that there is a lack of knowledge about pharmacovigilance. Futher studies with different settings and healthcare staff are needed to improve awareness about pharmacovigilance. PMID:28058321

Causality Patterns for Detecting Adverse Drug Reactions From Social Media: Text Mining Approach.

PubMed

Bollegala, Danushka; Maskell, Simon; Sloane, Richard; Hajne, Joanna; Pirmohamed, Munir

2018-05-09

Detecting adverse drug reactions (ADRs) is an important task that has direct implications for the use of that drug. If we can detect previously unknown ADRs as quickly as possible, then this information can be provided to the regulators, pharmaceutical companies, and health care organizations, thereby potentially reducing drug-related morbidity and saving lives of many patients. A promising approach for detecting ADRs is to use social media platforms such as Twitter and Facebook. A high level of correlation between a drug name and an event may be an indication of a potential adverse reaction associated with that drug. Although numerous association measures have been proposed by the signal detection community for identifying ADRs, these measures are limited in that they detect correlations but often ignore causality. This study aimed to propose a causality measure that can detect an adverse reaction that is caused by a drug rather than merely being a correlated signal. To the best of our knowledge, this was the first causality-sensitive approach for detecting ADRs from social media. Specifically, the relationship between a drug and an event was represented using a set of automatically extracted lexical patterns. We then learned the weights for the extracted lexical patterns that indicate their reliability for expressing an adverse reaction of a given drug. Our proposed method obtains an ADR detection accuracy of 74% on a large-scale manually annotated dataset of tweets, covering a standard set of drugs and adverse reactions. By using lexical patterns, we can accurately detect the causality between drugs and adverse reaction-related events. ©Danushka Bollegala, Simon Maskell, Richard Sloane, Joanna Hajne, Munir Pirmohamed. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 09.05.2018.

Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management.

PubMed

Eisenhofer, Graeme; Rivers, Graham; Rosas, Alejandro L; Quezado, Zena; Manger, William M; Pacak, Karel

2007-01-01

The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D(2) receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications.

Illicit drug use and adverse birth outcomes: is it drugs or context?

PubMed

Schempf, Ashley H; Strobino, Donna M

2008-11-01

Prenatal drug use is commonly associated with adverse birth outcomes, yet no studies have controlled for a comprehensive set of associated social, psychosocial, behavioral, and biomedical risk factors. We examined the degree to which adverse birth outcomes associated with drug use are due to the drugs versus surrounding factors. Data are from a clinical sample of low-income women who delivered at Johns Hopkins Hospital between 1995 and 1996 (n = 808). Use of marijuana, cocaine, and opiates was determined by self-report, medical record, and urine toxicology screens at delivery. Information on various social, psychosocial, behavioral, and biomedical risk factors was gathered from a postpartum interview or the medical record. Multivariable regression models of birth outcomes (continuous birth weight and low birth weight ([LBW] < 2,500 g)) were used to assess the effect of drug use independent of associated factors. In unadjusted results, all types of drug use were related to birth weight decrements and increased odds of LBW. However, only the effect of cocaine on continuous birth weight remained significant after adjusting for all associated factors (-142 g, p = 0.05). No drug was significantly related to LBW in fully adjusted models. About 70% of the unadjusted effect of cocaine use on continuous birth weight was explained by surrounding psychosocial and behavioral factors, particularly smoking and stress. Most of the unadjusted effects of opiate use were explained by smoking and lack of early prenatal care. Thus, prevention efforts that aim to improve newborn health must also address the surrounding context in which drug use frequently occurs.

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

Patterns in spontaneous adverse event reporting among branded and generic antiepileptic drugs.

PubMed

Bohn, J; Kortepeter, C; Muñoz, M; Simms, K; Montenegro, S; Dal Pan, G

2015-05-01

Spontaneous adverse event reports constitute an important source of information on previously unknown adverse reactions to marketed medicines. However, the dynamics of such reporting following generic introduction are poorly understood. Using adverse event reports on five antiepileptic drugs from the US Food and Drug Administration's Adverse Event Reporting System, we describe temporal trends in adverse event reporting before and after generic introduction, and survey the quality of product-identifying information contained therein. The majority of reports were sent by innovator drug manufacturers while few were sent by generic manufacturers, even when generics accounted for >90% of dispensed prescriptions. We manually reviewed narratives from 2,500 reports and found that the suspect product type (brand or generic) could not be determined in 84% of reports, while generic products (16%) were identified more often than brand-name products (<1%). These results suggest that pharmacovigilance stakeholders should act to promote more detailed reporting practices. © 2015 American Society for Clinical Pharmacology and Therapeutics.

[Characterization of adverse drug reactions in adults over 44 years of age in Bogota, January-December, 2012].

PubMed

Chaves, Marlén

2015-01-01

In Colombia, aging of the population is a reality and elders consume more drugs than the young do. Consequently, they are more exposed to adverse drug reactions. To characterize suspected adverse drug reactions in adults over 44 years of age in Bogota in 2012. We conducted a pharmacological surveillance study that included 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years old included in the database of Bogotá´s pharmacosurveillance program. We evaluated 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years of age. From these, 432 reports (91.9%) were classified as suspected adverse drug reactions and 28 (6%), as associated problems with the use of drugs. The incidence rate for adverse drug events reported in Bogotá was 22.5 for every 100,000 elders, which increased in direct proportion to patients´ age. The most frequently reported drug was antibacterials with 94 notifications (20%). The organ system with the highest number of alterations was the skin and annexes with 21.2% of cases. Regarding severity assessment, 69.5% of adverse drug reactions were moderate, and as for causality, most adverse drug reactions were classified as possible, with 45.8% of the reports. The characterization of adverse drug reactions in older adults in Bogotá is similar to that reported in the literature for this population age group.

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... identification number and adverse reaction term(s)); and (c) a history of actions taken since the last report...; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action... circumstance, the nonapplicant shall maintain a record of this action which shall include: (A) A copy of each...

Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury.

PubMed

García-Cortés, M; Lucena, M I; Pachkoria, K; Borraz, Y; Hidalgo, R; Andrade, R J

2008-05-01

Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (kappa(w)) test. A total of 249 ratings were generated. Between-observer agreement was 45% with a kappa(w) value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, kappa(w): 0.71). Concordance between the two scales was 24% (kappa(w): 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.

Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis.

PubMed

Caracò, Corrado; Mozzillo, Nicola; Marone, Ugo; Simeone, Ester; Benedetto, Lucia; Di Monta, Gianluca; Di Cecilia, Maria Luisa; Botti, Gerardo; Ascierto, Paolo Antonio

2013-12-01

Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option. This study was undertaken to analyze the short- and long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases. Between June 2007 and September 2012, 60 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease underwent 100 courses of ECT with intravenous injection of bleomycin. Response to treatment was evaluated three months after ECT. A long-lasting response was defined as no cutaneous or in-transit relapse after a minimum of six months. Three months after ECT, a complete response was observed in 29 patients (48.4%), a partial response in 23 patients (38.3%) and no change or progressive disease in 8 patients (13.3%). The objective response rate of all treated lesions was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long-lasting response after one ECT session and were disease-free after a mean duration of follow-up of 27.5 months. The favorable outcome obtained in the present study demonstrates that ECT is a reliable, and effective procedure that provides long-term benefit in terms of curative and palliative treatment for unresectable cutaneous lesions without adversely impacting the quality of life of patients.

Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis

PubMed Central

2013-01-01

Background Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option. This study was undertaken to analyze the short- and long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases. Methods Between June 2007 and September 2012, 60 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease underwent 100 courses of ECT with intravenous injection of bleomycin. Response to treatment was evaluated three months after ECT. A long-lasting response was defined as no cutaneous or in-transit relapse after a minimum of six months. Results Three months after ECT, a complete response was observed in 29 patients (48.4%), a partial response in 23 patients (38.3%) and no change or progressive disease in 8 patients (13.3%). The objective response rate of all treated lesions was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long-lasting response after one ECT session and were disease-free after a mean duration of follow-up of 27.5 months. Conclusions The favorable outcome obtained in the present study demonstrates that ECT is a reliable, and effective procedure that provides long-term benefit in terms of curative and palliative treatment for unresectable cutaneous lesions without adversely impacting the quality of life of patients. PMID:24289268

Adverse drug events in the oral cavity.

PubMed

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.

Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting.

PubMed

Aung, Ar Kar; Tang, Mei Jie; Adler, Nikki Rae; de Menezes, Sara Lee; Goh, Michelle Sue Yen; Tee, Hui Wen; Trubiano, Jason Anthony; Puy, Robert; Zubrinich, Celia Mary; Graudins, Linda Velta

2018-05-07

We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1-10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4-5.5, and P = .04, OR 4.2, 95%CI 1.2-18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9-7.9, and P < .0001, OR 11.4, 95%CI 4.6-27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety. © 2018, The American College of Clinical Pharmacology.

Personalized Medicine and Adverse Drug Reactions: The Experience of An Italian Teaching Hospital.

PubMed

La Russa, Raffaele; Finesch, Vittorio; Di Sanzo, Mariantonia; Gatto, Vittorio; Santurro, Alessandro; Martini, Gabriella; Scopetti, Matteo; Frati, Paola

2017-01-01

The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years. Comparing the data result from our analysis with several studies found in literature, it is evident that adverse drug reactions represent an important problem in the management of a health care system. However, the development of pharmacogenetics and pharmacogenomics, allowing a personalized treatment, can improve clinical practice. This study highlights the great potential of pharmacogenomics in reducing adverse reactions and suggests the need for further pharmacogenomic clinical trials to better personalize drug treatment and to refine the current pharmacovigilance strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO2) monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cutaneous carbon dioxide (PcCO2) monitor. 868.2480 Section 868.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2480 Cutaneous carbon dioxide (PcCO2) monitor. (a) Identification. A...

Adverse drug reactions: classification, susceptibility and reporting.

PubMed

Kaufman, Gerri

2016-08-10

Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme.

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

PubMed

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.

Completeness of serious adverse drug event reports received by the US Food and Drug Administration in 2014.

PubMed

Moore, Thomas J; Furberg, Curt D; Mattison, Donald R; Cohen, Michael R

2016-06-01

Adverse drug event reports to the US Food and Drug Administration (FDA) remain the primary tool for identifying serious drug adverse effects without adequate existing warnings. We assessed the completeness of reports the FDA received in 2014. Serious adverse drug event reports were evaluated for whether they included age, gender, event date, and at least one medical term describing the event in computer excerpts. Report sources were direct reports to the FDA, manufacturer expedited reports about events without adequate warnings, and manufacturer periodic reports about events with existing warnings. In 2014, the FDA received 528,192 new case reports indicating a serious or fatal outcome, 25,038 (4.7%) directly from health professionals and consumers, and 503,154 (95.3%) from drug manufacturers. Overall, 21,595 (86.2%) of serious reports submitted directly to the FDA provided data for all four completeness variables, compared with 271,022 (40.4%) of manufacturer expedited reports and 24,988 (51.3%) of periodic reports. Among manufacturer serious reports, 37.9% lacked age and 46.9% had no event date. Performance by 25 manufacturers submitting 5000 or more reports varied from 24.4% complete on all variables to 67% complete. Patient death cases had the lowest completeness scores in all categories. By these measures, report completeness from drug manufacturers was poor compared with direct submissions to the agency. The FDA needs to update reporting requirements and compliance policies to help industry capture better adverse event information from new forms of manufacturer interactions with health professionals and consumers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions.

PubMed

Kellihan, M J

1993-01-01

Selection of a drug for formulary inclusion involves evaluation of safety, efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and filgrastim have a broad range of potential indications and represent a costly formulary addition when acquisition price alone is considered; their comparative safety is unclear. These factors suggest that the CSFs should be closely scrutinized prior to formulary addition. In the absence of direct comparative studies, an assessment of the safety of CSFs involves evaluation of information provided in the product circular, official drug compendia, adverse biologic reports submitted to the United States Food and Drug Administration, and data from key clinical trials. Data in the product circulars report on adverse events in small numbers of patients treated for chemotherapy-induced neutropenia (filgrastim) or neutropenia subsequent to bone marrow transplantation (sargramostim). The official compendia and clinical trials include experience with CSFs produced in a variety of expression systems; these data are not limited to sargramostim and filgrastim. Importantly, there was a similar incidence of adverse events in patients who received sargramostim or filgrastim and in those who took placebo reported in the product circulars and the pivotal trials, suggesting that the underlying disease may have an important role in determining the side-effect profile of these agents. Adverse biologic reports represent experience with sargramostim and filgrastim obtained under actual clinical conditions and suggest that the same types of adverse events are seen with sargramostim as with filgrastim. This analysis suggests that a decision to select filgrastim over sargramostim for formulary inclusion based on the safety profile is not appropriate because currently available data are equivocal and that such decisions would more appropriately be based on efficacy and cost.

Effectiveness of adverse effects search filters: drugs versus medical devices.

PubMed

Farrah, Kelly; Mierzwinski-Urban, Monika; Cimon, Karen

2016-07-01

The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%-87%) than for drugs (88%-93%) in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%-81%) than in MEDLINE (67%-87%) for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs.

Idiosyncratic Adverse Drug Reactions: Current Concepts

PubMed Central

Naisbitt, Dean J.

2013-01-01

Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

The Potential Return on Public Investment in Detecting Adverse Drug Effects.

PubMed

Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

2017-06-01

Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

PubMed

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.

Use of a trigger tool to detect adverse drug reactions in an emergency department.

PubMed

de Almeida, Silvana Maria; Romualdo, Aruana; de Abreu Ferraresi, Andressa; Zelezoglo, Giovana Roberta; Marra, Alexandre R; Edmond, Michael B

2017-11-15

Although there are systems for reporting adverse drug reactions (ADR), these safety events remain under reported. The low-cost, low-tech trigger tool method is based on the detection of events through clues, and it seems to increase the detection of adverse events compared to traditional methodologies. This study seeks to estimate the prevalence of adverse reactions to drugs in patients seeking care in the emergency department. Retrospective study from January to December, 2014, applying the Institute for Healthcare Improvement (IHI) trigger tool methodology for patients treated at the emergency room of a tertiary care hospital. The estimated prevalence of adverse reactions in patients presenting to the emergency department was 2.3% [CI 95 1.3% to 3.3%]; 28.6% of cases required hospitalization at an average cost of US$ 5698.44. The most common triggers were hydrocortisone (57% of the cases), diphenhydramine (14%) and fexofenadine (14%). Anti-infectives (19%), cardiovascular agents (14%), and musculoskeletal drugs (14%) were the most common causes of adverse reactions. According to the Naranjo Scale, 71% were classified as possible and 29% as probable. There was no association between adverse reactions and age and sex in the present study. The use of the trigger tool to identify adverse reactions in the emergency department was possible to identify a prevalence of 2.3%. It showed to be a viable method that can provide a better understanding of adverse drug reactions in this patient population.

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

PubMed

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

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

PubMed Central

2015-01-01

Background 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. Methods 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. Results 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

Sharing adverse drug event data using business intelligence technology.

PubMed

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.

A novel system to diagnose cutaneous adverse drug reactions employing the cellscan--comparison with histamine releasing test and Inf-gamma Releasing Test.

PubMed

Goldberg, Ilan; Gilburd, Boris; Kravitz, Martine Szyper; Kivity, Shmuel; Chaim, Berta Ben; Klein, Tirza; Schiffenbauer, Yael; Trubniykovr, Ela; Brenner, Sarah; Shoenfeld, Yehuda

2005-03-01

There are several mechanisms to describe allergic drug reactions yet the methods to diagnose them are limited. To compare several conventional clinical and laboratory methods to diagnose skin reactions to drugs to a new method of diagnosing drug reactions by the CellScan system. The study entailed 21 patients who were diagnosed as suffering from drug eruptions, and 105 healthy controls with no history of drug allergy. The drugs were classified into two groups according to suspicion of causing drug allergy: high and low. Most of the patients were on more than one drug, leading to 41 patient-drug interactions (assays). Histamine releasing test (HRT), interferon (INF)-gamma releasing test and CellScan examination were performed on lymphocytes of the patients and controls. The HRTwas interpreted as positive in 9 out of 18 (50%) patients and in 13 out of 35 (37%) assays. Based on the INF-gamma releasing test, positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41 (59%) assays. In the CellScan test (CST), positive results were observed in 17 out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%) assays in the HRT, 20 out of 24 (83%) assays in the INF-gamma releasing test, and 21 out of 24 (87%) studies with the CellScan method. The rate of determining of the drug that caused the eruption in the low suspicion level drugs was 4 out of 13 (31 %) in the HRT, 4 out of 17 (24%) assays in the INF-gamma releasing test, and 8 out of 17 (47%) analyses in the CST. When examined in the CellScan, 99 out of 105 (94%) controls were interpreted as negative. This preliminary study indicates that the CellScan seems to be an easy and promising method for the detection of drugs responsible for adverse skin reactions. In contrast to the HRT and to the Interferon-gamma secretion test, the CellScan method is characterized by its ability to track and monitor the

Adverse drug reactions in Colombian patients, 2007-2013: Analysis of population databases.

PubMed

Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés

2016-03-03

Recognizing adverse drug reactions (ADRs) is becoming more important in clinical practice.  To determine the frequency of adverse drug reactions and ADR suspicions among the population affiliated to the Colombian health system and to describe the drugs, reactions and associated variables.  We revised ADRs and ADRs suspicion databases from drugs dispensed by Audifarma, S.A., both for inpatient and outpatient care from 2007 to 2013. Variables included ADR report date, city, drug, drug's Anatomical Therapeutic Classification (ATC), ADR severity, ADR type, ADR classification and ADR probability according to the World Health Organization's definitions.  We obtained 5,342 reports for 468 different drugs. The ATC groups with the most reports were anti-infectives for systemic use (25.5%), nervous system agents (17.1%) and cardiovascular system drugs (15.0%). The drugs with the highest number of reports were metamizole (4.2%), enalapril (3.8%), clarithromycin (2.8%), warfarin (2.5%) and ciprofloxacin (2.4%). The most common ADR, classified following the World Health Organization adverse reaction terminology, were: skin and appendages disorders (35.3%), general disorders (14.2%) and gastrointestinal system disorders (11.8%). Overall, 49.4% of the ADRs were classified as "moderate" and 45.1% as "mild".  An increasing number of ADR reports were found coinciding with a worldwide tendency. Differences between inpatient and outpatient ADR reports were found when compared to scientific publications. The information on ADR reports, mainly gathered by the Instituto Nacional de Vigilancia de Medicamentos y Alimentos - Invima, should be made public for academic and institutional use.

Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2018-06-07

Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of

Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies.

PubMed

Eaglstein, William H; Kirsner, Robert S; Robson, Martin C

2012-01-01

The rising costs of caring for chronic cutaneous ulcers (CCUs) and recent appreciation of the mortality of CCUs have led to consideration of the reasons for the failure to have new drug therapies. No new chemical entities to heal CCUs have been approved by the Food and Drug Administration (FDA) in over a decade, in part due to an inability to reach the FDA accepted end point of "complete wound closure." The frequent failure to reach the complete closure end point brings forward the question of the relevance of other healing end points such as improved quality of life, or partial healing. Because CCUs carry a prognosis and mortality rate worse than many cancers, it is reasonable to compare the FDA trial end points for cancer drug approval with those for CCUs. And the difference is quite striking. While there is only one end point for CCUs, there are five surrogate and three direct end points for cancers. In contrast to cancer, surrogate end points and partial healing are not acceptable for therapies aimed at CCUs. For example, making tumors smaller is an acceptable end point, but making CCUs smaller is not and improvement in the signs and symptoms of cancer is an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and mortality rate worse than many cancers, we believe a reconsideration of end points for CCUs is highly warranted. © 2012 by the Wound Healing Society.

Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials

PubMed Central

Derry, Sheena; Kong Loke, Yoon; Aronson, Jeffrey K

2001-01-01

Background We would expect information on adverse drug reactions in randomised clinical trials to be easily retrievable from specific searches of electronic databases. However, complete retrieval of such information may not be straightforward, for two reasons. First, not all clinical drug trials provide data on the frequency of adverse effects. Secondly, not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data. We have determined how often automated search methods, using indexing terms and/or textwords in the title or abstract, would fail to retrieve trials with adverse effects data. Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects, and measured the proportion that (i) were not assigned the appropriate adverse effects indexing terms in the electronic databases, and (ii) did not contain identifiable adverse effects textwords in the title or abstract. Results Of the 81 trials with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects in either database. Twenty-six trials were indexed in one database but not the other. Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper. Simultaneous use of textword and indexing terms retrieved only 82/107 (77%) papers. Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects. PMID:11591220

Commonality of drug-associated adverse events detected by 4 commonly used data mining algorithms.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Minami, Keiko; Okuno, Yasushi

2014-01-01

Data mining algorithms have been developed for the quantitative detection of drug-associated adverse events (signals) from a large database on spontaneously reported adverse events. In the present study, the commonality of signals detected by 4 commonly used data mining algorithms was examined. A total of 2,231,029 reports were retrieved from the public release of the US Food and Drug Administration Adverse Event Reporting System database between 2004 and 2009. The deletion of duplicated submissions and revision of arbitrary drug names resulted in a reduction in the number of reports to 1,644,220. Associations with adverse events were analyzed for 16 unrelated drugs, using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM). All EBGM-based signals were included in the PRR-based signals as well as IC- or ROR-based ones, and PRR- and IC-based signals were included in ROR-based ones. The PRR scores of PRR-based signals were significantly larger for 15 of 16 drugs when adverse events were also detected as signals by the EBGM method, as were the IC scores of IC-based signals for all drugs; however, no such effect was observed in the ROR scores of ROR-based signals. The EBGM method was the most conservative among the 4 methods examined, which suggested its better suitability for pharmacoepidemiological studies. Further examinations should be performed on the reproducibility of clinical observations, especially for EBGM-based signals.

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

PubMed

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.

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO 2) monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cutaneous oxygen (PcO 2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO 2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO 2) monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cutaneous oxygen (PcO 2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO 2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

In Vitro Activities of Eight Antifungal Drugs against 106 Waterborne and Cutaneous Exophiala Species

PubMed Central

Najafzadeh, M. J.; Saradeghi Keisari, M.; Vicente, V. A.; Feng, P.; Shamsian, S. A. A.; Rezaei-Matehkolaei, A.; de Hoog, G. S.; Curfs-Breuker, I.

2013-01-01

The in vitro activities of eight antifungal drugs against 106 clinical and environmental isolates of waterborne and cutaneous Exophiala species were tested. The MICs and minimum effective concentrations for 90% of the strains tested (n = 106) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.25 μg/ml; micafungin, 1 μg/ml; voriconazole, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 8 μg/ml; amphotericin B, 16 μg/ml; fluconazole, 64 μg/ml. PMID:24100491

Pattern Mining for Extraction of mentions of Adverse Drug Reactions from User Comments

PubMed Central

Nikfarjam, Azadeh; Gonzalez, Graciela H.

2011-01-01

Rapid growth of online health social networks has enabled patients to communicate more easily with each other. This way of exchange of opinions and experiences has provided a rich source of information about drugs and their effectiveness and more importantly, their possible adverse reactions. We developed a system to automatically extract mentions of Adverse Drug Reactions (ADRs) from user reviews about drugs in social network websites by mining a set of language patterns. The system applied association rule mining on a set of annotated comments to extract the underlying patterns of colloquial expressions about adverse effects. The patterns were tested on a set of unseen comments to evaluate their performance. We reached to precision of 70.01% and recall of 66.32% and F-measure of 67.96%. PMID:22195162

Biometrical issues in the analysis of adverse events within the benefit assessment of drugs.

PubMed

Bender, Ralf; Beckmann, Lars; Lange, Stefan

2016-07-01

The analysis of adverse events plays an important role in the benefit assessment of drugs. Consequently, results on adverse events are an integral part of reimbursement dossiers submitted by pharmaceutical companies to health policy decision-makers. Methods applied in the analysis of adverse events commonly include simple standard methods for contingency tables. However, the results produced may be misleading if observations are censored at the time of discontinuation due to treatment switching or noncompliance, resulting in unequal follow-up periods. In this paper, we present examples to show that the application of inadequate methods for the analysis of adverse events in the reimbursement dossier can lead to a downgrading of the evidence on a drug's benefit in the subsequent assessment, as greater harm from the drug cannot be excluded with sufficient certainty. Legal regulations on the benefit assessment of drugs in Germany are presented, in particular, with regard to the analysis of adverse events. Differences in safety considerations between the drug approval process and the benefit assessment are discussed. We show that the naive application of simple proportions in reimbursement dossiers frequently leads to uninterpretable results if observations are censored and the average follow-up periods differ between treatment groups. Likewise, the application of incidence rates may be misleading in the case of recurrent events and unequal follow-up periods. To allow for an appropriate benefit assessment of drugs, adequate survival time methods accounting for time dependencies and duration of follow-up are required, not only for time-to-event efficacy endpoints but also for adverse events. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd.

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

PubMed

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.

Retrospective analysis of drug photosensitivity in Norway

NASA Astrophysics Data System (ADS)

Selvaag, Edgar

1999-02-01

Reports on adverse drug reactions, as they were recorded at the Norwegian Medicines Control Authority beginning in the year 1970 up to 1994 were analyzed especially with regard to cutaneous reactions and photosensitivity reactions. During the time period, almost 13.000 side effects were reported. Out of these 799 reports involved the skin and appendages, and 64 out of these reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs which most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the background of experimental data and the prescription rates of these substances.

[Are non-clinical studies predictive of adverse events in humans?].

PubMed

Claude, N

2007-09-01

The predictibility of adverse events induced by drugs in non-clinical safety studies performed on in vitro and/or in vivo models is a key point for the safety of humans exposed to pharmaceuticals. The strength and the weakness of animal studies to predict human toxicity were assessed by an international study on the concordance of the toxicity of 150 pharmaceuticals observed in humans with that observed in experimental animals. The results showed a good correlation (70% of the adverse events in humans were detected in animal studies) and an early time to first appearance of concordant animal toxicity: 94% were first observed in studies of 1 month or less in duration. The highest incidence of overall concordance was seen in hematological and cardiovascular adverse effects and the least was seen in cutaneous and ophthalmological adverse effects. These studies, scientifically and regulatory standardized, need, in some cases to be adapted to specific problems linked to sensitive populations (young, old or with a pathology which could be worsened by the drug), or specific pharmaceuticals (produced by biotechnology). Some severe adverse events are not detected in conventional animal models (immuno-allergy, idiosyncrasy). Taken together, these elements support the value of toxicology studies to predict many human toxic events associated with pharmaceuticals. Nevertheless, a part of human toxicity is not detected by these experimental approaches, and new tools developed through progress in biology and bio-informatics should reduce this uncertainly margin.

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

PubMed

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.

PubMed

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.

Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration.

PubMed

Franzé, Silvia; Marengo, Alessandro; Stella, Barbara; Minghetti, Paola; Arpicco, Silvia; Cilurzo, Francesco

2018-01-15

The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm 2 /h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these

Refining adverse drug reaction signals by incorporating interaction variables identified using emergent pattern mining.

PubMed

Reps, Jenna M; Aickelin, Uwe; Hubbard, Richard B

2016-02-01

To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranking the drug families known to be true adverse drug reactions above those that are not. This was not the case without the inclusion of the candidate confounding interaction terms, where confounding leads to a non-adverse drug reaction being ranked highest. The methodology is efficient, can identify high-order confounding interactions and does not require expert input to specify outcome specific confounders, so it can be applied for any outcome of interest to quickly refine its signals. The proposed method shows excellent potential to overcome some forms of confounding and therefore reduce the false positive rate for signal analysis using longitudinal data. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO2) monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous carbon dioxide (PcCO2) monitor. 868.2480... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2480 Cutaneous carbon dioxide (PcCO2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive heated...

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO 2) monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cutaneous carbon dioxide (PcCO 2) monitor. 868... dioxide (PcCO 2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive... relative changes in a hemodynamically stable patient's cutaneous carbon dioxide tension as an adjunct to...

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO 2) monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cutaneous carbon dioxide (PcCO 2) monitor. 868... dioxide (PcCO 2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive... relative changes in a hemodynamically stable patient's cutaneous carbon dioxide tension as an adjunct to...

Adverse drug effects in hospitalized elderly: Data from the Healthcare Cost and Utilization Project

PubMed Central

Shamliyan, Tatyana

2010-01-01

We aimed to analyze trends in hospital admissions due to adverse drug effects between the years 2000 to 2007 among the elderly using the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project. We identified the discharges with the principal and all listed diagnoses related to adverse drug effects and associated hospital charges using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes. Between 2000 and 2007, 321,057 patients over 65 years were discharged with a principal diagnosis related to an adverse drug effect. Hospital charges were $5,329,276,300 or $666,159,537 annual cost. The number of discharges and total hospital charges did not change over the examined years, while mean charge per discharge increased on average by $1064 ± 384 per year. Total hospital charges for drug-induced gastritis with hemorrhage increased the most by $11,206,555 per year among those 66–84 years old and by $8,646,456 per year among those older than 85 years. During 2007, 791,931 elderly had adverse treatment effects among all listed diagnoses with hospital charges of $937,795,690. Effective drug management interventions are needed to improve safety of treatments in the elderly. PMID:22291486

Subcutaneous L-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats.

PubMed

Hung, Ching-Hsia; Chiu, Chong-Chi; Liu, Kuo-Sheng; Chen, Yu-Wen; Wang, Jhi-Joung

2015-10-15

The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. We showed that both L-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88-5.38] μmol)>L-tyrosine (39.1 [36.5-41.8] μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by L-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with L-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone. Copyright © 2015 Elsevier B.V. All rights reserved.

Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

PubMed

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

2009-08-01

Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects.

PubMed

Franco, Valentina; Perucca, Emilio

2015-01-01

Phenytoin, a widely prescribed old-generation antiepileptic drug, requires careful individualization of dosage to compensate for its prominent pharmacokinetic variability. This article reviews the contribution of genetic polymorphisms affecting the activity of CYP2C9, the main enzyme responsible for phenytoin metabolism, to the variation in phenytoin clearance and susceptibility to adverse effects. Comprehensive and critical review of available evidence concerning the influence of CYP2C9 genetic polymorphism on phenytoin pharmacokinetic and safety profile. There is extensive evidence that CYP2C9 polymorphisms are an important determinant of the rate of phenytoin metabolism, although other factors including expression of other enzymes such as CYP2C19 and the influence of drug interactions, physiological and disease-related factors may also play a role. Patients carrying CYP2C9 genotypes associated with reduced phenytoin clearance are at greater risk of developing CNS adverse effects as well as serious cutaneous adverse reactions when given usual dosages of phenytoin. The clinical value and cost-effectiveness of CYP2C9 genotyping in improving the safety of phenytoin therapy, however, have not been clearly established and require formal testing in well-designed prospective studies.

Detection of Adverse Drug Reactions using Medical Named Entities on Twitter.

PubMed

MacKinlay, Andrew; Aamer, Hafsah; Yepes, Antonio Jimeno

2017-01-01

Adverse Drug Reactions (ADRs) are unintentional reactions caused by a drug or combination of drugs taken by a patient. The current ADR reporting systems inevitably have delays in reporting such events. The broad scope of social media conversations on sites such as Twitter means that inevitably health-related topics will be covered. This means that these sites could then be used to detect potentially novel ADRs with less latency for subsequent further investigation. In this work, we investigate ADR surveillance using a large corpus of Twitter data, containing around 50 billion tweets spanning 3 years (2012-2014), and evaluate against over 3000 drugs reported in the FAERS database. This is both a larger corpus and broader selection of drugs than previous work in the domain. We compare the ADRs identified using our method to the FDA Adverse Event Reporting System (FAERS) database of ADRs reported using more traditional techniques, and find that Twitter is a useful resource for ADR detection up to 72% micro-averaged precision. Micro-averaged recall of 6% is achievable using only 10% of Twitter, indicating that with a higher-volume or targeted feed it would be possible to detect a large percentage of ADRs.

Nephrotic syndrome under treatment with dasatinib: be aware of a possible adverse drug reaction.

PubMed

Muller-Hansma, A H G; van der Lugt, J; Zwaan, C M

2017-12-01

The protein kinase inhibitor dasatinib, targeting BCR-ABL and Src family kinases, is used in chronic myeloid leukaemia and Philadelphia-chromosome positive acute lymphoblastic leukaemia. The Netherlands Pharmacovigilance Centre Lareb has received one report of nephrotic syndrome associated with the use of dasatinib. With some other protein kinase inhibitors, targeting vascular endothelial growth factor, nephrotic syndrome is a well-known adverse drug reaction. The Dutch and European pharmacovigilance databases and scientific literature contain several cases indicating a causal relationship between dasatinib and nephrotic syndrome. Nephrotic syndrome was recently added to the list of adverse drug reactions in the Dutch summary of product characteristics for dasatinib. It is important to recognise the possibility of this adverse drug reaction when a patient develops nephrotic syndrome under treatment with dasatinib.

Toward Understanding Drug Incorporation and Delivery from Biocompatible Metal-Organic Frameworks in View of Cutaneous Administration.

PubMed

Rojas, Sara; Colinet, Isabel; Cunha, Denise; Hidalgo, Tania; Salles, Fabrice; Serre, Christian; Guillou, Nathalie; Horcajada, Patricia

2018-03-31

Although metal-organic frameworks (MOFs) have widely demonstrated their convenient performances as drug-delivery systems, there is still work to do to fully understand the drug incorporation/delivery processes from these materials. In this work, a combined experimental and computational investigation of the main structural and physicochemical parameters driving drug adsorption/desorption kinetics was carried out. Two model drugs (aspirin and ibuprofen) and three water-stable, biocompatible MOFs (MIL-100(Fe), UiO-66(Zr), and MIL-127(Fe)) have been selected to obtain a variety of drug-matrix couples with different structural and physicochemical characteristics. This study evidenced that the drug-loading and drug-delivery processes are mainly governed by structural parameters (accessibility of the framework and drug volume) as well as the MOF/drug hydrophobic/hydrophilic balance. As a result, the delivery of the drug under simulated cutaneous conditions (aqueous media at 37 °C) demonstrated that these systems fulfill the requirements to be used as topical drug-delivery systems, such as released payload between 1 and 7 days. These results highlight the importance of the rational selection of MOFs, evidencing the effect of geometrical and chemical parameters of both the MOF and the drug on the drug adsorption and release.

21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

Code of Federal Regulations, 2013 CFR

2013-04-01

... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

Code of Federal Regulations, 2011 CFR

2011-04-01

... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

Code of Federal Regulations, 2012 CFR

2012-04-01

... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

Code of Federal Regulations, 2014 CFR

2014-04-01

... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

The Potential Return on Public Investment in Detecting Adverse Drug Effects

PubMed Central

Huybrechts, Krista F.; Desai, Rishi J.; Park, Moa; Gagne, Joshua J.; Najafzadeh, Mehdi; Avorn, Jerry

2017-01-01

Background Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Objective Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. Research Design We assessed three examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the healthcare system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. Results We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773 to $884 million for rofecoxib, $3 to $10 million for cerivastatin, and $38 to $63 million for troglitazone in the US through the prevention of adverse events. By contrast, the yearly public investment in FDA initiated population-based pharmacovigilance activities in the US is about $42.5 million at present. Conclusion These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public. PMID:28505041

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

PubMed Central

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

2013-01-01

Introduction: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. PMID:24347984

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

PubMed

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.

Toward Understanding Drug Incorporation and Delivery from Biocompatible Metal–Organic Frameworks in View of Cutaneous Administration

PubMed Central

2018-01-01

Although metal–organic frameworks (MOFs) have widely demonstrated their convenient performances as drug-delivery systems, there is still work to do to fully understand the drug incorporation/delivery processes from these materials. In this work, a combined experimental and computational investigation of the main structural and physicochemical parameters driving drug adsorption/desorption kinetics was carried out. Two model drugs (aspirin and ibuprofen) and three water-stable, biocompatible MOFs (MIL-100(Fe), UiO-66(Zr), and MIL-127(Fe)) have been selected to obtain a variety of drug–matrix couples with different structural and physicochemical characteristics. This study evidenced that the drug-loading and drug-delivery processes are mainly governed by structural parameters (accessibility of the framework and drug volume) as well as the MOF/drug hydrophobic/hydrophilic balance. As a result, the delivery of the drug under simulated cutaneous conditions (aqueous media at 37 °C) demonstrated that these systems fulfill the requirements to be used as topical drug-delivery systems, such as released payload between 1 and 7 days. These results highlight the importance of the rational selection of MOFs, evidencing the effect of geometrical and chemical parameters of both the MOF and the drug on the drug adsorption and release. PMID:29623304

Evaluation of a procedure to assess the adverse effects of illicit drugs.

PubMed

van Amsterdam, J G C; Best, W; Opperhuizen, A; de Wolff, F A

2004-02-01

The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering medical, health, legal, and criminalistic issues of the drugs. After this face-to-face discussion the drugs were scored again. Taking the assessment of ketamine as an example, it appeared that each expert used its own scale to score, and that policymakers do not score deviant from experts trained in the medical-biological field. Of the five drugs evaluated by the panel, p-methoxy-metamphetamine (PMMA), gamma-hydroxybutyric acid (GHB), and 4-methylthio-amphetamine (MTA) were assessed as more adverse than ketamine and psilocine and psilocybine-containing mushrooms. Whereas some experts slightly adjusted during the assessment procedure their opinion on ketamine and PMMA, the opinion on mushrooms was not affected by the discussion held between the two scoring rounds. All experts rank the five drugs in a similar way on the adverse effect scale i.e., concordance scale of the Electre model, indicating unanimity in the expert panel with respect to the risk classification of these abused drugs.

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

PubMed

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 of a database and processing method for detecting hematotoxicity adverse drug events.

PubMed

Shimai, Yoshie; Takeda, Toshihiro; Manabe, Shirou; Teramoto, Kei; Mihara, Naoki; Matsumura, Yasushi

2015-01-01

Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.

Physician access to drug profiles to reduce adverse reactions

NASA Astrophysics Data System (ADS)

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.

The impact of herbal drug use on adverse drug reaction profiles of patients on antiretroviral therapy in zimbabwe.

PubMed

Mudzviti, Tinashe; Maponga, Charles C; Khoza, Star; Ma, Qing; Morse, Gene D

2012-01-01

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.

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

PubMed Central

Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

2012-01-01

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. PMID:22506106

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Patient knowledge on reporting adverse drug reactions in Poland

PubMed Central

Staniszewska, Anna; Dąbrowska-Bender, Marta; Olejniczak, Dominik; Duda-Zalewska, Aneta; Bujalska-Zadrożny, Magdalena

2017-01-01

Aim The aim of the study was to assess patient knowledge on reporting of adverse drug reactions. Materials and methods A prospective study was conducted among 200 patients. The study was based on an original survey composed of 15 single- and multiple-choice questions. The study involved individuals who have experienced adverse reactions as well as individuals who have never experienced any adverse reactions; people over the age of 18; literate; residing in Mazowieckie Voivodeship, who have not been diagnosed with any disease that could compromise their logical thinking skills. Results The respondents who lived in the city had a greater knowledge compared to the respondents who lived in the countryside (Pearson’s χ2=47.70, P=0.0013). The respondents who lived in the city were also more statistically likely to provide a correct answer to the question about the type of adverse reactions to be reported (Pearson’s χ2=50.66, P=0.012). Statistically significant associations were found between the place of residence of the respondents and the correct answer to the question about the data that must be included in the report on adverse reactions (Pearson’s χ2=11.7, P<0.0001). PMID:28096661

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

PubMed

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

PubMed Central

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

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

PubMed

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.

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

PubMed

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.

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

NASA Technical Reports Server (NTRS)

Meyer, Peter F.; Oddsson, Lars I E.

2003-01-01

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes-Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. ( approximately 10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. ( approximately 246 mN) and averaged 4.97 a.u. ( approximately 92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.

Ampicillin/sulbactam and cefoxitin in the treatment of cutaneous and other soft-tissue abscesses in patients with or without histories of injection drug abuse.

PubMed

Talan, D A; Summanen, P H; Finegold, S M

2000-08-01

A randomized, double-blind trial compared the clinical and bacteriologic efficacy of ampicillin/sulbactam (2 g/1 g) and cefoxitin (2 g) administered intravenously every 6 h to patients with (n=49) or without (n=47) histories of injection drug abuse who presented with cutaneous or other soft-tissue infections. Cure or improvement occurred in 89.8% of ampicillin/sulbactam-treated patients, compared with 93.6% of cefoxitin-treated patients. The median time to resolution of all symptoms was 10.5 days with ampicillin/sulbactam treatment and 15.5 days with cefoxitin treatment. Mixed aerobic-anaerobic infection was encountered frequently in both treatment groups. A significantly higher percentage of Streptococcus species was found in the major abscesses of the patients with histories of injection drug abuse, compared with those without such histories (37% vs. 19%, respectively; P=.0009). Overall, ampicillin/sulbactam eradicated pathogens from the major abscesses in 100% of patients, whereas the eradication rate with cefoxitin was 97.9%. The 2 drugs were well tolerated. Ampicillin/sulbactam and cefoxitin were equally effective for the empirical treatment of cutaneous or other soft-tissue infections in injection drug abusers and patients who did not inject drugs.

Focal cutaneous squamous cell carcinoma following radium-223 extravasation.

PubMed

Benjegerdes, Katie E; Brown, Shannon C; Housewright, Chad D

2017-01-01

Long-term sequelae due to extravasation of intravenous radioisotopes resulting in radiation injuries are rarely reported. As the use of radioactive isotopes for the treatment of osteoblastic metastases increases, information regarding the prevention, treatment, and long-term monitoring of suspected extravasation injury will become increasingly important. We present a patient with no previous history of skin cancer who developed an aggressive cutaneous squamous cell carcinoma at the site of prior radium-223 extravasation. We recommend that patients who experience extravasation of therapeutic radioisotopes be monitored by dermatologists for long-term sequelae. Cutaneous squamous cell carcinoma should be recognized as a rare but potential adverse event following cutaneous extravasation of radium-223 and is likely a side effect that is severely underreported.

Issues and advances in the management and pathogenesis of cutaneous lupus erythematosus.

PubMed

Pelle, Michelle T

2006-01-01

Evidence-based therapy for cutaneous lupus is lacking. A new clinical assessment tool for cutaneous lupus, the CLASI score, will enable more standardized assessments of response to therapy. Anti-Ro autoantibodies are associated with photosensitive SLE and SCLE, and they play a role in cell survival following ultraviolet exposure. Ro also functions in quality control of small RNAs, important in the prevention of autoimmune disease. Drug-induced lupus erythematosus can be anti-Ro- or anti-dsDNA-associated; SCLE and photosensitivity are characteristic of Ro-positive drug-induced lupus. Biologic therapies and IVIg are being studied for the treatment of SLE and cutaneous lupus. Large, controlled trials are needed, not only to evaluate newer therapies, but also to substantiate and define the usage of traditional therapies for cutaneous lupus erythematosus.

Update on cutaneous tuberculosis*

PubMed Central

Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victória; do Nascimento, Leninha Valério; Nery, José Augusto da Costa; Azulay, David Rubem

2014-01-01

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

Drugp-Induced Rhabdomyolysis Atlas (DIRA) for idiosyncratic adverse drug reaction management.

PubMed

Wen, Zhining; Liang, Yu; Hao, Yingyi; Delavan, Brian; Huang, Ruili; Mikailov, Mike; Tong, Weida; Li, Menglong; Liu, Zhichao

2018-06-11

Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Given the lack of a centralized data resource to curate, organize, and standardize widespread DIR information, here we present a Drug-Induced Rhabdomyolysis Atlas (DIRA) that provides DIR-related information, including: a classification scheme for DIR based on drug labeling information; postmarketing surveillance data of DIR; and DIR drug property information. To elucidate the utility of DIRA, we used precision dosing, concomitant use of DIR drugs, and predictive modeling development to exemplify strategies for idiosyncratic ADR (IADR) management. Published by Elsevier Ltd.

[Analysis of rational clinical uses of traditional Chinese medicine injections and factors influencing adverse drug reactions].

PubMed

Sun, Shi-Guang; Li, Zi-Feng; Xie, Yan-Ming; Liu, Jian; Lu, Yan; Song, Yi-Fei; Han, Ying-Hua; Liu, Li-Da; Peng, Ting-Ting

2013-09-01

To rationalize the clinical use and safety are some of the key issues in the surveillance of traditional Chinese medicine injections (TCMIs). In this 2011 study, 240 medical records of patients who had been discharged following treatment with TCMIs between 1 and 12 month previously were randomly selected from hospital records. Consistency between clinical use and the description of TCMIs was evaluated. Research on drug use and adverse drug reactions/events using logistic regression analysis was carried out. There was poor consistency between clinical use and best practice advised in manuals on TCMIs. Over-dosage and overly concentrated administration of TCMIs occurred, with the outcome of modifying properties of the blood. Logistic regression analysis showed that, drug concentration was a valid predictor for both adverse drug reactions/events and benefits associated with TCMIs. Surveillance of rational clinical use and safety of TCMIs finds that clinical use should be consistent with technical drug manual specifications, and drug use should draw on multi-layered logistic regression analysis research to help avoid adverse drug reactions/events.

[Designing a tool to describe drug interactions and adverse events for learning and clinical routine].

PubMed

Auzéric, M; Bellemère, J; Conort, O; Roubille, R; Allenet, B; Bedouch, P; Rose, F-X; Juste, M; Charpiat, B

2009-11-01

Pharmacists play an important role in prescription analysis. They are involved in therapeutic drug monitoring, particularly for drugs with a narrow therapeutic index, prevention and management of drug interactions, and may be called in to identify side effects and adverse events related to drug therapy. For the polymedicated patient, the medical file, the list of prescribed drugs and the history of their administration may be insufficient to adequately assign the responsibility of a given adverse effect to one or more drugs. Graphical representations can sometimes be useful to describe and clarify a sequence of events. In addition, as part of their academic course, students have many occasions to hear about "side effects" and "drug interactions". However, in the academic setting, there are few opportunities to observe the evolution and the consequences of these events. In the course of their hospital training, these students are required to perform patient follow-up for pharmacotherapeutic or educational purposes and to comment case reports to physicians. The aim of this paper is to present a tool facilitating the graphic display of drug interaction consequences and side effects. This tool can be a useful aid for causality assessment. It structures the students' training course and helps them better understand the commentaries pharmacists provide for physicians. Further development of this tool should contribute to the prevention of adverse drug events.

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

PubMed

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.

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able

A prospective study of adverse drug reactions in hospitalized children

PubMed Central

Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

1999-01-01

Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

Epidemiology and risk factors for drug allergy

PubMed Central

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

2011-01-01

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. PMID:21480948

ICD-10 codes used to identify adverse drug events in administrative data: a systematic review.

PubMed

Hohl, Corinne M; Karpov, Andrei; Reddekopp, Lisa; Doyle-Waters, Mimi; Stausberg, Jürgen

2014-01-01

Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156-289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0-59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area.

ICD-10 codes used to identify adverse drug events in administrative data: a systematic review

PubMed Central

Hohl, Corinne M; Karpov, Andrei; Reddekopp, Lisa; Stausberg, Jürgen

2014-01-01

Background Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. Methods We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. Results Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156–289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0–59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. Conclusions Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area. PMID:24222671

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

PubMed

Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

2016-01-01

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 differed by gender

Chronic cutaneous lupus erythematosus presenting as periorbital edema and erythema.

PubMed

Cyran, S; Douglass, M C; Silverstein, J L

1992-02-01

We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs.

Vertigo/dizziness as a Drugs' adverse reaction.

PubMed

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].

PubMed

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.

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is

Necrotizing soft tissue infection masquerading as cutaneous abcess following illicit drug injection.

PubMed

Callahan, T E; Schecter, W P; Horn, J K

1998-08-01

To assess factors that might predict serious necrotizing soft tissue infections following illicit drug injection. A retrospective review of a consecutive case series. An urban municipal hospital. Thirty patients presenting with cutaneous abscesses resulting from illicit drug injections during a 5-year period. All cases presented clinically with fluctuance, erythema, or induration but required extensive debridement at the time of incision and drainage. Operative treatment employed wide incision, routine subfascial examination, and aggressive debridement. Clinical management included broad-spectrum antibiotics, critical care support, and reconstructive procedures. Mortality, extent of debridement, preoperative vital signs and laboratory values, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, bacteriologic and pathologic test results. Postoperatively, all patients were housed in the intensive care unit for 8.4 +/- 14.5 days. Six patients died (20%). On arrival at the intensive care unit, systolic blood pressure was 80 mm Hg or less in 2 patients, 1 of whom died. White blood cell count on hospital admission was elevated in 27 of 30 patients (mean, 27.2 +/- 15.3 x 10(9)/L) and 2 patients were identified as having human immunodeficiency virus infection. All patients underwent initial surgery less than 24 hours after admission; following debridement, the average wound size was 276 +/- 238 cm2 (range, 15-783 cm2). Five patients required extremity amputation, and all other survivors underwent reconstruction with skin grafts and/or myocutaneous flaps. All but 1 patient were reexamined in the operating room within 12 hours and underwent an average of 3.1 +/- 1.6 operative procedures. Of those wound cultures obtained in the operating room, there was no pattern to the bacteriologic isolates. Seventeen patients had mixed isolates and 11 had single organisms. Pathologic findings in 20 patients included panniculitis (3 patients), necrotizing fasciitis (11

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

PubMed

Santos, Rafael Silva; Loureiro, Kahynna; Rezende, Polyana; Nalone, Luciana; Barbosa, Raquel de Melo; Santini, Antonello; Santos, Ana Cláudia; da Silva, Classius F; Souto, Eliana Barbosa; de Souza, Damião Pergentino; Amaral, Ricardo Guimarães; Severino, Patrícia

2018-06-01

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

Adverse reactions to two intravenous antibiotics (Augmentin and Zinacef) used for surgical prophylaxis in dogs.

PubMed

Gosling, Mark James; Martínez-Taboada, Fernando

2018-01-20

Antibiotic prophylaxis in dogs undergoing surgical procedures frequently involves the administration of a product without a veterinary licence. Two drugs commonly used for this purpose are the clavulanate amoxicillin Augmentin and the cefuroxime Zinacef. This prospective observational study aims to compare the incidence of adverse events associated with these two antibiotics in a clinical setting. The authors hypothesised that a higher incidence of adverse effects would be observed with Augmentin. Sixty-five dogs were included in the study and adverse events were recorded using a modified scoring system. A significantly higher incidence of adverse events to Augmentin (8/22; 36 per cent) was observed compared with Zinacef (1/43; 2 per cent) (P=0.0003). The majority of these adverse events involved cutaneous signs and/or hypotension. These findings might be taken into consideration when selecting one of these intravenous antibiotics for prophylaxis in anaesthetised dogs undergoing surgery. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Adverse Drug Events caused by Serious Medication Administration Errors

PubMed Central

Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G

2013-01-01

OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100

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

PubMed

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.

Drug-induced Epistaxis: An Often-Neglected Adverse Effect.

PubMed

Meirinho, Sara; Relvas, Ricardo; Alves, Gilberto

2018-02-12

Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g., trauma and local inflammation). Nevertheless, it is also recognised that epistaxis can be induced after some drugs intake. Due to the increasing use of drugs or drug combinations that potentially may induce epistaxis, this review aims to alert healthcare professionals for this often neglected adverse drug effect and its possible complications. A comprehensive literature search was performed on PubMed and Google Scholar databases, considering the literature published from January 1985 to December 2015, using medical terms related to the scope of drug-induced epistaxis, nosebleeds and nasal blood supply. As expected, anticoagulant and antiplatelet drugs are the main pharmacotherapeutic agents associated with epistaxis, particularly warfarin, dabigatran, rivaroxaban and aspirin. However, it was reported that some selective serotonin reuptake inhibitors, intranasal corticosteroids, certain antibiotics and other drugs or drug associations can also be responsible by nosebleeds. Although most of these epistaxis episodes are mild to moderate, being spontaneously reversed or requiring only minor medical approaches to control it, there are also several case reports, as well as retrospective and prospective studies, documenting severe epistaxis episodes after specific medicines intake. In these cases some invasive medical interventions are demanded to manage the bleeding and avoid life-threatening consequences. This work provides an integrated and comprehensive review on drug-induced epistaxis bridging the gap in the current scientific literature addressing this topic. Therefore, the scientific information gathered and discussed will be valuable to raise awareness of doctors and pharmacists for this drug-related problem, as well as to promote their active

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

PubMed

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 P<0.01. A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands 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

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

PubMed Central

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

Anaphylaxis following intravenous ranitidine: a rare adverse reaction of a common drug.

PubMed

Chopra, Deepti; Arora, Pooja; Khan, Shamimullah; Dwivedi, Shridhar

2014-01-01

Ranitidine hydrochloride is a widely used drug that is generally well-tolerated. Anaphylaxis is rarely observed with ranitidine. We report a case who developed severe anaphylaxis following single dose of intravenous ranitidine. The article highlights the importance of recognition of this serious adverse event and re-emphasizes the need for cautious use of drugs, especially in those with known history of allergy.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

2016-01-01

Background 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. Methods and Findings 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. Conclusions Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported

Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.

PubMed

Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng

2012-12-01

Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

[Adverse reactions and other drug-related problems in an emergency service department].

PubMed

Güemes Artiles, M; Sanz Alvarez, E; Garcia Sánchez-Colomer, M

1999-01-01

Adverse Drug Reactions (ADR) and Drug-Related Problems (DRP's) are a frequency cause of hospital emergency room visits and require better assessment. An analysis was made of 1097 consecutive admission to the emergency room at the Nuestra Senora de los Volcanes, Hospital (currently the General Hospital of Lanzarote) in Arrecife de Lanzarote (Canary Islands) over a three-month period in order to detect any possible DAR or any other drug-related problems. Nineteen (19) of the 1097 admissions were due to Adverse Drug Reactions (ADR) (1.73%; 95% IC:0.96%-2.5%). Some of the most outstanding of the other "Drug-Related Problems" (DRP's) were medication overdose, which was diagnosed in 5 (0.45%) of the patients; the worsening of the symptoms due to ceasing to take the medication was involved in 8 (0.72%), and incorrect treatments which involved medical care at the emergency room totaled 11 (1.0%). The number of drug-related problems (DRP's) in the sample totaled 43 (3.9%). The drug-related problems (DRP's) led to hospitalization in 1.9% of the cases seen in the emergency room and led to hospitalization in 9.6% of all of hospital admission through the emergency room for the period of time under study. The ADR led to 4.1% of the hospital admissions. Drug-related problems are a frequent, major problem which has not been well-analyzed in the emergency rooms. Additionally, emergency rooms can function as the first point of detection of a ADR among an outpatient population.

Drug reaction with eosinophilia and systemic symptoms without skin rash

PubMed Central

Sasidharanpillai, Sarita; Binitha, Manikoth P.; Manikath, Neeraj; Janardhanan, Anisha K.

2015-01-01

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal. PMID:26729967

Drug reaction with eosinophilia and systemic symptoms without skin rash.

PubMed

Sasidharanpillai, Sarita; Binitha, Manikoth P; Manikath, Neeraj; Janardhanan, Anisha K

2015-01-01

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal.

[Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

PubMed

Prisco, Vincenzo; Iannaccone, Teresa; Tusciano, Adriano; Boccardi, Mariangela; Perris, Francesco; Capuano, Annalisa; Catapano, Francesco; Fabrazzo, Michele

2016-01-01

Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs). This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process. In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority.

Adverse drug reactions amongst adult patients admitted in Lagos State University Teaching Hospital Lagos, Nigeria.

PubMed

Aderemi-Williams, R I; Awodele, O; Boyle, C A

2015-01-01

Adverse drug reaction (ADR) is a global drug therapy problem. It has been rated as one of the top leading causes of morbidity and mortality. In Nigeria, not much is known about ADRs especially with the existing weak post marketing surveillance for monitoring drug use, and its effect on the population. The study is aimed at determining the incidence of ADRs, presentations of ADRs, classes of drugs that frequently cause ADRs and predictors of ADRs in adult medical in-patients in LASUTH. A retrospective study of six hundred and twenty four (624) case notes of all patients admitted to the medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried out. Information obtained included age, gender, and adverse drug reaction and drug details. The results obtained were analyzed using SPSS version 16 statistical software. Level of significance was set at p ≤ 0.05. A total of 624 case notes consisting of 358 males and 266 females were assessed. The number of patients who experienced adverse drug reactions was 67 (n = 624, 10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100 patients' population. Most of the ADRs observed were type A reactions (97.8%). Mostly implicated classes of drugs were antidiabetics (26.7%) and NSAIDs (29.3%). The incidence rate of ADRs was 10.7%. ADRs which are predictable and preventable occur in hospitalized patients, such may be prevented or minimized by implementing measures to target specific drugs that are commonly suspected.

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

PubMed Central

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung-eun; Jin, Xue-mei; Lee, Joongyub; Yang, Bo Ram

2017-01-01

Purpose 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). Materials and Methods 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. Results 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. Conclusion 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. PMID:28332362

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

PubMed

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

Epidemiology and risk factors for drug allergy.

PubMed

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

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

PubMed Central

Li, Qingfeng

2016-01-01

Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

Noninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children

PubMed Central

Rubiano, Luisa Consuelo; Miranda, María Consuelo; Muvdi Arenas, Sandra; Montero, Luz Mery; Rodríguez-Barraquer, Isabel; Garcerant, Daniel; Prager, Martín; Osorio, Lyda; Rojas, Maria Ximena; Pérez, Mauricio; Nicholls, Ruben Santiago

2012-01-01

Background. Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. Methods. A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2–12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8–2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). Results. Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%–28.7%) for miltefosine and 31% (98% CI, 16.9%–45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, −4.5% to 32%) (P = .04). Adverse events were mild for both treatments. Conclusions. Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. Clinical Trial Registration. NCT00487253. PMID:22238470

Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.

PubMed

Zhang, Patrick M; Sarkar, Indra Neil

2018-01-01

Recent technological advancements in genetic testing and the growing accessibility of public genomic data provide researchers with a unique avenue to approach personalized medicine. This feasibility study examined the potential of direct-to-consumer (DTC) genomic tests (focusing on 23andMe) in research and clinical applications. In particular, we combined population genetics information from the Personal Genome Project with adverse event reports from AEOLUS and pharmacogenetic information from PharmGKB. Primarily, associations between drugs based on co-occurring genetic variations and associations between variants and adverse events were used to assess the potential for leveraging single nucleotide polymorphism information from 23andMe. The results of this study suggest potential clinical uses of DTC tests in light of potential drug interactions. Furthermore, the results suggest great potential for analyzing associations at a population level to facilitate knowledge discovery in the realm of predicting adverse drug events.

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

PubMed

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

Anaphylaxis following intravenous ranitidine: A rare adverse reaction of a common drug

PubMed Central

Chopra, Deepti; Arora, Pooja; Khan, Shamimullah; Dwivedi, Shridhar

2014-01-01

Ranitidine hydrochloride is a widely used drug that is generally well-tolerated. Anaphylaxis is rarely observed with ranitidine. We report a case who developed severe anaphylaxis following single dose of intravenous ranitidine. The article highlights the importance of recognition of this serious adverse event and re-emphasizes the need for cautious use of drugs, especially in those with known history of allergy. PMID:24741203

Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat.

PubMed

Wu, Bor-Tsang; Chen, Kuan-Ting; Liu, Kuo-Sheng; Chen, Yu-Wen; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-06-01

The purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. Cutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. On the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95-4.18) μmol]>lidocaine [5.81 (5.70-5.98) μmol] (p<0.01). Clonidine at a dose of 0.12 μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12 μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. Our resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Study of Natural Health Product Adverse Reactions (SONAR): Active Surveillance of Adverse Events Following Concurrent Natural Health Product and Prescription Drug Use in Community Pharmacies

PubMed Central

Vohra, Sunita; Cvijovic, Kosta; Boon, Heather; Foster, Brian C.; Jaeger, Walter; LeGatt, Don; Cembrowski, George; Murty, Mano; Tsuyuki, Ross T.; Barnes, Joanne; Charrois, Theresa L.; Arnason, John T.; Necyk, Candace; Ware, Mark; Rosychuk, Rhonda J.

2012-01-01

Background Many consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NHP-prescription drug use. Methodology/Principal Findings Participating pharmacists asked individuals collecting prescription medications about (i) concurrent NHP/drug use in the previous three months and (ii) experiences of adverse events. If an adverse event was identified and if the patient provided written consent, a research pharmacist conducted a guided telephone interview to gather additional information after obtaining additional verbal consent and documenting so within the interview form. Over a total of 112 pharmacy weeks, 2615 patients were screened, of which 1037 (39.7%; 95% CI: 37.8% to 41.5%) reported concurrent NHP and prescription medication use. A total of 77 patients reported a possible AE (2.94%; 95% CI: 2.4% to 3.7%), which represents 7.4% of those using NHPs and prescription medications concurrently (95%CI: 6.0% to 9.2%). Of 15 patients available for an interview, 4 (26.7%: 95% CI: 4.3% to 49.0%) reported an AE that was determined to be “probably” due to NHP use. Conclusions/Significance Active surveillance markedly improves identification and reporting of adverse events associated with concurrent NHP-drug use. Although not without challenges, active surveillance is feasible and can generate adverse event data of sufficient quality to allow for meaningful adjudication to assess potential harms. PMID:23028841

Structured vs. Unstructured: Factors Affecting Adverse Drug Reaction Documentation in an EMR Repository

PubMed Central

Skentzos, Stephen; Shubina, Maria; Plutzky, Jorge; Turchin, Alexander

2011-01-01

Adverse reactions to medications to which the patient was known to be intolerant are common. Electronic decision support can prevent them but only if history of adverse reactions to medications is recorded in structured format. We have conducted a retrospective study of 31,531 patients with adverse reactions to statins documented in the notes, as identified with natural language processing. The software identified statin adverse reactions with sensitivity of 86.5% and precision of 91.9%. Only 9020 of these patients had an adverse reaction to a statin recorded in structured format. In multivariable analysis the strongest predictor of structured documentation was utilization of EMR functionality that integrated the medication list with the structured medication adverse reaction repository (odds ratio 48.6, p < 0.0001). Integration of information flow between EMR modules can help improve documentation and potentially prevent adverse drug events. PMID:22195188

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

PubMed Central

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

Dermatological adverse events with taxane chemotherapy

PubMed Central

Sibaud, Vincent; Lebœuf, Nicole R.; Roche, Henri; Belum, Viswanath R.; Gladieff, Laurence; Deslandres, Marion; Montastruc, Marion; Eche, Audrey; Vigarios, Emmanuelle; Dalenc, Florence; Lacouture, Mario E.

2017-01-01

Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel. PMID:27550571

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

PubMed

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.

Propylthiouracil-induced cutaneous vasculitis. Case presentation and review of the literature.

PubMed

Vasily, D B; Tyler, W B

1980-02-01

A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy.

Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001-2004.

PubMed

Martin, Richard M; May, Margaret; Gunnell, David

2006-02-01

To document the impact on clinical practice in England of media attention around possible adverse effects of paroxetine. Analysis of national selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow-card adverse drug reaction reports, 2001-2004. From a steady state in 2001, paroxetine prescribing declined sharply from April 2002, coinciding with a USA regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per month (95% confidence interval - 2.06, -1.68). Other SSRI prescribing increased by 1% per month until a major UK review of SSRIs in children in December 2003, after which prescribing plateaued. Media publicity was associated with short-term peaks in yellow-card reports related to paroxetine. Falls in paroxetine and other SSRI prescribing in the UK coincided, respectively, with regulatory communications from the USA and the UK, but associations may have noncausal or other explanations. Reports of adverse reactions to paroxetine appeared to increase after adverse media publicity about the drug.

Identifying adverse drug event information in clinical notes with distributional semantic representations of context.

PubMed

Henriksson, Aron; Kvist, Maria; Dalianis, Hercules; Duneld, Martin

2015-10-01

For the purpose of post-marketing drug safety surveillance, which has traditionally relied on the voluntary reporting of individual cases of adverse drug events (ADEs), other sources of information are now being explored, including electronic health records (EHRs), which give us access to enormous amounts of longitudinal observations of the treatment of patients and their drug use. Adverse drug events, which can be encoded in EHRs with certain diagnosis codes, are, however, heavily underreported. It is therefore important to develop capabilities to process, by means of computational methods, the more unstructured EHR data in the form of clinical notes, where clinicians may describe and reason around suspected ADEs. In this study, we report on the creation of an annotated corpus of Swedish health records for the purpose of learning to identify information pertaining to ADEs present in clinical notes. To this end, three key tasks are tackled: recognizing relevant named entities (disorders, symptoms, drugs), labeling attributes of the recognized entities (negation, speculation, temporality), and relationships between them (indication, adverse drug event). For each of the three tasks, leveraging models of distributional semantics - i.e., unsupervised methods that exploit co-occurrence information to model, typically in vector space, the meaning of words - and, in particular, combinations of such models, is shown to improve the predictive performance. The ability to make use of such unsupervised methods is critical when faced with large amounts of sparse and high-dimensional data, especially in domains where annotated resources are scarce. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

ADEpedia 2.0: Integration of Normalized Adverse Drug Events (ADEs) Knowledge from the UMLS.

PubMed

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

2013-01-01

A standardized Adverse Drug Events (ADEs) knowledge base that encodes known ADE knowledge can be very useful in improving ADE detection for drug safety surveillance. In our previous study, we developed the ADEpedia that is a standardized knowledge base of ADEs based on drug product labels. The objectives of the present study are 1) to integrate normalized ADE knowledge from the Unified Medical Language System (UMLS) into the ADEpedia; and 2) to enrich the knowledge base with the drug-disorder co-occurrence data from a 51-million-document electronic medical records (EMRs) system. We extracted 266,832 drug-disorder concept pairs from the UMLS, covering 14,256 (1.69%) distinct drug concepts and 19,006 (3.53%) distinct disorder concepts. Of them, 71,626 (26.8%) concept pairs from UMLS co-occurred in the EMRs. We performed a preliminary evaluation on the utility of the UMLS ADE data. In conclusion, we have built an ADEpedia 2.0 framework that intends to integrate known ADE knowledge from disparate sources. The UMLS is a useful source for providing standardized ADE knowledge relevant to indications, contraindications and adverse effects, and complementary to the ADE data from drug product labels. The statistics from EMRs would enable the meaningful use of ADE data for drug safety surveillance.

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

PubMed

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.

Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

PubMed

Oshima, Shinji; Enjuji, Takako; Negishi, Akio; Akimoto, Hayato; Ohara, Kousuke; Okita, Mitsuyoshi; Numajiri, Sachihiko; Inoue, Naoko; Ohshima, Shigeru; Terao, Akira; Kobayashi, Daisuke

2017-09-01

In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

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

PubMed

Su, Eric Wen; Sanger, Todd M

2017-01-01

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).

Cutaneous tolerability to tretinoin shows little variation with Fitzpatrick skin type.

PubMed

Webster, Guy F

2014-06-01

Determinants of skin irritability are poorly understood. This study aims to assess differences in cutaneous safety/irritation based on Fitzpatrick skin type among patients with acne treated with tretinoin gel microsphere (TGM). This was a phase 4, 12-week, prospective, nonrandomized, open-label, multicenter study. Approximately 500 patients with mild to moderate acne were treated with TGM 0.04% or 0.1% and assessed for cutaneous irritation at baseline and weeks 3, 6, and 12. In this post hoc analysis of patients with Fitzpatrick skin type I-III vs Fitzpatrick skin type IV-VI, there was a general trend toward initial worsening of cutaneous adverse events (AEs) by week 3 across all variables and groups. This was followed by a trend toward improvement and resolution of skin-related AEs from week 3 to week 12 regardless of Fitzpatrick skin type, with a few exceptions. Erythema was the only cutaneous AE that consistently decreased among patients with darker skin. Results from a subsequent 3-group analysis (Fitzpatrick I-II vs Fitzpatrick III-IV vs Fitzpatrick V-VI) generally mirrored those from the 2-group study. Study limitations include patient nonadherence, lack of a placebo arm, and lack of data regarding the impact of concurrent medications on outcomes. There was no correlation between irritation and Fitzpatrick skin type. ABBREVIATIONS USED: adverse event (AE), analysis of variance (ANOVA), benzoyl peroxide (BP), case report form (CRF), modified Global Acne Grading Score (mGAGS), tretinoin gel microsphere (TGM).

Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

PubMed

Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

2016-11-01

Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

Systemic Meglumine Antimoniate in Cutaneous Leishmaniasis of Children: Clinical and Laboratory Complications.

PubMed

Layegh, Pouran; Khademi, Zeinab; Afzal Aghaee, Monavar; Moghiman, Toktam

2015-12-01

Children account for 7%-20% of cutaneous leishmaniasis cases in Iran, but there are few safety data to guide pediatric antiparasitic therapy. We evaluated the clinical and laboratory tolerance of the systemic pentavalent antimonial compound meglumine antimoniate, in 70 Iranian children with cutaneous leishmaniasis. Adverse effects were similar to those seen in adults. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions.

PubMed

Galli, Jonathan A; Pandya, Aloknath; Vega-Olivo, Michelle; Dass, Chandra; Zhao, Huaqing; Criner, Gerard J

2017-08-01

The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation. We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event. Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy. Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions. © 2017 Asian Pacific Society of Respirology.

Cholesterol embolisms as possible adverse drug reaction of direct oral anticoagulants.

PubMed

Muller-Hansma, A H G; Daemen-Gubbels, C R G M; Schut, N H

2018-04-01

The Netherlands Pharmacovigilance Centre Lareb has received two reports of cholesterol crystal embolisms associated with the use of a direct oral anticoagulant (DOAC). The European pharmacovigilance database contains several other cases concerning this association, and one report was published in the scientific literature. Cholesterol crystal embolisms were described in association with the use of several other antithrombotic drugs, although the role as an independent risk factor is not conclusive. The case series described in this article, indicates the possibility of an adverse drug reaction when a patient develops cholesterol crystal embolisms while using a DOAC.

Rebound effect of modern drugs: serious adverse event unknown by health professionals.

PubMed

Teixeira, Marcus Zulian

2013-01-01

Supported in the Hippocratic aphorism primum non nocere, the bioethical principle of non-maleficence pray that the medical act cause the least damage or injury to the health of the patient, leaving it to the doctor to assess the risks of a particular therapy through knowledge of possible adverse events of drugs. Among these, the rebound effect represents a common side effect to numerous classes of modern drugs, may cause serious and fatal disorders in patients. This review aims to clarify the health professionals on clinical and epidemiological aspects of rebound phenomenon. A qualitative, exploratory and bibliographic review was held in the PubMed database using the keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor' and 'bisphosphonate'. The rebound effect occurs after discontinuation of numerous classes of drugs that act contrary to the disease disorders, exacerbating them at levels above those prior to treatment. Regardless of the disease, the drug and duration of treatment, the phenomenon manifests itself in a small proportion of susceptible individuals. However, it may cause serious and fatal adverse events should be considered a public health problem in view of the enormous consumption of drugs by population. Bringing together a growing and unquestionable body of evidence, the physician needs to have knowledge of the consequences of the rebound effect and how to minimize it, increasing safety in the management of modern drugs. On the other hand, this rebound can be used in a curative way, broadening the spectrum of the modern therapeutics. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Two cases of cutaneous leishmaniasis in Dutch military personnel treated with oral miltefosine.

PubMed

van der Snoek, Eric Martin; Couwenberg, S M; Stijnis, C; Kortbeek, L M; Schadd, E M

2017-02-01

In the Netherlands, cutaneous leishmaniasis is most commonly seen in military personnel deployed on a mission or training abroad. The treatment of two Dutch soldiers who acquired cutaneous leishmaniasis with oral miltefosine was evaluated. Adverse effects were monitored and the improvement of skin lesions was assessed. A military nurse with a painless Chiclero's ulcer due to Leishmania (Viannia) braziliensis acquired in Belize and a military physical training instructor with itchy swelling and small ulcer of the back of his left elbow due to L. donovani/infantum complex acquired in Ibiza were treated with oral miltefosine 50 mg three times a day for 28 days. Both patients responded well to oral miltefosine. Adverse effects were mild. Increase of creatinine levels was seen while liver transaminase levels were unremarkable. Miltefosine proved to be a convenient, effective and well-tolerated treatment option in the treatment of cutaneous leishmaniasis in Dutch military personnel. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cutaneous sarcoidosis.

PubMed

Noe, Megan H; Rosenbach, Misha

2017-09-01

Cutaneous sarcoidosis occurs in up to 30% of patients with sarcoidosis and skin findings are often the initial presenting symptom. Cutaneous sarcoidosis is a rare skin disease and many aspects of the disease presentation and treatment are not well understood. This review will highlight developments in the epidemiology, clinical presentation, diagnosis and treatment of cutaneous sarcoidosis over the past several years. Epidemiological studies from several different populations reaffirm that cutaneous sarcoidosis is more common in women and is often the presenting symptom of systemic sarcoidosis. Recently, more cases are being reported in association with oncologic immune modulators, which will be of great interest as use of those agents increases. Also, ultrasound has shown promise for the imaging of cutaneous granulomas for disease assessment and measuring response to treatment. Finally, the treatment of cutaneous sarcoidosis remains difficult and is based largely on retrospective data with a paucity of large, prospective trials. There have been recently introduced and validated cutaneous scoring tools which show promise and may lead to more high-quality studies going forward. The recent developments in cutaneous sarcoidosis have identified many new pharmacologic and physical triggers of disease, but the evidence for effective treatment is still lacking. Further research is necessary to improve the care of patients with cutaneous sarcoidosis.

Adverse drug event reporting systems: a systematic review

PubMed Central

Peddie, David; Wickham, Maeve E.; Badke, Katherin; Small, Serena S.; Doyle‐Waters, Mary M.; Balka, Ellen; Hohl, Corinne M.

2016-01-01

Aim Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems. Methods We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full‐texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software. Results We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA). Conclusion We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance. PMID:27016266

Adverse drug event reporting systems: a systematic review.

PubMed

Bailey, Chantelle; Peddie, David; Wickham, Maeve E; Badke, Katherin; Small, Serena S; Doyle-Waters, Mary M; Balka, Ellen; Hohl, Corinne M

2016-07-01

Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems. We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full-texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software. We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA). We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance. © 2016 The British Pharmacological Society.

Cutaneous metastatic tuberculous abcess in a patient with cervico-mediastinal lymphatic tuberculosis.

PubMed

Dekeyzer, S; Moerman, F; Callens, S; Vandekerckhove, L

2013-01-01

Metastatic tuberculous abcess or tuberculous gumma is a rare form of cutaneous tuberculosis resulting from haematogenous spread from a non-cutaneous tuberculous focus. A 26-year old patient of Pakistani origin presented at our clinic with an abcess on his right thigh that had slowly grown over a period of two months to a total size of 30 cm. Based on clinical findings, microbiology, CT thigh and CT chest, our patient was diagnosed with a tuberculous abcess and cervico-mediastinal tuberculous lymphadenitis. Antituberculosis drugs were initiated. Cutaneous tuberculosis should be included in the differential diagnosis of chronic cutaneous abcesses, especially in patients from tuberculosis endemic nations.

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

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

PubMed Central

Moore, Nicholas; Pollack, Charles; Butkerait, Paul

2015-01-01

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. PMID:26203254

Using constrained information entropy to detect rare adverse drug reactions from medical forums.

PubMed

Yi Zheng; Chaowang Lan; Hui Peng; Jinyan Li

2016-08-01

Adverse drug reactions (ADRs) detection is critical to avoid malpractices yet challenging due to its uncertainty in pre-marketing review and the underreporting in post-marketing surveillance. To conquer this predicament, social media based ADRs detection methods have been proposed recently. However, existing researches are mostly co-occurrence based methods and face several issues, in particularly, leaving out the rare ADRs and unable to distinguish irrelevant ADRs. In this work, we introduce a constrained information entropy (CIE) method to solve these problems. CIE first recognizes the drug-related adverse reactions using a predefined keyword dictionary and then captures high- and low-frequency (rare) ADRs by information entropy. Extensive experiments on medical forums dataset demonstrate that CIE outperforms the state-of-the-art co-occurrence based methods, especially in rare ADRs detection.

Overdose and adverse drug event experiences among adult patients in the emergency department.

PubMed

Bohnert, Amy S B; Walton, Maureen A; Cunningham, Rebecca M; Ilgen, Mark A; Barry, Kristen; Chermack, Stephen T; Blow, Frederic C

2017-11-16

Overdose is a leading cause of injury and death in the United States. Emergency Department (ED) patients have an elevated prevalence of substance use. This study describes overdose/adverse drug event experiences among adult ED patients to inform strategies to address overdose risk. Patients seeking care at a large ED in the city of Flint, Michigan participated in a computerized self-assessment during 2011-2013 (n=4571). Overdose was assessed with a broad definition and included occurrences that could be considered adverse drug events. Among those with this type of experience, additional items assessed symptoms, outcomes, and intent. 12% reported an overdose history. Of participants' most serious overdoses, 74% were without clear intent for self-harm, although this was true of only 61% of overdoses involving opiates or sedatives, and 52% had symptoms present that indicated that it was life-threatening. Binge drinking on a monthly basis (ORs=1.4) was associated with a medically serious overdose compared to never having an overdose. Compared to no drug use in the last year, use of one drug was associated with an OR of 1.8, two drugs was associated with an OR of 5.8, three drugs was associated with an OR of 8.4, and four or more drugs was associated with an OR of 25.1 of having had a medically serious overdose (all p<0.05). Most overdose experiences among ED patients were without clear intent of self-harm. The ED may be an appropriate setting for efforts to reduce overdose risk, especially among polysubstance users. Published by Elsevier Ltd.

Association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone.

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

The purpose of the present study was to examine the association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone. Thirty outpatients with schizophrenia receiving stable doses of risperidone were comprehensively evaluated for psychopathology, subjective well-being, and adverse drug effects. Subjective well-being was assessed using the Subjective Well-being Under Neuroleptics Scale (SWN). Adverse drug effects were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In correlation analysis controlling for relevant variables, the SWN score had significant negative correlations with the following subscale scores of the LUNSERS: extrapyramidal side effect (EPS) (r = -0.54, P < 0.01), akathisia (r = -0.46, P < 0.05), and autonomic adverse effect (r = -0.44, P < 0.05). The SWN score also had a significant negative correlation with the global severity of EPS as measured by the DIEPSS (r = -0.44, P < 0.05). The results of our study suggest that adverse effects, particularly EPS and akathisia, are significantly associated with subjective well-being, implying the necessity to develop rational strategies to control these variables effectively. The results also suggest that EPS and akathisia continue to be major adverse effects associated with a low level of subjective well-being in patients receiving risperidone. Further studies are required to investigate the multidimensional factors associated with subjective well-being in patients receiving atypical antipsychotics and to determine their relative contributions.

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

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

PubMed Central

Federer, Callie; Yoo, Minjae

2016-01-01

Abstract 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. PMID:27631620

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

PubMed

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.

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis

PubMed Central

Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay

2018-01-01

Abstract Objective To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Study selection Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Data extraction Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. Results 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Conclusions Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.

PubMed

Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay; Korenstein, Deborah

2018-03-14

To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Systematic review and meta-analysis. Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse

Treatment of Human Scabies with Oral Ivermectin. Eczematous Eruptions as a New Non-Reported Adverse Event.

PubMed

Sanz-Navarro, J; Feal, C; Dauden, E

2017-09-01

Oral ivermectin is an alternative therapy for human scabies infection due to its ease of administration and good safety profile. However, there is no definitive consensus on the optimal dosing regimen. To describe the treatment of human scabies with different dosages of oral ivermectin and the possible adverse events. 23 patients with human scabies were treated with oral ivermectin: 10 patients received a single oral dose of 200μg/kg and 13 a dose of 400μg/kg. A second, or even a third dose, was administered in cases of treatment failure. A complete clinical response was achieved by all of the patients. The first ten patients required at least two (80%) or three (20%) doses of ivermectin for complete resolution of the infection. The remaining cases resolved with a single 400μg/kg oral dose. Within the first 72h after the administration of oral ivermectin, new cutaneous lesions were observed in eleven patients (47.8%). Cutaneous biopsies showed signs of subacute eczema. The eruption was treated with topical corticosteroids and emollient therapy. There was no other new drug administration or a history of irritants. There was no history of atopic diathesis except for one patient. Oral ivermectin is an effective therapy for the treatment of human scabies. A single 400μg/kg oral dose demonstrated high efficacy and good tolerance. However, the appearance of eczematous cutaneous lesions induced by oral ivermectin has not previously been reported in the literature. Dermatologists should be aware of this possible adverse event. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

PubMed

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.

Markov Logic Networks for Adverse Drug Event Extraction from Text.

PubMed

Natarajan, Sriraam; Bangera, Vishal; Khot, Tushar; Picado, Jose; Wazalwar, Anurag; Costa, Vitor Santos; Page, David; Caldwell, Michael

2017-05-01

Adverse drug events (ADEs) are a major concern and point of emphasis for the medical profession, government, and society. A diverse set of techniques from epidemiology, statistics, and computer science are being proposed and studied for ADE discovery from observational health data (e.g., EHR and claims data), social network data (e.g., Google and Twitter posts), and other information sources. Methodologies are needed for evaluating, quantitatively measuring, and comparing the ability of these various approaches to accurately discover ADEs. This work is motivated by the observation that text sources such as the Medline/Medinfo library provide a wealth of information on human health. Unfortunately, ADEs often result from unexpected interactions, and the connection between conditions and drugs is not explicit in these sources. Thus, in this work we address the question of whether we can quantitatively estimate relationships between drugs and conditions from the medical literature. This paper proposes and studies a state-of-the-art NLP-based extraction of ADEs from text.

ADESSA: A Real-Time Decision Support Service for Delivery of Semantically Coded Adverse Drug Event Data

PubMed Central

Duke, Jon D.; Friedlin, Jeff

2010-01-01

Evaluating medications for potential adverse events is a time-consuming process, typically involving manual lookup of information by physicians. This process can be expedited by CDS systems that support dynamic retrieval and filtering of adverse drug events (ADE’s), but such systems require a source of semantically-coded ADE data. We created a two-component system that addresses this need. First we created a natural language processing application which extracts adverse events from Structured Product Labels and generates a standardized ADE knowledge base. We then built a decision support service that consumes a Continuity of Care Document and returns a list of patient-specific ADE’s. Our database currently contains 534,125 ADE’s from 5602 product labels. An NLP evaluation of 9529 ADE’s showed recall of 93% and precision of 95%. On a trial set of 30 CCD’s, the system provided adverse event data for 88% of drugs and returned these results in an average of 620ms. PMID:21346964

Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.

PubMed

Hernández, M Victoria; Sanmartí, Raimon; Cañete, Juan D; Descalzo, Miguel A; Alsina, Mercè; Carmona, Loreto; Gomez-Reino, Juan J

2013-12-01

To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases. Copyright © 2013 by the American College of Rheumatology.

[Drug eruptions caused by noncorticoid anti-inflammatory agents].

PubMed

Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R

1984-01-01

Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.

Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics.

PubMed

Elzagallaai, A A; Greff, Mje; Rieder, M J

2017-06-01

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

PubMed

Seibel, W; Sundberg, J P; Lesko, L J; Sauk, J J; McCleary, L B; Hassell, T M

1989-08-01

All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO2) monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cutaneous carbon dioxide (PcCO2) monitor. 868.2480 Section 868.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... (PcCO2) and Oxygen (PcO2) Monitors; Guidance for Industry and FDA.” See § 868.1(e) for the...

Characterisation of T cell phenotypes, cytokines and transcription factors in the skin of dogs with cutaneous adverse food reactions.

PubMed

Veenhof, Eveline Z; Knol, Edward F; Schlotter, Yvette M; Vernooij, Johannes C; Rutten, Victor P; Willemse, Ton

2011-03-01

The immunopathogenesis of cutaneous adverse food reactions (CAFRs) in dogs is unknown. Since the clinical manifestations in the skin are like those found in canine atopic dermatitis (AD), this study investigated the similarity in T cell phenotypes and gene expression of cytokines and transcription factors in CAFRs. In addition, the influence of an elimination diet on these parameters was tested. In the skin of canine CAFRs, a predominant presence of CD8(+) T cells and increased expression of the IL-4, IL-13, Foxp3 and SOCS-3 genes were observed. IFN-γ gene expression was increased in lesional compared to non-lesional skin. The predominance of CD8(+) T cells indicates that the immunopathogenesis of CAFRs is different from that of canine AD. The elimination diet relieved clinical signs, but did not influence T cell phenotypes or expression of the cytokine and transcription factor genes in the skin of dogs with CAFRs, indicating a continuously pre-activated immune status in dogs sensitised to food constituents. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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.

PubMed

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.

Adverse-drug-event data provided by pharmaceutical companies.

PubMed

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.

Rapidly progressing facial leishmaniasis: effective treatment with liposomal amphotericin B and a review of the management of Old World cutaneous leishmaniasis.

PubMed

Islam, Shamim

2018-05-01

Cutaneous leishmaniasis (CL), a common condition in many parts of the world, is being increasingly encountered in non-endemic countries secondary to immigration. The clinical manifestations and course can vary substantially, with appropriate management ranging from observation for self-healing lesions to urgent treatment to prevent damaging anatomical and cosmetic sequelae. While there are now several effective medications, optimal therapy is not well defined, and decision-making can be challenged by the location of lesions and various drug issues, including availability, mode of delivery and adverse effects. A 7-year-old Afghani boy who presented shortly after arriving in the United States with a rapidly progressing crusting and ulcerative facial rash caused by Leishmania tropica is described. The various drugs currently available for CL and experience of using liposomal amphotericin B specifically are reviewed.

Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs.

PubMed

Liu, Mei; Wu, Yonghui; Chen, Yukun; Sun, Jingchun; Zhao, Zhongming; Chen, Xue-wen; Matheny, Michael Edwin; Xu, Hua

2012-06-01

Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.

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

PubMed

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.

Drug-Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database.

PubMed

Welch, Hanna K; Kellum, John A; Kane-Gill, Sandra L

2018-06-08

Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Retrospective pharmacovigilance disproportionality analysis. FAERS database. We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known nephrotoxins, 18.6% were possible nephrotoxins, and 64.8% were new potential nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7,614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1,687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1,743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1,270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4,701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential nephrotoxins. AKI was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized

PCR analysis of a prescription vegetarian diet and use in three dogs with cutaneous adverse food reactions.

PubMed

Aufox, Erin E; May, Elizabeth R; Frank, Linda A; Kania, Stephen A

2018-04-24

Cutaneous adverse food reaction (CAFR) is diagnosed by performing an elimination diet trial utilizing prescription or home-cooked diets followed by provocative challenge. To report findings of PCR analysis of a prescription vegetarian diet (RCV) for undeclared proteins of animal origin, as well as to describe its utilization for diagnosis and management of dogs suspected of having CAFR. Three client-owned dogs. PCR analysis of RCV for 11 mammalian species and poultry. In three dogs, clinical examination, cytology, aerobic culture (if indicated) and at least one elimination diet trial with RCV. In our case series, all dogs had a history of pruritus and recurrent pyoderma that resolved with infection control and an elimination diet trial. In cases 1 and 2, a diagnosis of CAFR was made following an elimination trial with RCV and provocative challenge. Case 3 had a previously confirmed diagnosis of CAFR and RCV was successfully used to maintain remission of CAFR-related signs. PCR testing of RCV was negative for 11 mammalian species and poultry. The RCV diet was found not to contain any undeclared mammalian or avian proteins. In this case series, the RCV was successfully used to diagnose and maintain three dogs with CAFR. © 2018 ESVD and ACVD.

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

PubMed

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 <1. In the association rule mining, the score of lift for patients who were treated with cisplatin and co-administered furosemide, loxoprofen, or pemetrexed was high. Similarly, the scores for patients with hypertension or diabetes mellitus were high. Our findings suggest a potential risk of renal 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

[Patterns of drug consumption and the occurrence of adverse drug reactions among students of public health].

PubMed

Plichta, Danuta; Doryńska, Agnieszka; Spiewak, Radosław

2012-04-01

The research of drug consumption is focused mainly upon the elderly, while the knowledge of drug consumption patterns among young people remains insufficient. Public health students (PHS) seem of particular interest as future opinion leaders and drug policy makers. The aim of the study was to analyze opinions and patterns of drug consumption, and adverse drug reactions (ADR) in this group. 130 PHS took part in the anonymous questionnaire survey. All students admitted to using some drug at least once in their lives. While purchasing over-the-counter (OTC) drugs, 51.6% students trusted their own knowledge and experience. Women more often relied on a pharmacist's recommendation (47.2% vs 21.7% men; p = 0.045), while men were more influenced by advertising (34.8% vs 12.3% women, p = 0.008). Strict adherence to recommended dosage of OTC and prescription drugs (Rx) was declared by 41.1% and 71.9% students, respectively. Every fourth student (24.8%) admitted to having purchased a Rx drug at least once without having the prescription. Past episodes of ADR to OTC were reported by 7.8% students and to Rx by 38.4% (p < 0.001). Respectively 27.2% and 34.4% students were never, or hardly ever asked about past ADR by prescribing physicians. According to 89.2% students, drug advertising should be subject to regulation and policing, and 66.1% considered it inaccurate and unreliable. Forty-five percent of students had an OTC drug on them while responding the questionnaire, 20.0% had a prescription drug. Students of public health seem to be notorious consumers of drugs and their attitude seems not fully rational.

Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

2017-04-26

Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

[Cutaneous lupus erythematosus and skin manifestations in systemic lupus erythematosus].

PubMed

Sticherling, M

2013-06-01

Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.

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

PubMed

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.

Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions.

PubMed

Luo, Heng; Fokoue-Nkoutche, Achille; Singh, Nalini; Yang, Lun; Hu, Jianying; Zhang, Ping

2018-05-23

Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available. We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs. These models obtain an overall area under the receiver operating characteristic curve (AUROC) of 0.843 and an overall area under the precision-recall curve (AUPR) of 0.395, outperforming seven structural fingerprint-based prediction models. Using the method, we predicted skin striae for fluticasone propionate, dermatitis acneiform for mometasone, and decreased libido for irinotecan, as demonstrations. Furthermore, we analyzed the top binding proteins associated with some of the ADRs, which can help to understand and/or generate hypotheses for underlying mechanisms of ADRs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Adverse drug reaction reporting in emergency medicine].

PubMed

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 < or = 6%. A minority of physicians were responsible for the majority of ADR reporting. Sixty-four percent of emergency physicians underestimated the conditions required for ADR notification: 28% thought that certain causality was an absolute necessary condition for notification, while 37% considered that notification was required only for ADRs that were both severe and unexpected. Interventions focused on advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.

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

PubMed Central

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

Critically appraised topic on adverse food reactions of companion animals (3): prevalence of cutaneous adverse food reactions in dogs and cats.

PubMed

Olivry, Thierry; Mueller, Ralf S

2017-02-15

The prevalence of cutaneous adverse food reactions (CAFRs) in dogs and cats is not precisely known. This imprecision is likely due to the various populations that had been studied. Our objectives were to systematically review the literature to determine the prevalence of CAFRs among dogs and cats with pruritus and skin diseases. We searched two databases for pertinent references on August 18, 2016. Among 490 and 220 articles respectively found in the Web of Science (Science Citation Index Expanded) and CAB Abstract databases, we selected 22 and nine articles that reported data usable for CAFR prevalence determination in dogs and cats, respectively. The prevalence of CAFR in dogs and cats was found to vary depending upon the type of diagnoses made. Among dogs presented to their veterinarian for any diagnosis, the prevalence was 1 to 2% and among those with skin diseases, it ranged between 0 and 24%. The range of CAFR prevalence was similar in dogs with pruritus (9 to 40%), those with any type of allergic skin disease (8 to 62%) and in dogs diagnosed with atopic dermatitis (9 to 50%). In cats presented to a university hospital, the prevalence of CAFR was less than 1% (0.2%), while it was fairly homogeneous in cats with skin diseases (range: 3 to 6%), but higher in cats with pruritus (12 to 21%) than in cats with allergic skin disease (5 to 13%). Among dogs and cats with pruritus and those suspected of allergic skin disease, the prevalence of CAFR is high enough to justify this syndrome to be ruled-out with a restriction (elimination)-provocation dietary trial. This must especially be considered in companion animals with nonseasonal pruritus or signs of allergic dermatitis.

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

PubMed

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.

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

PubMed Central

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

Comparative study of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis.

PubMed

Francesconi, Glaucia; Francesconi do Valle, Antonio Carlos; Passos, Sonia Lambert; de Lima Barros, Mônica Bastos; de Almeida Paes, Rodrigo; Curi, André Luiz Land; Liporage, José; Porto, Cássio Ferreira; Galhardo, Maria Clara Gutierrez

2011-05-01

Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis. To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis. A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n = 4, 7.3%) and itraconazole (n = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

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

PubMed

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.

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

PubMed

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

Adverse drug events related to mood and emotion in paediatric patients treated for ADHD: A meta-analysis.

PubMed

Pozzi, Marco; Carnovale, Carla; Peeters, Gabriëlla G A M; Gentili, Marta; Antoniazzi, Stefania; Radice, Sonia; Clementi, Emilio; Nobile, Maria

2018-05-22

ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies. Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis. Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients' sex and age, drug dose and release formulation. Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury. Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms. Copyright © 2018. Published by Elsevier B.V.

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

PubMed

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.

Cutaneous Collagenous Vasculopathy

PubMed Central

Ortleb, Melanie; Boyd, Alan S.; Powers, Jennifer

2015-01-01

Cutaneous collagenous vasculopathy is a rare microangiopathy of dermal blood vessels. Clinically indistinguishable from generalized essential telangiectasia, this condition is diagnosed by its unique histological appearance. In contrast to other primary telangiectatic processes, cutaneous collagenous vasculopathy has dilated vascular structures that contain deposits of eosinophilic hyaline material within the vessel walls. To date, cutaneous collagenous vasculopathy has been described in a total of 19 cases in the medical literature. The first several cases were described exclusively in middle-aged to elderly men. Though it has now been described in both men and women, cutaneous collagenous vasculopathy is still most often described in middle-aged to older adults. No particular disease or medication has been linked to the development of cutaneous collagenous vasculopathy, and the etiology remains unknown. In this case series, the authors present three additional patients diagnosed with cutaneous collagenous vasculopathy and discuss their clinical and histopathologic features. PMID:26705441

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

PubMed

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.

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

PubMed

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.

[Liposomal amphotericin B treatment of cutaneous leishmaniasis contracted in Djibouti and resistant to meglumine antimoniate].

PubMed

Rapp, C; Imbert, P; Darie, H; Simon, F; Gros, P; Debord, T; Roué, R

2003-08-01

Pentavalent antimony (PA) compounds remain the main therapeutic agents of cutaneous leishmaniasis (CL). CL infection resistant to PA is difficult to cure, limited by severe side effects and requiring a long course treatment of parenteral administration of recommended second line drugs. We report a case of CL unresponsive to meglumine antimoniate contracted in Djibouti, successfully treated with a short course treatment of AmBisome. In this case the subject had a recurrent thick crusted erythematous lesion on his left elbow associated with spreading micropapula on arms and thorax. The diagnosis of CL was confirmed by direct examination and genomic amplification by PCR of skin samples, cultures were negative. A short course treatment of parenteral AmBisome (18 mg/kg) has lead to clinical cure with no side effects and no relapse. In our hospital, the high cost of medication was counterbalanced by easiest administration, reduction of hospitalization duration, absence of adverse events and a gain of comfort. For this patient, a short course treatment of AmBisome proved to be a suitable alternative to traditional drugs used in CL resistant to PA.

Cutaneous leishmaniasis in the dorsal skin of hamsters: a useful model for the screening of antileishmanial drugs.

PubMed

Robledo, Sara M; Carrillo, Lina M; Daza, Alejandro; Restrepo, Adriana M; Muñoz, Diana L; Tobón, Jairo; Murillo, Javier D; López, Anderson; Ríos, Carolina; Mesa, Carol V; Upegui, Yulieth A; Valencia-Tobón, Alejandro; Mondragón-Shem, Karina; Rodríguez, Berardo; Vélez, Iván D

2012-04-21

Traditionally, hamsters are experimentally inoculated in the snout or the footpad. However in these sites an ulcer not always occurs, measurement of lesion size is a hard procedure and animals show difficulty to eat, breathe and move because of the lesion. In order to optimize the hamster model for cutaneous leishmaniasis, young adult male and female golden hamsters (Mesocricetus auratus) were injected intradermally at the dorsal skin with 1 to 1.5 x l0(7) promastigotes of Leishmania species and progression of subsequent lesions were evaluated for up to 16 weeks post infection. The golden hamster was selected because it is considered the adequate bio-model to evaluate drugs against Leishmania as they are susceptible to infection by different species. Cutaneous infection of hamsters results in chronic but controlled lesions, and a clinical evolution with signs similar to those observed in humans. Therefore, the establishment of the extent of infection by measuring the size of the lesion according to the area of indurations and ulcers is feasible. This approach has proven its versatility and easy management during inoculation, follow up and characterization of typical lesions (ulcers), application of treatments through different ways and obtaining of clinical samples after different treatments. By using this method the quality of animal life regarding locomotion, search for food and water, play and social activities is also preserved.

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

PubMed

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.

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions.

PubMed

Correia, C T; Almeida, J P; Santos, P E; Sequeira, A F; Marques, C E; Miguel, T S; Abreu, R L; Oliveira, G G; Vicente, A M

2010-10-01

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.

A case of adverse drug reaction induced by dispensing error.

PubMed

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.

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

PubMed

Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

2016-01-01

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

Cutaneous manifestations of phosphate solution extravasation.

PubMed

Verykiou, S; Aljefri, K; Gopee, H; Taheri, L; Charlton, F; Langtry, J A; Blasdale, C

2018-01-01

Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations. © 2017 British Association of Dermatologists.

Treatment of cutaneous leishmaniasis with thermotherapy in Brazil: an efficacy and safety study*

PubMed Central

2018-01-01

BACKGROUND Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS Sample with a small number of patients and short follow-up. CONCLUSION Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials. PMID:29924242

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.

PubMed

Tassaneeyakul, Wichittra; Prabmeechai, Napat; Sukasem, Chonlaphat; Kongpan, Thachanan; Konyoung, Parinya; Chumworathayi, Pansu; Tiamkao, Somsak; Khunarkornsiri, Usanee; Kulkantrakorn, Kongkiat; Saksit, Niwat; Nakkam, Nontaya; Satapornpong, Patompong; Vannaprasaht, Suda; Sangviroon, Alisara; Mahasirimongkol, Surakameth; Wichukchinda, Nuanjun; Rerkpattanapipat, Ticha; Tassaneeyakul, Wongwiwat

2016-05-01

Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population. Sixty phenytoin-related SCAR (i.e. 39 SJS/TEN and 21 DRESS) and 92 phenytoin-tolerant patients were enrolled in the study. The genotypes of HLA class I and CYP2C9 were determined. Six HLA alleles including HLA-A*33:03, HLA-B*38:02, HLA-B*51:01, HLA-B*56:02, HLA-B*58:01, and HLA-C*14:02 were significantly associated with phenytoin-related SJS/TEN, whereas only the HLA-B*51:01 was significantly associated with phenytoin-related DRESS. The odds ratios of phenytoin-related SJS/TEN in the patients who carried one of these alleles ranged from 4- to 10-fold. The frequencies of patients who carried the HLA-B*15:02 in the SJS/TEN (12.82%) or the DRESS (9.52%) groups were not significantly different from that of the controls (14.13%). The higher risk of phenytoin-related SJS/TEN was observed in the patients with CYP2C9*3 (odds ratio=4.30, 95% confidence interval=1.41-13.09, P<0.05). Neither SJS/TEN nor DRESS caused by phenytoin was significantly associated with the HLA-B*15:02. The CYP2C9*3 variant was significantly associated with phenytoin-related SJS/TEN, but not DRESS. Certain alleles of HLA, particularly HLA-B*56:02, were significantly associated with phenytoin-related SCAR in the study population.

On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

PubMed

Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

2015-08-01

The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

PubMed

Ugarte, A; Porta, S; Ríos, R; Martinez-Zapico, A; Ortego-Centeno, N; Agesta, N; Ruiz-Irastorza, G

2018-01-01

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such

Gold standards in pharmacovigilance: the use of definitive anecdotal reports of adverse drug reactions as pure gold and high-grade ore.

PubMed

Hauben, Manfred; Aronson, Jeffrey K

2007-01-01

Anecdotal reports of adverse drug reactions are generally regarded as being of poor evidential quality. This is especially relevant for postmarketing drug safety surveillance, which relies heavily on spontaneous anecdotal reports. The numerous limitations of spontaneous reports cannot be overemphasised, but there is another side to the story: these datasets also contain anecdotal reports that can be considered to describe definitive adverse reactions, without the need for further formal verification. We have previously defined four categories of such adverse reactions: (i) extracellular or intracellular tissue deposition of the drug or a metabolite; (ii) a specific anatomical location or pattern of injury; (iii) physiological dysfunction or direct tissue damage demonstrable by physicochemical testing; and (iv) infection, as a result of the administration of an infective agent as the therapeutic substance or because of demonstrable contamination. In this article, we discuss the implications of these definitive ('between-the-eyes') adverse effects for pharmacovigilance.

Cutaneous metastasis of cholangiocarcinoma.

PubMed

Liu, Min; Liu, Bai-Long; Liu, Bin; Guo, Liang; Wang, Qiang; Song, Yan-Qiu; Dong, Li-Hua

2015-03-14

To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.

Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

PubMed

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.

PubMed

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

Adverse Drug Events in Children: How Big is the Problem?

PubMed

Zed, Peter J

2015-01-01

Adverse drug events in children is an under appreciated but significant cause of health care contact resulting in ED visits and hospital admissions with associated resource utilization. In recent years we have started to better understand the impact of ADEs in children but there remains significant questions that must be addressed to further improve our understanding of the etiology of these ADEs and strategies for prevention and management. This paper will describe what is known regarding the frequency, severity, preventability and classification of ADEs in children. It will also describe some of the challenges and unanswered questions regarding patient, drug and system factors, which contribute to ADEs in children. Finally, areas of future research will be identified to further improve our understanding of ADEs in children to inform prevention strategies as well as early recognition and management approaches to minimize the significant ADEs can have on children, families and our health care system.

Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

PubMed

Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

2017-05-01

Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

Travelers with cutaneous leishmaniasis cured without systemic therapy.

PubMed

Morizot, G; Kendjo, E; Mouri, O; Thellier, M; Pérignon, A; Foulet, F; Cordoliani, F; Bourrat, E; Laffitte, E; Alcaraz, I; Bodak, N; Ravel, C; Vray, M; Grogl, M; Mazier, D; Caumes, E; Lachaud, L; Buffet, P A

2013-08-01

Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42-60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

Cutaneous applications of lasers.

PubMed

Ries, W R; Speyer, M T

1996-12-01

The cutaneous application of lasers today includes more selective and less damaging devices. Carbon dioxide, neodymium:yttrium-aluminum-garnet, potassium titanyl phosphate, argon, and yellow lasers are most prevalent in treating cutaneous lesions. Specific techniques in skin resurfacing, keloid excision, rhinophyma, actinic cheilitis ablation, and excision of superficial cutaneous tumors are discussed. Proper management of cutaneous vascular lesions is also presented.

Adverse food reactions: Pathogenesis, clinical signs, diagnosis and alternatives to elimination diets.

PubMed

Mueller, R S; Unterer, S

2018-06-01

This review summarises available information about adverse food reactions in dogs and cats. Much of the published information on the pathogenesis of adverse food reactions in these species is transferred from what is known in mice and human beings. Clinical signs affect mostly the integument and gastrointestinal system. Pruritus of the distal limbs, face, ears and ventrum is the most common cutaneous presentation in dogs, although urticaria has also been reported. In cats, all so-called 'cutaneous reaction patterns' may be due to adverse food reactions. The most common gastrointestinal signs in both species are diarrhoea and vomiting. An elimination diet over several weeks using a protein source and a carbohydrate source previously not fed is still the diagnostic tool of choice. Improvement on such a diet, deterioration on re-challenge with the old food and improvement again on the elimination diet confirms the diagnosis of adverse food reaction, whereas alternative tests of blood, serum, saliva and hair have been found to be unsatisfactory. Patch testing with food antigens has been recommended as an aid to choose the elimination diet ingredients, since it has a reasonable negative predictability and likelihood ratio, but is laborious and costly. Copyright © 2018 Elsevier Ltd. All rights reserved.

An update on adverse drug reactions related to β-lactam antibiotics.

PubMed

Vardakas, Konstantinos Z; Kalimeris, Georgios D; Triarides, Nikolaos A; Falagas, Matthew E

2018-05-01

β-lactams have been consistently associated with the majority of drug-related adverse events. Generally, these are mild under proper dosing and judicious selection. Areas covered: Immediate hypersensitivity reactions are the most feared adverse events encountered after β-lactam administration. Emerging evidence shows that immediate reactions are not as common as previously thought. Specialist consultation and testing seems prudent before a patient is officially declared allergic to β-lactams. The risk of cross-reactions between not only members of the β-lactam super-family but also between specific classes is also lower than previously thought. Newer studies have shown that cross-reactions are not universal and pertain to specific agents with similar side chains or metabolites of the β-lactam core. The frequency of severe kidney or liver toxicity, neurotoxicity, cytopenias and Clostiridium difficile infection following β-lactam administration seem to be agent-specific. Expert opinion: The currently available data denote that in addition to age, gender, co-morbidity, renal or liver function, and co-administered agents, the antibiotic levels rather than the dose itself seem to be associated with the emergence of adverse events. Most of them subside with time after withdrawal of the offending agent, but the number of cases resulting in chronic disabilities or even deaths in not negligible.

Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France.

PubMed

Pathak, Atul; Raoul, Valérie; Montastruc, Jean-Louis; Senard, Jean-Michel

2005-07-01

The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring pharmacological treatment with at least one drug marketed in France for OH were included together with six patients with refractory neurocardiogenic syncope. Of the patients, 85 received a monotherapy-mainly with midodrine (49.4%)-and 42 received various combinations, the association of midodrine and fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88 suffered from a total of 141 ADRs (1.60 per patient) with no statistical difference in ADR frequency between monotherapy and drug combinations (P>0.05). Among ADRs, 24 (17.0%) were considered as "serious" and 16 (11.3%) were considered as "unexpected", most of them observed with heptaminol. This study shows a high frequency of ADRs (especially serious and unexpected ADRs) with antihypotensive drugs. It strongly suggests the need for a better evaluation of the safety profile of antihypotensive drugs and improvement in summary of product characteristics.

Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

PubMed Central

Phillips, Elizabeth J.; Chung, Wen-Hung; Mockenhaupt, Maja; Roujeau, Jean-Claude; Mallal, Simon A.

2011-01-01

Severe cutaneous adverse reactions (SCARs) include syndromes such as drug reaction, eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes including abacavir hypersensitivity reaction, allopurinol DRESS/DIHS and SJS/TEN and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of SCARs. The roll-out of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs such as carbamazepine where the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN may not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotype standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. PMID:21354501

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

PubMed

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.

Childhood adversities predict strongly the use of psychotropic drugs in adulthood: a population-based cohort study of 24,284 Finns.

PubMed

Koskenvuo, Karoliina; Koskenvuo, Markku

2015-04-01

Exposure to adverse childhood experiences has been shown to be associated with negative health outcomes including mental health problems, but only a few studies with register-based data have used psychotropic drugs as an outcome variable. The purpose of this study is to examine whether adverse emotional childhood experiences, such as serious conflicts in the family and frequent fear of a family member, predict the use of psychotropic drugs in adulthood. In addition, the association of a child-parent relationship during childhood with the use of psychotropic drugs is studied. The participants of the population-based Health and Social Support Study (24,284 working aged Finns) were followed up for 9 years. The information on childhood experiences and child-parent relationships was obtained from the questionnaires in 1998 and 2003. The number of psychotropic purchases (antipsychotics, drugs for bipolar disorder, antidepressants, anxiolytics, hypnotics and sedatives) was obtained from the National-Drug-Prescription-Register. Logistic and multinomial regression models were used. A graded association between childhood adversities and the use of psychotropic drugs was found, even after adjustments for occupational training, work status, recent life events and health behaviour. Frequent fear of a family member showed the strongest association: the OR for multiple use of antidepressants was 3.08 (95% CI 2.72 to 3.49) and 2.69 (2.27 to 3.20) for multiple use of anxiolytics. Use of psychotropic drugs was clearly increased among those with poor child-parent relationship and multiple childhood adversities. The results highlight the effect of environmental factors during childhood on mental health and the need for early recognition of families at risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cutaneous Pseudolymphomas.

PubMed

Romero-Pérez, D; Blanes Martínez, M; Encabo-Durán, B

2016-10-01

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

[Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

  The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

Drug-induced lupus erythematosus.

PubMed

Marzano, A V; Tavecchio, S; Menicanti, C; Crosti, C

2014-06-01

Drug-induced lupus erythematosus (DI-LE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to drug exposure and resolves after withdrawal of the implicated drug. Similarly to idiopathic lupus, DI-LE can be divided into systemic LE, subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE) and cutaneous LE tumidus. DI-SCLE is the most frequent variant of drug-induced cutaneous LE and presents mainly with annular-polycyclic lesions; the clinical picture is often widespread, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are typically present, whereas antihistone antibodies are uncommonly found. We have recently addressed the question whether DI-SCLE differs significantly from its idiopathic counterpart by virtue of clinical features and, based on our findings, we have suggested that the frequent occurrence of malar rash and bullous, erythema multiforme-like and vasculitic manifestations can be regarded as the hallmark of DI-SCLE. In contrast, the histology is not a useful diagnostic criterion for DI-SCLE, considering that the typical pattern of lichenoid interface dermatitis is seen only in the early stage of disease and tissue eosinophilia does not represent a differentiating histopathological feature. DI-CCLE and DI-LE tumidus, albeit possibly misdiagnosed, are rarely observed and are characterized by classic discoid lesions and erythematous-oedematous plaques on sun exposed areas, respectively. Management of DI-LE is based on the discontinuation of the offending drug; topical and/or systemic corticosteroids and other immunomodulating/immunosuppressive agents should be reserved for resistant cases.

[Adverse Event Trends Associated with Over-the-counter Combination Cold Remedy: Data Mining of the Japanese Adverse Drug Event Report Database].

PubMed

Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Motooka, Yumi; Fukuda, Akiho; Naganuma, Misa; Umetsu, Ryogo; Nakao, Satoshi; Shimauchi, Akari; Ueda, Natsumi; Hirade, Kouseki; Iguchi, Kazuhiro; Nakamura, Mitsuhiro

2018-01-01

 OTC combination cold remedies are widely used in Japan. In the present study, we aimed to evaluate the adverse event profiles of OTC combination cold remedy based on the components using the Japanese Adverse Drug Event Report (JADER) database. The JADER database contained 430587 reports between April 2004 and November 2016. 1084 adverse events associated with the use of OTC combination cold remedy were reported. Reporting odds ratio (ROR) was used to detect safety signals. The ROR values for "skin and subcutaneous tissue disorders", "hepatobiliary disorders", and "immune system disorders" stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 9.82 (8.71-11.06), 2.63 (2.25-3.07), and 3.13 (2.63-3.74), respectively. OTC combination cold remedy containing acetaminophen exhibited a significantly higher reporting ratio for "hepatobiliary disorders" than OTC combination cold remedy without acetaminophen. We demonstrated the potential risk of OTC combination cold remedy in a real-life setting. Our results suggested that the monitoring of individuals using OTC combination cold remedy is important.

New posology of potassium iodide for the treatment of cutaneous sporotrichosis: study of efficacy and safety in 102 patients.

PubMed

Macedo, P M; Lopes-Bezerra, L M; Bernardes-Engemann, A R; Orofino-Costa, R

2015-04-01

The first therapeutic choice for the treatment of cutaneous sporotrichosis is oral itraconazole; however, the increase in cases of zoonotic transmission outbreak necessitates a search for effective and safe treatment alternatives. To evaluate a new potassium iodide (KI) posology as an alternative for the treatment of limited cutaneous forms of sporotrichosis. One hundred and two patients with sporotrichosis diagnosed by isolation of Sporothrix sp. were included and were divided into 2 groups that received different doses of KI: group A received the conventional dose, and group B received the reduced dose. The cure criteria were based on clinical and serological data. Seventy-nine patients (77.4%) reached clinical cure: 70.6% and 84.3% of groups A and B respectively. Sixteen patients (15.6%) were lost during follow-up, and seven changed drug therapy: five in group A and two in group B. The incidence of adverse events was similar for both groups (64.7%): predominantly metallic taste (44%), followed by mild gastrointestinal intolerance and acneiform eruption (10.7% each). No serious adverse events occurred, and there were no recurrences. Analysis of the results showed no statistically significant difference between groups (P = 0.9255). The improvement in serologic titres was significant in both treatment groups. Through statistical analysis, the usual posology was not shown to be superior to the one proposed in this study. Serology for sporotrichosis may be used as a valuable tool in the clinical monitoring of these patients. © 2014 European Academy of Dermatology and Venereology.

The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).

PubMed

Dorato, Michael A; Engelhardt, Jeffery A

2005-08-01

The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.