Full Text Available In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.
Suástegui-Rodríguez, Irvin; Campos-Jiménez, Karin Ivette; Domínguez-Cherit, Judith; Méndez-Flores, Silvia
Adverse cutaneous reactions to drugs are any undesirable change in the structure or function of the skin. These are among the adverse side effects to common drugs. The most commonly implicated drugs are antibiotics and anticonvulsants. Cutaneous clinical manifestations are diverse ranging from mild or moderate reactions, such as urticaria and maculopapular rash, to severe cutaneous adverse reactions (SCAR), which are known due to their high morbidity and mortality (among these: Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). The clinical pattern, etiology, prognosis and treatment differ among these skin reactions, which is why it is necessary a clear diagnosis based on a comprehensive clinical examination, skin biopsy, and specific laboratory tests. The therapeutic options depend on the clinical diagnosis. For all reactions, a symptomatic and adequate supportive therapy is necessary; in some cases, a systemic immunomodulatory therapy can be useful.
limiting but they can be the initial presentation of more serious reactions such as Stevens-Johnson and drug hypersensitivity syndromes.3 It is thus important for the clinician to distinguish between self-limiting morbilliform drug eruptions that resolve solely with the withdrawal of the offending drug and the life-threatening ...
There are many different types of cutaneous adverse reactions. The most classical reactions are driven by T lymphocytes that specifically react towards a drug, with an individual genetic susceptibility linked to certain type I major histocompatibility complex alleles. These reactions are characterized by a wide variety of clinical and histopathological presentations, and a wide range of severity. The most frequent entity is the maculopapular rash, while the most aggressive forms are the Steven-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN). The histopathological alterations associated to each of these syndromes have been better described in the literature during the past 10 years, encompassing non-specific lesions, as in most drug induced maculopapular rashes, to more specific inflammatory patterns. The finding of confluent apoptotic keratinocytes with epidermal detachment is the prototypical aspect of SJS-TEN. There are however numerous pitfalls, and a similar aspect to those observed in each cutaneous drug reactions entities can be found in other diseases. DRESS syndrome can indeed present with dense and epidermotropic T-cell infiltrate, sometimes with nuclear atypias, and thus can be difficult to distinguish from a primary or secondary cutaneous T-cell lymphoma. The diagnosis of cutaneous adverse reactions relies on a clinical-pathological confrontation and requires an accurate evaluation of drug imputability. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Full Text Available Out of a total of 1147 patients on antihypertensive drugs, 23 (2.04% developed adverse cutaneous drug reactions (ACDR. The commonest antihypertensive drug group causing ACDR was beta-blockers of which atenolol was the commonest culprit. The second most common group was calcium channel blockers with amlodipine as the commonest offender. The most common patterns of ACDR observed included urticaria followed by lichenoid drug eruption (LDE. We noted 2 new patterns of reactions; (i one patient developed brownish blue pigmentation of nails while on atenolol for 3 years, which resolved in 4 months after withdrawal and (ii another patient on amlodipine for 8 years developed Schamberg′s like purpuric pigmentation, which resolved on withdrawal of drug within 3 months. These findings have not been reported in the literature earlier. This study is presented for paucity of Indian data on ACDR due to antihypertensive drugs, and remarkable advancement in area of cardiovascular and antihypertensive pharmacology and a large number of population taking antihypertensive drugs.
Drago, F; Cogorno, L; Agnoletti, A F; Parodi, A
The objective of this retrospective study was to verify whether peripheral eosinophilia (PE) may be a marker of severity for adverse cutaneous drug reactions (ACDR). We investigated for PE in sixty-three patients diagnosed as adverse cutaneous drug reactions. All the patients underwent blood tests at baseline visit. Only patients that showed a very likely connection between ACDR and the suspected causative drug were induced in the study. We found that 11 out of 63 patients (17%) presented PE for values ≥ 0.6 x 10(9) cells/l or for a percentage of total leukocytes ≥ 6%. These 11 patients compared to patients without eosinophilia had a longer recovery time, they showed diffuse severe cutaneous reactions and they all needed a systemic therapy compared to the 41% of patients without eosinophilia. These outcomes prompt us to believe that peripheral eosinophilia may be an index of severity for adverse cutaneous drug reactions. Therefore, we suggest physicians to always detect the presence of peripheral eosinophilia in order to not underestimate the reaction and to promptly start an appropriate therapy.
Marquès, S; Milpied, B; Foulc, P; Barbarot, S; Cassagnau, E; Stalder, J-F
Celecoxib (Celebrex) is a Cox 2 selective non steroidal anti-inflammatory agent. Adverse reactions reported are usually benign, such as maculopapular exanthema. However, recently severe toxiderma have started to appear. We report two patients who developed a sever celecoxib drug skin reaction. Case no 1. In a 73 year-old woman, treated with celecoxib for cervical arthralgia, a maculopapular exanthema five days after treatment was started. The exanthema, initially edematous and purpural became bullous with multi-visceral failure (disseminated intravascular coagulation, renal failure, hepatitis and pancreatic). The disease slowly regressed. Case no 2. A 72 year-old man, treated for cervicalgia with celecoxib, presented a pustular exanthema of the face and the trunk, ten days after introduction of the treatment, associated with an inflammatory syndrome and hepatic cytolysis. Within 8 days the disease had regressed. In both these patients, the celecoxib patch tests were positive. Until now, the side effects reported with celecoxib have been generally benign exanthemas. We report two cases of severe celecoxib-induced toxiderma: a hypersensitivity syndrome with multi-organ failure and an acute generalized atypical exanthematous pustulosis. These severe toxidermas have rarely been reported in the literature, but we now need to reassess the risks with these new molecules.
Full Text Available Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM, Stevens–Johnson syndrome (SJS, and toxic epidermal necrolysis (TEN provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP- like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis.
Patel, Tejas K; Thakkar, Sejal H; Sharma, DC
Background: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. Aims: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. Materials and Methods: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing “definite” and “probable” categories of causality analysis were labeled as “definite and probable causality (DPC) studies”. The other included studies were labeled as “non-DPC studies”. Results: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), β-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS
Background: Cutaneous drug reactions are a common impediment in therapy, the incidence ranging from 2% to 8%. This cross-sectional study was designed to compare different trends of cutaneous drug reaction in two different socioeconomic groups of patients in the same region. Aims: The aim was to evaluate common ...
Full Text Available Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.
Yang, C-Y; Dao, R-L; Lee, T-J; Lu, C-W; Yang, C-H; Hung, S-I; Chung, W-H
Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)-induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs. A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes. Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS. CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.
Deng, Qiancheng; Fang, Xia; Zeng, Qinghai; Lu, Jianyun; Jing, Chen; Huang, Jinhua
The rate of severe cutaneous adverse drug reactions is low, and these reactions can result in death or disability. An evidence-based epidemiological study of severe cutaneous adverse drug reactions in China has not been reported. The aim of this study was to analyze epidemiology and characteristics of severe cutaneous adverse drug reactions of Chinese inpatients during the recent 15 years with meta-analysis. We retrospectively reviewed Chinese literature reporting severe cutaneous adverse drug reactions and collecting data from 2000 to 2015, which were in accordance with our inclusion criteria. All included data were analyzed with the Launch Open Meta-Analyst software. Twenty-five articles involving 928 cases with severe cutaneous adverse drug reactions were included. Men to women ratio was 1.14:1. Twenty-one per cent of the patients had drug allergy history. Antibiotics (26.0%), sedative hypnotics and anticonvulsants (21.6%), and antipyretic analgesics (17.1%) were the most common causative drugs. The most frequent clinical subtype was Stevens-Johnson syndrome (50.1%), followed by toxic epidermal necrolysis (25.4%), exfoliative dermatitis (21.0%) and drug-induced hypersensitivity syndrome (1.6%). In addition to skin rashes, patients with severe cutaneous adverse drug reactions suffered mostly from fever (73%), and blood routine abnormality (66.7%). This meta-analysis is limited by its retrospective design and by its methodological variation. The most common causative drugs were antibiotics and sedative hypnotics and anticonvulsants. Stevens-Johnson syndrome was the most frequent clinical subtype of severe cutaneous adverse drug reactions. In addition to skin rashes, patients with severe cutaneous adverse drug reactions suffered mostly from fever, mucosal lesion, and hematologic abnormalities.
Singh, Punit Kumar; Kumar, Dharmendra; Kumar, Prashant
Introduction: Cutaneous manifestations of adverse drug reactions are a common occurrence and need to be differentiated from other causes of similar manifestations. Antiepileptic drugs (AED) usually are responsible for severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophillia and systemic symptoms (DRESS). There is paucity of published research regarding morphological pattern of CADR due to various antiepileptic drugs AED. Objective: To study the morphological patterns of CADR due to AED and common anticonvulsant drugs implicated particularly in severe CADR such as SJS/TEN and DRESS in a tertiary care teaching hospital in eastern India. Materials and Methods: A prospective, observational study was conducted over a period of 4 years from August 2009 to July 2013 after the approval of the Institutional Ethics Committee using self-reporting method for selection of cases. Settings: All patients with CADR after AED consumption for various conditions presenting to the Dermatology outpatient department (OPD) and Pediatric OPD and Indoor patients of a tertiary care teaching hospital located in Rohtas district of Bihar were included in this study. Results: During the study period, 64 cases of severe CADRs were included in this study. Out of 64 patients, 28 were male and 36 were female with mean age 36.1 years (range 6 years to 72 years). Most common AED implicated for CADR was Phenytoin. Maculopapular rash was the most common cutaneous manifestation of ADRs (42.85%). Serious CADR like TEN and SSJS were more likely in patients prescribed Phenytoin and Carbemazepine simultaneously. Conclusion: CADRs are a common occurrence and awareness about the same is essential for diagnosis and prevention. This study identified combined use of phenytoin and carbamezepine as a most important risk factor for serious CADR like SJS and TEN. PMID:25738068
Ding, Wen Yi; Lee, Chew Kek; Choon, Siew Eng
Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens-Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA-B*1502 and HLA-B*5801 which are genetic markers for carbamazepine-induced SJS/TEN and allopurinol-induced SJS/TEN/DRESS respectively. The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine
Jul 20, 2011 ... This cross-sectional study was designed to compare different trends of cutaneous drug reaction in two different socio- ... maculopapular rash, all other skin reactions were observed more frequently with NSAIDS in dental College whereas ..... and causative agents in a tertiary care center in South India.
Tertiary Care Hospital – a Prospective Study. SP Shah*, MK Desai and ... drug reactions manifest as skin rashes and/or eruptions. The incidence ..... Safety Monitoring on. Medicinal Products. Geneva (Switzerland):. Office of Publications, World Health. Organization; 2002. 6. Hartwig SC, Siegel J, Schneider PJ. Preventability.
Borch, Jakob E; Andersen, Klaus E; Bindslev-Jensen, Carsten
Patients with suspected cutaneous adverse drug reactions are often referred to allergy clinics or departments of dermatology for evaluation. These patients are selected compared with patients identified in prospective and cross-sectional studies of hospital populations. This explains the observed...... variation in prevalence of specific reactions and of eliciting drugs. This study investigated the prevalence of cutaneous adverse drug reactions in a university hospital department of dermatology that is specially focused on allergy. An 8-month survey was carried out during the period April-December 2003...... at injection sites were the most frequent reactions (25% and 18.8%, respectively). Beta-lactam antibiotics, extracts for desensitization and insulins were the main drug groups involved, and accounted for 22.8%, 17.1% and 14.2%, respectively, of the reactions. Extracts for desensitization and insulins elicited...
Le Guern, A; Kerrad, I; Oehler, E
Griseofulvin is an antifungal drug known to cause drug rash. However, it is widely prescribed outside its classic indications. Herein, we describe 2 cases in which griseofulvin was prescribed for off-label indications. Case No. 1. A 51-year-old woman was referred to the department of internal medicine for management of Stevens-Johnson Syndrome (SJS). The symptoms appeared 17 days after she had taken griseofulvin for inguinal intertrigo. Case No. 2. A 19-year-old female patient consulted for toxic epidermal necrolysis (TEN) affecting 30% of her body surface, with a positive Nikolsky sign and severe mucosal lesions. These symptoms appeared 9 days after she began taking griseofulvin, which had initially been prescribed for her husband for mycosis. Toxic epidermal necrolysis, a condition chiefly of drug-related origin, is a severe mucocutaneous syndrome characterized by massive keratinocytic apoptosis. Although there are few scientific publications referring to griseofulvin-induced drug eruption, they deserve to be mentioned since this drug is widely used for purposes other than the approved indications and can cause life-threatening reactions. We report two cases of toxic epidermal necrolysis related to the misuse of griseofulvin. It is important to bear in mind the precautions for use of oral antifungal drugs, which are strictly reserved for use against resistant or diffuse forms of mucocutaneous fungal infections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
medication and maintenance of prescription records. The cost associated with ADRs is high. ADR monitoring is essential to reduce patient suffering as well as to achieve the substantial savings in health care cost. Keywords: Cutaneous adverse ...
Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech
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.
Fang, Wendy C; Adler, Nikki R; Graudins, Linda V; Goldblatt, Caitlin; Goh, Michelle Sy; Roberts, Stuart K; Trubiano, Jason A; Aung, Ar Kar
Drug-induced liver injury can be associated with certain cutaneous adverse drug reactions. We aim to demonstrate the prevalence of drug-induced liver injury in patients with cutaneous adverse drug reactions. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. A retrospective cohort study of patients with cutaneous adverse drug reactions was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. 104 patients with cutaneous adverse drug reactions 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/toxic epidermal necrolysis. 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 Stevens-Johnson syndrome (OR=6.0, 95% CI:1.8-19.7, p=0.003). Antimicrobials were the most common class to be implicated in drug-induced liver injury. 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. Drug-induced liver injury commonly occurs in patients with cutaneous adverse drug reactions and is associated with longer inpatient stay. Patients with Stevens-Johnson/toxic epidermal necrolysis and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury. This article is protected by copyright. All rights reserved.
Lokhande, Archana J; Sutaria, Amita; Shah, Bela J; Shah, Asha N
To study the change in the incidence and pattern of nevirapine (NVP)-induced adverse cutaneous reactions (ADR) after commencement of revised National AIDS Control Organisation (NACO) guidelines for initiation of antiretroviral therapy (ART) since Nov 2011. The study was conducted on patients who developed cutaneous reactions after starting NVP based regimen. According to the revised NACO ART initiation guidelines Nov 2011, ART should be started if CD4 count is < 350 cells/mm(3) in stages 1, and 2 and irrespective of CD4 count in stages 3, and 4. Patients were divided in groups A and B. Group A consisted of patients enrolled on NVP-based regimen during Jan 2011 to Oct 2011, whereas, in Group B patients from Nov 2011 to Aug 2012 were included. Grading of rash, appropriate investigations and management was done. In Group A, out of 645 patients 30 (4.66%) patients developed cutaneous reactions, where as in Group B out of 720, 65 (9.03%) patients presented with drug reaction. In Group A (n = 30) developed reaction as Grade 1 in 1.55% (n = 10), Grade 2 in 1.86% (n = 12), grades 3 and 4 in 0.76% (n = 5) and 0.47% (n = 3), respectively. In Group B (n = 65) developed reaction, out of which Grade 1 reaction was seen in 1.39% (n = 10), Grade 2 was seen in 2.78% (n = 20), grades 3 and 4 was seen in 3.33% (n = 24) and, 1.53% (n = 11), respectively. There is a striking increase in the incidence of NVP-induced cutaneous reactions of all forms and considerable increase in frequency of severe kind of reactions with the revised guidelines.
Latha, S; Choon, S E
Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. A prospective study was conducted among medical inpatients from July to December 2014. A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.
Safrina Dewi Ratnaningrum
Full Text Available Carbamazepine as an antiepileptic drug that is used widely and was known can cause severe cutaneous adverse drug reactions like SJS-TEN. These adverse drug reactions is known to be associated with some specific HLA polymorphism in European populations (HLA-A*31: 01, China (HLA-A*31: 01; HLA-B*15:02, Japan (HLA-A*31 : 01; HLA-B*15: 11, Korea HLA-A*31: 01; HLA-B*15: 02; HLA-B*15: 11, India (HLA-B*15:02, Thailand (HLA-B*15: 02, and Malaysia (HLA-B*15: 02. Information related to certain HLA polymorphism is important to prevent adverse drug reaction but there is no sufficient data on the population of Indonesia.
Full Text Available AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR and to determine the causative drugs. MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study. The most common types of cutaneous ADR patterns were maculopapular rash (34.6%, fixed drug eruption (FDE (30% and urticaria (14%. The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%, anticonvulsants (22.2% and NSAIDs (18%. Anticonvulsants were implicated in 41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3% and penicillins(20%. Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations. Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.
Full Text Available INTRODUCTION There are a wide spectrum of adverse cutaneous drug reactions (ACDRs varying from transient maculopapular rash to fatal toxic epidermal necrolysis (TEN. With the advent of newer and targeted therapy in the field of dermatology, the pattern of cutaneous adverse drug eruptions and the drugs responsible for them keep changing every year. Hence, this study was undertaken to ascertain the clinical spectrum of ACDRs and the causative drugs, in a tertiary care centre in South India. MATERIALS AND METHODS This study was a prospective, observational study conducted in Department of Medical Oncology, Government Rajaji Hospital, Madurai Medical College, Madurai during the period of March 2015 - August 2015 (6 months. Severity of the reaction was assessed using CTCAE (Common Terminology Criteria for Adverse Events scale version 4.1. Causality of the drug was assessed using Naranjo Causality Assessment Scale. The scale was calculated first for the regimen and then for individual drugs separately. The adverse events with score of 6 or more (probable and definite adverse events were taken for the study. RESULTS AND CONCLUSION The overall incidence of ACDRs found in this study was 85%. Alopecia was the commonest ACDR occurring in 51.6% of patients. Nail pigmentation and supravenous pigmentation were the next common ACDRs, recorded in 35% and 16% of patients respectively. Imatinib caused generalised hypopigmentation in 40% of patients. Bleomycin induced, flagellate erythema and pigmentation in 17% of patients and stomatitis was seen in 11% of patients. Acneiform eruptions were recorded with erlotinib and gefitinib therapy. Supravenous pigmentation was common with 5-fluorouracil and docetaxel, occurring in 53% & 48% respectively. Newer targeted therapies like EGFR (Epidermal growth factor receptor inhibitors recorded low incidence of ACDRs like alopecia as against conventional antineoplastic agents. The cancer chemotherapeutic drugs are associated
Full Text Available Background: Cutaneous adverse drug reactions (CADRs may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. Aims: (a to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH and malondialdehyde (MDA levels, (b to determine the leukocyte migration inhibition (LMI response in these patients in response to the suspected drug (s, and (c to look for the association between oxidative stress parameters and LMI. Methods: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A during the acute phase of reaction and healthy control subjects (group B. MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients′ peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. Results: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001, but GSH levels were significantly reduced in group A when compared with group B (P = <0.001. LMI response against drug(s was performed in 33 cases (group A, out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25, SJS (5/25, urticaria (3/25, exfoliative dermatitis (2/25, morbilliform rash (2/25, erythroderma (1/25, vasculitis (1/25, and dapsone syndrome (1/25. The mean MDA levels were found to be significantly higher in the LMI positive
Ana Maria Abreu Velez
Full Text Available Introduction:Cutaneous drug reactions may be classified with regard to pathogenesis and clinical morphology. They may be mediated by both immunologic and non-immunologic mechanisms.Case report:A 56 year old female presented with widespread patches and macules, concentrated on her face, trunk and extremities. The lesions were pruritic, and temporally associated with intake of benzapril hydrochloride, imidapril and metformin.Methods:Biopsies for hematoxylin and eosin (H&E examination, as well as for immunohistochemistry (IHC and direct immunofluorescence (DIF analysis were performed for diagnostic purposes, and also to evaluate the lesional immune response.Results:Hematoxylin and eosin staining demonstrated a histologically unremarkable epidermis. Within the dermis, a moderately florid, superficial and deep, perivascular infiltrate of lymphocytes, plasmacytoid lymphocytes, histiocytes and rare eosinophils was identified, consistent with an allergic drug reaction. DIF demonstrated deposits of IgE, Complement/C3 and fibrinogen around dermal blood vessels. IHC demonstrated positive staining with HAM-56 and myeloid/histoid antigen in the cell infiltrate around the upper dermal blood vessels. HLA-ABC was overexpressed around those vessels, as well as around dermal sweat glands. COX-2 demonstrated positive staining in both the epidermis and upper dermis.Conclusion:Drug reactions are significant causes of skin rashes. In the current case, we were able to identify multiple antigen presenting cells in the area of the main inflammatory process. The immunologic case findings suggest that allergic drug eruptions may represent complex processes. An allergic drug reaction should be suspected whenever dermal, perivascular deposits of fibrinogen, Complement/C3 and other markers such as IgE are identified via DIF.
Dibek Misirlioglu, Emine; Guvenir, Hakan; Bahceci, Semiha; Haktanir Abul, Mehtap; Can, Demet; Usta Guc, Belgin Emine; Erkocoğlu, Mustafa; Toyran, Muge; Nacaroglu, Hikmet Tekin; Civelek, Ersoy; Buyuktiryaki, Betul; Ginis, Tayfur; Orhan, Fazil; Kocabas, Can Naci
The severe cutaneous adverse drug reactions (SCARs) are rare but could be life-threatening. These include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis. The purpose of this study was the evaluation of the clinical characteristics of patients with the diagnosis of SCARs. Patients who were diagnosed with SCARs between January 2011 and May 2016 by pediatric allergy clinics in the provinces of Ankara, Trabzon, Izmir, Adana, and Bolu were included in this multicenter study. Clinical and laboratory findings, the time between suspected drug intake and development of clinical findings, treatments they have received, and length of recovery time were recorded. Fifty-eight patients with SCARs were included in this study. The median age of the patients was 8.2 years (interquartile range, 5.25-13 years) and 50% (n = 29) were males. Diagnosis was Stevens-Johnson syndrome/TEN in 60.4% (n = 35), DRESS in 27.6% (n = 16), and acute generalized exanthematous pustulosis in 12% (n = 7) of the patients. In 93.1% of the patients, drugs were the cause of the reactions. Antibiotics ranked first among the drugs (51.7%) and antiepileptic drugs were the second (31%) most common. A patient who was diagnosed with TEN developed lagophthalmos and a patient who was diagnosed with DRESS developed secondary diabetes mellitus. Only 1 patient with the diagnosis of TEN died. SCARs in children are not common but potentially serious. Early diagnosis and appropriate treatment of SCARs will reduce the incidence of morbidity and mortality. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Full Text Available Background: Adverse cutaneous drug reactions (ACDRs are caused by a wide variety of agents. Aims: Our objective was to ascertain the clinical spectrum of ACDRs and the causative drugs in this part of India and to find any risk factors. Methods: Ninety patients with adverse cutaneous drug reactions were recruited for this study during 2001-2003. Hematological and biochemical investigations were done in all of them. The VDRL and HIV (ELISA tests were performed where the underlying risk factors were present. Patch testing, intradermal testing and oral provocation tests were done wherever feasible. Results: The mean age of the patients with cutaneous drug eruptions was 37.06 years. Most of them (52.2% were in the age group of 20-39 years. The male to female ratio was 0.87: 1. The most common eruptions observed were fixed drug eruption (31.1% and maculopapular rash (12.2%, and the most common causes were co-trimoxazole (22.2% and dapsone (17.7%. Conclusion: The pattern of ACDRs and the drugs causing them is remarkably different in our population. Knowledge of these drug eruptions, the causative drugs and the prognostic indicators is essential for the clinician.
Full Text Available We report a case of a 34-year-old woman presenting with an erythema multiforme (EM-like eruption. Lesions developed after a 12-day treatment with a slimming drug preparation (food integrator with thermogenic activity and a herbal remedy (pilosella tincture. Serological investigations excluded viral or bacterial infections. Patch testing with galenic preparations of both drugs demonstrated sensitization to the slimming drug preparation. According to literature reports and immune-chemical properties, those components that are likely to have triggered the skin eruption are clorazepate dipotassium and theobromine. Their interaction with other two constituents such as pseudoephedrine hydrochloride and dehydrocholic acid may have caused the adverse reaction by means of a summation effect. There are no reports specifically about EM caused by a slimming drug preparation and no studies have identified thermogenic pills as cause of EM/EM-like eruption. Weight-loss compounds in slimming preparations should be kept in mind as a possible cause of drug-induced EM-like eruption.
Trubiano, Jason A; Aung, Ar Kar; Nguyen, Mary; Fehily, Sasha R; Graudins, Linda; Cleland, Heather; Padiglione, Alex; Peleg, Anton Y
The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined. We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR. A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated. Copyright © 2016 American Academy of Allergy, Asthma & Immunology
Full Text Available Background: The epidemiological data based on intensive monitoring studies are limited for the cutaneous adverse drug reactions (CADRs in terms of incidence. Most of earlier Indian studies focused only on types and causative drugs of CADRs. Aim: The aim of this study is to analyze the CADRs with reference to the incidence, its subgroup analysis, causative drugs, and other clinical characteristics in Indian population. Methodology: Intensive monitoring study was carried out over a period of 3 years in the dermatology outpatient and inpatient department. CADRs due to only systematically administered drugs were considered. The WHO definition for CADR, the WHO causality definitions, modified Schumock and Thornton's criteria for preventability, and International Conference on Harmonisation E2A guidelines for seriousness were considered. Incidence was expressed in percentage and its 95% confidence interval. The incidence was analyzed on basis of characteristics of study population and CADRs. Results: A total of 171 CADRs were observed from 37,623 patients. The CADR incidence was 0.45% (95% CI: 0.39–0.53. The incidence did not significantly differ in different age groups and gender. Commonly observed CADRs were maculopapular rash (23.98%, urticaria (21.64%, and fixed drug eruptions (FDEs (18.13%. Antimicrobials (35.18% and nonsteroidal anti-inflammatory drugs (NSAIDs were suspected in all common CADRs. Anti-infective and NSAIDs were most commonly suspected drugs in overall CADRs, maculopapular rash, urticaria, FDEs, and erythema multiforme. The exact nature of drugs remained inaccessible in one-fourth cases due to use of the over-the-counter self-medications. The incidence of preventable and serious and fatal CADRs was 0.08% (95% CI: 0.05–0.11, 0.04% (95% CI: 0.02–0.06, and 0.003% (95% CI: 0.000–0.001, respectively. Conclusion: Ethnic characteristics should be considered while interpreting incidence from the international studies. The
Graudins, Linda Velta; Ly, Jenny; Trubiano, Jason; Aung, Ar Kar
To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). 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. 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. 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. © 2016 The British Pharmacological Society.
Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z
Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.
Chau Yee Ng
Full Text Available Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs, such as Stevens-Johnson syndrome (SJS and toxic epidermal necrosis (TEN with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite. Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.
Choon, Siew-Eng; Lai, Nai-Ming
The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively. The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.
Full Text Available Background: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR vary among the different populations previously studied. Aim: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN and drug rash with eosinophilia and systemic symptoms (DRESS in our population. Methods: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. Results: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases followed by SJS/TEN (110 cases and DRESS (34 cases. Antibiotics was the most commonly implicated drug group (146 cases followed by anticonvulsants (81 cases and antigout drugs (50 cases. The most frequently implicated drug was allopurinol (50 cases. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases. Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively Conclusions: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.
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.
Borch, Jacob Eli; Andersen, Klaus Ejner; Bindslev-Jensen, Carsten
2 weeks' duration. Patients were examined clinically and offered investigation for possible drug allergy, including blood tests, and skin tests when appropriate. Subsequent drug challenge tests were performed in selected cases. Finally, the history and test results were evaluated to determine...... of the case patients died within 6 months after the study period. The most common type of skin reactions were symmetrically distributed maculo-papular exanthema and eczematous eruptions. Several more rare types of skin reactions were each represented by a single case. Beta-lactam antibiotics...
Srivastava, Shivani; Ramanujam, Bhargavi; Ihtisham, Kavish; Tripathi, Manjari
Cutaneous adverse drug reaction (cADR) has limited epidemiological data in India. The older antiepileptic drugs, i.e., carbamazepine, phenytoin, valproic acid, phenobarbitone, etc., induce severe cADRs that have a strong associated with human leukocyte antigen (HLA)-related genetic risk factors. There is also evidence of association of certain HLA alleles with lamotrigine (LTG)-induced cADRs, but this has not been reported in the Indian population. Here, we report case series of three patients with LTG-induced "Stevens-Johnson syndrome (SJS)." Their HLA-B typing was also performed which showed the presence of HLA-B*15:02 in one case with SJS.
Lehman, Julia S; Gibson, Lawrence E; el-Azhary, Rokea A; Chavan, Rahul N; Hashmi, Shahrukh K; Lohse, Christine M; Flotte, Thomas J
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.
Ramani, Yerramalli Roja; Mishra, Sailen Kumar; Rath, Bandana; Rath, Saroj Sekhar
Cutaneous adverse effects to antimicrobials are a major health problem. Though majority of them are mild and self-limiting, severe variants like Steven Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) are not uncommon. Ofloxacin, a fluoroquinolone widely used for the treatment of urinary tract infections, acute bacterial diarrheas, enteric fever, STDs and other soft tissue infections either as a single drug or in combination with other drugs. Earlier a case of mucocutaneous maculopapular rash with oral ofloxacin and was reported in an adult. In the present hospital set up there were few reports of such reactions to adults. Here we report three different variants of reactions associated with oral ofloxacin in chlidren. Early detection of cutaneous lesions and immediate withdrawal of the offending drug can prevent progression of such reactions to their severe variants as well as morbidity and mortality.
Chew, Lita; Chuen, Vivianne Shih Lee
Docetaxel-based chemotherapy will remain clinically relevant and many of our patients will continue to receive the drug. In a recent phase 2 study of docetaxel 35 mg/m2 (weekly) in patients with metastatic breast cancer, the incidence of grade 3 cutaneous toxicity is 19%. The skin toxicity observed consists of limb/palmar-plantar erythematous reactions, or fixed-plaque erythrodysesthesia. Case series or reports have reported varied manifestations of skin reactions and include erythema multiforme, nail changes (onycholysis, pigmentation, paronychia), scleroderma, supravenous discoloration, radiation recall dermatitis, and flagellate erythema. We would like to report four patients with cutaneous reactions resulting from weekly administration of docetaxel. All cases are heavily pre-treated patients, receiving docetaxel as second or third line therapy. The cutaneous reactions occur at cycle 5. The time between chemotherapy to development of skin lesions is from 1 to 7 days. Lesions usually resolve with desquamation leaving behind areas with hyper-pigmentation or hypo-pigmentation over a period of 2 to 3 weeks. The management strategies include hand elevation, warm or cold compresses, topical and/or systemic antibiotics, topical and/or systemic corticosteroids, and cessation of drug. There is a need for a systematic approach to manage these cutaneous reactions. Oncology trained pharmacists play vital roles in assessing, managing, documenting and patient education.
Full Text Available Objectives: To detect cutaneous drug reactions through spontaneous reporting system in IGGMCand H, Nagpur and analyze them using standard assessment scales. Materials and Methods: An observational, prospective study was performed in patients attending dermatology OPD of IGGMC and H, Nagpur from 1 st June 05 to 31 st May 09. Patients were examined for cutaneous drug reactions (CDRs by spontaneous Adverse Drug Reaction reporting system. Results: Among 2693 total ADRs reported, 872 (33.04% were CDRs. Antimicrobials (55.5% were the main drugs involved followed by NSAIDs (18.56% and steroids (12.61%. Maculopapular rash (37.73% followed by fixed drug eruption (17.2% and urticaria (14.56% were the most frequently observed CDRs. The common drugs causing CDRs were cotrimoxazole (20.41%, topical steroids (betamethasone, ibuprofen (7.91%, ampicillin (6.54%, diclofenac (4.7% and iron dextran (3.44%. Conclusion : It was observed that commonly used drugs like antibiotics and NSAIDs lead to maximum number of CDRs. Hence strict vigilance is required while using them. This study provides a database of ADRs due to common drugs, which will help clinicians in safe use of these drugs.
Chattopadhyay, C; Chakrabarti, N
Cutaneous drug reactions are a common impediment in therapy, the incidence ranging from 2% to 8%. This cross-sectional study was designed to compare different trends of cutaneous drug reaction in two different socio-economic groups of patients in the same region. The aim was to evaluate common drugs implicated in causing reactions, describe the adverse cutaneous drug reactions, study the characteristics of patients presenting with the reactions. This is an observational study of cross-sectional type. The study was carried out in the department of Oral and Maxillofacial surgery in a Private dental College and department of General Medicine in a Medical College only on outdoor basis for 3 years. Out of 2000 patients observed in each college for their necessary treatment 75 patients in the dental College and 200 patients in the Medical College were reported to have various types of cutaneous drug reactions. Diagnosis was based on detailed history including temporal correlation between drug intake and onset of rash and thorough clinical examination Apart from history of drug intake, information regarding associated other allergy, comorbidity and severity (whether hospitalization was required or not) was recorded. Rechallenge with the drug was not possible due to ethical problem. Out of 2000 patients observed in each college 75 patients in dental College and 200 patients in Medical College were documented to have different kinds of cutaneous drug reactions. A total of 30 were male and 45 female in dental college whereas 90 male and 110 female patients were enrolled in Medical College. The age group of the patients in both the colleges ranged from 18 to 75 years. Common culprits observed in this study were antibiotics and NSAIDs. They had contributed 53% and 40% of the total skin reactions respectively in dental college and 47.5% and 45% in Medical College. We encountered 6 patients of systemic lupus erythematosus (SLE), 20 patients with allergic rhinitis and 12 patients
Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations. PMID:29445753
Full Text Available Severe cutaneous adverse reaction (SCAR is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS, acute generalized exanthematous pustulosis (AGEP, and generalized bullous fixed drug eruptions (GBFDE. In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations.
Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.
Chong, Kok Wee; Chan, Derrick W S; Cheung, Yin Bun; Ching, Leng Kee; Hie, Szu Liang; Thomas, Terrence; Ling, Simon; Tan, Ene Choo
To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7-12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses. 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.
Tempark, Therdpong; Satapornpong, Patompong; Rerknimitr, Pawinee; Nakkam, Nontaya; Saksit, Niwat; Wattanakrai, Penpun; Jantararoungtong, Thawinee; Koomdee, Napatrupron; Mahakkanukrauh, Ajanee; Tassaneeyakul, Wichittra; Suttisai, Sumitra; Pratoomwun, Jirawat; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha; Sukasem, Chonlaphat
A previous publication in Chinese leprosy patients showed that the HLA-B*13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B*13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients. HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens-Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe. The HLA-B*13:01 allele was significantly associated with dapsone-induced SCARs compared with dapsone-tolerant controls (odds ratio: 54.00, 95% confidence interval: 7.96-366.16, P=0.0001) and the general population (odds ratio: 26.11, 95% confidence interval: 7.27-93.75, P=0.0001). In addition, HLA-B*13:01 associated with dapsone-induced SJS-TEN (OR: 40.50, 95% confidence interval: 2.78-591.01, P=0.0070) and DRESS (OR: 60.75, 95% confidence interval: 7.44-496.18, P=0.0001). This study demonstrated an association between HLA-B*13:01 and dapsone-induced SCARs including Stevens-Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms in nonleprosy patients. Moreover, these results suggest that the HLA-B*13:01 allele may be a useful genetic marker for prediction of dapsone-induced SCARs in Thai and Han-Chinese populations.
Full Text Available 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.
... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...
Purpose: To build a microRNA and gene signature of severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: MicroRNA expression profiles were downloaded from miRNA expression profile of patients' skin suffering from TEN using an ...
Laurinaviciene, Rasa; Holm Sandholdt, Linda; Bygum, Anette
: To determine the proportion of patients with cutaneous lupus erythematosus (CLE) whose drugs are an inducing or aggravating factor. MATERIALS & METHODS: We conducted a retrospective chart review of patients diagnosed with CLE at a dermatological department over a 21-year period. We registered clinical......BACKGROUND: An increasing number of drugs have been linked to drug-induced subacute cutaneous lupus erythematosus (DI-SCLE). The recognition and management of DI-SCLE can be challenging, as the condition may be triggered by different classes of drugs after variable lengths of time. OBJECTIVES......, serological, and histological data with a focus on drug intake. RESULTS: Of 775 consecutive patients with a diagnosis of lupus erythematosus (LE) or suspected LE, a diagnosis of CLE could be confirmed in 448 patients. A total of 130 patients had a drug intake that could suggest DI-SCLE. In 88 cases, a drug...
Mataix, J; Silvestre, J F
Piercings and tattoos have become very popular in western society in recent decades, particularly among younger generations. Reports of medical complications associated with these decorative techniques have increased in parallel with the rise in their popularity. Due to their high frequency, adverse cutaneous reactions are particularly important among these potential complications. Tattoo-related complications include a number of cutaneous and systemic infections secondary to breach of the epidermal barrier, acute and delayed inflammatory reactions with different histopathological patterns, the appearance of benign and malignant tumors on tattooed areas of skin, and certain dermatoses triggered by isomorphic phenomena. Piercing-related complications are similar, though some, such as pyogenic skin infections, are much more common due to the delayed wound healing after piercing in certain sites. We must differentiate between complications that are independent of the site of piercing, and specific complications, which are closely related to the body area pierced. The rate of complications after performing piercings or tattoos depends on the experience of the artist, the hygiene techniques applied, and the postprocedural care by the customer. However, some of these complications are unpredictable and depend on factors intrinsic to the patient. In this article, we review the most common decorative techniques of body art, with particular focus on the potential cutaneous complications and their management.
During the last decade microdialysis has been successfully applied to assess cutaneous drug delivery of numerous substances, indicating the large potential for bioequivalence/bioavailability evaluation of topical formulations. The technique has been shown to be minimally invasive and supply...... pharmacokinetic information directly in the target organ for cutaneous drug delivery with high temporal resolution without further intervention with the tissue after implantation. However, there are a few challenges that need to be addressed before microdialysis can be regarded as a generally applicable routine...... technique for cutaneous drug delivery assessments. Firstly, the technique is currently not suitable for sampling of highly lipophilic compounds and, secondly, more studies are desirable for elucidation of the variables associated with the technique to increase reproducibility. The present literature...
Mamishi, Setareh; Fattahi, Fatemeh; Pourpak, Zahra; Aghaee, Farzaneh Mirza; Moinfar, Zeinab; Mohammadi, Mahmoud; Ashrafi, Mahmoud; Moin, Mostafa
The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates. The age of the affected children was between 2 and 11 years and they all had a history of taking barbiturates. Their symptoms started 1-3 weeks after the initiation of barbiturates, including a prodrome characterized by 2-3 days of malaise, fever, cough and anorexia, after which the skin and mucosal lesions appeared and worsened. The skin lesions varied from rash to large bullae, plus different forms of mucous membrane involvement. The offending drugs (barbiturates) were stopped immediately and care was largely supportive. As a result of the morbidity and/or mortality associated with EM, SJS and TEN, physicians should keep in mind their differential diagnosis when cutaneous reactions are observed in patients undergoing barbiturate therapy. Furthermore, although TEN and SJS are life-threatening diseases, early detection and appropriate care can lead to a decrease in the incidence of death. The strategies described here seem to be successful and safe because, despite the serious conditions, our patients responded well. All survived.
Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu
The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin
Kardaun, S. H.; Sekula, P.; Valeyrie-Allanore, L.; Liss, Y.; Chu, C. Y.; Creamer, D.; Sidoroff, A.; Naldi, L.; Mockenhaupt, M.; Roujeau, J. C.
BackgroundCases of severe drug hypersensitivity, demonstrating a variable spectrum of cutaneous and systemic involvement, are reported under various names, especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case definition and overlap with other severe cutaneous adverse
In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic compo...
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous......) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions...
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure......) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions...
In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic...... compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act...... as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure...
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions......Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous......, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure...
Marzano, Angelo V; Borghi, Alessandro; Cugno, Massimo
Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens-Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure...
Patton, K; Borshoff, D C
Adverse drug reactions are a cause of significant morbidity and mortality to patients and a source of financial burden to the healthcare system. Of the wide spectrum of adverse drug reactions, the most concerning to the anaesthetist remain anaphylaxis and malignant hyperthermia. Although the incidence of anaphylaxis under anaesthesia is difficult to ascertain, it occurs commonly enough that most anaesthetists will manage at least one case in their career. The wide range of drugs given in the peri-operative period and the variable presentation in the anaesthetised patient can delay diagnosis and treatment, and adversely affect outcome. Furthermore, despite improvements in testing, causative drugs can still be difficult to identify, as adverse reactions may be mediated by mechanisms other than IgE activation. With an increase in the reporting of anaphylaxis to newer anaesthetic drugs such as sugammadex, combined with change over the recent decades in the most likely causative peri-operative agents, it is imperative anaesthetists remain up to date on recent developments. In addition, they should be vigilant to patient characteristics, including pharmacogenetic variations that may predispose to adverse drug reactions, in order to help minimise risks of a reaction. The severity of adverse drug reactions to peri-operative drugs means morbidity and mortality remain high. © 2018 The Association of Anaesthetists of Great Britain and Ireland.
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis......) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions...
Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung
Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using
Dao, Ro-Lan; Su, Shih-Chi
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse reactions (SCAR) which are majorly caused by drugs. Though the incidence rate is low, SCAR sometimes can be life-threatening and leads to lifelong sequelae. Many pharmacogenomic associations in immune and nonimmune related genes with the development of SCAR have been discovered recently and the pharmacogenetic tests have been applied to prevent specific drug-induced SCAR. In this review, we discuss the recent advances of pharmacogenomics in SCAR. PMID:25938070
This study evaluates bullous cutaneous reactions and sequential histopathology in an individual sensitized to bed bug bites in an effort to better understand the allergic response and histology associated with these bites. There was a progression of the inflammatory response across time ranging from...
Saumita Ghosh Biswal
Full Text Available Background: The diagnosis of cutaneous adversities in the cancer patient is especially difficult, given the complexity of their illness and combination protocols used for the treatment. The present study was undertaken to know the spectrum of cutaneous adversities in patients undergoing chemotherapy and the drug(s most commonly associated with it. Materials and Methods: A total of 1000 patients with malignancies under chemotherapy in the oncology ward and outpatient department were screened in this observational study from January 2013 to February 2015. Relevant investigations for diagnosis of malignancies under chemotherapy and dermatological disorders were carried out. Results: Three hundred and eighty-four patients presented with cutaneous adversities of chemotherapy. The most common was anagen effluvium (78.6%, followed by xerosis (4.4%, thrombophlebitis (3.1%, generalised pruritus (2.9%, melanonychia (2.9%, hand-foot syndrome (2.6%, extravasation reactions (1.8%, flagellate dermatosis (1.3%, prurigo nodularis (0.8%, exfoliation (0.5%, ichthyosis (0.5%, papulopustular rash (0.3%, bullous photodermatitis (0.3%, and Sweet's syndrome (0.3%. Chemotherapeutic drugs were mostly given in combinations. Most common drugs to cause anagen effluvium were alkylating agents in combinations, hand-foot syndrome by taxanes (docetaxel, flagellate dermatoses by antitumour antibiotics (bleomycin, and exfoliation by antimetabolites (methotrexate. The limitation of this study was to imply a specific drug as the causation of the cutaneous adversities since the chemotherapy mostly consisted of combination protocols. Therefore, we have tried to associate the drug combination itself. Conclusion: Chemotherapeutic drugs produce a range of cutaneous adversities, certain specific adversities pertaining to drugs, and their combinations have been implicated which should be looked for and managed accordingly. Knowledge of the adverse effects of anticancer drugs will help
Negrini, Simone; Becquemont, Laurent
Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions. In this context, drug hypersensitivities that have more robust pharmacogenetic data include abacavir hypersensitivity syndrome and severe cutaneous adverse reactions induced by allopurinol and carbamazepine.
van der Bent, S A S; Wolkerstorfer, A; Rustemeyer, T
Tattooing involves the introduction of exogenous pigment into the dermis. Worldwide, tattoos are one of the most popular forms of permanent body art. In the Netherlands, 8-10% of the population older than 12 years old has a tattoo. A wide variety of cutaneous adverse effects can occur in tattoos, these can cause serious symptoms. However, recognition and appropriate knowledge of diagnosis and treatment is still frequently insufficient in many medical practitioners. The first case concerns a 57-year-old female, who developed an itching swelling in the red part of a tattoo on the left arm. Histology of a punch biopsy showed a pseudolymphomatous reaction. This plaque-like allergic reaction was successfully treated with intralesional injection of corticosteroids. Here we described four cases of cutaneous adverse reactions to tattoos. Allergic reactions in tattoos can present in a wide variety of clinical and histological patterns. The symptoms are often chronic itch and can appear weeks, months or years after placing the tattoo. Allergic reactions are uniformly manifested in one particular colour. Clinically, the reactions can present in a plaque-like, hyperkeratotic or rarely ulcerative or generalised reaction. In spite of changes to the compounds in tattoo inks, allergic reactions are still mostly observed to red ink. Treatment options are topical corticosteroids, intralesional injection of corticosteroids, laser treatment or dermatome shaving.
Full Text Available Rivastigmine is a cholinesterase inhibitor which improves cognitive function and is currently being used in patients with mild to moderate Parkinson's and Alzheimer's dementia. This drug can be given orally or topically, as transdermal patch. The latter form is currently used for most excellent compliance and few side effects. The most common cutaneous side effects are irritative dermatitis. We report the second case of active sensitization by the rivastigmine-patch in a patient suffering from Alzheimer's dementia.
Chung, Wen-Hung; Shih, Shin-Ru; Chang, Ching-Fen; Lin, Tzou-Yien; Huang, Yhu-Chering; Chang, Shih-Chen; Liu, Ming-Tsan; Ko, Yu-Shien; Deng, Ming-Chung; Liau, Yea-Ling; Lin, Lung-Huang; Chen, Tou-Hwei; Yang, Chih-Hsun; Ho, Hsin-Chun; Lin, Jheng-Wei; Lu, Chun-Wei; Lu, Chin-Fang; Hung, Shuen-Iu
The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.
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…
Lee, Woo Jin; Lee, Ji Hyun; Won, Chong Hyun; Chang, Sung Eun; Choi, Jee Ho; Moon, Kee Chan; Kang, Yoon-Koo; Lee, Mi Woo
Although many cases of cutaneous adverse reactions to imatinib have been reported, their clinical and histopathologic characteristics are not well documented. The present study investigated clinical and histopathologic characteristics of cutaneous adverse reactions to imatinib. This retrospective study referred to 46 patients who experienced cutaneous adverse reactions to imatinib. Clinical data including age, sex, skin lesion morphology, underlying disorders, and imatinib treatment parameters (duration of imatinib medication, initial dose, and treatment modifications at the time of the study) were collected. Histopathologic data were available for all patients. Cutaneous adverse reactions to imatinib developed at 1-24 weeks (median onset: 8 weeks) after imatinib administration. The severity of the reaction was categorized as grade 1 in 22%, grade 2 in 41%, and grade 3 in 37% of patients. Onset was earlier in high-severity reactions than in low-severity reactions. The severity of the reaction was dependent on imatinib dose. Grade 3 reactions were noted in nine of 16 (56%) patients administered "high-dose" (600 mg/d) imatinib. Spongiosis (78% of patients) and papillary dermal edema (83% of patients) were common histopathologic findings in the epidermis and dermis, respectively. Lymphohistiocytes were more predominant than eosinophils in dermal inflammatory infiltration. Histopathologic findings did not differ according to dose of imatinib or severity of the reaction. Although the clinical features of cutaneous adverse reactions to imatinib depend on imatinib dose and the severity of the reaction, histopathologic findings are not associated with these clinical variables. © 2015 The International Society of Dermatology.
Full Text Available Both immunologic and nonimmunologic drug reactions can be seen in oral mucosa. Since considerable number of these reactions heals spontaneously without being noticed by the patients, exact frequency of the lesions is unknown. Most common lesions are xerostomia, taste disorders, mucosal ulcerations and edema. In this article, oral lesions resulting from drug intake similar to those from oral lesions of local and systemic diseases, and diagnostic problems caused by these similarities, have been reviewed.
Karimzadeh, Parvaneh; Bakrani, Vahid
According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. In this descriptive study, children less than 14 years old with AED side effects referred to the Children's Medical Center and Mofid Childeren's Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions.
Carr, Daniel F; Pirmohamed, Munir
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
Zhu, Huiling; Zhu, Zhe; Huang, Weining; Cheng, Xiping; He, Jiaxi; Xiong, Chunping; Han, Jiande
This study presented common lesions with systemic toxicities and uncommon adverse cutaneous reactions such as anaphylactic dermatitis in patients undergoing treatment with erlotinib for the benefit of practicing dermatologists and oncologists. Adverse cutaneous reactions associated with erlotinib were reported in 20 Chinese patients with cancer. Adverse cutaneous reactions reported included six cases of anaphylactic dermatitis, 12 cases of acneiform rash, nine cases of xerosis, five cases of nail changes and four cases of hair changes. One case of anaphylactic dermatitis manifested as erythema with swelling on the face and neck, and others as erosive and scaly erythema on the fold of skin, or red macules, papules, plaques and pigmentation on the whole body. Clinical details indicated anaphylactic reactions, including a high percentage of eosinophils in the peripheral blood, eosinophilic infiltration in the dermis layer and good response to antihistamines and topical steroids. Systemic toxicities accompanied by cutaneous reactions occurred in five patients including one case of anaphylactic dermatitis and four cases of acneiform rash. Elevated hepatic enzymes were observed among all the patients with grade-3 or grade-4 acneiform rashes. One patient with anaphylactic dermatitis and one with acneiform rash discontinued erlotinib administration due to severe lesions, high fever or severe elevation of hepatic enzymes. Anaphylactic cutaneous reactions caused by erlotinib are rarely described hitherto. Systemic toxicities should be emphasized especially in cases with severe skin disorders. Timely detection and appropriate early intervention in patients who develop severe cutaneous reaction while on erlotinib therapy should be considered clinically.
Siripassorn, Krittaecho; Ruxrungtham, Kiat; Manosuthi, Weerawat
To evaluate the outcomes of anti-tuberculosis drug desensitization. This was a retrospective study. Inclusion criteria were as follows: age >18years, documented tuberculosis infection, a previous cutaneous allergic reaction to anti-tuberculosis drugs, and having undergone drug desensitization between January 2003 and March 2014. The definition of allergic reaction to anti-tuberculosis drugs included (1) a temporal relationship between drug use and the allergic reaction; (2) improvement in the allergic reaction after drug withdrawal; (3) recurrence of the allergic reaction after reintroduction of only the offending drug; and (4) absence of other causes. A total of 19 desensitization procedures were performed. The drugs used for these procedures were isoniazid (n=7), rifampicin (n=6), or ethambutol (n=6). Of note, severe allergic reactions (Stevens-Johnson syndrome (n=4), erythema multiforme (n=3), and drug rash with eosinophilia and systemic syndrome (n=1)) were included. All patients underwent resolution of the previous allergic reactions before desensitization. The median duration of desensitization was 18 days. The success rate was 78.9%. The allergic reactions following failed desensitization were not severe; most were maculopapular rashes. The desensitization protocol for anti-tuberculosis drugs was associated with a high success rate, and the individuals who failed desensitization experienced mild allergic reactions. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M
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.
Full Text Available Introduction: Little is known about the incidence and causes of heparin-induced skin lesions. The most commonly reported causes are delayed-type hypersensitivity reactions. We describe 3 patients who were referred to our staff between March and October 2009 for suspected heparin allergies. All were scheduled to undergo major surgery (cardiovascular or orthopedic. Materials and methods: All 3 patients reported the development of itchy, erythematous rashes a few days after the subcutaneous administration of heparin (nadroparin calcium in cases 1 and 2, unspecified in case 3. Each of them underwent a diagnostic work-up for heparin allergy, which included prick and intradermal tests with commonly used heparins and patch testing with undiluted heparins and disinfectants. Results: Patch tests with disinfectants were negative in all 3 cases. In case 2, all allergological tests were negative. In cases 1 and 3, delayed positivity emerged for nadroparin calcium and at least one other heparin tested. Intravenous and/or subcutaneous provocation testing was done with an alternative heparin which produced negative results in skin tests (heparin sodium in case 1, pentasaccharide fondaparinux in case 3. In both cases the alternative drug was tolerated. After our evaluation, all 3 patients underwent surgery with no heparin-related complications. Discussion: The presenting clinical features in these 3 cases provided no information on which reactions were likely to be allergic: all 3 patients presented with similar local delayed reaction. The allergic reactions were identified only after cutaneous testing.
Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan
the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened...... for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical...... most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0...
Pavlos, Rebecca; Mallal, Simon; Ostrov, David; Pompeu, Yuri; Phillips, Elizabeth
Drug hypersensitivity syndromes such as abacavir hypersensitivity and the severe cutaneous adverse drug reactions have been associated with significant short- and long-term morbidity and mortality. More recently, these immunologically mediated and previously unpredictable diseases have been shown to be associated with primarily class I but also class II HLA alleles. The case of the association of HLA-B*57:01 and abacavir hypersensitivity has created a translational roadmap for how this knowledge can be used in the clinic to prevent severe reactions. Although many hurdles exist to the widespread translation of such HLA screening approaches, our understanding of how drugs interact with the major histocompatibility complex has contributed to the discovery of new models that have provided considerable insights into the immunopathogenesis of severe cutaneous adverse drug reactions and other T-cell-mediated drug hypersensitivity syndromes. Future translation of this knowledge will facilitate the development of preclinical toxicity screening to significantly improve efficacy and safety of drug development and design. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan; Dirksen, Asger; Elberling, Jesper
Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. The aetiology is unknown, but chemical related respiratory symptoms have been found associated with positive patch test. The purpose of this study was to investigate the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical sensitivity. Associations were controlled for the possible confounding effects of sex, age, asthma, eczema, atopic dermatitis, psychological and social factors, and smoking habits. In unadjusted analyses we found associations between allergic and non-allergic cutaneous reactions on patch testing and the two most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0.006). Our results suggest that individuals with self-reported chemical sensitivity show increased non-allergic cutaneous reactions based on day 2 readings of patch tests. Copyright © 2011 Elsevier GmbH. All rights reserved.
Full Text Available Nuclear, biological and chemical warfare have in recent times been responsible for an increasing number of otherwise rare dermatoses. Many nations are now maintaining overt and clandestine stockpiles of such arsenal. With increasing terrorist threats, these agents of mass destruction pose a risk to the civilian population. Nuclear and chemical attacks manifest immediately while biological attacks manifest later. Chemical and biological attacks pose a significant risk to the attending medical personnel. The large scale of anticipated casualties in the event of such an occurrence would need the expertise of all physicians, including dermatologists, both military and civilian. Dermatologists are uniquely qualified in this respect. This article aims at presenting a review of the cutaneous manifestations in nuclear, chemical and biological warfare and their management.
Dervis, Emine; Ayer, Mesut; Akin Belli, Asli; Barut, Saime Gul
Imatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Cutaneous adverse reactions of imatinib therapy have been reported in 7%-88.9% patients. We sought to evaluate the prevalence rates of cutaneous adverse reactions of imatinib therapy and to investigate the clinical and pathological characteristics of these reactions. Sixty-six patients (36 men, 30 women; age range 19-83 years) with CML treated with imatinib between 2008 and 2014 were included in the study. Clinical and pathological features of the adverse reactions were investigated. Cutaneous adverse reactions were the most common adverse effects of imatinib therapy and were seen in nine patients with a prevalence rate of 13.6%. The second most common adverse effect was musculoskeletal pain (12.1%). The following cutaneous reactions were observed in patients: edema, rash, pigmentary changes, aphthous stomatitis, alopecia, cutaneous dryness, hyperhidrosis and cheilitis. Imatinib therapy was discontinued in four patients because of various adverse effects. Although the prevalence rate of cutaneous adverse reactions in our study was lower than that in several other studies, cutaneous reactions were common in our study. The relatively low prevalence rate of adverse reactions may be related to the low dosage of imatinib (400 mg/day) used to treat our patients and may have been affected by pharmacogenetic characteristics of our population.
Background: Adverse food reactions (AFR) in dogs are reactions to apparently harmless food antigens, with an unknown etiology i.e. immunopathogenesis. In the majority of dogs with AFR, the signs are only associated with the skin (CAFR). Despite the entry of food allergens via the intestinal tract,
Full Text Available Background: Differentiation of cutaneous tuberculosis from other infective granulomas of the skin is difficult due to paucity of the organisms in tissue biopsies. Polymerase chain reaction (PCR is a newer technique to identify the DNA of Mycobacterium tuberculosis in the tissues. Aim: We examined the utility of PCR as a tool for rapid diagnosis of cutaneous tuberculosis especially in cases negative by ZN staining and culture. Material and Methods: Twenty five random skin biopsies from patients with various types of cutaneous tuberculosis were subjected to PCR. Results: An overall positivity of 64% was observed, which is comparable to other series. Seventy five percent of lupus vulgaris cases, 62.2% of tuberculosis verrucosa cutis and 50% of scrofuloderma cases showed PCR positivity. Conclusion: Though useful, the cost and the technique involved limit the use of PCR in developing countries like ours.
Cohen, Philip R
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.
Stracke, Frank; Schneider, Marc; Weiss, Barbara; Lehr, Claus-Michael; Schäfer, Ulrich F.; König, Karsten
The trans-cutaneous pathway for drug delivery is of particular interest since it allows a simple and non-invasive administration of pharmaceutically relevant compounds. As the skin is an effective barrier for many of these compounds, various strategies have been developed to enable and control the trans-cutaneous transport. Here we discuss, how multiphoton microscopy and spectral imaging can be valuable tools for the analysis of the penetration pathways of topically applied drugs. A time dependent study of the cutaneous penetration of a fluorescent drug model released from a nano-particular carrier is presented. The localization of single nano-particles in human skin (ex vivo) and the discrimination of different fluorescent compounds, as the drug model, the particle's label and the cutaneous endofluorescence by spectral imaging and selective excitation is shown. Multiphoton imaging techniques were found to be excellent methods for the non-invasive evaluation of cutaneous drug delivery strategies and analysis of dermal penetration pathways down to the sub-cellular level.
Full Text Available Adverse drug reactions (ADRs remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs, such as Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01. The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI. In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.
The need for systematic follow up of medicines for adverse drug reactions once they are introduced into general use has been widely recognised today. Even in developing countries like India, national pharmacovigilance programme has been started for monitoring adverse drug reactions. In its first year this program mainly aimed to foster the culture of ADR notification among health care professionals. As a part of health care team every pharmacist must have knowledge about adverse drug reaction...
Adibi, N.; Faghihimani, E.; Mirbagher, L.; Sohrabi, H.; Toghiani, A.
Objective: The most commonly reported side effects of salsalate are gastrointestinal events, and few reports are available on its cutaneous side effects. We therefore assessed cutaneous side effects among diabetic/pre-diabetic patients treated with salsalate. Methodology: In a randomized placebo-controlled trial, we evaluated cutaneous side effects in 52 diabetic and 124 pre-diabetic patients, 90 of whom received 3 g/day salsalate and 86 of whom receive a placebo for four weeks. The evaluation was carried out every week using a checklist completed by a single general practitioner. Results: The difference between the salsalate- and placebo-treated groups in overall prevalence of cutaneous reactions was not significant (26.7% versus 17.4%; P < 0.05). Side effects included urticaria (nine (10.1%) salsalate-treated versus six (6.9%) placebo-treated), rashes (five (5.5%) salsalate-treated versus three (3.4%) placebo-treated), pruritus (six (6.7%) salsalate-treated versus three (3.4%) placebo-treated), and edema (two (2.2%) salsalate-treated versus one (1.2%) placebo-treated); in addition, one (1.1%) case of erythema nodosum and one (1.1%) of vasculitis were observed in the salsalate-treated group. In the salsalate group, therapy was discontinued by the physician for three (3.3%) patients because of acute and severe vasculitis, erythema nodosum and urticaria and two (2.2%) patients stopped the treatment themselves because of mild urticaria compared with two patients who stopped using the placebo. Conclusions: Salsalate can cause several and, in some cases, severe cutaneous side effects in patients with diabetes/pre-diabetes. Because these cutaneous eruptions can raise various concerns, including patient non-compliance, greater attention should be paid to dermatological problems in patients under salsalate treatment. (author)
Full Text Available Neil Brickel,1 Haris Shaikh,1 Andrew Kirkham,2 Greg Davies,1 Michelle Chalker,1 Pascal Yoshida3 1Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Uxbridge, Middlesex, UK; 2Classic and Established Products, GlaxoSmithKline, Brentford, Middlesex, UK; 3Clinical Safety and Post-marketing Surveillance, GlaxoSmithKline KK, Tokyo, Japan Abstract: Pharmacovigilance presents many challenges, particularly when managing unpredictable, rare conditions, eg, severe cutaneous adverse reactions (SCARs. Such rare events are often only detected from spontaneous reports, which present their own limitations, particularly during a prolonged global launch schedule. GlaxoSmithKline’s routine pharmacovigilance includes regular reviews of global adverse event (AE reports and aggregate data from a central safety database. Lamotrigine is one of the several antiepileptic drugs associated with SCARs. After identification of increased rates of fatal SCAR cases with lamotrigine in Japan between September and December 2014, this analysis investigated the global incidence of fatal SCARs with lamotrigine and explored whether known risk factors may have contributed to these cases. Global fatal SCAR cases reported with lamotrigine administration from launch until January 2015 were reviewed for evidence of temporal association with dosing and the presence of risk factors, including comorbidities, concomitant medications, and noncompliance with the prescribing information (PI. Worldwide, the estimated cumulative exposure to lamotrigine was >8.4 million patient-years. Globally, there were 54,513 AE reports for lamotrigine, of which 3,454 (6.3% concerned SCARs. Of these, 122 (3.5% had a fatal outcome (attributable and nonattributable to lamotrigine, equating to 0.01 fatal SCARs per 1,000 patient-years. In Japan (estimated cumulative exposure 141,000 patient-years, 17 fatal SCARs were reported (attributable and nonattributable, equating to 0.12 per 1,000 patient
Salami, T A T; Asalu, A F; Samuel, S O
Adverse cutaneous drug eruptions are dreaded complication of drug use and this is more so when it occurs in the setting of human immune virus (HIV) infection and acquired immune deficiency syndrome (AIDS). This study aims to look at the prevalence of cutaneous drug eruptions in adult Nigerians with HIV/AIDS and find out the etiological agents, outcome, and prognosis of such occurrence in Irrua Specialist Teaching Hospital, Irrua Edo State Nigeria. A retrospective study of cutaneous drug eruptions in patients with HIV/AIDS managed in this centre over the past five years (between January 2001 and December 2005 prior to initiation of antiretroviral therapy) was carried out. A total of 900 patients with HIV/AIDS were managed during this period (antiretroviral treatment was not available during this period). Twenty five of these patients (2.8%) not had cutaneous drug eruptions (2.8%). Erythema multiforme major or Steven Johnson Syndrome (SJS)-40% and Toxic epidermal necrolysis (TEN)-20% were the most frequent types of adverse cutaneous drug events found while combination antituberculosis agent of Isoniazid/Thiacethazone (64%) and anti malarial Sulphadoxine/Pyrimethamine (20%) were the notable culprit drugs found to be responsible for these. There was a 20% fatality rate. Treatment of tuberculosis which is the most common AIDS presenting illness with anti tuberculosis regimen that includes thiacethazone and the ready availability of anti malarials over the counter without prescription are responsible for the findings of this study. Avoiding drugs such as those found to be culprit agents in this study in patients with HIV/AIDS; right prescription practice by health practitioners as well as more intense health education of the public on the hazards of self prescription will all go a long way in minimising the occurrence of these events.
de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa
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.
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.
Larsen, Jesper; Cornett, Claus; Jaroszewski, Jerzy Witold
The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR...
Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A
Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. © 2013 The British Pharmacological Society.
Aagaard, Lise; Nielsen, Lars Hougaard; Hansen, Ebba Holme
BACKGROUND: Reporting adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. Since 2003 in Denmark, consumers have been able to report ADRs directly to the authorities. The objective of this study was to compare ADRs reported by consumers with ADRs...... be actively included in systematic drug surveillance systems, including clinical settings, and their reports should be taken as seriously as reports from other sources....
Full Text Available Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs induced by this class of medicinal products seems necessary.Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3% patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5% and the lowest rate with Atenolol (3%. Headache was the most frequent detected ADR (23%. Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05. ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05. With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05. Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.
Minciullo, Paola Lucia; Allegra, Alessandro; D'Angelo, Anna; Musolino, Caterina; Gangemi, Sebastiano
Bisphosphonates are a commonly used class of drugs with known efficacy in the prevention and treatment of postmenopausal and steroid-induced osteoporosis, Paget's disease of bone, hypercaelcemia of malignancy, osteolytic lesions of multiple myeloma, and bone metastases. Nitrogen-containing bisphosphonates have a favourable tolerability and safety profile, cutaneous reactions have been reported. This is a retrospective case series study, based on the analysis of data from 1429 patients admitted to the Allergy and Clinical Immunology Division of the University of Messina between January 2011 and December 2012. Most patients had previous adverse drug reactions (ADRs) and referred to us for a challenge test with an alternative drug. We observed six patients with a past history of adverse drug reaction who needed to be tested for bisphosphonates: three patients for risedronate, two for clodronate and one for alendronate. In two years only two patients were referred to us for an adverse reaction to bisphosphonates: one to alendronate and one to risedronate. Another patient presented a previous reaction to strontium ranelate. The other three patients reported previous hypersensitivity reactions to at least two different classes of drugs. All the patients experienced no reaction using the tested drugs. In our experience drug challenge tests for bisphosphonates are safe and reliable. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.
Bouvy, Jacoline C; De Bruin, Marie L; Koopmanschap, Marc A
Adverse drug reactions (ADRs) cause considerable mortality and morbidity but no recent reviews are currently available for the European region. Therefore, we performed a review of all epidemiological studies quantifying ADRs in a European setting that were published between 1 January 2000 and 3...... regarding the epidemiology of ADRs in this setting....
Koch, Lukas; Kränke, Birger; Aberer, Werner
To present information on the frequency of drug-drug interactions and adverse drug reactions, and to provide assistance on how to minimize these major problems in the pharmacological treatment of dermatological inpatients. The medications given to 1,099 dermatological inpatients were retrospectively analyzed for drug-drug interactions and adverse drug reactions using web-based drug interaction software (Diagnosia ® Check). We report an overall frequency of relevant drug-drug interactions of 51.7 %, with an average of 3.2 interactions per affected inpatient. Drug combinations that should have been avoided were found in 5.7 % of the study population. Total drug count was the most important risk factor. Drug groups involved in the majority of interactions were analgesics, cardiovascular and antithrombotic agents, as well as antidepressants. The risk of developing adverse drug reactions was rated as "high" in 53.1 % of inpatients. The top five adverse reactions in this patient group were bleeding, constipation, anticholinergic effects, sedation, and orthostatic effects. Potential drug-drug interactions as well as adverse drug reactions are alarmingly common in dermatological inpatients. Every other patient is at risk of experiencing such interactions or adverse reactions, and every twentieth patient receives a drug combination that should not be administered. Increased alertness is a must in order to identify patients at risk. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V
Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology. Copyright © 2015 Elsevier Inc. All rights reserved.
Muthu S Kumaran
Full Text Available 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.
Kumaran, Muthu S; Narang, Tarun; Jitendriya, Madhukara; Tirumale, Rajalakshmi; Manjunath, Suraj; Savio, Jayanthi
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.
Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Hernández, José L; Pina, Trinitario; González-Vela, María C; Fernández-Llaca, Héctor; Calvo-Río, Vanesa; Loricera, Javier; Armesto, Susana; González-López, Marcos A; Rueda-Gotor, Javier; González-Gay, Miguel A
The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides defined drug-associated immune complex vasculitis as a distinct entity included within the category of vasculitis associated with probable etiology. In the present study we assessed the clinical spectrum of patients with drug-associated cutaneous vasculitis (DACV). Case records were reviewed of patients with DACV treated at a tertiary referral hospital over a 36-year period. A diagnosis of DACV was considered if the drug was taken within a week before the onset of the disease. From a series of 773 unselected cutaneous vasculitis cases, 239 patients (30.9%; 133 men and 106 women; mean age 36 yrs) were diagnosed with DACV. Antibiotics (n=149; 62.3%), mainly β-lactams and nonsteroidal antiinflammatory drugs (NSAID; n=24; 10%) were the most common drugs. Besides skin lesions (100%), the most common clinical features were joint (51%) and gastrointestinal (38.1%) manifestations, nephropathy (34.7%), and fever (23.8%). The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). Despite drug discontinuation and bed rest, 108 patients (45.2%) required medical treatment, mainly corticosteroids (n=71) or immunosuppressive drugs (n=7). After a median followup of 5 months, relapses occurred in 18.4% of patients, and persistent microhematuria or renal insufficiency in 3.3% and 5%, respectively. DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.
The Medicines Control Authority of Zimbabwe monitors reactions to medicines through the Adverse Drugs Reactions Surveillance System. The system relies on health professionals to report adverse drug reactions to maximize patient safety. We report results of an evaluation of the Adverse Drugs Reactions Surveillance ...
Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS or drug-induced hypersensitivity syndrome (DIHS involves a unique and severe adverse drug reaction. Patients present with fever, rash, lymphadenopathy, hematological abnormalities, systemic illness, and may suffer from prolonged courses. Although the precise pathogenesis of DRESS/DIHS is not fully understood, it is widely considered to be an immunological reaction to a drug or drug metabolites. In this review article, we discuss the historical aspects of nosology, variable clinical and histopathological features, advantages and disadvantages of using an international Registry of Severe Cutaneous Adverse Reactions (RegiSCAR and Japanese DIHS criteria, pathogenesis, treatment, and long-term sequelae of DRESS/DIHS. Early recognition of this syndrome, withdrawal of suspected culprit drugs, and adequate supportive care are mainstays of improving patient prognosis and reducing morbidities and mortality. Moreover, some DRESS/DIHS patients may develop long-term sequelae, especially autoimmune diseases and end organ failure. Physicians should be aware of these possibilities in patients after DRESS/DIHS and cautiously follow-up symptoms and laboratory tests for early detection of these sequelae.
Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective: The intent of the study was to rank ADRs according to severity. Methods: We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results: There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions: ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.
Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel; Altman, Russ B
There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. The intent of the study was to rank ADRs according to severity. We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.
Common adverse drug reactions with psychiatric medications and an approach to their management: Adverse drug reactions are as important in psychiatric practice as they are in any other branch of medicine.
Ugburo, A O; Ilombu, C A; Temiye, E O; Fadeyibi, I O; Akinolai, O I
Lyells syndrome also called Toxic epidermal necrolysis is the extreme form of idiosyncratic drug reaction that is called Steven Johnsons Syndrome: The condition results in an extensive loss of the skin with mucous membrane involvement. Lyells syndrome has been induced by many agents. The commonest agent in the literature being sulphonamides. However, in our search of the medical literature there was no report of dihydroarthemisinin as a cause of Lyells syndrome. We report three patients seen at two tertiary health institutions with Lyells syndrome after treatment for malaria with dihydroarthemisinin. This resulted from administration of dihydroarthemisinin with chloroquine in two patients and dihydroarthemisinin with Amodiaquine in one patient. The first patient was a seven year old child who developed 90% cutaneous involvement and died from hemorrhagic shock. The second was a 28 old female that developed a 76% body surface involvement and died from septicemia. The third patient was a pregnant 37 year old woman that developed 52% body involvement and died from septic shock. In these patients the earliest symptoms were not recognized and there was considerable delay before referral. In view of the recent WHO recommendation ofArthemisinin Combination Treatment (ACT) for malaria, we expect more cases of Steven Johnson Syndrome and Lyells syndrome from ACT treatment. The aim of this report is to raise the awareness of clinicians to this potentially fatal complication.
Jan 24, 2018 ... Hyperglycemia is one of the severe adverse drug reactions (ADRs) in cancer treatment. The aim was to analyze the blood glucose‑related ADR of ... can be suggested. Keywords: Adverse drug reaction, antineoplastic, hyperglycemia, pancreatic cancer, VigiBase. Glycaemic Adverse Drug Reactions from ...
Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves
A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.
Full Text Available Background: In India, hydrogen cyanamide (Dormex ® is a plant growth regulator used mainly for the bud-breaking of grapevines. The use of this chemical may result in severe cutaneous reactions simulating erythema multiforme (EM, Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN. Methods: Studies were conducted on four seasonal grapevine workers who developed severe cutaneous reactions following the unprotected use of Dormex ® (hydrogen cyanamide. Results: Two of the patients had EM-like skin lesions and the other two developed SJS-TEN-like skin lesions. A latent period of 5-7 days existed between the contact with the chemical and the development of the skin lesions. The histopathological picture was suggestive of EM. All the patients responded to systemic steroids and antihistamines. Conclusions: Hydrogen cyanamide may act as a hapten, initiating cytotoxic immunological attack on keratinocytes, resulting in EM- and SJS-TEN-like clinical picture. Awareness regarding such severe cutaneous reactions due to the inappropriate handling of Dormex ® is required. The use of personal protection equipments while handling agricultural chemicals is essential.
R.J.J. Troost (Roger)
textabstractThis thesis is about the application of immunological insights and techniques to improve diagnosis, treatment and follow-up of inflammatory skin diseases, like allergic contact dermatitis (ACD) and allergic drug eruptions (ADE). The cells and mediators involved in cutaneous inflammation,
Kreilgaard, Mads; Kemme, M J; Burggraaf, J
The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method....
Full Text Available Abstract Many medicines are prescribed to the paediatric population on an unlicensed or 'off-label' basis because they have not been adequately tested and/or formulated and authorized for use in appropriate paediatric age groups. Regulatory authorities also need to remind health professionals about the importance of their contribution towards the process of paediatric pharmacovigilance thanks to their reporting of adverse drug reactions. The lack of reliable data in the paediatric population is associated with specific problems including: limited availability of safety data due to the lack of clinical trials in the paediatric population; under- or over-dosing in some age groups due to the lack of pharmacokinetics data or dose-finding studies; maturation, growth and development of the paediatric population susceptible to drug-induced growth and development disorders as well as to delayed ADRs not findable in adults. Pre-marketing trials are able to provide information about the benefits of drugs but do not manage to establish a safety profile. Spontaneous reporting of suspected ADRs become an important means to promote reasonable warning signs. Therefore some ADRs may be known in their qualitative aspect and quantitative aspect only after successful marketing and use in the population during a "normal" use. When the drug is used in clinical practice in large unselected populations, epidemiological post-marketing studies are useful as they find their major confirmation in recalling all the events that occur during monitoring, with estimates of incidence of ADRs that can not be obtained by spontaneous reports. In these studies a significant role can be played by the Family Pediatricians with the participation to active pharmacovigilance projects.
Barreira, Rebeca Iglesias; García, Belén Bardán; López, Mónica Granero; Legazpi, Iria Rodríguez; Díaz, Hortensia Álvarez; Penín, Isaura Rodríguez
To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.
Shimakura, Hidekatsu; Uchiyama, Jumpei; Saito, Taku; Miyaji, Kazuki; Fujimura, Masato; Masuda, Kenichi; Okamoto, Noriaki; DeBoer, Douglas J; Sakaguchi, Masahiro
Dogs with cutaneous adverse food reactions (CAFR) often have specific IgE to food allergens. Egg white, which is majorly composed of ovomucoid, ovalbumin, ovotransferrin, and lysozyme, is a food allergen in dogs. Information of the IgE reactivity to purified egg white allergens supports accurate diagnosis and efficiency treatment in humans. However, to the best of our knowledge, there have been no studies on the IgE reactivity to purified egg white allergens in dogs. Here, we investigated the IgE reactivity to crude and purified allergens of hen egg white in dogs with CAFR. First, when we examined serum samples from 82 dogs with CAFR for specific IgE to crude egg white by ELISA, 9.8% (8/82) of the dogs with CAFR showed the IgE reactivity to crude egg white. We then used sera from the eight dogs with positive IgE reactivity to crude egg white to examine the IgE reactivity to four purified allergens, ovomucoid, ovalbumin, ovotransferrin, and lysozyme, by ELISA. We found that 75% (6/8) of the dogs showed IgE reactivity to both ovomucoid and ovalbumin, and that 37.5% (3/8) of the dogs showed IgE reactivity to ovotransferrin. None (0/8) showed IgE reactivity to lysozyme. Moreover, validating these results, the immunoblot analyses were performed using the sera of the three dogs showing the highest IgE reactivity to crude egg white. Both anti-ovomucoid and anti-ovalbumin IgE were detected in the sera of these dogs, while anti-ovotransferrin IgE was not detected. Considering these, ovomucoid and ovalbumin appears to be the major egg white allergens in dogs with CAFR. Copyright © 2016 Elsevier B.V. All rights reserved.
Zurita-Garaicoechea, Ana; Reis-Carvalho, Joana; Ripa-Aisa, Irantzu; Jiménez-Mendoza, Ana; Díaz-Balén, Almudena; Oroviogoicoechea, Cristina
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.
Ram Chandra Adhikari
Full Text Available ABSTRACTLeishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus Leishmania, and transmitted by a bite of infected female sandfly. Primary cutaneous leishmaniasis is not common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety of skin diseases, inflammatory like impetigo, eczema, or granulomatous like sarcoidosis, lupus vulgaris, to skin tumor like basal cell carcinoma & squamous cell carcinoma. There are various procedures and laboratory techniques used to diagnose leishmaniasis. Punch skin biopsy is widely used & popular technique to diagnose cutaneous leishmaniasis. Different drugs like sodium stibogluconate, sodium antimony gluconate, Amphotericin B and Miltefosine: are used for its treatment. No vaccines are available for prevention.
Background: Spontaneous adverse drug reaction reporting is the most widely used and cost effective method of monitoring the safety of drugs. This method is heavily afflicted by underreporting by healthcare professionals. The study aims at assessing adverse drug reaction (ADR) reporting rate by doctors, knowledge of the ...
Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung
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 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 contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.
Andresen, K; Gaafar, A; El-Hassan, A M
We have compared the sensitivity of the polymerase chain reaction (PCR) as a diagnostic tool against conventional microscopical diagnostic techniques in patients with cutaneous leishmaniasis from the Sudan. Twenty-eight patients were diagnosed according to clinical criteria followed......%, respectively. The PCR should be considered as a valuable and sensitive diagnostic tool in the diagnosis of cutaneous leishmaniasis; it has the added advantage of identification of the species of Leishmania causing the lesion....
Full Text Available Taxanos são drogas quimioterápicas cada vez mais utilizadas no tratamento adjuvante de um grande número de cânceres, principalmente câncer de mama e de pulmão. Os efeitos colaterais não cutâneos mais importantes e limitantes do uso destas drogas são neutropenia e mucosite. Os efeitos colaterais cutäneos, além de muito frequente, interfere de forma importante na qualidade de vida dos doentes. Não existem tratamentos totalmente eficazes, mas algumas orientações podem diminuir os sintomas e prevenir recidivas em novas sessões de quimioterapiaChemotherapy with taxanes has recently become part of the treatment for many advanced neoplastic diseases, specially breast and lung cancer. Their main noncutaneous adverse reactions include neutropenia and mucositis, which eventually lead to drug discontinuation. Cutaneous adverse reactions are frequent and significantly interfere with the patient's quality of life. Treatments are poorly effective, but special recommendations may improve symptoms and prevent relapses requiring drug rechallenge
Golembiewski, Julie A
Clinically, one must be able to differentiate between an allergic reaction and an adverse reaction. Clinical manifestations of allergic reactions range from urticaria and rash to bronchoconstriction, laryngeal edema, hematologic disorders, and other serious reactions. Many drugs administered in the perioperative setting can cause allergic reactions. Antibiotics such as penicillins, beta-lactam antibiotics, and sulfonamides are the most common class of drugs that produce allergic reactions. A detailed allergy history is important when deciding if a patient can receive a drug that may cross-react (eg, a cephalosporin in a patient with a penicillin allergy). Vancomycin can cause a reaction that ranges from erythema and pruritus to clinically significant hypotension. Proper dilution and rate of administration are essential in minimizing the histamine from vancomycin that is thought to produce this reaction. "Sulfa allergy" describes an allergy to sulfonamide antibiotics; a patient with a "sulfa allergy" is not allergic to drugs containing sulfur, sulfites, or sulfates. Although true allergic reactions to opioids are rare, naturally occurring compounds like morphine and codeine can cause allergic reactions. After stopping the offending drug, mild allergic reactions can be managed with diphenhydramine, with or without a steroid. Significant allergic reactions require more aggressive management with oxygen, intravenous fluids, epinephrine, and histamine blockers. Copyright 2002 by American Society of PeriAnesthesia Nurses.
Background : Adverse drug reactions, (ADRs), constitute an important cause of morbidity and mortality worldwide. Spontaneous adverse drug reaction (ADR) reporting is the bedrock of post-marketing surveillance but under-reporting remains its major drawback. Objectives : This study aimed at evaluating the attitude and ...
Background: Antiretrovirals have been associated with serious adverse drug reactions. Several factors have been suggested as independent risk factors for their development. Identification of these factors may help in prevention and management of the adverse drug reactions. Objective: To describe the factors associated ...
Background: There has been an increased access to anti-retrovirals in resourceconstrained settings. However, few studies have addressed the area of adverse drug reactions in these settings. Objective: To determine the prevalence of adverse drugs reactions in HIV-infected persons receiving anti-retrovirals. Design: A ...
I O Fadeyibi
Full Text Available Introduction: Idiosyncratic drug reactions (IDRs are unexpected responses to a drug. The spectrums of severe cutaneous reactions include Stevens-Johnson Syndrome (SJS, SJS/Lyell Syndrome and Toxic Epidermal Necrolysis (TEN. The conditions are associated with high mortality. This study was designed to determine the causal agents, patterns of presentations, review the management and make recommendations to reduce the incidence and mortality of this class of drug reactions. Materials and Methods: A retrospective study was made of patients seen with IDR in the Lagos State University Teaching Hospital, LASUTH, between January, 2004 and December, 2008. They were cases admitted with bullous skin eruptions with associated systemic symptoms. Results: Sixty-seven patients were seen, with 45 (67.2% satisfying the inclusion criteria. Fifteen males and 30 females were involved, giving a male to female (M:F ratio of 1:2. Their ages ranged from 7 to 79 years (mean, 40.02 ± 17.89 years. Peak incidences occurred among the 20-24 and 30-34 year age groups. The causal agents were antibiotics (48.89%, sulphonamides (24.44%, herbal preparations (17.78% and artemisinin drugs (8.89%. Conclusions: The age groups with the peak incidence are the most likely to indulge more in drug abuse in environments with poor drug control. Diagnosis of SJS, SJS/TEN and TEN were missed in many patients at first contact due to the progressive nature of the conditions. Patients needed reviews at regular intervals when IDR was suspected. Health education to prevent drug abuse is important and herbal preparations should be scientifically studied to determine the efficacy and side-effects.
Wenande, Emily; Erlendsson, Andrés Már; Haedersdal, Merete
lesions, scars, cutaneous infections, and vitiligo as well as for topical anesthetic and aesthetic procedures. Substantiated by randomized controlled clinical trials, strong evidence is available for LADD's usefulness for photodynamic therapy (PDT), for which improved efficacy using laser...
Full Text Available 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.
Iammatteo, Melissa; Ferastraoaru, Denisa; Koransky, Rebecca; Alvarez-Arango, Santiago; Thota, Niharika; Akenroye, Ayobami; Jerschow, Elina
Graded challenges are performed to exclude hypersensitivity reactions in patients with a low likelihood of drug allergy. Literature regarding optimal protocols with a defined number of steps and use of placebo is lacking. To identify allergic drug reactions (ADRs) through a 3-step protocol composed of placebo followed by a 2-step graded drug challenge. We performed a 5-year retrospective chart review of all patients with historical ADRs who underwent single-blind, placebo-controlled graded drug challenges between October 2010 and November 2015 at an outpatient drug allergy clinic. Patients' demographic characteristics and description of historical reaction were obtained. Outcomes of challenges to drug versus placebo were compared by drug class. Two hundred twenty-nine patients underwent at least 1 single-blind placebo-controlled graded challenge. The most commonly challenged drug class was beta-lactams (70.8%) followed by nonsteroidal anti-inflammatory drugs (17.5%). The reaction rate to drug and placebo was similar during beta-lactam challenges (9.4% vs 8.2%; P = .9) and during nonsteroidal anti-inflammatory drug challenges (14% vs 7%, P = .5), respectively. Only 10 patients (4.4%) had objective findings during drug challenges. Patients who reacted to placebo before beta-lactam challenges had an increased number of drug allergies (4.3 ± 1.0) compared with nonreactors (2.4 ± 0.1) and to beta-lactam reactors (3.3 ± 0.7) (P = .002). All placebo reactors were female (20 of 183 vs 0 of 46 males; P = .02). Two-step graded challenges are safe in appropriately selected patients with a low risk of reaction. Placebo should be considered to reduce false-positive results, especially in females and in patients with multiple drug allergies. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Andresen, K; Gaafar, A; El-Hassan, A M
We have compared the sensitivity of the polymerase chain reaction (PCR) as a diagnostic tool against conventional microscopical diagnostic techniques in patients with cutaneous leishmaniasis from the Sudan. Twenty-eight patients were diagnosed according to clinical criteria followed by microscopi......We have compared the sensitivity of the polymerase chain reaction (PCR) as a diagnostic tool against conventional microscopical diagnostic techniques in patients with cutaneous leishmaniasis from the Sudan. Twenty-eight patients were diagnosed according to clinical criteria followed......%, respectively. The PCR should be considered as a valuable and sensitive diagnostic tool in the diagnosis of cutaneous leishmaniasis; it has the added advantage of identification of the species of Leishmania causing the lesion....
Chen, Yong; Zahui, Tiphaine; Alberti, Ingo; Kalia, Yogeshvar N
The objective was to determine the cutaneous biodistribution of aciclovir (ACV), that is, the amount of drug as a function of depth within the skin following topical iontophoretic administration of amino acid ester prodrugs of ACV (ACV-X, where X=Arg, Ile or Val). The results were compared to those obtained with marketed formulations of aciclovir and penciclovir (PCV), and following topical iontophoresis of ACV. Quantification of molecules as a function of position in the skin was achieved by snap-freezing and cryotoming skin samples to obtain coarse or fine lamellae with a thickness of either 100 μm or 20 μm. The molecules--ACV, ACV-X or PCV--were extracted and quantified by validated UHPLC-MS/MS analytical methods. Passive delivery of ACV or PCV from marketed cream and ointment formulations after application for 60 min resulted in modest cutaneous deposition (QDEP,ACV and QDEP,PCVACV and PCV were found mainly in the stratum corneum or superficial viable epidermis. The levels in the deeper skin layers (100-200 μm), corresponding to the basal epidermis and adjacent area, where the virus would be found, were negligible. In contrast, iontophoresis of ACV-Ile or ACV-Arg for only 10 min at 0.25 mA/cm(2) resulted in much greater deposition of ACV species at the same skin depths (100-200 μm): for ACV-Ile - QDEP,ACV and QDEP,ACV-Ile were 17.2 ± 6.9 nmol/cm(2) and 8.2 ± 1.3 nmol/cm(2), respectively; in the case of ACV-Arg there was complete bioconversion and only ACV was recovered (QDEP,ACV was 41.2 ± 9.2 nmol/cm(2)). In the higher resolution biodistribution studies, with 20 μm lamellae, short duration iontophoresis at 0.25 mA/cm(2) for only 5 min of ACV-Arg or ACV-Ile still enabled considerable amounts of ACV species to be delivered to the basal epidermis and neighboring layers (QDEP,ACV was 4.0 ± 1.6 nmol/cm(2) and 6.1 ± 1.7 nmol/cm(2), respectively). Iontophoresis of ACV under the same conditions resulted in negligible ACV deposition in these layers
Hagen-Plantinga, E A; Leistra, M H G; Sinke, J D; Vroom, M W; Savelkoul, H F J; Hendriks, W H
Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for
Hagen-Plantinga, E.A.; Leistra, M.H.G.; Sinke, J.D.; Vroom, M.W.; Savelkoul, H.F.J.; Hendriks, W.H.
Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for
Lisha, Joshua; Annalakshmi, Velu; Maria, Jose; Padmini, Devi
The prevalence of adverse drug reactions is reported to be high in critical care units. We conducted a systematic review to study the prevalence, drugs implicated, preventability, predictability, severity and determinants of adverse drug reactions in critical care settings. We searched MEDLINE, EMBASE, PROQUEST and OVID (January 1995 to June 2015) using pre-specified appropriate medical subject heading terms. Of 1552 studies, 34 studies were included for data extraction and synthesis. Overall, the prevalence of adverse drug reactions was 0.3% to 17% in paediatric intensive care units and 4.5% to 34.1% in adult intensive care units. The highest prevalence reported among critical care settings was 117.4 per 1000 patient days. The most common drug classes implicated were antimicrobials in the medical intensive care units, cardiovascular drugs and anticoagulants in the coronary care units, and analgesics and sedatives in the surgical care units. The prevalence of fatal and severe adverse drug reactions ranged from 0.9 to 19% and 5.7 to 28.6% respectively. The predictable and preventable adverse drug reactions ranged from 74.3 to 90.2% and 8.6 to 62.8% respectively. Only 8 studies reported patient outcomes. About 5.6% to 25.5% of patients died. There is wide variation in prevalence, characteristics and drug classes implicated in the occurrence of adverse drug reactions by type of intensive care unit. Findings of this study would help health care professionals to optimise pharmacotherapy in critical care settings. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Salazar-Mejía, Patricia Guadalupe; Tejeda-Aguirre, Celia Rosa; López-Moreno, Héctor Samuel
To detect Leishmania mexicana antigens reacting with sera of patients with cutaneous leishmaniasis (CL). A crude extract of L. mexicana was used as antigen for 2-D Western blot using sera from 5 patients with CL and controls from Sinaloa, Mexico during 2008. Five antigens were detected in the five infected patients analyzed; their molecular weights and isoelectric points were: 26 kDa (pI 7.8), 27 kDa (pI 8.1), 28 kDa (pI 8.6), 29 kDa (pI 8.5) and 31 kDa (pI 9.0). New potentially immunodominant L. mexicana antigens were detected, suggesting that this parasite could be the species responsible for human infection in Sinaloa.
Purpose: The study was carried out to evaluate the incidence of adverse reactions to antimalarial drugs among residents of a Nigeria university community with a focus on artemisinin-based combination therapy (ACT). Specifically, the profile of use, and the reporting culture of people with respect to experienced reactions ...
Hanif, M. M.; Akram, K.; Mustafa, G.
Objective: To compare intralesional versus oral chloroquine in cutaneous leishmaniasis and determine the cure rate, duration of treatment, and total dose of drug. Study Design: Randomized controlled study. Place and Duration of Study: Department of Dermatology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from November 2013 to June 2014. Methodology: Consecutive 86 patients of cutaneous leishmaniasis, with single to multiple lesions of various sizes were enrolled and divided randomly into group A and B for the purpose of intralesional and oral chloroquine administration, respectively to compare the effect of the two routes on duration of treatment and total dose of the drug. SPSS version 16 was used for data analysis after data entry into it. Quantitative variables like, duration, cost and total dose of treatment were calculated as mean and standard deviation and compared by using T-test. P-value of less than 0.05 was taken as significant. Results: Cure rate was 100% in both groups towards the end of treatment. Mean duration of treatment was 9.17 ± 3 weeks in intralesional (A) group as against 11.37 ± 3 weeks in oral (B) group (p = 0.0028). Mean total dose of the drug given to each patient in group A was 5.8 ± 0.5 gm and in group B, it was 19.2 ± 1.5 gm, which is significantly higher (p=0.001). The total cost of treatment in group A was Rs. 90 ± 8 and in group B it was Rs. 91 ± 1 (p=0.446). Conclusion: Duration of treatment is significantly shorter and total dose is lesser with intralesional compared to oral chloroquine in treatment of cutaneous leishmaniasis. (author)
Ramírez, Elena; Medrano-Casique, Nicolás; Tong, Hoi Y; Bellón, Teresa; Cabañas, Rosario; Fiandor, Ana; González-Ramos, Jessica; Herranz, Pedro; Trigo, Elena; Muñoz, Mario; Borobia, Alberto M; Carcas, Antonio J; Frías, Jesús
We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors. All peripheral eosinophilia >700 × 10 6 cells l -1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed. The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected. Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia. © 2016 The British Pharmacological Society.
Rentia van Graan
This retrospective analysis can serve as a platform for future ADR studies within this district. Sustainable and continuous efforts should be made to train and create more awareness among healthcare workers in this district. Keywords: antiretroviral therapy, adverse drug reactions, drug safety, pharmacovigilance, gender ...
The objective of this study was to establish the detection, prevalence and management of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care Centre (CCC) of Kiambu District Hospital. The study was a cross sectional survey where the patients included ...
Background: Information about the prevalence of adverse drug reactions (ADRs) among HIV infected and HIV uninfected patients receiving anti-tuberculous therapy in Africa is limited due to unavailability of local data or publications and hence the basis of this study. Objective: To determine the prevalence of adverse drug ...
235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...
Benjamin D. Singer
Full Text Available A 57-year-old man was admitted to our hospital for evaluation and management of stroke in the setting of an atrial septal defect. Shortly after receiving gadobenate dimeglumine for magnetic resonance imaging of the pelvic vessels, he experienced cardiac arrest from which he was resuscitated. His course was complicated by profound distributive shock. The presumed cause was a severe anaphylactic or anaphylactoid reaction to the gadolinium-based compound that he received.
Dei-Cas, Ignacio; Wright, Dolores; Rigo, Bettina; Cohen Sabban, Emilia; Lacasagne, Jorgelina; Pietropaolo, Nelida; Cabo, Horacio; Molina, Malena
Radiation recall refers to a tissue reaction produced by the use of certain drugs, usually chemotherapeutic agents, in a previously irradiated area. We report a patient with cutaneous radiation recall associated with chlorambucil, drug previously unreported as a causative agent in the literature. (author) [es
Mittal, Lavanya; Zhang, Lingqiao; Feng, Rui; Werth, Victoria P
Although existing evidence demonstrates the efficacy of antimalarials for rheumatic skin disease, the safety of these medications, and particularly quinacrine, remains debated. We investigated the toxicity risk associated with antimalarials in patients with cutaneous lupus erythematosus and dermatomyositis. A total of 532 patients (mean age, 52.29 years; sample composition by sex, 85.15% female vs 14.85% male) were selected from 2 databases on cutaneous lupus erythematosus (69.92%) and dermatomyositis (30.08%). Details regarding treatment and toxicities were extracted and 5 treatment courses were defined (ie, hydroxychloroquine [HCQ], chloroquine [CQ], quinacrine [Q], HCQ-Q combination therapy [HCQ-Q], and CQ-Q combination therapy [CQ-Q]). The hazard ratio for each major toxicity was estimated by using the Cox proportional hazard model to compare the different treatments with HCQ. The most common toxicities included cutaneous eruption, gastrointestinal upset, mucocutaneous dyspigmentation, neurologic toxicity, and retinopathy. The hazards of cutaneous eruption, gastrointestinal upset, and neurologic toxicities were lower with HCQ-Q than with HCQ; however, this may represent selection bias. Although there was increased retinopathy risk with CQ and CQ-Q versus with HCQ, retinopathy was not seen with Q. Retrospective analysis. With the exception of retinopathy, which was not seen with Q, the risks for other toxicities associated with Q monotherapy or combination treatment were not significantly different from those with HCQ. Published by Elsevier Inc.
Full Text Available Zeshan Ahmed Chaudhry,1 Umer Najib,2 Zahid H Bajwa,3 W Carl Jacobs,4 Javed Sheikh,5 Thomas T Simopoulos61Department of Diagnostic and Interventional Neuroradiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; 2Department of Neurology, Robert C Byrd Health Sciences Center of West Virginia University, Morgantown, WV, USA; 3Boston Headache Institute, Waltham, MA, USA; 4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, Allergy and Immunology, 6Department of Anesthesia, Beth Israel Deaconess Medical Center, Brookline, MA, USAAbstract: The use of spinal cord stimulation (SCS devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1–3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. “In vivo” testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and
Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun
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.
Moberg, S.; Mobacken, H.
The influence of irradiation with UV-A and PUVA (8-methoxy-psoralen and UV-A) on delayed hypersensitivity reactions to microbial antigens was studied in healthy human individuals. Skin reactions to Candida albicans antigen and PPD were enhanced by UV-A als well as by PUVA compared with nonirradiated tests. A statistically significant difference was reached with UV-A for both antigens. For PUVA, erythemogenic doses to Candida tests produced a significant increase of response. (orig.)
Maria Cristina Soares Rodrigues
Full Text Available 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.
Pavlos, Rebecca; White, Katie D; Wanjalla, Celestine; Mallal, Simon A; Phillips, Elizabeth J
Adverse drug reactions (ADRs) are a significant source of patient morbidity and mortality and represent a major burden to health care systems and drug development. Up to 50% of such reactions are preventable. Although many ADRs can be predicted based on the on-target pharmacologic activity, ADRs arising from drug interactions with off-target receptors are recognized. Off-target ADRs include the immune-mediated ADRs (IM-ADRs) and pharmacologic drug effects. In this review, we discuss what is known about the immunogenetics and pathogenesis of IM-ADRs and the hypothesized role of heterologous immunity in the development of IM-ADRs. Copyright © 2017 Elsevier Inc. All rights reserved.
Tripathy, Swagata; Nair, Priya V
Background and Aim: Patent blue vital (PBV) dye is used for varied perioperative indications, and has a potential for causing life-threatening allergic reactions. In this retrospective case series study, at a tertiary level neurosciences centre, we analysed the nature, management and outcome of adverse drug reaction to the preoperative use of PBV for marking vertebral level prior to back surgeries. Methods: Patients were identified from the theatre and radiology database. Data were collected ...
Epelboin, L; Klement, E; Chemali, N; Danis, M; Bricaire, E; Caumes, E
Cysticercosis is an helminthic disease which is usually observed in endemic areas or in immigrants coming from these areas. Cases described in travellers coming back from endemic areas are rare. We describe a case of neurocysticercosis that was revealed by a paradoxical reaction. This reaction occurred during the early phase of the treatment of cutaneous cysticercosis by albendazole in a tourist coming back from the sub Indian continent. This case report leads to discuss the modes of infestation in tourists, and the management of cutaneous cysticercosis and paradoxical reaction that may impair the outcome of cysticercosis during the treatment with antihelminthic drugs.
Veenhof, Eveline Z; Knol, Edward F; Schlotter, Yvette M; Vernooij, Johannes C; Rutten, Victor P; Willemse, Ton
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.
van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G
OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable
Aagaard, Lise; Weber, Camilla Blicher; Hansen, Ebba Holme
BACKGROUND: The potential risk of adverse drug reactions (ADRs) in the paediatric population has become a public health concern and regulatory agencies in Europe and the US have acknowledged that there is a need for more research in this area. Spontaneous reporting systems can provide important new...
van Grootheest, K; de Graaf, L; de Jong-van den Berg, LTW
The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports. We present an overview of experiences with consumer reporting in various countries of the
East African Medical Journal Vol. 88 No. 10 October 2011. ADVERSE DRUG REACTIONS AMONG HIV INFECTED AND UNINFECTED ADULTS RECEIVING ANTI-. TUBERCULOUS THERAPY AT KENYATTA NATIONAL HOSPITAL. J. O. Masese, M. Pharm (Clin. Pharm), Department of Pharmaceutics and Pharmacy ...
Background: Life-saving highly active anti-retroviral therapy (HAART) has been accompanied by the challenge of incident adverse drug reactions (ADRs). Locally generated data is scanty, inadequately documented, and therefore not available to inform revision of clinical protocols. Objective: To study and document the ...
Aagaard, Lise; Hansen, Ebba Holme
on the occurrence and characteristics of adverse drug reactions (ADRs) in children, reported for asthma medications licensed for paediatric use. Methods We systematically reviewed the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed, Embase...
South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, ...
The high prevalence of HIV in KwaZulu-Natal Province, South Africa, has greatly increased the demand for antiretroviral therapy (ART), resulting in an exponential increase in the number of patients initiated on highly active antiretroviral treatment (HAART). However, little information about adverse drug reactions in these ...
Introduction: The burden of both community and hospital acquired adverse drug reactions (ADRs) are some of the important issues in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. Objective: This study was done to determine the frequency and characteristics of ADRs in ...
Jun 1, 2017 ... in cancer treatment. The aim was to analyze the blood glucose‑related ADR of antineoplastics in treating pancreatic cancer. Materials and Methods: .... Figure 2: Record numbers on general adverse drug reactions (metabolism and nutrition disorder ratio = metabolism and nutrition disorder/total number.
Bakhtiari, Sedigheh; Sehatpour, Marziye; Mortazavi, Hamed; Bakhshi, Mahin
Adverse reaction to medication is common and may have a variety of clinical manifestations in the oral cavity. The present review paper aimed to describe adverse drug reactions (ADRs) which might be encountered by dental practitioners in every discipline. In this narrative review article, the specialized databases such as PubMed, PubMed Central, MEDLINE, EBSCO, Science Direct, Scopus, and reference books from the years 2000-2016 were used to find relevant documents by using MeSH terms: Adverse Drug Reaction, Drug induced, Medication Related, Mouth, Oral Manifestation, Tooth, Hard Tissue, Soft Tissue. The data were categorized in 4 groups as follows: saliva and salivary glands involvement, soft tissue (mucosal) involvement, hard tissue involvement, and non specific conditions (taste disorders, halitosis, neuropathies, movement disturbances, and infection). Most articles were about the adverse effect of drugs on the function of salivary glands, which often cause a decrease in saliva secretion. Other reactions were less common; meanwhile, the side effect of bisphosphonate was increasing in the alveolar bone, because of its unlimited prescription. Oral health care providers should be familiar with such events, as they will be confronted with them in their practice.
Background: Adverse Drug Reactions (ADRs) are an important contributor to patient morbidity and hospitalisation in Uganda. Under-reporting of ADRs may increase medicine-induced morbidity and mortality among patients. This study determined the extent of ADR reporting, and associated factors, among healthcare ...
Adverse drug reaction (ADR) is poorly reported globally but more in developing countries with poor participation by health professionals. Currently, there is no known literature on the Nigerian pharmacy students' knowledge on ADR reporting. Hence the purpose of this study was to find out the level of knowledge of ...
van Grootheest, AC; van Puijenbroek, EP; de Jong-van den Berg, LTW
Purpose The aim of the study is to get a better view about the possible contribution of pharmacists' reports to the quantity and the quality of reports and in this way to the quality of a voluntary reporting system of adverse drug reactions. Methods A total of 15 293 reports, sent to the Netherlands
An Unrecognised Adverse Drug Reaction of Enalapril. Led to Suspicion of Pulmonary Tuberculosis Infection. 1. 2. 2. 2. 1. Kosamu T., Mwanza K., Mbayo E., Gondwe K. and Besa C. 1School of Medicine, The Copperbelt University, Ndola Campus, Ndola, Zambia. 2 Kitwe Central Hospital, Ministry of Health, Kitwe, Zambia.
Methods: The study analyzed the number of adverse drug reaction case reports received by DACA in a period of six years (2002 – 2007GC). ... Conclusions: The level of ADR case reporting is very low showing the need to address major constraints of ongoing ... admissions; and it saves substantial amount of financial.
Hulshoff, A.; Lingeman, H.
Alkylation, acylation, silylation and other derivatization reactions applied to the gas chromatographic analysis of drugs in biological matrices are reviewed. Reaction conditions are discussed in relation to reaction mechanisms. Detector-oriented labelling of drugs, and derivatization with chiral
Herintha Coeto Neitzke-Abreu
Full Text Available Cutaneous leishmaniasis (CL can occur in skin and mucosa, causing disfiguring lesions. The laboratory diagnosis of CL involves immunological methods and optical detection of the parasite, al of which have limitations. There is a need for more effective diagnostic methods for CL which wil allow treatment to be initiated more promptly in order to help prevent the development of severe forms of mucosal disease, and to estimate the prognosis of the infection. The polymerase chain reaction (PCR has been widely used to diagnose CL, because of its higher sensitivity. This study estimated the accuracy and compared PCRs of samples from lesion scarification (PCR-L and blood sample-enriched leukocytes (PCR-B with three conventional diagnostic techniques: parasite direct search (DS, Montenegro skin test (MST, and indirect immunofluorescence reaction (IIF. The study included 276 patients under suspicion of CL. We conducted a cross-sectional study, in which patients were selected by convenience sampling. We used MP3H/MP1L primers to generate a Leishmania (Viannia (minicircle kDNA fragment of 70-bp. Of 106 patients with CL, 83.87%, 51.67%, 64.52%, 85.71%, or 96.10% tested positive by PCR-L, PCR-B, DS, IIF, or MST, respectively. Five patients tested positive only by PCR-L, and two other patients only by PCR-B. PCR-L is indicated for use in patients with chronic lesions or Leishmania reinfection, which may progress to mucosal lesion. PCR-B is indicated for use in patients with negative results in conventional tests or for patients with no apparent lesion. PCR is not only useful in diagnosing CL but also helps to identify the infecting species.
Santini-Oliveira, Marilia; Grinsztejn, Beatriz
Antiretroviral (ARV) drug use during pregnancy significantly reduces mother-to-child HIV transmission, delays disease progression in the women and reduces the risk of HIV transmission to HIV-serodiscordant partners. Pregnant women are susceptible to the same adverse reactions to ARVs as nonpregnant adults as well as to specific pregnancy-related reactions. In addition, we should consider adverse pregnancy outcomes and adverse reactions in children exposed to ARVs during intrauterine life. However, studies designed to assess the safety of ARV in pregnant women are rare, usually with few participants and short follow-up periods. In this review, we discuss studies reporting adverse reactions to ARV drugs, including maternal toxicity, adverse pregnancy outcomes and the consequences of exposure to ARV in infants. We included results of observational studies, both prospective and retrospective, as well as randomized clinical trials, systematic reviews and meta-analyses. The benefits of ARV use during pregnancy outweigh the risks of adverse reactions identified to date. More studies are needed to assess the adverse effects in the medium- and long term in children exposed to ARVs during pregnancy, as well as pregnant women using lifelong antiretroviral therapy and more recently available drugs.
Spriet, Sarah; Banks, Taylor A
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening adverse drug reaction. To increase awareness of the potential for recurrence in patients with a history of DRESS syndrome and provide a brief review of the clinical characteristics, diagnosis, and management of this disease process. The authors selected and reviewed salient articles on the topic and incorporated pertinent information from the patient's clinical course. A case of recurrent DRESS triggered by a structurally unrelated drug is presented, followed by discussion of the clinical characteristics, diagnosis, and management. Clinical pearls and pitfalls are emphasized for the practicing allergist, clinical immunologist, and fellow-in-training. The most important steps in the treatment of this condition are the identification and removal of the offending agent. Providers should be aware of the potential for recurrent DRESS and recognize the importance of prompt management.
Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne
INTRODUCTION: 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...
Tripathy, Swagata; Nair, Priya V
Patent blue vital (PBV) dye is used for varied perioperative indications, and has a potential for causing life-threatening allergic reactions. In this retrospective case series study, at a tertiary level neurosciences centre, we analysed the nature, management and outcome of adverse drug reaction to the preoperative use of PBV for marking vertebral level prior to back surgeries. Patients were identified from the theatre and radiology database. Data were collected from the patients' notes retrieved from the medical records division. Eleven of 1247 (0.88%) patients experienced adverse reactions: 6 (0.48%) patients had minor grade I reactions (urticaria, blue hives, pruritis or generalised rash), 4 (0.32%) had grade II reactions (transient hypotension/bronchospasm/laryngospasm) and grade III reaction (hypotension requiring prolonged vasopressor support) was noted in 1 (0.08%) patient. No mortality was seen. The time of onset (range 10-45 min) frequently coincided with induction of anaesthesia or prone positioning of patient. Seven (63.6%) cases were cancelled or postponed (range 2-63 days). Treatment varied independent of the grade of reaction. Allergy workup (often incomplete) was done for 6 (54%) patients. An awareness of the time of onset and infrequency of life-threatening reactions to patent blue dye may result in better management, less postponement, more complete workup and referral of these events.
Full Text Available Background and Aim: Patent blue vital (PBV dye is used for varied perioperative indications, and has a potential for causing life-threatening allergic reactions. In this retrospective case series study, at a tertiary level neurosciences centre, we analysed the nature, management and outcome of adverse drug reaction to the preoperative use of PBV for marking vertebral level prior to back surgeries. Methods: Patients were identified from the theatre and radiology database. Data were collected from the patients′ notes retrieved from the medical records division. Results: Eleven of 1247 (0.88% patients experienced adverse reactions: 6 (0.48% patients had minor grade I reactions (urticaria, blue hives, pruritis or generalised rash, 4 (0.32% had grade II reactions (transient hypotension/bronchospasm/laryngospasm and grade III reaction (hypotension requiring prolonged vasopressor support was noted in 1 (0.08% patient. No mortality was seen. The time of onset (range 10-45 min frequently coincided with induction of anaesthesia or prone positioning of patient. Seven (63.6% cases were cancelled or postponed (range 2-63 days. Treatment varied independent of the grade of reaction. Allergy workup (often incomplete was done for 6 (54% patients. Conclusion: An awareness of the time of onset and infrequency of life-threatening reactions to patent blue dye may result in better management, less postponement, more complete workup and referral of these events.
Rende, Pierandrea; Paletta, Laura; Gallelli, Giuseppe; Raffaele, Gianluca; Natale, Vincenzo; Brissa, Nazareno; Costa, Cinzia; Gratteri, Santo; Giofrè, Chiara; Gallelli, Luca
The use of cardiovascular drugs is related to the development of adverse drug reactions (ADRs) in about 24% of the patients in the Cardiovascular Care Unit. Here, we evaluated the ADRs in patients treated with antihypertensive drugs. The study was conducted in two phases: In the first phase, we performed a retrospective study on clinical records of Clinical Divisions (i.e., Internal Medicine Operative Unit and Geriatric Operative Unit) from January 1, 2012 to December 31, 2012. Moreover from January 1, 2013 to March 30, 2013 we performed a prospective study on the outpatients attending the Emergency Department (ED) of the Pugliese-Ciaccio Hospital of Catanzaro, by conducting patient interviews after their informed consent was obtained. The association between a drug and ADR was evaluated using the Naranjo scale. We recorded 72 ADRs in the Clinical Divisions and six in the ED, and these were more frequent in women. Using the Naranjo score, we showed a probable association in 92% of these reactions and a possible association in 8%. The most vulnerable age group involved in ADRs was that of the elderly patients. In conclusion, our results indicate that antihypertensive drugs may be able to induce the development of ADRs, particularly in elderly women receiving multiple drug treatment. Therefore, it is important to motivate the healthcare providers to understand their role and responsibility in the detection, management, documentation, and reporting of ADRs, as also all the essential activities for optimizing patient safety. PMID:24347982
Tresa Muir McNeal
Full Text Available Tresa Muir McNeal1, Colleen Y Colbert1, Christian Cable1, Curtis R Mirkes1, June G Lubowinski2, John D Myers11Department of Medicine, Texas A&M University System HSC College of Medicine, Scott & White Healthcare, Temple, TX, USA; 2RD Haynes Medical Library, Scott & White Healthcare, Temple, TX, USAIntroduction: Medications are critical to the management of patient conditions, and they can have significant effects on the success or failure of medical interventions. Patient perceptions of drug warnings play an important role in medication compliance and ultimately disease management. Several factors may affect patients’ understanding of drug warnings and drug labeling, including health literacy and interactions with physicians and pharmacists.Purpose: The purpose of this article is to provide a review of the literature related to patient perceptions of drug warnings and drug labeling. Descriptive articles and studies regarding patient perceptions and knowledge of adverse drug reaction warnings were reviewed.Methods: The following databases were utilized to search the literature related to patient perceptions of drug warnings: PubMed, Academic Search Premiere, CINAHL, Medline, Psych Info, Business Source Complete, Alternative Healthwatch, Health Source (both Nursing/Academic and Consumer additions, JSTOR, and Master File Premiere. For the purpose of this review, any peer-reviewed article was eligible. Exclusionary criteria included: articles published in languages other than English, articles/studies on patient perceptions of vaccines and chemotherapy, and articles related to perceptions of medications administered in the inpatient setting. Forty-six articles were included in the review.Results: Health literacy has been shown to have a major impact on patients’ ability to understand potential adverse reactions and instructions on correct dosing of medications. Direct communication with physicians and pharmacists is one of the most important and
Palaniappan, Muthiah; Selvarajan, Sandhiya; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan
Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. The study used descriptive statistics and the values were expressed in numbers and percentages. During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo's scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be enalapril (17.5%), atorvastatin (14.9%), aspirin (8.4%) and metoprolol (8.4%). The cardiovascular
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
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, Pcaused 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.
Agaba Emmanuel I
Full Text Available Abstract Introduction Parkinsonism puts a high direct cost burden on both patient and caregiver. Several reports of drug-induced parkinsonism have been published, but to the best of our knowledge, there has not been any report of quinine or halothane inducing parkinsonism. Case presentation We describe two cases of parkinsonism possibly caused by adverse drug reaction to quinine in a 29-year-old black Nigerian woman and to halothane in a 36-year-old black Hausa (Nigerian man who received it as general anaesthesia for appendicectomy in our teaching hospital. Conclusion These are two unusual cases of parkinsonism caused by adverse drug reactions to high-dose quinine and to halothane as general anaesthesia. We consider that these two cases are important in bringing this potential side-effect to the attention of both pharmacologists and primary care physicians as these are two of the most commonly used medications in our clinics. We conclude that parkinsonism should be included among the adverse drug reactions to high-dose quinine and halothane general anaesthetic.
Petzold, Max; Hägg, Staffan
Background Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. Methods Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO’s or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. Results Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2–3.2%) had preventable adverse drug reactions and 52% (95% CI: 42–62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1–51%) had preventable adverse drug reactions and 45% (95% CI: 33–58%) of adverse drug reactions were preventable. Conclusions This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be
Mendes, Diogo; Alves, Carlos; Batel Marques, Francisco
The aims of this study were to analyse spontaneously reported adverse drug reactions according to their previous description, seriousness, causality and the reporting professional. Previous findings showed that fewer nurses than physicians and pharmacists report adverse drug reactions. This is not attributed to any lack of ability in identifying adverse drug reactions. Adverse drug reactions received by the Central Portugal Regional Pharmacovigilance Unit, between 2001 and 2011, were studied. Certain and probable adverse drug reactions were included to test differences between professional groups for serious and non-serious adverse drug reactions. The Central Portugal Regional Pharmacovigilance Unit received 1014 adverse drug reactions. Fifty-four nurses reported 66 adverse drug reactions, whereas 232 physicians and 145 pharmacists reported 589 and 357 adverse drug reactions, respectively. Considering the number of practising professionals, it was estimated that 0.55% of nurses, 3.96% of physicians and 7.08% of pharmacists have reported an adverse drug reaction. Of the 633 adverse drug reactions assessed as certain or probable, 46 (21 serious), 387 (192 serious) and 198 (77 serious) were reported from nurses, physicians and pharmacists, respectively. There were no differences in the reporting of serious adverse drug reactions among nurses, physicians and pharmacists. Nurses are able to identify serious adverse drug reactions although they report less than other professionals. Nurses need to increase their involvement in spontaneous reporting schemes by taking responsibility for routinely reporting suspected adverse drug reactions. © 2012 John Wiley & Sons Ltd.
Hu, Yusun; Cantarero-Arévalo, Lourdes
BACKGROUND: Information on ethnic diversity of adverse drug reactions (ADRs) to asthma medications is rare despite evidence suggesting higher risk for African Americans when using β2-adrenergic receptor agonists. The objectives are to investigate how ethnic background was involved in ADR assessment...... studies disaggregated information by ethnic background, and reports of ADRs to asthma medications in different ethnic groups were rare. We suggest that the inclusion of ADR analysis by different ethnic backgrounds is desirable....
Huang, Liang-Chin; Wu, Xiaogang; Chen, Jake Y
The prediction of adverse drug reactions (ADRs) has become increasingly important, due to the rising concern on serious ADRs that can cause drugs to fail to reach or stay in the market. We proposed a framework for predicting ADR profiles by integrating protein-protein interaction (PPI) networks with drug structures. We compared ADR prediction performances over 18 ADR categories through four feature groups-only drug targets, drug targets with PPI networks, drug structures, and drug targets with PPI networks plus drug structures. The results showed that the integration of PPI networks and drug structures can significantly improve the ADR prediction performance. The median AUC values for the four groups were 0.59, 0.61, 0.65, and 0.70. We used the protein features in the best two models, "Cardiac disorders" (median-AUC: 0.82) and "Psychiatric disorders" (median-AUC: 0.76), to build ADR-specific PPI networks with literature supports. For validation, we examined 30 drugs withdrawn from the U.S. market to see if our approach can predict their ADR profiles and explain why they were withdrawn. Except for three drugs having ADRs in the categories we did not predict, 25 out of 27 withdrawn drugs (92.6%) having severe ADRs were successfully predicted by our approach. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Charlston, Samuel; Siller, Gregory
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.
Manolopoulos, Vangelis G
Pharmacogenetics and pharmacogenomics deal with genetically determined variations in how individuals respond to drugs. They hold the potential to revolutionize drug therapy. The clinical need for novel approaches to improve pharmacotherapy stems from the high rate of adverse reactions to drugs and their lack of effectiveness in many individuals. Despite the accumulation of research findings showing the potential for clinical benefit for several drug-metabolizing enzymes and some receptors that constitute drug targets, the translation of these findings into tangible clinical applications occurs very slowly. The main steps for clinical implementation of pharmacogenomics include: a) education of clinicians and all other parties involved in the use and benefits of pharmacogenomics; b) execution of large prospective clinical and pharmacoeconomic studies showing the benefit of pharmacogenomic genotyping; c) provision of incentives to develop tests; d) development of specific clinical guidelines; and e) creation of a solid regulatory and ethical framework. Furthermore, the potential should be explored to use existing therapeutic drug monitoring laboratories to introduce pharmacogenomic testing into hospitals. Overall, our thesis is that pharmacogenomics is already a reality in clinical practice and is bound to continue gaining acceptance by clinicians in the coming years.
Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N
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.
Olivry, Thierry; Mueller, Ralf S
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.
Ariza, Adriana; Fernandez, Tahia D; Doña, Inmaculada; Aranda, Ana; Blanca-Lopez, Natalia; Melendez, Lidia; Canto, Gabriela; Blanca, Miguel; Torres, Maria J; Mayorga, Cristobalina
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in allergic reactions of which two main types exist: IgE-mediated and crossintolerance. The diagnosis of crossintolerance reactions is often based on the drug provocation test. The potential value of the basophil activation test (BAT) was evaluated using different basophil markers in the diagnosis of patients with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen at four different concentrations using CD193 and CD203c as basophil markers and CD63 as activation marker. We compared BAT results using CD193⁺ or CD193⁺ CD203c⁺ for basophil selection and found a significant increase in the stimulation index when using CD193⁺ CD203c⁺ in both patients and controls (P = 0.004 and P = 0.017, respectively). Selection of living cells only produced an increase in basophil stimulation in patients for both CD193⁺ and CD193⁺ CD203c⁺ (P < 0.001 for both), whereas in controls there was no change with CD193⁺ and a decrease with CD193⁺ CD203c⁺ (P = 0.001). We found that CD193⁺ CD203c⁺ increased the percentage of positive cases in patients and controls when compared with CD193⁺. When excluding dead cells, there was an increase of 21.7% in patients and 10% in controls. These results indicate that using CD193⁺ CD203⁺, excluding dead cells, is the best approach for BAT although this test is not recommended for the diagnosis of patients with crossintolerance to NSAIDs owing to its low sensitivity and specificity. © 2014 International Society for Advancement of Cytometry.
Staniszewska, Anna; Dąbrowska-Bender, Marta; Olejniczak, Dominik; Duda-Zalewska, Aneta; Bujalska-Zadrożny, Magdalena
The aim of the study was to assess patient knowledge on reporting of adverse drug reactions. 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. The respondents who lived in the city had a greater knowledge compared to the respondents who lived in the countryside (Pearson's χ 2 =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 χ 2 =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 χ 2 =11.7, P <0.0001).
Fricke-Galindo, Ingrid; LLerena, Adrián; López-López, Marisol
Adverse drug reactions (ADRs) are considered as an important cause of morbidity and mortality. The hypersensitivity reactions are immune-mediated ADRs, which are dose-independent, unpredictable and have been associated with several HLA alleles. The present review aimed to describe HLA alleles that have been associated with different ADRs in populations worldwide, the recommendations of regulatory agencies and pharmacoeconomic information and databases for the study of HLA alleles in pharmacogenetics. A systematic search was performed in June 2016 of articles relevant to this issue in indexed journals and in scientific databases (PubMed and PharmGKB). The information of 95 association studies found was summarized. Several HLA alleles and haplotypes have been associated with ADRs induced mainly by carbamazepine, allopurinol, abacavir and nevirapine, among other drugs. Years with the highest numbers of publications were 2013 and 2014. The majority of the reports have been performed on Asians and Caucasians, and carbamazepine was the most studied ADR drug inducer. Two HLA alleles' databases are described, as well as the recommendations of the U.S. Food and Drug Administration, the European Medicine Agency and the Clinical Pharmacogenetics Implementation Consortium. Pharmacoeconomic studies on this issue are also mentioned. The strongest associations remain for HLA-B*58:01, HLA-B*57:01, HLA-B*15:02 and HLA-A*31:01 but only in certain populations; therefore, studies on different ethnic groups would be useful. Due to the improvement of drug therapy and the economic benefit that HLA screening represents, investigations on HLA alleles associated with ADR should continue.
Full Text Available Background. Antituberculosis multidrug regimens have been associated with increased incidence of adverse drug reactions (ADRs. This study aimed to determine the incidence and associated factors of ADRs due to antituberculosis therapy. Methods. This is a retrospective cross-sectional study on tuberculosis patients who were treated in tuberculosis clinics in Markazi province in Iran. The information contained in the medical files was extracted and entered into the questionnaire. Data was descriptively analyzed by using statistical package for social sciences (SPSS 18. Results. A total of 940 TB patients of 1240 patients’ medical records available in 10 medical offices were included in this study. Of the 563 ADRs found in this study, 82.4% were considered minor reactions and 17.6% were major reactions. No death from antituberculosis ADR was observed. We found that the risk of major ADRs was higher in females (P value=0.0241, age >50 y (P value=0.0223, coinfection with HIV (P value=0.0323, smoking (P value=0.002, retreatment TB (P value=0.0203, and comorbidities (P value=0.0005. Conclusions. This study showed that severe side effects of anti-TB drugs are common in patients who have risk factors of ADRs and they should be followed up by close monitoring.
Soraia Aparecida da Silva
Full Text Available SUMMARY Objective: To review the hypersensitivity reaction to drugs known as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome, based on a case report. We also intend to discuss the difficulty and importance of disease recognition, since none of the changes is pathognomonic of this disease and failure to identify it may have disastrous consequences for the patient. Method: To describe this case report, in addition to the information collected for clinical assessment, a literature review was performed in the PubMed and Bireme databases in order to retrieve the latest information published in literature on DRESS syndrome. Results: The case of a 20-year old patient is reported. After anamnesis, physical examination and laboratory tests a diagnosis of DRESS syndrome was performed, characterized by rash, hematologic alterations, lymphadenopathy and lesions in target organ. This is a rare syndrome, whose frequency varies according to the drug used and the immune status of the patient, being more often associated with the use of anticonvulsants. Conclusion: The approach and discussion of the topic are of paramount importance, in view of the potential lethality of this treatable syndrome. Recognizing the occurrence of DRESS syndrome and starting treatment as soon as possible is crucial to reduce the risk of mortality and improve prognosis.
Full Text Available BACKGROUND The geriatric population is increasing as a result of advanced medical facilities. This population also faces a number of medical health challenges. They tend to receive multiple medications often leading to Drug-Drug Interactions (DDIs Adverse Drug Reactions (ADRs and other clinical consequences, which compromises their quality of life if not endangering it as well. There are few Indian studies focusing on this problem. Hence, this study was undertaken with the aim to assess the polypharmacy pattern, proportion of DDIs and adverse drug reactions in the geriatric population in a tertiary care hospital. MATERIALS AND METHODS This was a cross-sectional study wherein data from 201 geriatric inpatient’s prescriptions were collected. The prescriptions were assessed for demographic details such as age, gender, comorbidities and drugs prescribed. All prescriptions were evaluated for polypharmacy, DDIs and ADRs. DDIs were assessed using Micromedex software. Patients were stratified into groups and DDIs were compared between the groups, gender and also with number of drugs used. RESULTS There were 201 patients with a mean age of approximately 70 years. Polypharmacy occurred in 73.63% of them with mean number of drugs being 6.23. The number of drugs used increased significantly with age (p=0.0001. Hypertension was the most common comorbidity. Polypharmacy was strongly associated with hypertension and dyslipidaemia. A total of 129 (64.17% patients accounted for 425 potential DDIs. The most common drug involved in DDIs was aspirin. A subset analysis of ADRs showed an occurrence of 50.68% with 10.81% being definitely avoidable. CONCLUSION Elderly individuals are at increased risk of being on polypharmacy. This comes with the risk of several potential DDIs, which in turn may lead to adverse drug reactions, which results in morbidity. Doctors involved in the care of the elderly should be aware of these facts and exercise caution while adding any
Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J
Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Aagaard, Lise; Hansen, Ebba Holme
Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs...... not mentioned in PIs issued in the United States. In conclusion, information about possible ADRs associated with the use of a specific product should be made available worldwide, as the prescriber information about medicines' safety profile should not depend on the country in which the medication is licensed....
Witcher, Robert; Dzierba, Amy L; Kim, Catherine; Smithburger, Pamela L; Kane-Gill, Sandra L
Therapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs). A retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres. Medications commonly used during TH were screened for association with significant ADRs (grade 3 or greater per Common Terminology Criteria for Adverse Events) using three published ADR detection instruments. A total of 229 patients were included, the majority being males with median age of 62 presenting with an out-of-hospital cardiac arrest in pulseless electrical activity or asystole. The most common comorbidities were hypertension, coronary artery disease, and diabetes mellitus. There were 670 possible ADRs and 69 probable ADRs identified. Of the 670 possible ADRs, propofol, fentanyl, and acetaminophen were the most common drugs associated with ADRs. Whereas fentanyl, insulin, and propofol were the most common drugs associated with a probable ADR. Patients were managed with TH for a median of 22 hours, with 38% of patients surviving to hospital discharge. Patients undergoing TH after cardiac arrest frequently experience possible adverse reactions associated with medications and the corresponding laboratory abnormalities are significant. There is a need for judicious use and close monitoring of drugs in the setting of TH until recommendations for dose adjustments are available to help prevent ADRs.
Singh, Shruti; Dhasmana, D C; Bisht, Manisha; Singh, Prashant Kumar
Anticancer drugs contribute significantly to the global burden of adverse drug reactions (ADRs). Any attempt to quantify their magnitude and provide upgraded knowledge would help oncologists in writing safer prescriptions. This observational follow-up study was conducted on newly diagnosed cancer patients receiving anticancer therapy with an aim to determine the frequency, severity, causality, predictability, and preventability of ADRs. The patients were followed up for 6 months for the appearance of adverse events. Data were analyzed using IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY) and presented in the form of descriptive statistics. Each patient was prescribed approximately 6.85 ± 1.51 (mean ± standard error) drugs on average. All the patients (100%) receiving anticancer chemotherapy had ADRs. Alopecia, nausea and vomiting, burning tingling, and numbness were the most frequently encountered ADRs. The incidence of alopecia ( P reactions were of Grade 2 (69.53%). Most of the reactions (75.80%) appeared within 10 days of receiving the first cycle. 99.58% reactions were not serious. According to the WHO - The Uppsala Monitoring Centre criteria, 99.47% ADRs fell in possible category. According to the Naranjo's algorithm, 100% ADRs fell in probable category. About 94.80% reactions were found to be predictable. About 56.47% reactions were probably preventable, and 43.53% reactions were not preventable. Multiple ADRs were seen in newly diagnosed cancer patients. Most of them were predictable, of mild-to-moderate severity, nonserious, and preventable. A majority of the ADRs recovered over time.
Crüger, Anne-Mette Torp; Kaur-Knudsen, Diljit; Zachariae, Claus
tertiary dermatological departments during a ten-year period. RESULTS: In a total of 192 cases (77.4%), the primary diagnosis of EM (66.5%), SJS (62.2%) and TEN (100%) was confirmed, whereas the remaining cases (22.6%) were diagnosed differently. Antibiotics and allopurinol were predominantly associated...
Crüger, Anne-Mette Torp; Kaur-Knudsen, Diljit; Zachariae, Claus
INTRODUCTION: The aim of this study was to examine risk factors and mortality among patients with erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: This was a retrospective evaluation of the med-ical records of 250 patients from two Danish...... (HR) = 11.2 (95% confidence interval (CI): 3.65-34.35); p risk of death was also increased among patients with SJS relative to patients with EM: HR = 2.60 (95% CI: 1.10-6.16); p = 0.030; however, this did not remain statistically significant after adjustment...
Rodrigues, Maria Cristina Soares; Oliveira, Cesar de
to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. 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. 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. 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. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a
Blumenthal, Kimberly G; Kuhlen, James L; Weil, Ana A; Varughese, Christy A; Kubiak, David W; Banerji, Aleena; Shenoy, Erica S
Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired pneumonia (CAP). We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women's Hospital who received ceftaroline between May 2012 and February 2015. ADRs diagnosed by clinical providers during the course of clinical care were subsequently verified and classified. Risk factors for ADRs were identified. Among 96 patients (median age, 57 years; 54% females) who received a median of 28 (interquartile range, 6-63) ceftaroline doses, 54% were being treated for methicillin-resistant Staphylococcus aureus and treatment indications other than SSTI and CAP comprised 59% of care. There were 31 ADRs observed in 20 (21%) patients; hematologic (n = 15) and cutaneous (n = 9) findings were most common. Observed HSRs included rash with mucosal lesions (n = 1), rash with skin desquamation (n = 1), and possible organ-specific HSRs (n = 2). Patients who suffered an ADR received more doses of ceftaroline (median, 46 vs 21; P = .013). There was no increased risk of ceftaroline ADR among patients with reported beta-lactam allergy history (P > .5). Ceftaroline is used to treat a range of infections beyond SSTI and CAP. We observed a high rate of ADRs from ceftaroline, including signs of severe HSRs. More data are needed to understand the frequency and predictors of ceftaroline ADRs and HSRs. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Blumenthal, Kimberly G.; Kuhlen, James L.; Weil, Ana A.; Varughese, Christy A.; Kubiak, David W.; Banerji, Aleena; Shenoy, Erica S.
Background Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA) and community acquired pneumonia (CAP). Objective We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. Methods We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women’s Hospital who received ceftaroline between May 2012 and February 2015. ADRs diagnosed by clinical providers during the course of clinical care were subsequently verified and classified. Risk factors for ADRs were identified. Results Among 96 patients (median age 57 years, 54% female) who received a median of 28 [IQR 6, 63] ceftaroline doses, 54% were being treated for MRSA and treatment indications other than SSTI and CAP comprised 59% of care. There were 31 ADRs observed in 20 (21%) of patients; hematologic (n=15) and cutaneous (n=9) findings were most common. Observed HSRs included rash with mucosal lesions (n=1), rash with skin desquamation (n=1) and possible organ specific HSRs (n=2). Patients who suffered an ADR received more doses of ceftaroline (median 46 vs. 21, p=0.013). There was no increased risk of ceftaroline ADR among patients with prior reported beta-lactam allergy (p >0.5). Conclusions Ceftaroline is used to treat a range of infections beyond SSTI and CAP. We observed a high rate of ADRs from ceftaroline, including signs of severe HSRs. More data are needed to understand the frequency and predictors of ceftaroline ADRs and HSRs. PMID:27130709
Ribeiro, Marisa Rosimeire; Motta, Antonio Abílio; Marcondes-Fonseca, Luiz Augusto; Kalil-Filho, Jorge; Giavina-Bianchi, Pedro
To assess the risk factors, incidence and severity of adverse drug reactions in in-patients. This prospective study evaluated 472 patients treated at a teaching hospital in Brazil between 2010 and 2013 by five medical specialties: Internal Medicine, General Surgery, Geriatrics, Neurology, and Clinical Immunology and Allergy. The following variables were assessed: patient age, gender, comorbidities, family history of hypersensitivity, personal and family history of atopy, number of prescribed drugs before and during hospitalization, hospital diagnoses, days of hospitalization. The patients were visited every other day, and medical records were reviewed by the investigators to detect adverse drug reactions. There were a total of 94 adverse drug reactions in 75 patients. Most reactions were predictable and of moderate severity. The incidence of adverse drug reactions was 16.2%, and the incidence varied, according to the medical specialty; it was higher in Internal Medicine (30%). Antibiotics were the most commonly involved medication. Chronic renal failure, longer hospital stay, greater number of diagnoses and greater number of medications upon admission were risk factors. For each medication introduced during hospitalization, there was a 10% increase in the rate of adverse drug reaction. In the present study, the probability of observing an adverse drug reaction was 1 in 104 patients per day. Adverse drug reactions are frequent and potentially serious and should be better monitored in patients with chronic renal failure or prolonged hospitalization and especially in those on 'polypharmacy' regimens. The rational use of medications plays an important role in preventing adverse drug reactions.
Namazi, Soha; Sagheb, Mohammad Mahdi; Karimzadeh, Iman
To evaluate the pattern of immunosuppressive drug adverse reactions in adult kidney transplant recipients in Iran. Adult kidney transplant outpatients under immunosuppressive therapy were recruited into the study. All adverse drug reactions to immunosuppressants and their relevant clinical and paraclinical characteristics were recorded. Causality assessment was performed by the Naranjo algorithm. The seriousness of adverse drug reactions was determined by the World Health Organization definition. The Schumock and Thornton questionnaire was used to assess the preventability of adverse drug reactions. Statistical analyses were performed. A total of 1100 adverse drug reactions were detected from 120 kidney transplant recipients. Increased appetite (9.09%) was the adverse reaction reported most frequently. Causality assessment revealed that 1019 adverse drug reactions (92.64%) were possible. Forty adverse drug reactions (3.64%) were identified as serious. Six hundred seventy-one adverse drug reactions (61%) were preventable. Posttransplant duration was significantly correlated with the number of adverse drug reactions (R=0.19; P = .035). All renal allograft recipients experienced at least 1 immunosuppressant-related adverse reaction. Prolongation of immunosuppressive treatment resulted in an increase in adverse drug reactions.
Hadi, Muhammad Abdul; Neoh, Chin Fen; Zin, Rosdi M; Elrggal, Mahmoud E; Cheema, Ejaz
Globally, adverse drug reactions (ADRs), one of the leading causes of morbidity and mortality, will continue to pose a threat to public health as long as drugs are being used to treat various ailments. Prompt ADR reporting is crucial in ensuring drug safety. The aim of this narrative review was to highlight the role of pharmacists in pharmacovigilance and to identify barriers and facilitators toward ADR reporting documented in the literature. The perspective of pharmacy students on pharmacovigilance and ADR reporting has also been discussed with an aim to highlight the need to improve content related to ADR reporting and pharmacovigilance in undergraduate pharmacy curriculum. Globally, although the role of pharmacists within national pharmacovigilance systems varies, it is very well recognized. In general, pharmacists acknowledge that ADR reporting is part of their professional responsibility and have a positive attitude toward reporting ADRs. However, current research evidence suggests that there are still critical knowledge gaps with regard to ADR reporting among pharmacists, especially in countries where the role of pharmacists within the health care system is limited. These knowledge gaps can be fulfilled through continuous professional development programs and reinforcing theoretical and practical knowledge in undergraduate pharmacy curriculums. Without adequately identifying and fulfilling training needs of pharmacists and other health care professionals, the efficiency of national pharmacovigilance systems is unlikely to improve which may compromise patient’s safety. PMID:29354555
Reacções cutâneas adversas aos inibidores do receptor do factor de crescimento epidérmico: estudo de 14 doentes Adverse cutaneous reactions to epidermal growth factor receptor inhibitors: a study of 14 patients
and their management in patients undergoing treatment with cetuximab and erlotinib. PATIENTS AND METHODS: Between March/2005 and September/2009, we observed 14 patients with a mean age of 59.6 years undergoing treatment with cetuximab (7 or erlotinib (7, due to lung(10 or colorectal cancer (4. We evaluated the interval between introduction of the drug and onset of symptoms, treatment response, and the clinical pattern of evolution of the cutaneous reaction retrospectively. RESULTS: Twelve patients presented papular-pustular eruption typically affecting the face, chest and back, which appeared in average 13.5 days after starting the drug treatment. The patients underwent oral treatment with minocycline or doxycycline and topical treatment with metronidazole, benzoyl peroxide and/or corticosteroids. All patients showed improvement of the lesions. Five patients presented periungual pyogenic granulomas, which were associated with paronychia in 4 cases, after an average of 8 weeks of treatment. There was improvement of the lesions with topical treatment (antibiotics, corticosteroids and antiseptics. Xerosis was observed in some patients. Other less frequent adverse side effects such as telangiectasia and angiomas, hair and eyelash alterations, and eruptive melanocytic nevi were also described. Treatment with epidermal growth factor receptor inhibitor was maintained in most patients. CONCLUSION: The increasing use of these targeted therapies requires knowledge of their adverse cutaneous side effects to ensure timely intervention in order to allow the continuation of the therapy
Le, Patricia; Wood, Benjamin; Kumarasinghe, Sujith Prasad
The use of 2,4-dinitrophenol (DNP) has regained popularity as a weight loss aid in the last two decades due to increased marketing to bodybuilders and the increasing availability of this banned substance via the Internet. 2,4-DNP is a drug of narrow therapeutic index and toxicity results in hyperthermia, diaphoresis, tachycardia, tachypnoea and possible cardiac arrest and death. Skin toxicity from 2,4-DNP has not been reported since the 1930s. We report a case of a 21-year-old bodybuilding enthusiast who presented with a toxic exanthem after taking 2,4-DNP, and describe the first skin biopsy findings in a case of 2,4-DNP toxicity. © 2014 The Australasian College of Dermatologists.
DDI(Φ,didj) must be higher than 0 for a synergis- tic DDI-induced ADR. The higher the DDI score, the more severe is its effect. Data for drug-protein...pairs; and vestibular disorder (C0042594), 1,022 drug pairs. Figure 4 shows the model performance results, with bar heights representing mean AUC...Unified Medical Language System code C0035439), heat stroke (C0018843), spontaneous abortion (C0000786), and vestibular disorder (C0042594). These ADRs
Warrer, Pernille; Jensen, Peter Bjødstrup; Aagaard, Lise
information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about......Objective: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood......-glucose lowering medicines" (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood glucose lowering medicines" (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment...
Silas Arandas Monteiro e Silva
Full Text Available ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1 and SLC2 (S2. These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05, indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.
Ramesh V; Kumar Joginder
ABSTRACTLeishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus Leishmania, and transmitted by a bite of infected female sandfly. Primary cutaneous leishmaniasis is not common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety...
Akman, Canan; Duran, Arif; Kalafat, Utku Murat; Ocak, Tarık
Antibiotics are natural or synthetic substances that are used to control bacterial infections because antibiotics are by definition only effective against bacteria. A 30-year-old female came to our emergency clinic complaining rubor in both eyes, especially in the left eye, with swelling, rubor and pain in ears, and eruption in lips extremities. In her anamnesis, it has been determined that she did not have any medical disease that requires regular utilization of drugs. After the patient received cefuroxime axetil for acute tonsillitis, she observed eruptions in lip extremities on the 3rd day, but she did not care about it. On the 5th day, rubor in both eyes and, especially in the left eye, have been developed, and complaints such as unable to look toward light and pain have started together with swelling, rubor, and pain in both ears. She came to our clinic because she was very much worried about the situation. In this study, we aimed to discuss a drug reaction characterized by face and ear skin observations, due to uveitis after the use of antibiotics including cefuroxime axetil for acute tonsillitis.
Sandholdt, L H; Laurinaviciene, R; Bygum, Anette
Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized.......Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized....
Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro
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: firstname.lastname@example.org.
Angelis, Alessia De; Pancani, Luca; Steca, Patrizia; Colaceci, Sofia; Giusti, Angela; Tibaldi, Laura; Alvaro, Rosaria; Ausili, Davide; Vellone, Ercole
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.
Beyhan, Yunus E; Karakus, Mehmet; Karagoz, Alper; Mungan, Mesut; Ozkan, Aysegul T; Hokelek, Murat
To characterize the cutaneous leishmaniasis (CL) isolates of Syrian and Central Anatolia patients at species levels. Methods: Skin scrapings of 3 patients (2 Syrian, 1 Turkish) were taken and examined by direct examination, culture in Novy-MacNeal-Nicole (NNN) medium, internal transcribed spacer polymerase chain reaction and sequence analysis (PCR). Results:According to microscopic examination, culture and PCR methods, 3 samples were detected positive. The sequencing results of all isolates in the study were identified as Leishmania tropica. The same genotypes were detected in the 3 isolates and nucleotide sequence submitted into GenBank with the accession number: KP689599. Conclusion: This finding could give information about the transmission of CL between Turkey and Syria. Because of the Syrian civil war, most of the Syrian citizens circulating in Turkey and different part of Europe, this can be increase the risk of spreading the disease. So, prevention measurements must be taken urgently.
Yunus E. Beyhan
Full Text Available Objectives: To characterize the cutaneous leishmaniasis (CL isolates of Syrian and Central Anatolia patients at species levels. Methods: Skin scrapings of 3 patients (2 Syrian, 1 Turkish were taken and examined by direct examination, culture in Novy-MacNeal-Nicole (NNN medium, internal transcribed spacer polymerase chain reaction and sequence analysis (PCR. Results:According to microscopic examination, culture and PCR methods, 3 samples were detected positive. The sequencing results of all isolates in the study were identified as Leishmania tropica. The same genotypes were detected in the 3 isolates and nucleotide sequence submitted into GenBank with the accession number: KP689599. Conclusion: This finding could give information about the transmission of CL between Turkey and Syria. Because of the Syrian civil war, most of the Syrian citizens circulating in Turkey and different part of Europe, this can be increase the risk of spreading the disease. So, prevention measurements must be taken urgently.
Lindegaard Christiansen, Anne; Aagaard, Lise; Krag, Aleksander
and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. From the Danish Porphyria Register, we present the incidences and approximate prevalences of cutaneous porphyrias within the last 25 years. A total of 650 patients with porphyria...
Mallory, Emily K; Acharya, Ambika; Rensi, Stefano E; Turnbaugh, Peter J; Bright, Roselie A; Altman, Russ B
Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug. Understanding the complete space of drugs that are metabolized by the human gut microbiome is critical for predicting bacteria-drug relationships and their effects on individual patient response. Discovery and validation of drug metabolism via bacterial enzymes has yielded >50 drugs after nearly a century of experimental research. However, there are limited computational tools for screening drugs for potential metabolism by the gut microbiome. We developed a pipeline for comparing and characterizing chemical transformations using continuous vector representations of molecular structure learned using unsupervised representation learning. We applied this pipeline to chemical reaction data from MetaCyc to characterize the utility of vector representations for chemical reaction transformations. After clustering molecular and reaction vectors, we performed enrichment analyses and queries to characterize the space. We detected enriched enzyme names, Gene Ontology terms, and Enzyme Consortium (EC) classes within reaction clusters. In addition, we queried reactions against drug-metabolite transformations known to be metabolized by the human gut microbiome. The top results for these known drug transformations contained similar substructure modifications to the original drug pair. This work enables high throughput screening of drugs and their resulting metabolites against chemical reactions common to gut bacteria.
Kim, Mi Hyae; Hong, Ju Hee; Lee, Yeon Su; Cha, Kyung Soo; Chang, Suk Il; Lee, Young Chul; Kim, Yeong Soo
Gadopentetate dimenglumine(Gd-DTPA) has low toxicity and good tolerance and it is said that the observed adverse drug reaction of Gd-DTPA is compatible to those of iodinated nonionic contrast media. The overall incidence of adverse drug reaction of Gd-DTPA is even lower than those of iodinated nonionic contrast media. Then, the possibility of potential adverse drug reaction of these contrast media is not fully known and recently, many authors have a growing interest in this point. We have taken 2501 cases of MRI and executed 1467 case of Gd-DTPA enhancement scanning(58.7%) and experienced 12 cases of adverse drug reaction(11 cases: mild reaction, 1 case: severs anaphylactic shock) and the overall incidence of our adverse drug reaction of Gd-DTPA was 0.8%. In conclusion, the adverse drug reaction of Gd-DTPA is not rare and the severe adverse drug reaction of Gd-DTPA may occur. So, the possibility of adverse drug reaction after Gd-DTPA injection should always be kept in mind, especially when the patient has a history of reaction to contrast material, allergy(particularly asthma) and cardiac disease. For the safe use of Gd-DTPA, well trained personnel and nearby emergent care facilities should be available
Kim, Mi Hyae; Hong, Ju Hee; Lee, Yeon Su; Cha, Kyung Soo; Chang, Suk Il [Sung Ae Gernral Hospital, Seoul (Korea, Republic of); Lee, Young Chul; Kim, Yeong Soo [Chung Ang University Colege of Medicine, Seoul (Korea, Republic of)
Gadopentetate dimenglumine(Gd-DTPA) has low toxicity and good tolerance and it is said that the observed adverse drug reaction of Gd-DTPA is compatible to those of iodinated nonionic contrast media. The overall incidence of adverse drug reaction of Gd-DTPA is even lower than those of iodinated nonionic contrast media. Then, the possibility of potential adverse drug reaction of these contrast media is not fully known and recently, many authors have a growing interest in this point. We have taken 2501 cases of MRI and executed 1467 case of Gd-DTPA enhancement scanning(58.7%) and experienced 12 cases of adverse drug reaction(11 cases: mild reaction, 1 case: severs anaphylactic shock) and the overall incidence of our adverse drug reaction of Gd-DTPA was 0.8%. In conclusion, the adverse drug reaction of Gd-DTPA is not rare and the severe adverse drug reaction of Gd-DTPA may occur. So, the possibility of adverse drug reaction after Gd-DTPA injection should always be kept in mind, especially when the patient has a history of reaction to contrast material, allergy(particularly asthma) and cardiac disease. For the safe use of Gd-DTPA, well trained personnel and nearby emergent care facilities should be available.
Bohm, Kelley J; Ciralsky, Jessica B; Harp, Joanna L; Bajaj, Shirin; Sippel, Kimberly C
Severe cutaneous adverse reactions to drugs (SCARs) such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) serve as one of the main reasons for inpatient ophthalmic consultation. Although it is well-recognized that SJS/TEN is associated with severe ocular mucosal inflammation and cicatrizing, potentially blinding, sequelae, this association has not been described in relation to other SCARs. We present a patient fulfilling the diagnostic criteria for probable DRESS/DIHS but not for SJS/TEN, yet exhibiting the severe ocular surface involvement characteristic of SJS/TEN. Case report. A 64-year-old man presented with bilateral pseudomembranous conjunctivitis and conjunctival denudation (sloughing) in the setting of a maculopapular rash, fever, liver dysfunction, and hematologic abnormalities 1 month after initiating several medications. A skin biopsy was not consistent with SJS/TEN. The patient was diagnosed with probable DRESS/DIHS and treated with high-dose systemic corticosteroids. The ocular surface inflammation was addressed with intensive topical corticosteroid ointment. The pseudomembranes resolved over a 6-week period, but the patient exhibited residual conjunctival scarring of all palpebral surfaces. The development of severe ocular surface mucosal inflammation and denudation with cicatrizing sequelae in a patient carrying a diagnosis of DRESS/DIHS has diagnostic and therapeutic implications for the ophthalmologist. Careful ophthalmic assessment is indicated in any SCAR patient with ophthalmic symptoms, regardless of formal diagnosis. Furthermore, the early therapeutic interventions recently recommended in SJS/TEN to limit the ophthalmic cicatricial sequelae, such as systemic or topical corticosteroids, may be indicated.
Full Text Available Background: Many new psychotropic drugs/ agents have been developed and found to be effective in the treatment of psychiatric disorders. However, these drugs also exhibit adverse drug reactions (ADRs which may affect compliance in psychiatric patients. Hence the present study was aimed at monitoring and assessing ADRs caused by psychotropic drugs. Methods: A hospital based prospective observational study was carried out in the psychiatry outpatient department of a tertiary care teaching hospital for the duration of six months. Two hundred and two patients were included in the study and ADRs were documented using a predesigned data collection form. The causality assessment was carried out as per the criteria of both the World Health Organization- Uppsala Monitoring Centre (WHO-UMC and Naranjo scale. Severity and predictability assessment of ADRs were also performed. Results: A total of 106 ADRs were observed during the study period with majority of them occurring in 25-35 years of age group (40.56%. Weight gain (18.86% followed by sedation (16.03% and insomnia (11.32% were found to be the commonest ADRs. Risperidone (19.8% and escitalopram (12.3% were the drugs responsible for majority of the ADRs. Causality assessment showed that most of ADRs were possible and probable. 94.33% of ADRs were found to be mild and 89% of them were predictable. Conclusion: A wide range of ADRs affecting central nervous and metabolic systems were reported with psychotropic drugs. The study findings necessitate the need for an active pharmacovigilance programme for the safe and effective use of psychotropics.
Saini, V K; Sewal, R K; Ahmad, Yusra; Medhi, B
Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy.
Matsuda, Tomoko; Ly, Nhung Thi My; Kambe, Naotomo; Nguyen, Chuyen Thi Hong; Ueda-Hayakawa, Ikuko; Son, Yonsu; Okamoto, Hiroyuki
Hydroxychloroquine (HCQ) is an effective treatment of lupus erythematosus. Although adverse effects, mainly gastrointestinal and cutaneous manifestations, are rare, they may result in the cessation of medication in some patients with severe reactions. Therefore, the evaluation of a patient's condition is important for a dermatologist to decide whether to cease or continue HCQ. We herein report a case of a 36-year-old Japanese woman with systemic lupus erythematosus and cutaneous eruptions caused by the p.o. administration of HCQ. Because she wanted to continue the medication and had only mild cutaneous eruptions without any adverse effects in other organs, we continued HCQ with careful monitoring. All cutaneous eruptions disappeared within 1 week. We also reviewed published case reports on skin lesions that developed after HCQ treatments, and propose strategies for early cutaneous eruptions after HCQ treatments. When the cutaneous reactions are mild without any reactions in other organs, withdrawal of the drug is not required. However, when cutaneous eruptions are accompanied by some common reactions, HCQ needs to be stopped for a period of time and may subsequently be carefully re-administrated. © 2017 Japanese Dermatological Association.
Glauciene Santana Damasceno
Full Text Available OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%, the skin and appendages (21.4%, and the central and peripheral nervous systems (14.3%. Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. "Probable reactions" (75% predominated over "possible reactions" (24%. In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6% of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I. A high dropout rate from tuberculosis treatment (24.4% was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs.
Full Text Available Nicholas Moore,1 Charles Pollack,2 Paul Butkerait2 1Department of Pharmacology, Université de Bordeaux, Bordeaux, France; 2Pfizer Consumer Healthcare, Madison, NJ, USA Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. Keywords: adverse effects, nonsteroidal anti-inflammatory drugs, gastrointestinal, cardiovascular, renal
Full Text Available Cutaneous angiosarcoma is a rare malignant tumor showing blood or lymphatic vessel differentiation, corresponding to < 2% of all sarcomas. It preferably affects elderly, with predilection for the head and neck. Diagnosis is frequently late due to the early interpretation by the patient as a benign lesion similar to ecchymosis, which explains its aggressiveness with high metastasis and recurrence rates. We report the case of an elderly man whose histopathologic diagnosis confirmed the clinical suspicion of cutaneous angiosarcoma.
Ponnusankar, S; Tejaswini, M; Chaitanya, M
Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program.
Acne (46) was commonly reported reaction. Topical steroids, betamethasone sodium phosphate and clobetasol were reported to induce maximum number of reactions (59). Skin (227, 66.9%) was commonly affected organ system. Most of the adverse drug reactions were possible (240, 94.1%) and mild (222, 87%) in nature.
Mayorga, C.; Celik, G.; Rouzaire, P.; Whitaker, P.; Bonadonna, P.; Rodrigues-Cernadas, J.; Vultaggio, A.; Brockow, K.; Caubet, J. C.; Makowska, J.; Nakonechna, A.; Romano, A.; Montanez, M. I.; Laguna, J. J.; Zanoni, G.; Gueant, J. L.; Oude Elberink, H.; Fernandez, J.; Viel, S.; Demoly, P.; Torres, M. J.
Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because invivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation
Petersen, Lars Jelstrup; Skov, P S
BACKGROUND: Salmeterol is a long-acting beta2-agonist which in animal studies has been shown to possess anti-inflammatory effects on early (EAR) and late (LPR) phase allergic responses. PURPOSE: To evaluate the anti-inflammatory effects of intradermally injected salmeterol and salbutamol...... on clinical and biochemical EAR and LPR in human skin. METHODS: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and prostaglandin D2 (PGD2) release by microdialysis technique in EAR, and measurement of mediators in LPR...... by suction blister technique. RESULTS: Both beta2-agonists inhibited allergen-induced histamine release and wheal and flare reactions with maximum inhibition of 40-50% at 10(-6) M, a concentration which reduced PGD2 synthesis by approximately 55%. Histamine release by codeine and skin reactions to codeine...
Egron, Adeline; Olivier-Abbal, Pascale; Gouraud, Aurore; Babai, Samy; Combret, Sandrine; Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle
Antineoplastic drugs are one of the pharmacological classes more frequently involved in occurrence of "serious" adverse drug reactions. However, few epidemiological data are available regarding the preventability of adverse drug reactions with ambulatory cancer chemotherapy. We assessed the rate and characteristics of "preventable" or "potentially preventable" "serious" adverse drug reactions induced by oral protein kinase inhibitors (PKIs). We performed a retrospective study with all "serious" adverse drug reactions (ADRs) recorded from 1 January 2008 to 31 December 2009 in the French Pharmacovigilance Database with the eight oral protein kinase inhibitors marketed in France: sorafenib, imatinib, erlotinib, sunitinib, dasatinib, lapatinib, nilotinib and everolimus (Afinitor®) using the French adverse drug reactions preventability scale. This study was carried out on 265 spontaneous notifications. Most of adverse drug reactions were "unpreventable" (63.8 %). Around one third were "unevaluable" due to notifications poorly documented (medical history, dosage, use of drugs as first or second intention, concomitant drugs). One (0.4 %) adverse drug reaction was "preventable" with dasatinib (subdural hematoma) and three (1.1 %) were "potentially preventable" (hepatic adverse drug reactions): two with imatinib and one with sorafenib. For these four cases, we identified some characteristics: incorrect dosages, drug interactions and off-label uses. An appropriate prescription could avoid the occurrence of 1.5 % "serious" adverse drug reactions with oral PKIs. This rate is low and further studies are needed to compare our results by using other preventability instruments and to improve the French ADRs Preventability Scale.
Trubiano, Jason A; Strautins, Kaija; Redwood, Alec J; Pavlos, Rebecca; Konvinse, Katherine C; Aung, Ar Kar; Slavin, Monica A; Thursky, Karin A; Grayson, M Lindsay; Phillips, Elizabeth J
For severe cutaneous adverse reactions (SCARs) associated with multiple antibiotics dosed concurrently, clinical causality is challenging and diagnostic approaches are limited, leading to constricted future antibiotic choices. To examine the combined utility of in vivo and ex vivo diagnostic approaches at assigning drug causality in a cohort of patients with antibiotic-associated (AA)-SCARs. Patients with AA-SCARs were prospectively recruited between April 2015 and February 2017. In vivo testing (patch testing or delayed intradermal testing) was performed to the implicated antibiotic(s) at the highest nonirritating concentration and read at 24 hours through 1 week. Ex vivo testing used patient peripheral blood mononuclear cells (PBMCs) stimulated with a range of pharmacologically relevant concentrations of implicated antibiotics to measure dose-dependent IFN-γ release from CD4+ and CD8+ T cells via an enzyme-linked immunoSpot assay. In 19 patients with AA-SCARs, combined in vivo and ex vivo testing assigned antibiotic causality in 15 (79%) patients. Ten patients (53%) with AA-SCARs were positive on IFN-γ release enzyme-linked immunoSpot assay, with an overall reported sensitivity of 52% (95% CI, 29-76) and specificity of 100% (95% CI, 79-100), with improved sensitivity noted in acute (within 1 day to 6 weeks after SCAR onset) testing (75%) and in patients with higher phenotypic scores (59%). There was increased use of narrow-spectrum beta-lactams and antibiotics from within the implicated class following testing in patients with a positive ex vivo or in vivo test result. We demonstrate the potential utility of combined in vivo and ex vivo testing in patients with AA-SCARs to assign drug causality with high specificity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro
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.
Full Text Available Leishmaniasis is used to describe a spectrum of diseases caused by the parasitic protozoa leishmania spp. and transmitted by infected female sandflies. There are three main forms of the disease; cutaneous, mucocutaneous, and visceral. According to the World Health Organization, almost 12 million people from 98 countries worldwide are currently infected with leishmaniasis, while 350 million people are at risk. It was reported that 2 million new cases are diagnosed every year, with three-fourth are cutaneous leishmaniasis (CL cases. The scientific and medical communities have learnt a lot about CL during the 20th and early 21st centuries. However, the management and control of the disease remains a difficult task. This article was focused on the most common form of the disease, cutaneous leishmaniasis, and especially its epidemiological aspects and treatment.
Antico, A; Arisi, M; Lima, G
Paediatric age, active eczema and high number of allergens tested in poly-sensitized patients have been pinpointed as possible risk factors of systemic reactions by skin prick testing. As far as atopic eczema concerns, the higher penetration of the allergens into the skin because of the scraping or micro-injuries is an intuitive rationalization. Purpose of the present study is to provide documentary evidence that adverse reactions elicited by anomalous absorption of allergens can occur also in adult patients with apparently normal skin. Report of some exemplifying clinical and experimental observations. Measuring the inoculum volume into impaired skin and its variability in relation to the variation of the chemical-physical characteristic of the solutions used for the tests by means of a method of direct assay based on the use of a gamma-camera. Localized impairments of the skin permeability can cause a significant increase in inoculum volume by prick-test. Critical amounts of allergens can be introduced into the skin because of the possibility of direct absorption, also without pricking, of allergy diagnostic solutions. The greater water content of the solutions used for prick-testing can significantly increase the inoculum volume. This study adds clinical and experimental evidences that localized impairments of permeability can occur in adult patients with apparently normal skin. Special precautions should be taken when a change of the drops' normal shape and cohesion is seen, because allergy prick-testing in such areas is potentially associated with increased risk of large local or systemic reactions.
Quist, S R; Heimburg, A; Bank, U; Mahnkopf, D; Koch, G; Gollnick, H; Täger, M; Ansorge, S
Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body. To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families. Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography. Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel. It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up. © 2017 British Association of Dermatologists.
Azizi, Kourosh; Badzohreh, Abdollah; Sarkari, Bahador; Fakoorziba, Mohammad Reza; Kalantari, Mohsen; Moemenbellah-Fard, Mohammad Djaefar; Ali-Akbarpour, Mohsen
Geographical distribution of zoonotic cutaneous leishmaniasis (ZCL) has continuously been extended in recent years in Iran. The Beiza District is one of the newly-emerged endemic foci of ZCL in southern Iran. The main aim of the present study was to detect the vector(s) of ZCL in this area. To detect the fauna and vectors of ZCL in this district, sand flies were caught using sticky papers. Seventy randomly selected female sand flies out of 730 were molecularly investigated for Leishmania infection using species-specific nested polymerase chain reaction (PCR) assay between April and October 2010. A total of 2543 sand flies were caught. The fauna was identified as 10 species (five Phlebotomus spp. and five Sergentomyia spp.). Phlebotomus papatasi was the most dominant species both indoors and outdoors (37.55% and 16.35 %, respectively). L. major was detected in 5 out of 48 investigated Phlebotomus papatasi (10.41%). Sequence-based characterization was carried out to confirm the PCR findings. The positive samples were shown to have 75-88% similarity with L. major sequences in GenBank. According to the findings of the present study, similar to the other foci of ZCL in Iran, P. papatasi is the proven and primary vector of CL. This study could be drawn upon for future strategy planning in this newly emerged endemic focus.
Wall, Emma C; Watson, Julie; Armstrong, Margaret; Chiodini, Peter L; Lockwood, Diana N
This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998-2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were in soldiers. Polymerase chain reaction was more sensitive and faster for detecting Leishmania DNA (86% for Old World CL and 96% for New World CL) than culture. This is the largest study of imported leishmaniasis, and demonstrates that tourists to the Mediterranean and backpackers in Central and South America are at risk for this disease.
Narama, I; Kobayashi, Y; Yamagami, T; Ozaki, K; Ueda, Y
Canine pigmented epidermal nevus (CPEN) is a skin disorder of some breeds of dog characterized by multiple black plaques of the haired and non-haired skin. Three cases of pigmented cutaneous papillomatosis (previously described also as CPEN) in pug dogs were investigated histopathologically, immunohistochemically and electron microscopically. Additionally, DNA analyses with the polymerase chain reaction (PCR) were performed in two cases. Many nuclei of the stratum granulosa were diffusely immunolabelled for specific structural antigens of bovine papillomavirus (subgroup A), but nuclear inclusion bodies were not detected by retrospective examination of haematoxylin and eosin-stained sections of the affected skin. Aggregates of small numbers of viral particles (ranging from 37 to 43 nm in diameter) with a hexagonal structure were sparsely scattered throughout the nuclei of some of the superficial keratinocytes. PCR amplification targeted for the L1 gene of papillomavirus cloned from a case of CPEN yielded an expected fragment of 194-bp in the two CPEN cases examined but not in a case of canine oral papilloma.
Tian, Feng; Xie, Yanming
Following more and more new drugs are authorized into market, new, serious or unexpected adverse drug reactions appear frequently, which is a serious threat to people health and life. Through making laws and guidelines, governments of various countries aim to strengthen and standardize the surveillance and reporting of postmarketing drugs. The drugs management department of our country are doing related jobs positively, but there are some problems, such as drug risk-menagement is not emphasized well, and the management department lacks clarity on operating related regulations. This article tries to explore foreign countries' laws and regulations on the surveillance and reporting of postmarketing drugs, aiming to provide reference for our courtry.
Carneiro, Sueli Coelho da Silva; Azevedo-e-Silva, Melissa Chaves; Ramos-e-Silva, Marcia
Because the older group of the population is becoming more numerous, we see a high prevalence in drug adverse reactions among the elderly. Polypharmacy, which is the use of five or more medications, is one reason why this group has a greater risk of adverse drug reactions. Cutaneous adverse reactions to drugs are not always life threatening, but they can be an important factor for a poor quality of life among older patients. The potential benefits of appropriately prescribed medications are unquestionable, but the possibility of an adverse reaction must be recognized and prevented in older people so they can have a better quality of life. Copyright © 2011. Published by Elsevier Inc.
In the second of a two-part article on adverse drug reactions Agnes Kanneh describes the six 'rights' of the recipient of a drug. These are: that the right person should receive the right drug, in the right dose, at the right time within the right intervals, via the right route, followed by the right (correct) documentation. The author argues that the observance of these 'rights' by children's nurses ensures the best pharmacotherapeutic practice, thus a robust practical safeguard in adverse drug reactions and threats to the good reputation of the nursing profession.
Hagen-Plantinga, E A; Leistra, M H G; Sinke, J D; Vroom, M W; Savelkoul, H F J; Hendriks, W H
Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for identifying food allergens in dogs, by challenging dogs with specific food ingredients, selected on the basis of IgG reactivity in serum samples. A total of 24 adult dogs with CAFR were enrolled into the study and 16 healthy dogs were included as a control group. Blood samples were obtained for measurement of specific IgG antibodies against 39 commonly used pet food ingredients by ELISA. Participating owners were surveyed to obtain information on their pet's dietary history. Eleven healthy control dogs and 12 dogs with CAFR were subsequently challenged in a blinded cross-over design experiment with both positive and negative food ingredients, selected on the basis of the ELISA test results. There was substantial individual variation in ELISA test results to the various food allergens, but no significant difference in IgG reactivity comparing the CAFR and control groups. None of the control dogs developed any clinical signs of an allergic reaction during the dietary challenge study. In the CAFR group, six of 12 dogs developed clinical signs after the negative challenge, and two of nine dogs developed clinical signs after the positive challenge. It was concluded that the ELISA test for dietary allergen-specific IgG is of limited value in the management of dogs with CAFR. Copyright © 2017 Elsevier Ltd. All rights reserved.
Aagaard, Lise; Hansen, Ebba Holme
Background Information about safety issues from use of asthma medications in children is limited. Spontaneous adverse drug reaction (ADR) reports can provide information about serious and rarely occurring ADRs in children. Objective To characterize paediatric ADRs reported for asthma medications...
Testa, Bernard; Pedretti, Alessandro; Vistoli, Giulio
In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences. Copyright © 2012 Elsevier Ltd. All rights reserved.
Full Text Available Background: Acute dystonic reactions following the administration of safe, reliable drugs can occur and must be promptly recognized and treated in the emergency room.Phenomenology Shown: The entire clinical course of an acute dystonic reaction due to metoclopramide, from early motor signs to full-blown clinical symptoms and resolution.Educational Value: Providing elements for early recognition of a drug-induced movement disorder phenomenology.
Anacin; a brand of aspirin tablets (containing 300mg acetylsalicylic acid), is a widely used analgesics. It is recognized as ... Additionally, a detailed history should be taken prior to prescribing and appropriate reporting should be made to relevant health authorities when such severe reactions are observed. Keyword: Anacin ...
Nguyen, D V; Vidal, C; Chi, H C; Do, N T Q; Fulton, R; Li, J; Fernando, S L
HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/μL. The unit cost of this assay is less than $5 USD with total time of 110 minutes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
bleeding, deafness, erectile dysfunction and loss of libido, amenorrhoea, alopecia, insomnia, dry mouth, nausea, vomiting, nightmares, peripheral neuropathy, seizures, rashes, fever, weight gain and spontaneous tendon damage. The liver and kidney are important organs in metabolism and excretion of drugs, respectively.
psychiatry' yielded 113 entries, implicating a wide range of psychiatric drugs in ADRs. Most of these papers were case reports, but there are in addition a range of ADR studies over a number of years that have reported on psychiatric patient samples.
Aagaard, Lise; Christensen, Arne; Hansen, Ebba Holme
included empirically based articles on ADRs in populations aged 0 to 17 years. Studies monitoring ADRs in patients with particular conditions or drug exposure were excluded. We extracted information about types and seriousness of ADRs, therapeutic groups, age and gender of the child and category...
2. Embassy of India. 2006. Market survey on bulk drug and pharmaceutical products. [Online]. Embassy of. India. Available from the World Wide Web: . [Accessed 14 May, 2008]. 3. Pirmohamed M, Atuah K, Dodoo A, Winstanley P. Pharmacovigilance in developing countries. British.
Rates of spontaneous reports of adverse drug reactions for drugs reported in children: a cross-sectional study with data from the Swedish adverse drug reaction database and the Swedish Prescribed Drug Register.
Wallerstedt, Susanna M; Brunlöf, Gertrud; Sundström, Anders
Knowledge of drug safety is limited in the paediatric population, especially for drugs not used as labelled. Spontaneous reporting of adverse drug reactions (ADRs) may be an important source for increased knowledge, but the extent of the overall rate of reporting in children is not known. The main objective of the study was to determine the extent of the spontaneous reporting of ADRs in children with a focus on drugs not used as labelled; this involved investigations of reporting rates of individual case safety reports (ICSRs) per 1000 treated individuals for drugs reported in children, to compare these between drugs labelled and not labelled for use in children, and to compare the rates for children with those of adults. ICSRs (extracted from the Swedish ADR database) and number of treated individuals (extracted from the Swedish Prescribed Drug Register) were analysed for a 2-year period (2006-7). For drugs with one or more ICSR regarding children, rates of ICSRs per 1000 treated individuals were determined and compared between children (10% of the volume was sold over-the-counter or for in-hospital use were excluded. The overall reporting ratio of aggregated ICSRs per 1000 treated individuals was calculated between drugs not labelled and drugs labelled for use in children, separately for children and adults. The overall reporting ratio was also calculated between children and adults, separately for drugs labelled and drugs not labelled for use in children. A total of 255 (children) and 1402 (adults) ICSRs concerning 94 drugs were included in the analysis. Seventy-four (29%) and 711 (51%) ICSRs in children and adults, respectively, were registered as serious (p rates of ICSRs per 1000 treated individuals varied between (range) 0.01-6.45 (children) and 0.01-6.39 (adults). For 17 of the drugs (18%) the rates of ICSRs per treated individual were significantly higher for children than for adults, and for 2 of the drugs (2%) the result was the opposite. The overall
Calogiuri, G F; Muratore, L; Nettis, E; Casto, A M; Di Leo, E; Vacca, A
Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.
Arun Kumar Agnihotri
Aug 31, 2015 ... He regained his memory, no longer had bad dreams or demonstrated any irrational behavior or attitude. Physicians who are involved in the care of HIV infected patients need to be aware of the possibility of adverse Drug reactions occurring in patients who have been on antiretroviral drugs for years.
Levy, J H
Any drug or blood product administered in the perioperative period has the potential to produce a life-threatening allergic (immune reaction) called anaphylaxis. Anaphylactic reactions represent adverse reactions mediated by immunospecific antibodies (IgE and IgG) that interact with mast cells, basophils, or the complement system to liberate vasoactive mediators and recruit other inflammatory cells. Activation of humoral and cellular pathways produces characteristic responses in the respiratory (bronchospasm and upper airway edema), cardiovascular (vasodilation and increased capillary permeability), and cutaneous systems (wheal and flare). Other predictable adverse drug reactions may mimic anaphylaxis to produce similar physiologic consequences independent of allergy (immune responses). Rapid and timely cardiopulmonary intervention with airway maintenance, epinephrine, and volume expansion is essential to avoid an adverse outcome. Severe reactions may be protracted, especially during anesthesia, requiring even larger doses of catecholamines and intensive care observation.
Stevic, Marija; Milojevic, Irina; Bokun, Zlatko; Simic, Dusica
Preoperative use of midazolam sedation is mandatory during induction of anesthesia in noncooperative and hyperactive children to prevent possible obstacles. Unusual drug reactions rarely occur in patients undergoing anesthesia or in intensive care unit. This report describes an unpredictable drug reaction after a routine midazolam premedication in a patient with no history of allergy. There has been no literature data yet to show that midazolam can provoke respiratory problems in patients with Cornelia de Lange Syndrome. In our opinion midazolam should be avoided in patients with Cornelia de Lange Syndrome, which we enforced after first unpredictable reaction.
Bumbăcea, Roxana Silvia; Olariu, Sandra; Bumbăcea, Dragoş; Strâmbu, Irina
Hypersensitivity reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are a challenge to the clinicians, due to their severity. In susceptible individuals, NSAIDs induce a wide spectrum of reactions with various timing and organ manifestations, involving immunological and non-immunological mechanisms. Diagnosis of hypersensitivity to NSAID is based on characteristic symptoms precipitated with ASA/NSAIDs. Oral challenge with NSAID is the "gold standard" for the diagnosis and can be performed in order to confirm hypersensitivity to the culprit drug or to confirm or exclude tolerance to an alternative drug. Diagnosis process includes understanding of the underlying mechanism, and is mandatory for prevention of future events.
Buhari, Gözde Köycü; Keren, Metin; Dursun, Adile Berna; Güler, Müjgan; Dulkar, Güngör; Kalaç, Nilgün; Özkara, Şeref; Erkekol, Ferda Öner
Little is known about drug hypersensitivity reactions from antituberculosis drugs. To determine the frequency, risk factors, and characteristics of immediate-type hypersensitivity reactions from first-line antituberculosis drugs and to evaluate the usefulness of a readministration protocol for culprit drugs in this group of patients. The study population consisted of patients with tuberculosis who were hospitalized and treated in the authors' hospital in 2011. Demographics and disease and treatment characteristics of patients with immediate-type hypersensitivity from antituberculosis drugs were compared with the other patients. Culprit drugs were readministered gradually according to a defined protocol to patients with immediate-type hypersensitivity. Tree hundred seventy-nine patients were included in the study. Eighteen immediate-type hypersensitivity reactions were detected in 13 patients (3.43%). The only identified risk factor was female sex (odds ratio 4.085). Isoniazid, rifampicin, pyrazinamide, and ethambutol were readministered in 11 patients and rifampicin was readministered in 2 patients, with 6- to 8-step protocols for each drug. Only in 2 patients did allergic reactions with rifampicin develop during the procedure. In these patients, after treatment and complete remission of allergic symptoms, the last tolerated dose was administered and the protocol was completed with the same adjustments. Immediate-type allergic reactions from antituberculosis drugs are not rare and not related to disease or treatment characteristics. The protocols used in this study provide a useful and safe method for readministration of culprit drugs to patients with antituberculosis drug hypersensitivity. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Zhao, Qingying; Li, Min; Luo, Jun
In nanomachine applications towards targeted drug delivery, drug molecules released by nanomachines propagate and chemically react with tumor cells in aqueous environment. If the nanomachines release drug molecules faster than the tumor cells react, it will result in loss and waste of drug molecules. It is a potential issue associated with the relationship among reaction rate, release rate and efficiency. This paper aims to investigate the relationship among reaction rate, release rate and efficiency based on two drug reception models. We expect to pave a way for designing a control method of drug release. We adopted two analytical methods that one is drug reception process based on collision with tumors and another is based on Michaelis Menten enzymatic kinetics. To evaluate the analytical formulations, we used the well-known simulation framework N3Sim to establish simulations. The analytical results of the relationship among reaction rate, release rate and efficiency is obtained, which match well with the numerical simulation results in a 3-D environment. Based upon two drug reception models, the results of this paper would be beneficial for designing a control method of nanomahine-based drug release.
De Angelis, Alessia; Colaceci, Sofia; Giusti, Angela; Vellone, Ercole; Alvaro, Rosaria
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.
Full Text Available Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat and different modes of administration (intramuscular, intravenous and intraperitoneal injection and different times (15 min, 30 min and 60 min were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which
Olivry, Thierry; Bizikova, Petra
Several hydrolysate-based diets have been commercialized for helping diagnose or treat dogs with cutaneous adverse food reactions (CAFR). This systematic review was performed to examine the evidence in favour of reduced immunological and clinical allergenicity of hydrolysates in dogs with CAFR. Citation databases, meeting abstracts and article bibliographies were scanned for relevant citations, and companies were contacted to provide unpublished reports. Eleven studies relevant to this study were identified. Some evidence of reduced serum IgE binding to a soy hydrolysate (1 study) and decreased intradermal test reactivity to hydrolysed proteins (three studies) was found. In four reports, the feeding of dogs suspected of having CAFR with hydrolysate-based diets reduced or eliminated clinical signs in a variable proportion of subjects. The percentage of dogs with CAFR that still reacted to these hydrolysate-based diets could not be assessed, however. Importantly, up to 50% of dogs with CAFR enrolled in three controlled studies exhibited increases in clinical signs after ingesting partial hydrolysates derived from foods to which they were hypersensitive. In conclusion, the limited number of studies undertaken point to reduced - but not eliminated - immunological and clinical allergenicity of hydrolysate-based commercial diets. A variable proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Clinicians must weigh the clinical benefit of these diets versus their high cost and low risk of reduced appetence or gastrointestinal sign development. At this time, hydrolysate-containing diets are probably best used in dogs suspected not to be hypersensitive to their individual components.
de Almeida, Silvana Maria; Romualdo, Aruana; de Abreu Ferraresi, Andressa; Zelezoglo, Giovana Roberta; Marra, Alexandre R; Edmond, Michael B
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.
Steiner, Markus; Harrer, Andrea; Himly, Martin
Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions.
Mori, Francesca; Cianferoni, Antonella; Barni, Simona; Pucci, Neri; Rossi, Maria Elisabetta; Novembre, Elio
The drug provocation test (DPT) is the gold standard to rule out drug hypersensitivity. There are standardized DPT protocols to diagnose immediate reactions to drugs, but not for nonimmediate reactions. The aim of this study was to show the sensitivity and specificity of an allergy work-up that included a 5-day DPT in children with histories of nonimmediate reactions to amoxicillin through focusing on a pediatric population with histories of immediate and nonimmediate reactions to amoxicillin. Two hundred consecutive patients with histories of amoxicillin reactions referred to the Allergy Unit of Anna Meyer Children's Hospital for suspected drug allergy from 2008 to 2011 underwent in vivo tests with the culprit drug according to European Academy of Allergy and Clinical Immunology guidelines. Moreover, most of those children, regardless of the skin tests results, were challenged with amoxicillin for a total of 5 days. In 4 years, 200 patients were evaluated for a history of drug hypersensitivity to amoxicillin. The majority of patients (76%) had a history of mild nonimmediate reactions. All 200 patients underwent skin tests, and 9 of 200 tested positive. A total of 177 DPTs were performed with amoxicillin for 5 days in each child. Diagnosis of amoxicillin allergy was confirmed by a DPT in 17 patients (9.6%); 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5. According to our results, a long-term DPT protocol increases the sensitivity of the allergy work-up, and it should be recommended for patients with a history of amoxicillin nonimmediate reaction. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Full Text Available BACKGROUND The introduction of Highly Active Antiretroviral Therapy (HAART has led to a significant decrease in AIDS-related mortality and morbidity. However, adverse reactions to these drugs, being inevitable, have led to major obstacles in its success, especially in developing nations like India. Moreover, the latest changes made by W.H.O. in the treatment guidelines of ART naive patients would expectedly lead to changes in the Adverse Drug Reaction (ADR patterns as well. Hence, this study aimed at evaluating the ADRs of currently prescribed ART regimens in a tertiary care hospital in Kolkata (WB. METHODOLOGY 168 ART naive patients enrolled initially were studied prospectively over a period of 1 year; each patient being followed up individually for 6 months. All patients were asked to visit the ART centre once a month or whenever they developed any symptom. They were screened clinically and investigated suitably by the physician according to the latest NACO guidelines. RESULTS Majority were males (56% with an M:F ratio of 1:0.774; 93.3% patients belonging to the 15-49 yrs. age group. TDF+3TC+EFV (56% was the commonest 1st line regimen prescribed. 76.6% patients experienced ADRs. Total 184 ADRs were noted, of which, GIT contributed the most (27.17%. Majority (66.67% of neurological ADRs was contributed by neuropsychiatric manifestations. Rash (10.3% was the commonest cutaneous ADR. Anaemia (13.6% was the commonest haematological ADR with a statistically significant female preponderance. Most ADRs were grade 1 (63.04%. Majority ADRs were “possible” (65.76% while 34.24% were “probable” by Naranjo scale. Maximal ADRs (48.37% were noted from patients under AZT+3TC+NVP regime. IRIS was observed as a paradoxical reaction to ART in 10% cases. CONCLUSION It should not be forgotten that ADRs are the inevitable consequence of pharmacotherapy. Hence, proper implementation of current protocols designed for screening of patients especially during
Erkoçoğlu, Mustafa; Kaya, Aysenur; Civelek, Ersoy; Ozcan, Celal; Cakır, Banu; Akan, Aysegül; Toyran, Müge; Ginis, Tayfur; Kocabas, Can Naci
Despite drug-related hypersensitivity reactions are an important health problem, epidemiologic data on drug allergy and hypersensitivity are limited, and studies including diagnostic work-up are scarce. The aim of this study was to determine the actual frequency of immediate type drug hypersensitivity using diagnostic tests in school children with parent-reported drug allergies. This study involved three phases. The first phase is a survey of children with a mean age of 12.9 yrs attending grades 6-8 of primary schools with a questionnaire asking drug-related symptoms within 2 h of ingestion. The total population of sixth to eight grade school children was 210,000, and a sample size of 9096 was deemed to be representative of Ankara [(p) = 1.0%, α immediate type drug hypersensitivity reaction. Overall, 11,233 questionnaires were distributed, 10,096 of which were retrieved after completion by parents. The rate of parent-reported immediate type drug hypersensitivity was 7.87% (792 children). However, phone survey revealed a clinical history suggestive of drug allergy in only 117 children (1.16%). After further diagnostic work-up, the true frequency of immediate type drug hypersensitivity was 0.11%. Our results suggest that a positive clinical history is not enough to make a diagnosis of drug allergy, which highlights the significance of undertaking further diagnostic evaluation. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Testa, Bernard; Krämer, Stefanie D
This review continues a general presentation of the metabolism of drugs and other xenobiotics begun in three recent issues of Chemistry & Biodiversity. The present Part is dedicated to reactions of conjugation, namely methylation, sulfonation, and phosphorylation, glucuronidation and other glycosidations, acetylation and other acylations, the formation and fate of coenzyme A conjugates, glutathione conjugation, and the reaction of amines with carbonyl compounds. It presents the many transferases involved, their nomenclature, relevant biochemical properties, catalytic mechanisms, and the reactions they catalyze. Nonenzymatic reactions, mainly of glutathione conjugation, also receive due attention. A number of medicinally, environmentally, and toxicologically relevant examples are presented and discussed.
Helfenstein, M; Zweifel, S; Barthelmes, D; Meier, F; Fehr, J; Böni, C
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.
Because the drug-induced severe adverse reaction (SAR) is rare and often occur in the unexpected organs, the physician could be unfamiliar to SAR. In that case the early stage of the SAR is easy to overlook. So the Ministry of the Health and Welfare of Japan (MHLW) started the "Comprehensive project to deal with the disorders due to adverse drug reactions" as a four years plan since 2005. In this project, the MHLW published "the manual for handling disorders due to adverse drug reactions" in corporation with the academia. This manual is constituted by two parts, one is intended for the parents, and the other is for the general healthcare providers. In this article, the aim and the progress of the manuals and the brief summary of the SAR induced by the antibiotics will be explained. By the end of the June 2008, 29 manuals have been released, and 16 of them are antibiotics-related. It is needless to say that antibiotics are essential in the modern medical care, close monitoring of the symptom of SAR in untargeted organ is required in use of the antibiotics.
Bean, Daniel M; Wu, Honghan; Iqbal, Ehtesham; Dzahini, Olubanke; Ibrahim, Zina M; Broadbent, Matthew; Stewart, Robert; Dobson, Richard J B
Unknown adverse reactions to drugs available on the market present a significant health risk and limit accurate judgement of the cost/benefit trade-off for medications. Machine learning has the potential to predict unknown adverse reactions from current knowledge. We constructed a knowledge graph containing four types of node: drugs, protein targets, indications and adverse reactions. Using this graph, we developed a machine learning algorithm based on a simple enrichment test and first demonstrated this method performs extremely well at classifying known causes of adverse reactions (AUC 0.92). A cross validation scheme in which 10% of drug-adverse reaction edges were systematically deleted per fold showed that the method correctly predicts 68% of the deleted edges on average. Next, a subset of adverse reactions that could be reliably detected in anonymised electronic health records from South London and Maudsley NHS Foundation Trust were used to validate predictions from the model that are not currently known in public databases. High-confidence predictions were validated in electronic records significantly more frequently than random models, and outperformed standard methods (logistic regression, decision trees and support vector machines). This approach has the potential to improve patient safety by predicting adverse reactions that were not observed during randomised trials.
Diatta, B-A; Diallo, M; Diadie, S; Faye, B; Ndiaye, M; Hakim, H; Diallo, S; Seck, B; Niang, S-O; Kane, A; Dieng, M-T
In Senegal, reported cases of cutaneous leishmaniasis are often due to Leishmania major. Immunosuppression related to HIV infection contributes to the emergence of leishmaniasis in humans and to cutaneous localization of viscerotropic species. We report the first observed case in Senegal of opportunistic cutaneous leishmaniasis due to Leishmania infantum associated with HIV. A 5-year-old boy presented crusted ulcerative lesions of the scalp and left forearm, together with axillary and cervical lymphadenopathy present for two months. Direct parasitological examination of the scalp and arm lesions, coupled with liquid aspiration of lymph nodes and bone marrow, enabled identification of amastigote forms of Leishmania. Polymerase chain reaction performed on skin, lymph node and bone marrow biopsy samples allowed identification of L. infantum. The child was positive for HIV1. Treatment of HIV infection and leishmaniasis resulted in clinical improvement. Co-infection with cutaneous leishmaniasis due to L. infantum and HIV is a complex combination in terms of the related therapeutic issues. The clinical and laboratory outcomes depend on restoration of immunity and on the efficacy, safety and availability of anti-leishmaniasis drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés
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.
Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G M; Dheda, Mukesh; Haaijer-Ruskamp, Flora M; Taxis, Katja; Mol, Peter G M
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.
Full Text Available Nitrite, which is present in preserved meat and can be produced in the oral cavity by reduction of nitrate taken from vegetables, could react in stomach with nitrosatable drugs, giving genotoxic-carcinogenic N-nitroso compounds (NOC. The mutagenicity of reaction mixtures formed by sodium nitrite and selected sulfa-drugs (sulfathiazole, HST; phtalylsulfathiazole, PhST; complex Co(II-sulfathiazole, Co(II-ST in acidic medium was evaluated using the Salmonella typhimurium reverse mutation assay (Ames test, with TA98 and TA 100 strains. The reactions were carried out at room temperature, with a mole ratio [nitrite]/[sulfa-drug] > 1. The three reaction mixtures showed mutagenic effects in the considered range.
Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K
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.
Full Text Available Ceftriaxone is a third-generation cephalosporin antibiotic, which has broad-spectrum activity against Gram-positive and Gram-negative bacteria. It is a frequently used antibiotic in children worldwide. Studies revealed a number of adverse reactions related to this third generation antibiotic. A survey was done where data related with adverse drug reactions (ADRs were collected for three months from the Department of Pediatrics of a tertiary care hospital, Kolkata, West Bengal, India and then evaluated. In the study, fifteen ADRs were detected. Ceftriaxone itself or its combinations correlated with more than thirty three percent (33.4% adverse reaction cases in this study. Most common adverse drug reactions in the present study population were different types of rashes like urticaria and maculopapular eruptions.
La Russa, Raffaele; Finesch, Vittorio; Di Sanzo, Mariantonia; Gatto, Vittorio; Santurro, Alessandro; Martini, Gabriella; Scopetti, Matteo; Frati, Paola
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 email@example.com.
Dr. Rohan C. Hire
Full Text Available Abstract Objective: 1 To assess the adverse drug reactions of second line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR TB in central India on the basis of causality, severity and avoidability scales. 2 To study the relationship of type of MDR TB (primary or secondary and presence of diabetes mellitus (DM with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug resistant tuberculosis patients enrolled for DOTS‑Plus regimen at TB and Chest Disease Department from January to December 2012. They were followed for 9 months thereafter and encountered adverse drug reactions (ADRs were noted along with the time of sputum conversion. The data were analysed by Chi-square or Fisher’s exact test and unpaired student’s‘t’ test. Results: Total 64 ADRs were reported in 55 patients out of total 110 patients (n = 110. As per the Naranjo causality assessment of ADRs, 7 patients had “definite” causal relation, 45 had “probable” causal relation and 3 had “possible” causal relation with drugs of DOTS Plus regime. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being “Definitely avoidable”, 26 “Possibly avoidable”, 23 “Not avoidable” and 3 “unevaluable”. . Mean sputum smear conversion time is significantly higher in patients with secondary type than that of primary type of MDR TB (p = 0.0001 and in patients with DM than those without DM (p <0.0001. Conclusion: ADRs were common in patients of MDR TB on DOTs-Plus drug regime. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regime compared to DOTS regime in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and
Yu, He; Cornett, Claus; Larsen, Jesper; Hansen, Steen Honoré
Reactions between active drug substances and excipients are of interest in the drug formulation process and should also be considered in the following storage of final preparations. Some excipients react more readily with certain chemical groups in drug substances and in the present paper the ester formation between a drug substance having a carboxylic acid moiety and some polyols are described. The drug substance cetirizine was chosen as the model substance as it is already marketed and used as a common drug for treatment of allergic reactions. Among the marketed products are oral solutions and oral drops containing excipients like sorbitol and glycerol. It was found that the carboxylic acid cetirizine readily reacts with sorbitol and glycerol to form monoesters. At a temperature as low as 40 degrees C, more than 1% of the cetirizine content was transformed into a monoester within 1 week using concentrations similar to those used in marketed preparations. The kinetic studies of the reaction performed at 40, 60 and 80 degrees C also revealed that the esters were unstable and they degraded especially at higher temperatures. Analysis of two marketed preparations having expiry dates in 2011 showed content of the cetirizine esters corresponding to a range from 0.1 to 0.3% of the declared cetirizine content. Copyright (c) 2010 Elsevier B.V. All rights reserved.
Plaza, Jose Antonio; Morrison, Carl; Magro, Cynthia M
While some unequivocally benign infiltrates are easy to distinguish from cutaneous T-cell lymphoma (CTCL), drug-associated lymphomatoid hypersensitivity reaction and cutaneous lesions of collagen vascular disease can show cytologic atypia, clonality and an immunophenotypic profile that closely simulates CTCL and cause diagnostics difficulties. Similar immunophenotypic and molecular abnormalities to those of malignant lymphoma can also be observed in pityriasis lichenoides chronica (PLC), large plaque parapsoriasis (LPP), pigmented purpuric dermatosis (PPD) and atypical lymphocytic lobular panniculitis leading one to consider these entities as forms of cutaneous lymphoid dyscrasia. The purpose of our study was to evaluate the distinction of these various subcategories of cutaneous T-cell infiltrates by assessment of T-cell receptor (TCR)-beta gene rearrangement. Formalin-fixed paraffin-embedded skin biopsies from 80 patients containing a T-cell dominant lymphocytic infiltrate were analyzed for TCR-beta gene rearrangement. Our findings indicate that monoclonality is a reliable characteristic of CTCL with polyclonality being very infrequent. However, some cases of drug associated lymphomatoid hypersensitivity, collagen vascular disease and the various cutaneous lymphoid dyscrasias (i.e. PLC, PPD and atypical lymphocytic lobular panniculitis) could manifest restricted molecular profiles in the context of an oligoclonal process or frank monoclonality.
Marília Berlofa Visacri
Full Text Available The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.
Perry, Melissa E O; Almaani, Noor; Desai, Nemesha; Larbalestier, Nick; Fox, Julie; Chilton, Daniella
This case report describes two severe antiretroviral drug adverse reactions that occurred in the same patient. A 55-year-old HIV-positive African woman received a single epidural triamcinolone injection for pain relief of postherpetic neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's syndrome due to the drug-drug interaction between triamcinolone and her boosted protease inhibitor therapy. The patient's antiretroviral regimen was thus changed to replace her protease inhibitor with the integrase inhibitor raltegravir. Shortly after commencing the drug, the patient developed a severe adverse drug reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity syndrome presents with severe skin reaction as well as fever, rash, lymphadenopathy and internal organ involvement with marked eosinophilia. Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the potential for drug-drug interactions due to protease inhibitor-based therapy.
Lee, Sungmun; Al-Kaabi, Leena; Mawart, Aurélie; Khandoker, Ahsan; Alsafar, Habiba; Jelinek, Herbert F; Khalaf, Kinda; Park, Ji-Ho; Kim, Yeu-Chun
Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N 2 ) by chemical reaction when it reacts with hydrogen peroxide (H 2 O 2 ), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N 2 microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of H 2 O 2 . HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.
Oussalah, A.; Mayorga, C.; Blanca, M.; Barbaud, A.; Nakonechna, A.; Cernadas, J.; Gotua, M.; Brockow, K.; Caubet, J.-C.; Bircher, A.; Atanaskovic, M.; Demoly, P.; K Tanno, L.; Terreehorst, I.; Laguna, J. J.; Romano, A.; Guéant, J.-L.
Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations,
Conclusions: Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for >90% of cases.
de Vries, Tjalling W; van Roon, Eric N
OBJECTIVE: Randomised controlled trials (RCT) offer an opportunity to learn about frequency and character of adverse drug reactions. To improve the quality of reporting adverse effects, the Consort group published recommendations. The authors studied the application of these recommendations in RCTs
Aagaard, Lise; Hansen, Ebba Holme
Reporting of adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. In the European Union, more countries have allowed consumers to report ADRs directly to the regulatory agencies. The aim of this study was to characterize ADRs reported by European...
O'Connor, Marie N
adverse drug reactions (ADRs) are a major cause of morbidity and healthcare utilisation in older people. The GerontoNet ADR risk score aims to identify older people at risk of ADRs during hospitalisation. We aimed to assess the clinical applicability of this score and identify other variables that predict ADRs in hospitalised older people.
Conclusion: The results demonstrate a high incidence of ADRs in HIV-patients treated with HAART, which should be monitored closely during follow-up therapy. Keywords: HIV, AIDS, Highly active antiretroviral therapy (HAART), Adverse drug reaction. Tropical Journal of Pharmaceutical Research is indexed by Science ...
Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)
textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis
van Puijenbroek, E P; van Grootheest, K; Diemont, W L; Leufkens, H G; Egberts, A C
AIMS: Detection of new adverse drug reactions (ADR) after marketing is often based on a manual review of reports sent to a Spontaneous Reporting System (SRS). Among the many potential signals that are identified, only a limited number are important enough to require further attention. The goal of
van Puijenbroek, Eugène; Diemont, Willem; van Grootheest, Kees
The primary aim of spontaneous reporting systems (SRSs) is the timely detection of unknown adverse drug reactions (ADRs), or signal detection. Generally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative
Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl...
Kaguelidou, Florentia; Beau-Salinas, Frédérique; Jonville-Bera, Annie Pierre; Jacqz-Aigrain, Evelyne
Term and preterm neonates are at high risk for serious adverse drug reactions (ADRs). A descriptive study of reports registered in the French pharmacovigilance database from 1986 to 2012 were obtained. All reports concerning neonates (≤1 month of life) with direct drug exposure were retrieved. Characteristics of the reports, including reported ADR(s), drug(s) and the causality assessment using the French causality assessment method, were described. A total of 1688 reports were analyzed and more than half of them were classified as serious (n = 995). Median age at ADR occurrence was 9 days. Overall, 3127 ADRs were described in these reports in relation to 2238 suspect/interacting drugs. The most commonly reported system organ classes (SOCs) were injury, poisoning and procedural complications (16%), general disorders and administration site conditions (12.5%) and blood and lymphatic system disorders (12%). In the majority of ADRs reported (73%), infants fully recovered and less than 4% of neonates deceased as a consequence of the reported ADR. One out of five ADRs was associated with drug administration errors. Therapeutic classes commonly incriminated were anti-infectives, nervous system and alimentary tract drugs. Substances most frequently related to serious ADRs were zidovudine, ibuprofen and nevirapine. Among the 10 most frequently encountered drug-ADR pairs, two substances were mainly implicated, zidovudine in haematological adverse reactions and phytomenadione in maladministrations. Anti-infective drugs, mainly antiretroviral therapy, account for the majority of ADRs reported in neonates. The specific issue of drug maladministration and medication errors remains to be addressed in neonates. © 2016 The British Pharmacological Society.
Patel, Tejas K.; Patel, Parvati B.; Barvaliya, Manish J.; Tripathi, C. B.
Background: Epidemiological data on drug-induced anaphylactic reactions are limited in India and are largely depending on studies from developed countries. Aim: The aim was to analyze the published studies of drug-induced anaphylaxis reported from India in relation with causative drugs and other clinical characteristics. Materials and Methods: The electronic databases were searched for Indian publications from 1998 to 2013 describing anaphylactic reactions. The information was collected for demographics, set up in which anaphylaxis occurred, causative drugs, incubation period, clinical features, associated allergic conditions, past reactions, co-morbid conditions, skin testing, IgE assays, therapeutic intervention and mortality. Reactions were analyzed for severity, causality, and preventability. Data were extracted and summarized by absolute numbers, mean (95% confidence interval [CI]), percentages and odds ratio (OR) (95% CI). Results: From 3839 retrieved references, 52 references describing 54 reactions were included. The mean age was 35.31 (95% CI: 30.52–40.10) years. Total female patients were 61.11%. Majority reactions were developed in perioperative conditions (53.70%), ward (20.37%) and home (11.11%). The major incriminated groups were antimicrobials (18.52%), nonsteroidal antiinflammatory drugs-(NSAIDs) (12.96%) and neuromuscular blockers (12.96%). Common causative drugs were diclofenac (11.11%), atracurium (7.41%) and β-lactams (5.96%). Cardiovascular (98.15%) and respiratory (81.48%) symptoms dominated the presentation. Skin tests and IgE assays were performed in 37.03% and 18.52% cases, respectively. The fatal cases were associated with complications (OR =5.04; 95% CI: 1.41–17.92), cerebral hypoxic damage (OR =6.80; 95% CI: 2.14–21.58) and preventable reactions (OR =14.33; 95% CI: 2.33–87.97). Conclusion: Antimicrobials, NSAIDs, and neuromuscular blockers are common causative groups. The most fatal cases can be prevented by avoiding allergen
Demner-Fushman, Dina; Shooshan, Sonya E; Rodriguez, Laritza; Aronson, Alan R; Lang, Francois; Rogers, Willie; Roberts, Kirk; Tonning, Joseph
Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a drug may have, are one of the leading causes of morbidity and mortality during medical care. To date, there is no structured machine-readable authoritative source of known ADRs. The United States Food and Drug Administration (FDA) partnered with the National Library of Medicine to create a pilot dataset containing standardised information about known adverse reactions for 200 FDA-approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to exchange information about drugs and other products, were manually annotated for adverse reactions at the mention level to facilitate development and evaluation of text mining tools for extraction of ADRs from all SPLs. The ADRs were then normalised to the Unified Medical Language System (UMLS) and to the Medical Dictionary for Regulatory Activities (MedDRA). We present the curation process and the structure of the publicly available database SPL-ADR-200db containing 5,098 distinct ADRs. The database is available at https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and validating the data is available at https://github.com/lhncbc/fda-ars.
Full Text Available Aim To monitor the adverse drug reactions (ADRs caused by antihypertensive medicines prescribed in a university teaching hospital.Methods:he present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO, Government of India.Results:A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29 % than males, 7 (3.64 %. Combination therapy was associated with more number of adverse drug reactions (66.7 % as against monotherapy (33.3 %. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7, followed by diuretics (n = 5, and beta- blockers (n = 4. Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7, followed by torasemide (n = 3. Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8 % followed by musculo-skeletal complaints (23.8 % and gastro-intestinal disorders (14.3 %. Conclusions:The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.
Smithburger, Pamela L; Buckley, Mitchell S; Culver, Mark A; Sokol, Sarah; Lat, Ishaq; Handler, Steven M; Kirisci, Levent; Kane-Gill, Sandra L
Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. Multicenter, observational study : Medical ICUs at three academic medical centers. Adult patients (age ≥ 18 yr old) receiving medication therapy. All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication
Petrova, Guenka; Stoimenova, Assena; Dimitrova, Maria; Kamusheva, Maria; Petrova, Daniela; Georgiev, Ognian
Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig's Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig's Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people's everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for novphyllin (relative risk = 0
Clarke, John D; Cherrington, Nathan J
Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored.
Zhang, Xiao-Meng; Li, Fan; Zhang, Bing; Chen, Xiao-Fen; Piao, Jing-Zhu
The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication
Full Text Available An adverse drug reaction (ADR is a serious concern for practicing veterinarians and other health professionals, and refers to an unintended, undesired and unexpected response to a drug that negatively affects the patient's health. It may be iatrogenic or genetically induced, and may result in death of the affected animal. The ADRs are often complicated and unexpected due to myriad clinical symptoms and multiple mechanisms of drug-host interaction. Toxicity due to commonly used drugs is not uncommon when they are used injudiciously or for a prolonged period. Licosamides, exclusively prescribed against anaerobic pyoderma, often ends with diarrhoea and vomiting in canines. Treatment with Penicillin and β-lactam antibiotics induces onset of pemphigious vulgare, drug allergy or hypersensitivity. Chloroamphenicol and aminoglycosides causes Gray's baby syndrome and ototoxicity in puppies, respectively. Aminoglycosides are very often associated with nephrotoxicity, ototoxicity and neuromuscular blockage. Injudicious use of fluroquinones induces the onset of arthropathy in pups at the weight bearing joints. The most effective therapeutic measure in managing ADR is to treat the causative mediators, followed by supportive and symptomatic treatment. So, in this prospective review, we attempt to bring forth the commonly occurring adverse drug reactions, their classification, underlying mechanism, epidemiology, treatment and management as gleaned from the literature available till date and the different clinical cases observed by the authors.
Full Text Available A 24-year-old lady presented with four days history of fever, non-pruritic rash, ankle pain and swelling. She had consumed herbal supplement five days before the onset of symptoms. Examinations revealed erythematous maculo-papular lesions of varying sizes on sun exposed areas. Patient was suspected to have Drug Induced Lupus Erythematosus (DILE and subsequently symptoms subsided rapidly on withholding the herbal medication.
Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K
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.
Biersack, Bernhard; Ahmed, Khursheed; Padhye, Subhash; Schobert, Rainer
The versatile multicomponent Mannich reaction occupies a salient position in organic chemistry and drug design. Sound knowledge of its scope and variations and of the biological activities of Mannich bases is crucial for the development and improvement of drugs for various diseases. Areas covered: The following article provides an overview of the latest developments in the field of drugs based on the Mannich reaction. Web-based literature searching tools such as PubMed and SciFinder were applied to obtain useful articles. In addition, pertinent literature that was recently published by the authors is discussed in this manuscript. The chemical structures of bioactive Mannich bases are also given. Expert opinion: The Mannich reaction represents a feasible and cost-effective procedure with great potential for drug development. Several newly discovered Mannich bases exhibit sound activities against various human diseases as well as favorable pharmacokinetics. Thus, scientific research about Mannich bases is prospering and appears very attractive both for chemists and for clinicians.
Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne
%). 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. CONCLUSION: 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. FUNDING: none. TRIAL REGISTRATION: not relevant. ....
Myers, Amy P; Watson, Troy A; Strock, Steven B
The likelihood of a drug reaction with lamotrigine is increased by dose escalation that is too rapid or drug interactions that increase the concentration of lamotrigine. There is a well-documented interaction between valproic acid and lamotrigine in which lamotrigine levels are increased, subsequently increasing the risk of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. This syndrome is characterized by fever, lymphadenopathy, diffuse maculopapular rash, multivisceral involvement, eosinophilia, and atypical lymphocytes and has a mortality rate of 10-40%. We describe the first case, to our knowledge, of DRESS syndrome that was probably induced by a drug interaction between lamotrigine and ginseng. A 44-year-old white man presented to the emergency department after experiencing a possible seizure. His medical history included two other lifetime events concerning for seizures at ages 14 and 29 years old. After referral to the neurology clinic, he was diagnosed with generalized tonic-clonic seizure disorder, and lamotrigine was started with up-titration according to the drug's package insert to a goal dosage of 150 mg twice/day. The patient had also been taking deer antler velvet and ginseng that he continued during his lamotrigine therapy. On day 43 of therapy, the patient presented to the emergency department with a pruritic rash that had started on his extremities and spread to his torso. He was thought to have experienced a drug reaction to lamotrigine, and the drug was discontinued. Thirteen days later, the patient was admitted from the acute care clinic for inpatient observation due to laboratory abnormalities in the setting of continued rash, headache, and myalgias. His admission laboratory results on that day were remarkable for leukocytosis, with a white blood cell count up to 17.6 × 10(3) /mm(3) , with a prominent eosinophilia of 3.04 × 10(3) /mm(3) ; his liver enzyme levels were also elevated, with an aspartate
Deshpande, Rushikesh Prabhakar; Motghare, Vijay Motiram; Padwal, Sudhir Laxman; Pore, Rakesh Ramkrishna; Bhamare, Chetanraj Ghanshyam; Deshmukh, Vinod Shivaji; Pise, Harshal Nutan
Objectives The study was carried out with the aim of evaluation of the adverse drug reaction profile of anti-snake venom serum (ASV) in a rural tertiary care hospital. Methods An observational study was conducted in SRTR Medical College, Ambajogai, Maharashtra, India. A total number of 296 indoor case papers of snake bite from February to September 2011 and June to August 2012 were retrieved from the record section and the antivenom reactions were assessed. In addition, basic epidemiological data and prescribing practices of ASV were also analyzed. Results Vasculotoxic snake bites were more common (50.61%) than neuroparalytic ones (22.56%). Mild envenomation was the commonest presentation. A total of 92 (56.10%) patients who received ASV suffered from antivenom reactions. The most common nature of reaction was chills, rigors (69.56%) followed by nausea and vomiting (34.8%). 10-15% patients suffered from moderate to severe reactions like hypotension and sudden respiratory arrest. We did not find any dose response relationship of ASV to risk of reactions (odds ratio 0.37). Intradermal sensitivity test was performed in about 72% cases. Conclusion Our study showed a higher incidence of reactions to ASV at our institute. PMID:24396245
Full Text Available The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug-drug interaction (DDI and potential adverse drug reaction (ADR in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to identify risk factors for the occurrence of DDI and possible ADRs. All the statistical calculations were performed using SPSS; software. A total of 12,334 prescriptions were dispensed during the study period of which, 2,180 prescriptions were containing two or more drugs per prescription. A total of 21,210 drugs were prescribed and the average number of drugs per prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and Minor were analyzed and DDI were detected in 711 (32.6% prescriptions. Sex was not found to be a risk factor for the occurrence of DDI and ADR, while age and number of medications per prescription were found to be significant risk factors for the occurrence of DDI and ADR. The mean number of drugs per prescription was 1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar hospital was able to maintain the limit and prescriptions containing multiple drugs supposed to be taken systemically. Numbers of drugs per prescription as well as older age were found to be predisposing factors for the occurrence of DDI and potential ADRs while sex was not a risk factor.
Full Text Available The Veterinary Pharmacovigilance Centre received 59 reports of suspected adverse drug reactions during the period January 1998 - February 2001. The number of reports received increased after the establishment of a formal procedure for recording and responding to reports. The number of reports received per species was: dogs 19, cats 15, cattle 7, sheep/ goats 6, chickens 4, pigs 3, horses 2 and giraffe 1. Many different types of adverse reactions were reported, including lack of efficacy, hypersensitivity, inappropriate use of products by non-veterinarians, known adverse effects and adverse effects encountered with extra-label use of products.
Illing, Patricia T; Purcell, Anthony W; McCluskey, James
Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA) molecules enables presentation of a wide range peptide ligands thus maximising immune surveillance of pathogens. A consequence of the diversification of the HLA Ag-binding pocket is the enhanced opportunity for off-target binding of small drugs by HLA molecules, with subsequent immune reactivity. These potential off-target interactions are 'set up' to generate T cell-mediated adverse drug reactions even though the precise mechanisms of most HLA-drug interactions are still poorly understood. The association between abacavir hypersensitivity syndrome and HLA-B*57:01 is one exception that has been resolved at a molecular and mechanistic level. Here, we explore the road to understanding the interaction between abacavir and the HLA-B*57:01 molecule and review the current state of understanding of interactions between other drugs and HLA molecules implicated in adverse drug reactions, which appear to involve multiple mechanisms. The continued expansion of the pharmacopoeia generates an imperative to understand these interactions at the molecular level in order to prevent the continued burden on individuals and the health care system.
Full Text Available Context: Herbal drugs are a mixture of active compounds and the chemical complexity of each formulation increase with the possibility of interactions between them and conventional drugs. Many mechanisms are implicated in the interactions; scientific community has dedicated the attentions to enzymes as P-gp and CYP450. Aims: To investigate in the literature the principal plants with suspicions of adverse reactions in Cuba and their potential interactions with conventional drugs. Methods: PubMed was the database used as source of information until February 2014. Key words: Herb-Drug, Drug-Plant, Herbal–Drug, Interactions with scientific names of plants was used. Information was structured and analysed with EndNote X4. Analysis and integration of the information: Allium sativum L. (garlic was the plant with the high number of studies related with CYP450 and P-gp. Plants with great demand as Morinda citrifolia L. (noni, Psidium guajava L. (guayaba, Zingiber officinale Roscoe (ginger and Eucalyptus spp. (eucalyptus have a very small number of studies. The professionals of the health should keep in mind the possibility of interactions between herbal products and conventional drugs to increase the effectiveness of phytotherapy. Conclusions: It is necessary enhance reports and investigations and to put to disposition of the system of health information on the interactions of plants and to stimulate the investigation that offers information for the rational use of our medicinal plants.
von Stebut, E; Sunderkötter, C
Infections with Leishmania are increasing worldwide because of tourism and job-related travel; central Europe is no exception. Infections often first become apparent after return from an endemic region. Depending on the Leishmania species and the host immune status, different forms of cutaneous (CL), mucocutaneous (MCL) (L. brasiliensis complex) or visceral leishmaniasis (L. donovani as well as L. infantum) may develop. CL may heal spontaneously with scarring but can evolve into diffuse CL (with reduced immune response to L. amazonensis, L. guyanensis, L. mexicana or L. aethiopica) or into recurrent CL. Diagnostic criteria include travel to an endemic area as well as ulcerated plaques or nodules on an exposed site which show no tendency towards healing over 3-4 weeks. Differential diagnostic considerations include ecthyma, other infectious ulcers, and malignant neoplasms. The diagnosis is confirmed by finding Leishmania in a smear or tissue biopsy, as well as by culture. Therapy options range from topical treatment of simple CL of the Old World caused by L. major to systemic therapy which is needed for most complex cases of CL as well as MCL. Miltefosine is a less toxic option to replace the antimony compounds.
Ruokolainen, Miina; Gül, Turan; Permentier, Hjalmar; Sikanen, Tiina; Kostiainen, Risto; Kotiaho, Tapio
The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and
Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S
The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased
Johnson Segun Showande
Full Text Available Adverse drug reaction (ADR is poorly reported globally but more in developing countries with poor participation by health professionals. Currently, there is no known literature on the Nigerian pharmacy students’ knowledge on ADR reporting. Hence the purpose of this study was to find out the level of knowledge of pharmacy students on the concept of pharmacovigilance and adverse drug reaction reporting and also to evaluate their opinions on the National Pharmacovigilance Centre guidelines on adverse drug reaction reporting. A pretested 34-item semi-structured questionnaire was administered among 69 pharmacy undergraduate students in their penultimate and final years that consented to take part in the study, in one of the universities in Nigeria. The study was carried out strictly adhering to the principles outlined in the Helsinki declaration of 1964, which was revised in 1975. The questionnaire used had four sections which included a section on biographical data, a section which evaluated the students knowledge on the concept of pharmacovigilance and adverse drug reaction reporting, a section on students personal experiences of adverse drug reactions and modes of reporting them and the final section of the questionnaire evaluated the students’ opinions on the National Pharmacovigilance Centre guidelines for reporting adverse drug reactions. Descriptive statistics, Mann-Whitney U and Kruskal Wallis statistical tests were used to analyze the data obtained. None of the participants knew the sequence of reporting ADR. More than half, 40(58.0% had heard about pharmacovigilance at symposiums, 7(10.1% during clinical clerkship program and 18(26.1% from media jingles. Twenty nine (42.0% agreed that pharmacovigilance was in their curriculum, however only 16(23.2% could define the term correctly. None of the participants had seen or used an ADR form prior to the study, but the students could easily identify and describe the type of ADR they had
Muren, C.; Strandberg, O.
The case histories of two patients with cavitary pulmonary nodules and the findings at chest radiography are reviewed. The first patient had a connective tissue disease with features common to systematic lupus erythematosus and Wegener's granulomatosis. In the second patient the lung changes developed as part of a drug reaction to carbamezapine and/or phenytoin. The common denominator of the cavitating nodules is probably the presence of granulomas, developing as a sequela of pulmonary vasculitis. (orig.).
Smith, Robert J; Boos, Markus D; McMahon, Patrick
A 9-year-old boy presented with fever, rash, anterior cervical lymphadenopathy, high liver enzymes, atypical lymphocytosis, and eosinophilia (drug reaction with eosinophilia and systemic symptoms [DRESS]). His history was notable for having taken griseofulvin for 3 weeks prior to onset of these findings. He improved after treatment with oral prednisone. We present a rare case of probable DRESS secondary to griseofulvin. © 2016 Wiley Periodicals, Inc.
Baniasadi, Shadi; Habibi, Maryam; Haghgoo, Roodabeh; Karimi Gamishan, Masoumeh; Dabaghzadeh, Fatemeh; Farasatinasab, Maryam; Farsaei, Shadi; Gharekhani, Afshin; Kafi, Hamidreza; Karimzadeh, Iman; Kharazmkia, Ali; Najmeddin, Farhad; Nikvarz, Naemeh; Oghazian, Mohammad Bagher; Rezaee, Haleh; Sadeghi, Kourosh; Tafazzoli, Ali; Shahsavari, Nahid; Fahimi, Fanak
Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents' involvement in the ADR reporting program could improve the ADR reporting system. PMID:24734083
Chowdhury, Dipak K; Sarker, Haripada; Schwartz, Paul
In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.
Cliff-Eribo, Kennedy Obebi; Sammons, Helen; Choonara, Imti
To perform a systematic review of studies describing paediatric adverse drug reactions (ADRs) conducted from national pharmacovigilance databases. A systematic literature search of studies describing results for paediatric ADRs from national pharmacovigilance databases was performed. PubMed database, Embase and MEDLINE were searched up to March 2015. The descriptive studies included were analysed for country of origin, reporters, and ADR reporting rate, drugs, ADRs and number of fatalities. 20 studies were identified. Doctors were the largest group of reporters in all the studies, and with more consumer reports seen in USA. The studies ranged from 3 - 37 years. The highest ADR reporting rate was 1458 reports per year per million children in Cuba. Antibiotics and vaccines were the most frequently reported drugs, in almost all the studies. The most frequent ADRs were skin and nervous system disorders. The highest proportion of fatalities and serious reports was from North America. Drugs used for treating attention deficit hyperactivity disorders (ADHD) and isotretinoin were the most frequently reported drugs for ADRs in North America. There were geographical differences in drugs responsible for ADRs and their seriousness, especially in North America. Very few studies were conducted in Asia and Latin America, none were found from Africa.
Namazi, Soha; Borhani-Haghighi, Afshin; Karimzadeh, Iman
To evaluate the pattern and possible risk factors of adverse reactions to antiepileptic drugs (AEDs) in epileptic outpatients in Iran. We conducted a cross-sectional study for a period of 1 year on epileptic outpatients under antiepileptic therapy. All present adverse drug reactions (ADRs) to antiepileptics and their clinical and paraclinical characteristics were recorded. Causality assessment was performed by the Naranjo algorithm. Seriousness of ADRs was assessed by the World Health Organization's definition. Schumock and Thornton questionnaire was applied to determine the preventability of ADRs. Statistical-descriptive analyses were performed. A total of 1055 adverse reactions to AEDs were recorded from 201 epileptic outpatients. Their mean ± SD age was 28.63 ± 15.06 years. The most frequent detected adverse reactions to AEDs were sedation (7.29%) and amnesia (6.35%). According to the Naranjo algorithm, 604 (57.25%) ADRs were possible. The rate of preventable ADRs was 57%. Only 8 (0.76%) ADRs were identified as serious. No statistically significant association was found between the number of ADRs and age, sex, type of epilepsy, and AED generation (P > 0.05). In contrast, polytherapy was associated with more ADRs than monotherapy (P = 0.039). According to multivariate logistic regression analysis, females were at a higher risk of experiencing an adverse reaction to AEDs than males (odds ratio, 3.676; 95% confidence interval, 1.198-11.283; P = 0.023). Adverse reactions to AEDs were very common among epileptic outpatients. The female sex was identified as a risk factor for experiencing an ADR.
Jorge Enrique Machado-Alba
Full Text Available This study describes the adverse drug reactions (ADRs and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART. A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years; these patients were from a cohort of 1 364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9. The cohort was mostly female (366, 87.4% and had a mean age of 52.7 years (± 13.1. The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively. The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.
Finkelstein, Joseph; Chen, Qinlang; Adams, Hayden; Friedman, Carol
Academic literature provides rich and up-to-date information concerning adverse drug reactions (ADR), but it is time consuming and labor intensive for physicians to obtain information of ADRs from academic literature because they would have to generate queries, review retrieved articles and summarize the results. In this study, a method is developed to automatically detect and summarize ADRs from journal articles, rank them and present them to physicians in a user-friendly interface. The method studied ADRs for 6 drugs and returned on average 4.8 ADRs that were correct. The results demonstrated this method was feasible and effective. This method can be applied in clinical practice for assisting physicians to efficiently obtain information about ADRs associated with specific drugs. Automated summarization of ADR information from recent publications may facilitate translation of academic research into actionable information at point of care.
Sauer, Brian; Nebeker, Jonathan; Shen, Shuying; Rupper, Randall; West, Suzanne; Shinogle, Judith A; Xu, Wu; Lohr, Kathleen N; Samore, Matthew
We present a framework for detecting possible adverse drug reactions (ADRs) using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs): known reactions (gastrointestinal, psychological disturbances), potential reactions (respiratory disturbance), novel reactions (hepatic, hematological disturbances), and death. Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression. Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6) in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3). We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential ADEs and generate hypotheses for future investigations
Full Text Available Introduction and objectives: drug use is associated with multiple complications with an increase in morbidity, with death by acute drugs reactions (ADR being the most serious. A large percentage of the prison population has problems associated with drug additions, and substance abuse is also a common internal problem of penal institutions, despite their control measures. The goal of this study is to analyse the prevalence of ADR in penitentiaries, deceased sociodemographic characteristics as well as the circumstances in which they are produced. Material and methods: All deaths by ADR between 2001-2010 in Galicia are studied, in particular, those deaths that took place inside prisons. Results: In the whole sample (n=510 male (90.6%, single (46.1% with an average age of 35.8 and with a prevalent factor of long experience in drug abuse. Thirty seven of them died in Penal/Correctional Institutions, representing 7.3% of the total sample. The characteristics of this population subtype were similar to the total sample (average age: 34.7 years; 89.2% were males but we found significant differences regarding the substances detected. Discussion: ADR is the most frequent cause of death among drug addict convicts in prisons. The pattern of the detected substances in the toxicological analysis as well as the socio-demographic characteristics can help to establish a higher risk profile and preventive measures.
Miguel-Arias, D; Pereiro-Gómez, C; Bermejo-Barrera, A M; Vázquez-Ventoso, C; Rodríguez-Barca, T
drug use is associated with multiple complications with an increase in morbidity, with death by acute drugs reactions (ADR) being the most serious. A large percentage of the prison population has problems associated with drug additions, and substance abuse is also a common internal problem of penal institutions, despite their control measures. The goal of this study is to analyse the prevalence of ADR in penitentiaries, deceased sociodemographic characteristics as well as the circumstances in which they are produced. All deaths by ADR between 2001-2010 in Galicia are studied, in particular, those deaths that took place inside prisons. In the whole sample (n=510) male (90.6%), single (46.1%) with an average age of 35.8 and with a prevalent factor of long experience in drug abuse. Thirty seven of them died in Penal/Correctional Institutions, representing 7.3% of the total sample. The characteristics of this population subtype were similar to the total sample (average age: 34.7 years; 89.2% were males) but we found significant differences regarding the substances detected. ADR is the most frequent cause of death among drug addict convicts in prisons. The pattern of the detected substances in the toxicological analysis as well as the socio-demographic characteristics can help to establish a higher risk profile and preventive measures.
Full Text Available Drugs used for the treatment of cardiovascular disorders are frequently reported to cause adverse drug reactions (ADRs, second only to antimicrobials. ADRs strain the patients′ health and finances further and could prove fatal too. Pharmacovigilance programs aim to detect, monitor and understand ADRs in order to prevent them. Pharmacovigilance provides vital input to drug regulatory agencies to monitor safety of new as well as old drugs. Spontaneous reporting of suspected ADRs by healthcare professionals forms the backbone of pharmacovigilance programs worldwide including the Pharmacovigilance Program of India (PvPI launched in 2010. The PvPI has significantly contributed to strengthening pharmacovigilance in India but suffers from under-reporting of ADRs like similar programs worldwide. Consumer-initiated reporting of ADRs incorporated in pharmacovigilance programs of several countries has been found to decrease under-reporting rates besides supplementing traditional pharmacovigilance information. The PvPI has recently introduced the facility for consumers to report ADRs by contacting a hotline (1800-180-3024, through e-mail (firstname.lastname@example.org or by filling specifically designed ADR reporting forms, either in English language or vernacular translations, and submitting them to the nearest ADR monitoring centre. This is a welcome step in empowering patients as consumers of drugs with the mechanism to monitor their safety. It could potentially fill the huge gap in spontaneous ADR reporting and supplement the indigenous drug safety database with patients′ perspectives regarding ADRs e.g. effect on their quality of life. Whether it encourages rational prescription practices by doctors or enhances transparency regarding safety of investigational drugs in clinical trials needs to be seen.
Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David
Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.
Hall David Jeffrey
Full Text Available Abstract Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. Case presentation We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Conclusion Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.
Aziz, Zoriah; Siang, Tan Ching; Badarudin, Nurul Suhaida
Malaysia like many other countries worldwide uses spontaneous reporting systems as a mean of collecting data on suspected adverse drug reaction (ADR). However, compared to other countries, which use the system, the reporting rate in Malaysia is very low. Why some physicians do not report ADRs is not well understood. To identify factors, which would predict physicians' failure to send ADR reports. Face-to-face interview using a structured questionnaire involving physicians working at the University of Malaya Medical Centre, Malaysia. About a third of the physicians in the Centre participated. Sixty-five of the 415 approached refused to participate. A high proportion of the respondents (81.4%) indicated that they had suspected an ADR but did not report it, while about 40% of the respondents were not aware of the existence of the national reporting system in Malaysia. Logistic regression modelling identified the variable 'ADR considered to be too trivial or too well known to report' as the strongest predictor of not reporting, followed by physicians' category and uncertainty that the reaction had been definitely caused by a drug. Important predictor variables, which limit physicians from reporting ADR in Malaysia, were related to uncertainty of types of reaction to report, lack of awareness about the existence, function and purpose of national ADR reporting. The findings could be useful for planning strategies to improve the reporting rate.
Bérard, C; Cerruti, L; Cotteret, C; Lebel, D; Bussières, J-F
As part of our antimicrobials stewardship program, we were interested in the use of antimicrobials and prevalence of adverse drug reactions associated with the use of these drugs. The retrospective and descriptive study was conducted over a one year-period between April 1st 2012 and March 31st 2013 in a mother-child Hospital. We determined the ratio: number of adverse drug reactions over 10,000 defined daily dose or 10,000days of therapy. We identified the ratios higher than average for which the confidence interval did not cross the calculated average. The severity of the adverse drug reactions was codified using the Common Terminology Criteria for Adverse Events. We found 570 adverse drug reactions including 100 (17.5%) adverse drug reactions related to antimicrobials during the financial year 2012-2013. It represented 96 patients. Thus, five antimicrobials, for which the confidence interval does not cross the calculated average value, may be targeted in risk management because they have a higher ratio than average: piperacillin (290 [113-722]), valganciclovir (244 [43-1260]), ceftriaxone (114 [56-234]), acyclovir (76 [26-220]) and liposomal amphotericin B (72 [20-258]). In a mother-child university hospital, we calculated a ratios of 19 [15-23] and 13 [10-15], it allows us targeting some antimicrobials in our approach to prevention and management of adverse drug reactions. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.
Borgsteede, Sander; Van Puijenbroek, Eugene; Van Grootheest, Kees
Background: The Reporting Odds Ratio (ROR) is one of the expressions to analyse disproportionallity of adverse drug reactions (ADRs) in a spontaneous reporting system. The ROR is defined as the extent to which the association between a suspected drug and ADR stands out against the background
Saint-Martin, Caroline; Kanagaratnam, Lukshe; de Boissieu, Paul; Azzouz, Brahim; Abou Taam, Malak; Trenque, Thierry
To describe the adverse drug reactions (ADR) and the drugs involved in pediatrics. An observational study on all ADR notifications recorded in the French pharmacovigilance database by the Regional Pharmacovigilance Center of Champagne-Ardenne between 1 January 1985 and 31 December 2014 involving children from 0 to 17 years inclusive was performed. For all notifications, we studied the patient and the ADR characteristics. During the study period, 632 notifications were collected. The most frequently reported ATC (anatomical, therapeutic and chemical) classes were vaccines (15.9%), antineoplastics (12%) and antibiotics (11.1%). Forty-six percent of the notifications were serious. For serious ADRs, the most involved drugs were paracetamol, asparaginase and ibuprofen. Skin reactions were the most often reported ADRs. The most common lowest level terms (LLT) were urticaria (4.9%), hypersensitivity (4.1%), fever (2.9%) and vomiting (2.8%). ADR reporting to the pharmacovigilance system, in particular pediatric ADRs, should be encouraged. Information on the use of medicinal products, especially on self-medication use, need to be improve. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid. A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily. Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment. Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.
Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza
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.
Full Text Available Older patients are at an increased risk of developing adverse drug reactions (ADR. Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1 develop and (2 validate an ADR risk prediction model.We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset.Six-hundred-ninety patients (median age 85 years were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively.We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days, some of which have not been previously reported.
Bae, Kyung Soo; Jeon, Kyung Nyeo; Moon, Jin Il; Choi, Bo Hwa; Baek, Hye Jin; Cho, Soo Buem [Dept. of Radiology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon (Korea, Republic of); Lee, Sang Min; Ha, Ji Young; Choi, Dae Seob; Cho, Jae Min; Na, Jae Beom [Dept. of Radiology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)
To evaluate the incidence, severity, and risk factors of adverse drug reactions (ADR) to intravenous administration of nonionic iodinated contrast media in computed tomography (CT), and to determine the recurrence rate after premedication in patients with a previous history of ADR. We prospectively recorded all ADR to intravenous CT contrast media in 32313 consecutive outpatients (54572 cases) who underwent contrast enhanced CT examinations. Clinical report forms and electronic medical records were reviewed to search for the incidence of ADR, treatment, and clinical outcome of patients. The risk factors of ADR to CT contrast media (age, sex, history of previous ADR, season) were evaluated using statistical analysis. Of the 54572 cases, a total of 191 (0.35%) had adverse reactions. Of the 191 cases, 157 (82%) were categorized as mild reactions, 29 (15%) were moderate, and 5 (3%) were severe. A total of 165 (86.4%) cases had acute adverse reactions (which occurred within 1 hour after administration), while 26 (13.6%) had delayed adverse reactions (occurred 1 hour after the administration). The rate of ADR was significantly higher in females [relative risk (RR) = 2.05, 95% confidence interval (CI) 1.53-2.75], patients under the age of 60 years (RR = 1.45, 95% CI 1.07-1.98), patients with a history of previous ADR (RR = 6.51, 95% CI 3.13-13.57), and in the spring season (RR = 1.44, 95% CI 1.07-1.95). The recurrence rate after premedication in patients with previous ADR to CT contrast media was 3.2% (8/247). No deaths occurred that were attributed to the contrast media. The incidence of ADR to nonionic CT contrast media was 0.35%; most of which were mild reactions. Risk factors for ADR included female gender, an age of under 60 years, a history of previous ADR, and spring season.
Gurmesa, Lense Temesgen; Dedefo, Mohammed Gebre
Background. Adverse drug reactions are global problems of major concern. Adverse drug reaction reporting helps the drug monitoring system to detect the unwanted effects of those drugs which are already in the market. Aims. To assess the knowledge, attitude, and practice of health care professionals working in Nekemte town towards adverse drug reaction reporting. Methods and Materials. A cross-sectional study design was conducted on a total of 133 health care professionals by interview to asse...
Sabrina Sisto Alessi
Full Text Available INTRODUCTION: There are various approaches to the treatment of cutaneous tumors; one of them is treatment with imiquimod, a synthetic toll-like receptor agonist with a low molecular weight that offers a topical, noninvasive, and non-surgical therapeutic option. The main objective of our study was to provide data on 89 patients who used a 5% imiquimod cream for the treatment of cutaneous tumors at the Cutaneous Oncology Group of the Dermatology Department of Hospital das Clinicas from 2003 to 2008. MATERIALS AND METHODS: Here, we present our experience in the treatment of 123 cutaneous tumors of various types, including basal cell carcinoma (BCC, squamous cell carcinoma (SCC, Bowen's disease, erythroplasia of Queyrat, Paget's disease, and trichoepithelioma, with 5% imiquimod cream from 2003 to 2008 in the Cutaneous Oncology Group of the Dermatology Department of Hospital das Clinicas. Patients were divided into two separate groups according to their diagnosis and comorbidities; these comorbidities included epidermodysplasia verruciformis, xeroderma pigmentosum, albinism, basal cell nevus syndrome, Brooke-Spiegler syndrome, HIV, chronic lymphocytic leukemia, B-cell lymphoma, and kidney transplantation. Treatment duration, response to imiquimod, follow-up, recurrence, and local and systemic reactions associated with use of the drug were analyzed. Epidemiological data were obtained and cure rates were calculated. RESULTS: The ratio of women to men was 1.28:1, and the mean age was 63.1 years. Tumors were located mainly on the face, back, trunk, and legs. For patients with comorbidities, the overall cure rate was 38%. These specific patients demonstrated cure rates of 83.5% for superficial BCC and 50% for Bowen's disease. Aggressive BCC and superficial and nodular BCC did not present a good response to treatment. Trichoepitheliomas and nodular BCC showed a partial response, and erythroplasia of Queyrat showed a complete response. For patients without
Patel, Tejas K; Bhabhor, Prakash H; Desai, Nimisha; Shah, Saurabh; Patel, Parvati B; Vatsala, Ela; Panigrahi, Sanjibani
The epidemiological data are limited for the spontaneous adverse drug reaction (ADR) reporting system in psychiatry and its comparison with intensive monitoring studies in terms of causative drugs, seriousness, preventability and drug interactions. This spontaneous ADR reporting study was carried out over a period of three years in the psychiatry department. We adopted WHO definition for an ADR, Naranjo's algorithm for causality, WHO-ADR terminology for the labeling of involved organ-system, International conference on harmonisation (ICH) E2A guidelines for seriousness, modified Schumock and Thornton's criteria for preventability and Medscape drug interaction checker for drug interactions. Two subgroup analyses were performed to find out the risk factors for the serious and preventable reactions. A total of 97 ADRs from 67 patients were included for analysis. The incidence of 'overall' and 'serious ADRs were 0.69% (95% CI: 0.54%, 0.88%) and 0.18% (95% CI: 0.12-0.29%), respectively. The females experienced more ADRs than males. The most commonly reported ADR, incriminated pharmacology group and drug, were extrapyramidal movement disorders (22.68%), atypical antipsychotics (35.62%) and escitalopram (13.91%), respectively. One out of five and one out three reactions were considered as 'serious' and 'preventable', respectively. The drug interactions contributed in 34.02% reactions. The factors significantly associated with 'serious' reactions were typical antipsychotics [OR: 5.47 (1.68, 17.87)], central and peripheral nervous system disorders [OR: 24.00 (5.12, 112.5)] and extrapyramidal reactions [OR: 14.03 (4.43, 44.43)]. The polypharmacy [OR: 5.85 (1.90, 18.03)] was significantly associated with 'preventable' reactions. The spontaneous reporting system is efficient to detect serious reactions and preventable reactions. Copyright © 2015 Elsevier B.V. All rights reserved.
Cho, Tiffany; Uetrecht, Jack
Little is known with certainty about the mechanisms of idiosyncratic drug reactions (IDRs); however, there is substantive evidence that reactive metabolites are involved in most, but not all, IDRs. In addition, evidence also suggests that most IDRs are immune mediated. That raises the question of how reactive metabolites induce an immune response that can lead to an IDR. The dominant hypotheses are the hapten and danger hypotheses. These are complementary hypotheses: a reactive metabolite can act as a hapten to produce neoantigens, and it can also cause cell damage leading to the release of danger-associated molecular pattern molecules that activate antigen presenting cells. Both are required for an immune response. In addition, drugs may induce an immune response through inflammasome activation. We have found examples in which the ability to activate inflammasomes differentiated drugs that cause IDRs from similar drugs that do not. There are other hypotheses that do not involve an immune mechanism such as mitochondrial injury and bile salt export pump (BSEP) inhibition. With some possible exceptions, these hypotheses are unlikely to be able to completely explain IDRs. However, some types of mitochondrial injury or BSEP inhibition could produce danger signals. The major mechanism that protects us from IDRs appears to be immune tolerance. Consistent with this hypothesis, we used checkpoint inhibition to develop the first animal model of idiosyncratic drug-induced liver injury that has the same characteristics as the idiosyncratic injury in humans. This was accomplished by treating Pd-1 -/- mice with anti-CTLA-4 antibodies and amodiaquine. The combination of the Pd-1 -/- mouse and anti-CTLA-4 also unmasks the ability of other drugs such as isoniazid to cause delayed type liver injury. This model should allow rigorous testing of mechanistic hypotheses that was impossible in the past.
Full Text Available We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.
Sessa, Maurizio; Rossi, Claudia; Rafaniello, Concetta; Mascolo, Annamaria; Cimmaruta, Daniela; Scavone, Cristina; Fiorentino, Sonia; Grassi, Enrico; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata
The current study aims to assess the preventability of the contrast media adverse drug reactions reported through the Campania spontaneous reporting system, identifying the possible limitations emerged in this type of evaluation. All the individual case safety reports validated by the Campania Pharmacovigilance Regional Centre from July 2012 to September 2015 were screened to select those that reported contrast media as suspected drug. Campania Preventability Assessment Committee, in collaboration with clinicians specialized in Radiology, assessed the preventability according to the P-Method, through a case-by-case approach. From July 2012 to September 2015, 13798 cases were inserted by pharmacovigilance managers in the Italian Pharmacovigilance Network database (in the geographical contest of the Campania Region), of which 67 reported contrast media as suspected drug. Five preventable cases were found. The most reported causes for preventability were the inappropriate drug use for the case clinical conditions and the absence of the preventive measure administrated prior to the contrast media administration. Several limitations were found in the evaluation of the critical criteria for the preventability assessment. Educational initiatives will be organized directly to the healthcare professionals involved in the contrast media administration, to promote an appropriate use of the contrast media.
Jiang, Pinliang; Li, Shihui; Lai, Jinping; Zheng, Hong; Lin, Changjian; Shi, Peng; Wang, Yong
A surface directly connects the bulk of a material to its surroundings. The ability to dynamically regulate the surface without affecting the bulk of a material holds great potential for new applications. The purpose of this work was to demonstrate that the surface can be dynamically changed using nanoparticles and oligonucleotides (ODNs) in a reversible and reiterative manner. A dual-functional nanogel was synthesized as the model of nanoparticles using miniemulsion polymerization and click chemistry. The nanogel can not only adsorb drugs for sustained drug release but also bind a surface functionalized with complementary ODNs. Importantly, hybridization reaction and ODN degradation can drive reversible and reiterative nanogel binding to the surface for dynamic change, which in principle is unlimited. Moreover, nanogel-mediated dynamic change offers the surface with the drug-releasing function for inhibiting the growth of surrounding cells. Because nanogels can be replaced by any functional nanoparticles with a diverse array of properties, nanoparticle-programmed surface change constitutes a promising platform for various applications such as drug delivery and stent implantation.
Lopez-Gonzalez, Elena; Herdeiro, Maria T; Figueiras, Adolfo
A voluntary reporting system of adverse drug reactions (ADRs) is fundamental to drug safety surveillance but under-reporting is its major limitation. This bibliographic review sought to assess the influence of personal and professional characteristics on ADR reporting and to identify knowledge and attitudes associated with ADR reporting. A systematic review was conducted using the MEDLINE and EMBASE databases. We included papers that were published in English, French and Spanish, and covered a study population made up of health professionals. In each case, the following data were extracted: study population; workplace; study type; sample size; type of questionnaire; type of scale for measuring knowledge; response rate; personal and professional factors; and knowledge and attitudes (based on Inman's 'seven deadly sins') associated with reporting. Based on a search of computerized databases, we identified a total of 657 papers in MEDLINE and 973 in EMBASE. In all, the review covered 45 papers that fulfilled the inclusion criteria. Medical specialty was the professional characteristic most closely associated with under-reporting in 76% of studies involving physicians. Other factors associated with under-reporting were ignorance (only severe ADRs need to be reported) in 95%; diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 72%; lethargy (an amalgam of procrastination, lack of interest or time to find a report card, and other excuses) in 77%; indifference (the one case that an individual doctor might see could not contribute to medical knowledge) and insecurity (it is nearly impossible to determine whether or not a drug is responsible for a particular adverse reaction) in 67%; and complacency (only safe drugs are allowed on the market) in 47% of studies. While personal and professional factors display a weak influence, the knowledge and attitudes of health professionals appear to be strongly related with reporting in a high proportion of
Helen I. Zgurskaya
Full Text Available Gram- negative bacteria utilize a diverse array of multidrug transporters to pump toxic compounds out of cells. Some transporters together with periplasmic membrane fusion proteins (MFPs and outer membrane channels assemble trans-envelope complexes that expel multiple antibiotics across outer membranes of Gram-negative bacteria and into the external medium. Others further potentiate this efflux by pumping drugs across the inner membrane into the periplasm. Together these transporters create a powerful network of efflux that protect bacteria against a broad range of antimicrobial agents. This review is focused on the mechanism of coupling transport reactions located in two different membranes of Gram-negative bacteria. Using a combination of biochemical, genetic and biophysical approaches we have reconstructed the sequence of events leading to the assembly of trans-envelope drug efflux complexes and characterized the roles of periplasmic and outer membrane proteins in this process. Our recent data suggest a critical step in the activation of intermembrane efflux pumps, which is controlled by MFPs. We propose that the reaction cycles of transporters are tightly coupled to the assembly of the trans-envelope complexes. Transporters and MFPs exist in the inner membrane as dormant complexes. The activation of complexes is triggered by MFP binding to the outer membrane channel, which leads to a conformational change in the membrane proximal domain of MFP needed for stimulation of transporters. The activated MFP-transporter complex engages the outer membrane channel to expel substrates across the outer membrane. The recruitment of the channel is likely triggered by binding of effectors (substrates to MFP or MFP-transporter complexes. This model together with recent structural and functional advances in the field of drug efflux provides a fairly detailed understanding of the mechanism of drug efflux across the two membranes.
CORREIA, RION BRATTIG; LI, LANG; ROCHA, LUIS M.
Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this “Bibliome”, the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products—including cannabis—which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015. We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that
Correia, Rion Brattig; Li, Lang; Rocha, Luis M
Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this "Bibliome", the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products-including cannabis-which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015.We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that Instagram
Maeda, Akimitsu; Ando, Hitoshi; Ura, Takashi; Komori, Azusa; Hasegawa, Ayako; Taniguchi, Hiroya; Kadowaki, Shigenori; Muro, Kei; Tajika, Masahiro; Kobara, Makiko; Matsuzaki, Masahide; Hashimoto, Naoya; Maeda, Mieko; Kojima, Yasushi; Aoki, Masahiro; Kondo, Eisaku; Mizutani, Akiyoshi; Fujimura, Akio
Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings. .
Yang, Ming; Kiang, Melody; Shang, Wei
Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides
Full Text Available About 39330, new patients were examined over a period of two years and it was revealed that 104 patients (0.26% had cutaneous tuberculosis. Most of the tuberculosis patients (61.52% were between the age of 5 to 25 years. Lupus vulgaris was the commonest variant (57.69%, followed by scrofuloderma (21.15%. Males suffered more than females (2.25:1 and all patients belonged to lower socio-economic class. 62 cases (59.61% showed evidence of BCG vaccination that failed to protect cutaneous tuberculosis. Mantoux test was positive in all cases except 4. Bacteriological examination was negative in all cases. Response to antitubercular therapy was very good except in two cases which required addition of an extra drug and also took more time.
de Vries, Sieta T.; Wong, Lisa; Sutcliffe, Alastair; Houyez, Francois; Ruiz, Carmen Lasheras; Mol, Peter G.M.
Introduction A mobile app may increase the reporting of adverse drug reactions (ADRs) and improve the communication of new drug safety information. Factors that influence the use of an app for such two-way risk communication need to be considered at the development stage. Objective Our aim was to
Rolfes, Leàn; van Hunsel, Florence; van der Linden, Laura; Taxis, Katja; van Puijenbroek, Eugène
Introduction Clinical information is needed to assess the causal relationship between a drug and an adverse drug reaction (ADR) in a reliable way. Little is known about the level of relevant clinical information about the ADRs reported by patients. Objectives The aim was to determine to what extent
Knopf, Hildtraud; Du, Yong
Drug safety in paediatric medication is a public health concern. According to previous studies, the incidence of adverse drug reactions (ADRs) varies greatly from 0.7% to 2.7% among paediatric outpatients and from 2.6% to 18.1% among paediatric inpatients. Little has been reported on the risks of drug use in the general child population. Our study showed that the prevalence of perceived ADRs in Germany was 0.9% among non-institutionalized children in general and 1.7% among children who had used at least one medicine within the 7 days before the medical interview. Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and for identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems. Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non-institutionalized children in Germany. All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0-17 years who participated in the 2003-06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children's parents and confirmed by trained medical professionals during the medical interview. One hundred and fifty-seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders
Rehan, Harmeet Singh; Sah, Ravinder; Gupta, Anubhuti; Nagar, Parvesh
The Pharmacovigilance Program of India recently initiated a process for direct patient reporting of Adverse Drug Reactions (ADRs) with a designated form. A survey of 200 patients reporting ADRs filling the form. Forms were analysed for patient data, the suspected medication(s), ADRs and possible causality. 54.3% of respondents provided their contact information; the implicated medicine was mentioned in 60% and the description of ADRs in 80% although 46.2% were not interpretable. The severity of ADRs was mentioned in 73.5%. No responder filled the expiry date component of the implicated modification and a causality assessment from most forms was unclassifiable (57%) or unclassified (26%). Details of concomitant drugs were missing. Missing information was a deterrent in analysing the consumer ADR reports for signal detection. It is recommended that the following fields are highlighted in the form: consumer's initials, address, date suspected reaction started, description of event, name, dose, and the reason for the use the medication as well as its expiry date. These should be mandatory in the existing form and new fields added for weight and height, batch number for vaccines and biological products, de challenge and rechallenge results to the suspected medicine and concomitantly used medicines. To improve the quality of information in the consumer reporting form an awareness campaign is also suggested. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Zhang, Xi-Lian; Li, Meng; Rong, Ping; Ma, Rong
We aimed to analyse the adverse drug reactions (ADR) in children due to traditional Chinese medicine (TCM) injections and the related factors, and explored the rational use of medicines and safty countermeasures in clinical. We preformed statistical analyses on data from the CNKI and researched on literatures, from April 1987 to May 2012, relevant to the TCM injections which lead to reactions of clinical adverse, to conduct a analysis of the species, cases, clinical manifestations and related factors of these injections. The incidence of ADR in children leaded by TCM injections is high and the manifestations were chiefly characterized by the luscious of skin and appendages. In addition to the correlation with the physiological and pathologic characteristic in childhood, the ADR is also closely related with preparing technology, irrational use and imperfect supervisory system. Because of the high incidence, we should taking appropriate measures, such as constructing strict supervision system and strengthening rational drug use, to reduce the occurrence of ADRs to the greatest extent.
Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...
Fernandez, Javier; Doña, Inmaculada
Diagnosing and managing drug hypersensitivity is challenging because there are no clear limits between different types of drug reactions. Distinguishing between type A (predictable) and type B (hypersensitivity) reactions when a drug is introduced on the market is not easy. When many people use a drug, adverse reactions can occur, conditioned by diverse genetic profiles, viral infections or concomitant therapy. Occasionally the only tool clinicians have on which to base the diagnosis is the clinical history. Skins tests or in vitro tests sometimes have low sensitivity or are unavailable, and drug provocation tests may be dangerous or strictly forbidden in case of severe cutaneous reactions. Areas covered: This paper reviews the diagnosis and management of the two main types of immunological reactions: IgE-mediated immediate drug hypersensitivity reactions (IDHRs) and non-immediate drug hypersensitivity reactions (NIDHRs). Expert commentary: Although Europe and the United States use different diagnostic methods, patients with history of drug hypersensitivity must avoid the suspicious drug, and clinicians must assess tolerance to safe alternatives under medical surveillance. Sometimes desensitization may be required. There is a consensus about the need to perform genetic testing for specific drugs and give patients proper documentation to prevent future exposure to culprit drugs.
Garcia, Daniel; Cohen, Philip R
Dapsone is a sulfone drug used to treat infectious conditions and also numerous dermatologic diseases. Fixed drug eruption is a distinctive adverse cutaneous reaction associated with the initial administration and subsequent delivery of a specific agent. Areas covered: The authors preformed a literature search using the following keywords: dapsone, fixed drug eruption, and adverse cutaneous drug reaction. Bibliographies were also reviewed for pertinent articles. The results were combed for relevant papers and reviewed. Articles pertaining to dapsone-associated fixed drug eruption were included. Expert commentary: The majority of cases of dapsone-associated fixed drug eruption in the literature come from Africa or India where there is a high prevalence of patients treated for leprosy. Characteristics of these cases are similar to fixed drug eruption described in the western literature, with differences in frequency of multiple versus solitary lesions. Dapsone-associated fixed drug eruption should be considered when reviewing the drug history of a patient with fixed drug eruption. In the case of darker pigmented individuals, multiple fixed drug eruption lesions may be more common. Multiple lesions may mimic Kaposi's sarcoma in human immunodeficiency virus positive patients. Dapsone-associated fixed drug eruption should be considered in the differential diagnosis of multiple hyperpigmented lesions.
Full Text Available Information extraction and knowledge discovery regarding adverse drug reaction (ADR from large-scale clinical texts are very useful and needy processes. Two major difficulties of this task are the lack of domain experts for labeling examples and intractable processing of unstructured clinical texts. Even though most previous works have been conducted on these issues by applying semisupervised learning for the former and a word-based approach for the latter, they face with complexity in an acquisition of initial labeled data and ignorance of structured sequence of natural language. In this study, we propose automatic data labeling by distant supervision where knowledge bases are exploited to assign an entity-level relation label for each drug-event pair in texts, and then, we use patterns for characterizing ADR relation. The multiple-instance learning with expectation-maximization method is employed to estimate model parameters. The method applies transductive learning to iteratively reassign a probability of unknown drug-event pair at the training time. By investigating experiments with 50,998 discharge summaries, we evaluate our method by varying large number of parameters, that is, pattern types, pattern-weighting models, and initial and iterative weightings of relations for unlabeled data. Based on evaluations, our proposed method outperforms the word-based feature for NB-EM (iEM, MILR, and TSVM with F1 score of 11.3%, 9.3%, and 6.5% improvement, respectively.
Nguyen, Thin; Larsen, Mark E; O'Dea, Bridianne; Phung, Dinh; Venkatesh, Svetha; Christensen, Helen
This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale. Copyright © 2017 Elsevier B.V. All rights reserved.
Natasha S Kate
Full Text Available Psychotropic drugs are commonly used to manage mental and behavioral problems in geriatric patients. This is, however, accompanied by the risk of developing adverse drug reactions (ADRs, impacting the safety with which the drug can be used. In this article, we provide an overview of the factors associated with the ADRs due to psychotropic medication in the elderly, and the ADRs associated with the use of antipsychotics and sedative-hypnotics in the geriatric population. For this, literature searches were conducted through MEDLINE, PubMed, and Google Scholar using keyword terms: Geriatric, elderly, safety, adverse events, ADRs, antipsychotic, names of individual antipsychotics, benzodiazepine, sedative, hypnotic, zolpidem, zaleplon, zopiclone. Research data indicate that antipsychotics are associated with an increased risk of metabolic syndrome, thromboembolism, cerebrovascular and cardiac events, pneumonia, fractures, and increased mortality. Among antipsychotics, aripiprazole seems to have fewer ADRs while other antipsychotics (typical and atypicals have reports of troublesome side effect profiles. Sedative-hypnotics are associated with a risk of falls, fractures, cognitive impairment, and may increase the risk of developing dementia with long-term use. The risk of these complications is present with both benzodiazepines and medications such as zolpidem and zopiclone.
An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.
Full Text Available Izumi Sato,1 Manabu Akazawa21Department of Epidemiology and Statistics, Graduate School of Medicine, The University of Tokyo Tokyo, Japan; 2Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, JapanBackground: The concomitant use of multiple medications by elderly patients with hypertension is a relatively common and growing phenomenon in Japan. This has been attributed to several factors, including treatment guidelines recommending prescription of multiple medications and a continuing increase in the elderly population with multiple comorbidities.Objective: This study was aimed at investigating the association between polypharmacy, defined as the concomitant use of five or more medications, and risk of adverse drug reaction (ADR in elderly Japanese hypertensive patients to examine the hypothesis that risk of ADR increases with the administration of an increasing number of co-medications.Methods: Using a retrospective cohort design, the data regarding all hypertensive patients aged 65 years or older were extracted from the Risk/Benefit Assessment of Drugs – Analysis and Response Council antihypertensive medication database. The data were reviewed for classification of patients into one of three groups according to drug use at the initiation of therapy – a monotherapy group composed of patients who had taken the investigated drug only, a co-medication group composed of patients who had taken the investigated drug and a maximum of three other medications, and a polypharmacy group composed of patients who had taken the investigated drug and four or more other medications – and determination of the number of ADR events experienced. Estimated rate ratios (RRs and 95% confidence intervals (CIs were calculated using a Poisson regression model adjusted for drug category and patient age and sex. Various sensitivity analyses were performed to confirm the robustness of the study findings.Results: Of 61,661 elderly
Bousslimi, N; Ben Abda, I; Ben Mously, R; Siala, E; Harrat, Z; Zallagua, N; Bouratbine, A; Aoun, K
Three forms of cutaneous leishmaniasis (CL) are endemic in Tunisia. The identification of the causative species is useful to complete epidemiological data and to manage the cases. The aim of this study is to assess PCR-RFLP technique in the identification of Leishmania species responsible of CL in Tunisia and to compare the results of this technique to those of isoenzyme analysis. Sixty-one CL lesions were sampled. Dermal samples were tested by culture on NNN medium and analyzed by PCR-RFLP assay targeting the ITS1 region of ribosomal DNA. Species identification was performed by both iso-enzymatic typing for positive cultures and analysis of restriction profiles after enzymatic digestion by HaeIII of the obtained amplicons. Thirty-eight (62%) samples were positive by culture. The iso-enzymatic typing of 32 isolates identified 3 L. infantum, 23 L. major MON-25 and 6 L. tropica MON-8. Sixty samples were positive by PCR. The PCR-RFLP digestion profiles of the 56 PCR products identified 12 L. infantum, 38 L. major and 6 L. tropica. The results of both techniques were concordant in the 32 strains identified by both techniques. Species identification correlated with the geographical distribution of CL forms endemic in Tunisia. Results of PCR-RFLP revealed highly concordant with those of isoenzyme electrophoresis. Thanks to its simplicity, rapidity and ability to be performed directly on biological samples, this technique appears as an interesting alternative for the identification of Leishmania strains responsible of CL in Tunisia. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Aparecida T. Nagao-Dias
, por meio de ações de farmacovigilância, bem como a identificação dos possíveis mecanismos imunológicos envolvidos através de testes laboratoriais, história e avaliação clínica detalhadas.OBJECTIVE: This review addresses the most recent published literature regarding drug allergy, in order to provide physicians with a background for a better understanding of this problem of great relevance for public health. SOURCES OF DATA: The sources of data for obtaining the original and review articles published in the last 10 years were MEDLINE, Pubmed and Lilacs. The articles chosen for this review relate drug allergy to immunological mechanisms, epidemiology, clinical and laboratory evaluation, skin lesions, clinical management, and re-exposure to the drug. SUMMARY OF THE FINDINGS: Allergic reactions represent one third of adverse drug reactions. They are considered rare but with high morbimortality. Gell & Coombs' definition has been useful for classifying some types of drug allergic reactions; however, some still remain without classification because of poor knowledge of the mechanisms involved. The existence of T cell subpopulations with diverse characteristics reveals the complexity of the subject and, at the same time, elucidates several questions raised about it. It was recently postulated a new concept of chemically inert drug presentation to T cells, restricted to the major histocompatibility complex, but in a non-covalent and labile way. In clinical practice, without adequate laboratory tests, it is difficult to correlate clinical symptoms and immunological mechanisms. In vitro and in vivo skin tests have been employed in cases of suspected drug allergy reaction. However, there are very few commercially available reagents. CONCLUSIONS: Drug allergy constitutes an important problem in adverse drug reactions because of its potential of morbidity and mortality. It is necessary to emphasize the relevance of pharmacovigilance during treatment of patients, as
Full Text Available Objective: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. Materials and Methods: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo′s algorithm, severity (Hartwig and Siegel scale, and preventability (Schumock and Thornton criteria. Results: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%. The common causal drug group was antitubercular (129, 34.4% followed by antiretroviral (76, 20.3% agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7% followed by hospitalization (158, 42.1%. Majority of the serious ADRs were continuing (191, 50.9% at the time of reporting, few recovered (101, 26.9%, and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8% followed by probable (173, 46.1% in nature. Conclusion: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.
Davies, Emma C; Green, Christopher F; Mottram, David R; Pirmohamed, Munir
Adverse drug reactions (ADRs) are a reporting category in the National Patient Safety Agency (NPSA) incident reporting system, though the Medicines and Healthcare Products Regulatory Agency (MHRA) pharmacovigilance system is the more established method for collecting ADR data. The majority of ADRs were shown to be of moderate risk to the patient, though some have a severe or catastrophic impact. Classification and reporting of ADRs according to NPSA guidance is possible but offers limited additional value to efforts to improve patient safety over and above the Yellow Card Scheme. In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications. ADRs identified in a 6-month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA. Seven hundred and thirty-three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as 'low' (minor treatment), 181 (24.7%) as 'moderate' (moderate increase in treatment, no permanent harm), 14 (1.91%) as 'severe' (permanent harm) and 1 (0.14%) was categorized as 'catastrophic' (direct cause of death). In terms of impact on the organization, none was categorized as 'no harm/no risk', 508 (69.3%) as 'insignificant', 188 (25.6%) as 'minor', 25 (3.4%) as 'moderate', 12 (1.6%) as 'major' and none was classed as 'catastrophic'. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection. Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card
Ortega, Ana; Aguinagalde, Aránzazu; Lacasa, Carlos; Aquerreta, Irene; Fernández-Benítez, Margarita; Fernández, Luis M
Adverse drug reaction (ADR) spontaneous reporting is the primary method of postmarketing drug surveillance; although it is an important part of postmarketing drug surveillance, it is underused. Before 2004, almost no ADRs were reported in our 400-bed hospital. As an electronic hospital information system was available in our hospital, we developed a tool (ADR-RS-IHIS) for ADR reporting integrated into the hospital information system to facilitate reporting through easy use, automatic input of certain information, increased accessibility, real-time review, and intervention. To analyze the efficacy of the ADR-RS-IHIS in increasing ADR reporting to the national drug surveillance system, propose and implement improvements to increase ADR reporting, and evaluate the impact of these improvements. Every ADR reported through the ADR-RS-IHIS was evaluated retrospectively. Two study phases for evaluating ADR-RS-IHIS efficacy were identified. Phase I took place April 2004-August 2006; in April 2006, an interim analysis was performed to propose improvements. Phase II took place September 2006-April 2007 for evaluation of the impact made by the proposed improvements. Efficacy in the phase I and improvement impact on phase II were measured as the number of ADRs reported to the national drug surveillance system. The rate of ADRs reported per month to the national system increased from 0 before 2004 to 0.91 in phase I and 1.62 in phase II (2.25 if delayed reporting was considered). Improvement measures included: allowing nurses to report ADRs in the same way as physicians and pharmacists, automatic form filling of certain information from the electronic hospital information system, easier ADR report analysis, and automatic notification to the allergy department regarding suspected allergies. An ADR reporting system integrated into the electronic hospital information system is effective for increasing the number of ADRs reported to the national drug surveillance system. Allowing
Deng, Sheng; He, Yanchun; Yin, Tao; Long, Liping; Zhang, Wei
To summarize the occurrences of adverse drug reactions (ADR) of gatifloxacin, and to guide the rational usage of antibacterial agents in clinical practice in the future. A total of 1 077 ADR patient who received gatifloxacin were retrospectively studied in Hunan province from August 2003 to July 2007. Gatifloxacin could cause multi-system and multi-organ ADRs with wide variety of clinical manifestations. Of the 1 077 ADR patients, ADR incidence rate was slightly lower in males than that in females, the age of 821 (76.23%) ADR patients were 20 approximately 59 years; 905 (84.03%) were administered intravenously; and 682 (33.07%) had severe lesions of the digestive system, followed by lesions of the skin and the appendants (490 cases, 23.76%) and the nervous system (298 cases, 14.45%). ADR caused by gatifloxacin should be monitored and reported so as to reduce or avoid ADR.
Rafael San-Miguel Carrasco
Full Text Available Geriatrics Medicine constitutes a clinical research field in which data analytics, particularly predictive modeling, can deliver compelling, reliable and long-lasting benefits, as well as non-intuitive clinical insights and net new knowledge. The research work described in this paper leverages predictive modeling to uncover new insights related to adverse reaction to drugs in elderly patients. The differentiation factor that sets this research exercise apart from traditional clinical research is the fact that it was not designed by formulating a particular hypothesis to be validated. Instead, it was data-centric, with data being mined to discover relationships or correlations among variables. Regression techniques were systematically applied to data through multiple iterations and under different configurations. The obtained results after the process was completed are explained and discussed next.
de Vries, Tjalling W; van Hunsel, Florence
Antihistamines are used for the treatment of allergic rhinitis, allergic conjunctivitis, chronic spontaneous urticaria and atopic eczema. To study the reports of adverse drug reactions (ADRs) in children using antihistamines to provide prescribers with an overview of the possible toxicity. We studied ADRs in children reported to the Netherlands Pharmacovigilance Centre Lareb in the years 1991-2014, assessed the Naranjo score and, when possible, computed the reporting OR. Serious ADRs included one death (malignant neuroleptic syndrome), cardiac arrhythmia (one case) and convulsions (three cases). Skin eruptions, headache and somnolence were the most frequently reported ADRs. Aggression and agitation were also reported. Toxicity can occur with second-generation antihistamines. The main toxicity relates to skin eruptions and central nervous system problems. 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/
Sasani, F.; Javanbakht, J.; Samani, R.; Shirani, D.
Canine cutaneous leishmaniasis (CCL) is a significant veterinary problem. Infected dogs also serve as parasite reservoirs and contribute to human transmission of cutaneous leishmaniasis. Histologically, the lesions were nodular to diffuse interstitial granulomatous dermatitis with histiocytic pseudorosettes together with numerous amastigotes within macrophages and occasionally within the interstitium. Organisms were often contained within clear and intracellular vacuoles. The other inflammato...
Li, Haochu; Marley, Gifty; Ma, Wei; Wei, Chongyi; Lackey, Mellanye; Ma, Qingyan; Renaud, Françoise; Vitoria, Marco; Beanland, Rachel; Doherty, Meg; Tucker, Joseph D
Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions may influence ARV adherence. Thirty-nine articles were identified, and 33 reported that ARV adverse drug reactions decreased adherence and six studies found no influence. Visually noticeable adverse drug reactions and psychological adverse reactions were reported as more likely to cause non-adherence compared to other adverse drug reactions. Six studies reported a range of adverse reactions associated with EFV-containing regimens contributing to decreased adherence. Informing HIV-infected individuals about ARV adverse drug reactions prior to initiation, counselling about coping mechanisms, and experiencing the effectiveness of ARVs on wellbeing may improve ARV adherence.
Oussalah, A; Mayorga, C; Blanca, M; Barbaud, A; Nakonechna, A; Cernadas, J; Gotua, M; Brockow, K; Caubet, J-C; Bircher, A; Atanaskovic, M; Demoly, P; K Tanno, L; Terreehorst, I; Laguna, J J; Romano, A; Guéant, J-L
Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Full Text Available Prerna Upadhyaya,1 Vikas Seth,2 Vijay V Moghe,1 Monika Sharma,1 Mushtaq Ahmed11Department of Pharmacology, Mahatma Gandhi Medical College, Sitapura, Jaipur, Rajasthan, 2Department of Pharmacology, Hind Institute of Medical Sciences, Safedabad, Barabanki, Lucknow, Uttar Pradesh, IndiaIntroduction: Poor reporting of adverse drug reactions (ADRs by doctors is a major hindrance to successful pharmacovigilance. The present study was designed to assess first-year residents’ knowledge of ADR reporting.Methods: First-year postgraduate doctors at a private medical college completed a structured questionnaire. The responses were analyzed by nonparametric methods.Results: All doctors were aware of the term “adverse drug reactions.” Fifty percent of the doctors reported being taught about ADR reporting during their undergraduate teaching, and 50% had witnessed ADRs in their internship training. Ten percent of patients suffering an ADR observed and reported by doctors required prolonged hospitalization for treatment as a result. Only 40% of interns reported the ADRs that they observed, while 60% did not report them. Twenty-eight percent reported ADRs to the head of the department, 8% to an ADR monitoring committee, and 4% to the pharmacovigilance center. Eighty-six percent of the doctors surveyed felt that a good knowledge of undergraduate clinical pharmacology therapeutics would have improved the level of ADR reporting.Conclusion: The knowledge of first-year doctors regarding ADR reporting is quite poor. There is a dire need to incorporate ADR reporting into undergraduate teaching, and to reinforce this during internships and periodically thereafter.Keywords: ADR reporting, pharmacovigilance, first-year postgraduate doctors
Subiela, José D; Dapena, Elida
Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.
... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...
Batel Marques F
,192.36.Discussion: Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings, validated methods to measure ADE-associated costs need future research efforts. Keywords: drug costs, health care costs, drug-related side effects and adverse reactions, review
In Young Jung
Full Text Available Background. Adverse drug reactions (ADRs are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea. Methods. This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated. Results. 1,277 (62.8% patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%. Totally, 44 (3.4% patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%, followed by third-generation cephalosporins (14.9%. The most frequently experienced side effects were skin manifestations (45.1% followed by gastrointestinal disorders (32.6%. Conclusion. Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.
Torelló Iserte, J; Castillo Ferrando, J R; Laínez, M M; García Morillas, M; Arias González, A
To discover the sort of adverse reactions to medication (ARM) notified by Primary Care doctors and identify the under-notification of those cases having special clinical-epidemiological interest. Retrospective study in which 2,597 ARM corresponding to 1,467 Yellow Cards (YC) were analysed. These were notified by Primary Care doctors to the Centro Andaluz de Farmacovigilancia (Andalusian Drug-watch centre) during the period from 1/6/90 to 31/12/92. To assess the seriousness of the ARM, their terminological classification and imputability, the criteria used in the WHO's international "Yellow Card" programme of spontaneous notification were followed. 77.2% of all notifications were from Primary Care, of which 7.4% were of special interest due to their serious or novel character. However an undernotification of serious and well-known ARM was detected, such as digestive haemorrhages (1.07/10(6) inhibitants per year), anaphylactic shock (0.34/10(6) inhab/year), agranulocytosis (0.23/10(6) inhab/year) and aplastic anaemia (0.05/10(6) inhab/year), among others. Most of the main under-notified ARM are generated in the community but treated in hospital Casualty departments. Therefore it would be useful to develop specific Drug-watch programmes in the hospitals themselves.
Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R
Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/. © The Author(s) 2016. Published by Oxford University Press.
Schnippel, K; Firnhaber, C; Berhanu, R; Page-Shipp, L; Sinanovic, E
To estimate the provider costs of managing adverse drug reactions (ADRs) to standard long-course treatment for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) according to South African guidelines. We parameterised a published Markov health state model for MDR/RR-TB with guidelines-based, bottom-up public-sector provider costing of ADR management. Frequency of ADR occurrence was extracted from the literature. Costs were estimated over 10 years, discounted 3% annually and tested using probabilistic sensitivity analysis. On average, guidelines-based costing of moderate ADRs weighted by the frequency of occurrence was US$135.76 (standard deviation [SD] US$17.18) and the cost of serious ADRs was US$521.29 (SD US$55.99). We estimated that the incremental costs of ADR management were US$380.17 annually per patient initiating MDR/RR-TB treatment. The incremental costs of ADR management for the public health sector in South Africa was US$4.76 million, 8.3% of the estimated cohort costs of MDR/RR-TB treatment ($57.55 million) for the 2015 cohort of 12 527 patients. Management of multiple ADRs and serious ADRs, which are common during the first 6 months of standard, long-course MDR/RR-TB treatment, substantially increases provider treatment costs. These results need to be taken into account when comparing regimen costs, and highlight the urgent need to identify drug regimens with improved safety profiles.
Inácio, Pedro; Gomes, João José; Airaksinen, Marja; Cavaco, Afonso
Adverse drug reactions (ADRs) are recognized as a leading cause of morbidity and mortality, and an important cost factor to health systems. Patient reporting of ADRs has emerged as an important topic in recent years but reporting rates are still low in many countries. To explore different countries' sociodemographic and economic features as explanatory factors for population ADRs reporting, including the propensity of patients' reporting to pharmacovigilance authorities. Cross-sectional observational design. A data set of 42 global sociodemographic and economic factors for 44 countries were retrieved, as to analyse statistical associations between these factors and the patient reporting rate of ADRs. Multivariate logistic regression models were designed to identify the predictive covariables. Health investment indicators, such as per capita public health expenditure, hospital bed density and under five mortality rate were the relevant factors responsible to discriminate between countries that have higher patient reporting rates. This study shows that healthcare investment-related factors help explain the propensity of patients to report suspected ADRs, while pharmacovigilance features were not directly associated with higher patient participation in drug safety mechanisms. Although general, these results point a direction in further policy making to improve resources allocation concerning the promotion of patients' participation. Copyright © 2017 Elsevier B.V. All rights reserved.
Jelínek, F; Tachezy, R
Three of four heifers housed together developed multiple cutaneous tumours in the linea alba and on the teats 3 months after the application of plastic muzzle plates with sharp tips to prevent mutual sucking and licking. Fibropapilloma with many koilocytes but few intranuclear inclusions was diagnosed histologically. The dermis showed neoplastic fibroblasts and a structureless intercellular matrix, and nonpurulent vasculitis was also recorded. Immunohistochemical examination with an antibody against L1 papillomavirus antigen demonstrated intranuclear positivity in single cells of the granular and cornified layers and in many mesenchymal cells in the fibrous parts of the tumours. CD3-positive lymphocytes were present in the wall of some blood vessels, and in the dermis and epidermis. Proliferating cell nuclear antigen was detected predominantly in the basal layer of the epidermis and in the superficial dermis. Electron microscopy revealed small intranuclear aggregates of virus particles in an epidermocyte, damage to desmosomes and disorganization of cytokeratin filaments in many epidermocytes. Aggregates of virus particles were revealed also in a fibroblast in the dermis. In blood capillaries of the corium, acute swelling, inflammation and necrosis of the endothelium were observed. By means of the polymerase chain reaction (PCR) and nucleotide DNA sequencing of the PCR product, the virus was identified as bovine papilloma virus type 1 (BPV 1). The presence of this virus in the tissue was further confirmed by in-situ hybridization with a BPV 1 probe.
Muñoz, Emir; Novácek, Vít; Vandenbussche, Pierre-Yves
Timely identification of adverse drug reactions (ADRs) is highly important in the domains of public health and pharmacology. Early discovery of potential ADRs can limit their effect on patient lives and also make drug development pipelines more robust and efficient. Reliable in silico prediction of ADRs can be helpful in this context, and thus, it has been intensely studied. Recent works achieved promising results using machine learning. The presented work focuses on machine learning methods that use drug profiles for making predictions and use features from multiple data sources. We argue that despite promising results, existing works have limitations, especially regarding flexibility in experimenting with different data sets and/or predictive models. We suggest to address these limitations by generalization of the key principles used by the state of the art. Namely, we explore effects of: (1) using knowledge graphs-machine-readable interlinked representations of biomedical knowledge-as a convenient uniform representation of heterogeneous data; and (2) casting ADR prediction as a multi-label ranking problem. We present a specific way of using knowledge graphs to generate different feature sets and demonstrate favourable performance of selected off-the-shelf multi-label learning models in comparison with existing works. Our experiments suggest better suitability of certain multi-label learning methods for applications where ranking is preferred. The presented approach can be easily extended to other feature sources or machine learning methods, making it flexible for experiments tuned toward specific requirements of end users. Our work also provides a clearly defined and reproducible baseline for any future related experiments. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin
Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development
Wang, Kejian, E-mail: email@example.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)
Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.
Full Text Available Mikhail Sergeevich Zastrozhin,1,2 Vadim Markovich Brodyansky,3 Valentin Yurievich Skryabin,4 Elena Anatolievna Grishina,5 Dmitry Vladimirovich Ivashchenko,5 Kristina Anatolievna Ryzhikova,5 Ludmila Mikhaylovna Savchenko,1 Alexander Olegovich Kibitov,3 Evgeny Alekseevich Bryun,1,4 Dmitry Alekseevich Sychev6 1Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia; 2Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Center for the Prevention of Dependent Behavior, Moscow, Russia; 3Federal Medical Research Centre of Psychiatry and Addictology, Laboratory of Molecular Genetics, Moscow, Russia; 4Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Department of Addictology, Moscow, Russia; 5Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Research Centre, Moscow, Russia; 6Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Department of Clinical Pharmacology and Therapy, Moscow, Russia Background: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane are described.Objective: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methods: The study
Joshua C. Pritchett
Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.
Liang, Zhaohui; Huang, Jimmy Xiangji; Zeng, Xing; Zhang, Gang
Genomic variations are associated with the metabolism and the occurrence of adverse reactions of many therapeutic agents. The polymorphisms on over 2000 locations of cytochrome P450 enzymes (CYP) due to many factors such as ethnicity, mutations, and inheritance attribute to the diversity of response and side effects of various drugs. The associations of the single nucleotide polymorphisms (SNPs), the internal pharmacokinetic patterns and the vulnerability of specific adverse reactions become one of the research interests of pharmacogenomics. The conventional genomewide association studies (GWAS) mainly focuses on the relation of single or multiple SNPs to a specific risk factors which are a one-to-many relation. However, there are no robust methods to establish a many-to-many network which can combine the direct and indirect associations between multiple SNPs and a serial of events (e.g. adverse reactions, metabolic patterns, prognostic factors etc.). In this paper, we present a novel deep learning model based on generative stochastic networks and hidden Markov chain to classify the observed samples with SNPs on five loci of two genes (CYP2D6 and CYP1A2) respectively to the vulnerable population of 14 types of adverse reactions. A supervised deep learning model is proposed in this study. The revised generative stochastic networks (GSN) model with transited by the hidden Markov chain is used. The data of the training set are collected from clinical observation. The training set is composed of 83 observations of blood samples with the genotypes respectively on CYP2D6*2, *10, *14 and CYP1A2*1C, *1 F. The samples are genotyped by the polymerase chain reaction (PCR) method. A hidden Markov chain is used as the transition operator to simulate the probabilistic distribution. The model can perform learning at lower cost compared to the conventional maximal likelihood method because the transition distribution is conditional on the previous state of the hidden Markov
Otani, Iris M; Banerji, Aleena
PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE-mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs.
Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge
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.
Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra
Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT
Full Text Available Dragana Protić,1 Nada Vujasinović-Stupar,2 Zoran Bukumirić,3 Slavica Pavlov-Dolijanović,4 Snežana Baltić,5 Slavica Mutavdžin,6 Ljiljana Markovic-Denić,7 Marija Zdravković,8 Zoran Todorović1 1Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 2Department 2, Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 3Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 4Department 5, Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 5Department 5, Institute of Rheumatology, Belgrade, Serbia; 6Institute of Physiology “Rihard Burjan”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 7Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 8Department of Cardiology, Medical Center “Bežanijska kosa”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia Background: Adverse drug reactions (ADRs have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system. Methods: Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261 completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history. Results: Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found
Sicherer, Scott H; Leung, Donald Y M
This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams.
Full Text Available Introduction: The Wilson disease is an autosomal recessive disease in which the liver, central nervous system, eyes, blood and other parts of the body involved. Timely diagnosis and appropriate treatment of the disease requires awareness of the clinical presentations of this disease in children.Methods: This case series study included 62 patients with Wilson disease who admitted to children's Medical Center in the years 2012-2003.Results: 56% of patients were male. The average age of diagnosis was 9.73 years old (5-17 years and this was higher in patients with early neurologic symptoms (P = 0.85.( 64.5% of the patients had the hepatic symptoms at the time of diagnosis and the most common type of hepatic involvement was cirrhosis (39.3% and hepatitis (17.5% respectively. 17.7% of the patients also had early neurological symptoms. A positive family history for the Wilson Disease were found in 27.4% of patients. 74.2% of patients had KF ring and the frequency of these symptom was higher in patients with early neurological involvement. 83.9% of patients were treated successfully with D-penicillamine and In 30% of patients, adverse drug reactions were seen.Conclusion: Children with unknown liver disease should be evaluated for Wilson disease and the first-degree relatives of patients should be screened. . D-penicillamine have important side effects, but due to the low cost and the availability is an appropriate drug to treat the Wilson disease..Key words: Wilson Disease, Hepatic Involvement, Neurologic Involvement , KF ring ,D-Penicillamine.
Full Text Available Objectives: Adverse drug reactions (ADRs are an important cause of morbidity and mortality worldwide and generate high health costs. Therefore, the aims of this study were to determine the treatments which produce more ADRs in general population and the main symptoms they generate. Methods: An observational, cross-sectional study consisting in performing a self-rated questionnaire was carried out. 510 patients were asked about the treatments, illnesses and ADRs, they had suffered from. Results: 26.7% of patients had suffered from some ADR. Classifying patients according to the type of prescribed treatment and studying the number of ADR that they had, we obtained significant differences (p ≤ 0.05 for treatments against arthrosis, anemia and nervous disorders (anxiety, depression, insomnia. Moreover, determining absolute frequencies of these ADRs appearance in each treatment, higher frequencies were again for drugs against arthrosis (22.6% of patients treated for arthrosis suffered some ADR, anemia (14.28%, nerve disorders (13.44% and also asthma (16%. Regarding the symptoms produced by ADRs, the most frequent were gastrointestinal (60% of patients who suffered an ADR, had gastrointestinal symptoms and nervous alterations (dizziness, headache, sleep disturbances etc (24.6%. Conclusion: Therapeutic groups which produce more commonly ADRs are those for arthrosis, anemia, nervous disorders and asthma. In addition, symptoms which are generated more frequently are gastrointestinal and nervous problems. This is in accordance with the usual side effects of mentioned treatments. Health professionals should be informed about it, so that they would be more alert about a possible emergence of an ADR in these treatments. They also could provide enough information to empower patients and thus, they probably could detect ADR events. This would facilitate ADR detection and would avoid serious consequences generated to both patients' health and health economics.
Kazeem Adeola Oshikoya
Full Text Available CONTEXT AND OBJECTIVES: Adverse drug reactions (ADRs may cause prolonged hospital admissions with high treatment costs. The burden of ADRs in children has never been evaluated in Nigeria. The incidence of pediatric ADRs and the estimated cost of treatment over an 18-month period were determined in this study. DESIGN AND SETTING: Prospective observational study on children admitted to the pediatric wards of the Lagos State University Teaching Hospital (LASUTH in Nigeria, between July 2006 and December 2007. METHODS: Each patient was assessed for ADRs throughout admission. Medical and non-medical costs to the hospital and patient were estimated for each ADR by reviewing the medical and pharmacy bills, medical charts and diagnostic request forms and by interviewing the parents. Cost estimates were performed in 2007 naira (Nigeria currency from the perspectives of the hospital (government, service users (patients and society (bearers of the total costs attributable to treating ADRs. The total estimated cost was expressed in 2007 United States dollars (USD. RESULTS: Two thousand and four children were admitted during the study; 12 (0.6% were admitted because of ADRs and 23 (1.2% developed ADR(s during admission. Forty ADRs were suspected in these 35 patients and involved 53 medicines. Antibiotics (50% were the most suspected medicines. Approximately 1.83 million naira (USD 15,466.60 was expended to manage all the patients admitted due to ADRs. CONCLUSIONS: Treating pediatric ADRs was very expensive. Pediatric drug use policies in Nigeria need to be reviewed so as to discourage self-medication, polypharmacy prescription and sales of prescription medicines without prescription.
Ezeuko, Amaka Y.; Ebenebe, Uzo E.; Nnebue, Chinomnso C; Ugoji, John O.
Background: Under-reporting of adverse drug reactions (ADRs) by the prescribers is a common public health problem. Monitoring of factors that influence ADR reporting will reduce risks associated with drug use; improve patients care, safety and treatment outcome. The aim of this study was to determine the factors associated with the reporting of ADRs by health workers in Nnewi Nigeria. Methods: A cross-sectional study of 372 health workers in different health facilities in Nnewi North Local Government Area of Anambra state, selected using multistage sampling technique was done. Data collection employed pretested, self-administered structured questionnaires. Data were analyzed using Statistical Package for Social Sciences version 17. Tests of statistical significance were carried out using Chi-square tests for proportions. A P < 0.05 was considered significant. Results: Out of the 372 respondents studied, 255 (68.5%) were females, and 117 (31.5%) were males. The modal age range (37.6%) was 31–40 years. Factors related by the respondents to influence ADR reporting include: Unavailability of electronic reporting (83.6%), unavailability of reporting forms (66.4%) and ignorance (58.2%). The difference among medical practitioners who related unavailability of electronic reporting process as obstacle to ADR reporting was not significant (P = 0.18). Conclusions: The study results revealed the factors associated with the reporting of ADRs among health workers in Nnewi Nigeria. It is desirable to initiate electronic reporting process, training programs on ADR reporting and make reporting forms/guidelines available to relevant health workers. PMID:25949775
Sales, Ibrahim; Aljadhey, Hisham; Albogami, Yasser; Mahmoud, Mansour A
Purpose: To assess the general public awareness and perception about Adverse Drug Reactions (ADRs) reporting and pharmacovigilance. Method: A cross-sectional study conducted on June 2012 during awareness campaign held in two malls in Riyadh city for two days. A self-administered questionnaire consisting of three parts was distributed to the attendees who accepted to participate in the study. Results: A total of 204 questionnaires were collected with a response rate of 68%. Twenty-three percent could correctly define ADRs. Only 13(15.7%) of responders were familiar with the term "Pharmacovigilance" and only 78.6% were aware about the Saudi Pharmacovigilance Center. Sixty-seventy percent indicated that their physicians or pharmacists don't actively encourage them to report ADRs that may occur when they take their medications. The majority of responders (73.2%) believed that the medical team, rather than consumers, should report ADRs. When asked why patients do not report ADRs, 19.1(48.5%) believed that patients do not know whether the ADR is from the medication or not, 18.1(46.1%) stated that the reason was because patients don't know about the Pharmacovigilance Center, 16(40.7%) think that patients don't know about the importance of ADRs reporting, and 14(36.3%) responded that patients probably don't know how to report ADRs. Conclusion: The general public in Saudi Arabia are not aware about ADRs reporting and the pharmacovigilance system. The Saudi Food and Drug Authorities (FDA) need to put more efforts to increasing public awareness about the importance of ADRs reporting process and the importance of pharmacovigilance system in promoting patient safety.
João Guilherme Lino da Silva
Full Text Available INTRODUCTION: The study analyzed positivity of polymerase chain reaction (PCR on detection of DNA from Leishmania in patients' samples. METHODS: Extracted DNA was submitted to L150/L152, 13Y/13Z, and seminested PCR (snPCR. RESULTS: Results were evidenced by bands of approximately 120, 720, and 670 bp for L150/L152, 13Y/13Z, and snPCR, respectively. L150/L152, 13Y/13Z, and snPCR positivity indexes were 76.9, 56.4, and 9.2 (p>0.05, respectively, for suspected and 93.7, 68.7, and 84.4 (p<0.05, respectively, for confirmed. CONCLUSIONS: Preliminary results showed that these assays, mainly L150/L152 and snPCR, can detect Leishmania DNA and carry potential on laboratory diagnosis of leishmaniasis.
Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl
all indication areas.The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner.We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified...... patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength.When applying the method to the 3,394 patients......Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across...
Heijden, P.G.M. van der; Puijenbroek, E.P. van; Buuren, S. van; Hofstede, J.W. van der
A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting
Lardon, Jérémy; Abdellaoui, Redhouane; Bellet, Florelle; Asfari, Hadyl; Souvignet, Julien; Texier, Nathalie; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Burgun, Anita; Bousquet, Cédric
The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients' experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance. A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance. Daubt et al's recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2. Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified. This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding extraction, no study proposed a generic approach to easily
Gomes,Ciro Martins; Damasco,Fabiana dos Santos; Morais,Orlando Oliveira de; Paula,Carmen Dea Ribeiro de; Sampaio,Raimunda Nonata Ribeiro
We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because...
Almandil, Noor B.
Objectives To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia, between April 2015 and April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU. PMID:27874152
Morales-Ríos, Olga; Jasso-Gutiérrez, Luis; Garduño-Espinosa, Juan; Olivar-López, Víctor; Muñoz-Hernández, Onofre
Spontaneous notification depends on the ability of pediatricians to identify adverse drug reactions (ADRs) along with their habit of reporting these incidents. During the years 2008 and 2009, the frequency of reports of ADRs to the Electronic Program of Pharmacovigilance (SISFAR) in the Hospital Infantil of Mexico Federico Gomez (HIMFG) was low (0.44% and 0.20%, respectively). Because of the above, the ability of pediatricians from the Emergency Department (ED) to identify ADRs using the clinical chart review was evaluated in 2010 in this study. A descriptive, observational, cross-sectional retrospective study was conducted in the ED from March 1 to August 31. ADRs were classified and quantified as "ADRs identified by pediatricians" when there was evidence in the clinical chart that pediatricians associated a clinical sign, symptom and laboratory value with an ADR. The numbers of notifications reported in SISFAR were quantified. Descriptive analysis was done using SPSS v.18. Considering patients who were admitted to the ED, the frequency of ADRs was 21.8%. The frequency of ADRs identified by physicians in clinical charts was 86%. The pharmacist detected 14% of ADRs. The frequency of ADRs reported by physicians was 6.1%. Although identification of ADRs in the clinical charts by pediatricians was high, it is possible that some ADRs were undetected. Because underreporting was very high, it is necessary to take actions to improve the reporting process. Copyright © 2015. Publicado por Masson Doyma México S.A.
Herdeiro, María T; Polonia, Jorge; Gestal-Otero, Juan J; Figueiras, Adolfo
The spontaneous reporting of adverse drug reactions (ADRs) through the yellow card and made concrete by the knowledge and attitudes of doctors, has been rousing a great deal of bibliographical interest in recent years. However, there does not seem to be any actual revision in the theme on which the theoretical models that explain the process of decision in reporting are proposed. In this work an explanatory model of the factors that condition reporting is proposed and a revision of the literature on the subject has also been carried out. The proposed model is centralized in the medical professional and it considers the habit of reporting as the result of the doctor's formation and his interaction with the environment. The combination of knowledge-attitudes-practices and the theory of the satisfaction of needs seemed very adequate for ADR systematization. The results also indicate that, to improve the participation of health professionals in surveillance systems through spontaneous reporting, it might be necessary to design combined strategies that modify both intrinsic (knowledge, attitudes) and extrinsic (relationship between health professionals and their patients, the national health system and pharmaceutical companies) factors.
Vallano Ferraz, Antonio; Agustí Escasany, Antonia; Pedrós Xolvi, Consuelo; Arnau de Bolós, Josep M
Adverse drug reactions (ADRs) are an important healthcare problem. The objective of this study was to review published articles analyzing the cost of ADRs in any healthcare setting. We conducted a search of articles published on the cost of ADRs in the bibliographic databases from 1970 to 2010. We identified 28 studies and selected 16 that included cases of ADR fitting the World Health Organization's definition of these events. The information on the characteristics of the study design, the types of costs analyzed and the reported results were reviewed. The design features and populations included in the studies were heterogeneous. Only two studies explicitly defined the perspective adopted. Only five studies compared cases of ADR with matched controls without ADRs. All studies analyzed direct healthcare costs, but none analyzed indirect or intangible costs. Fourteen publications analyzed the costs of length of hospital stay. The average (SD) percentage of ADRs was 3.04% (0.2) [median 2.4%, range 0.7% to 26.1%]. The median length of hospital stay in patients with ADRs was 8.8 days (range: 0.15 to 19.2 days). Accounting systems and monetary costs varied widely. Studies on the costs of ADRs are highly heterogeneous and have evaluated direct healthcare costs in hospitals. Their results indicate that ADRs generate substantial costs. More studies using appropriate methodology are needed on the costs of ADRs. Copyright © 2011 SESPAS. Published by Elsevier España. All rights reserved.
Kimmoun, Antoine; Dubois, Elsa; Perez, Pierre; Barbaud, Annick; Levy, Bruno
Some patients with drug reaction with eosinophilia and systemic symptoms (DRESS) are probably admitted in intensive care unit (ICU), but data concerning their clinical features at admission are scarce. Therefore, in the present study, we used a clinical network of French intensivists to study the clinical features and evolution of DRESS patients hospitalized in ICU. A national, retrospective, multicenter study collected DRESS cases hospitalized in ICU for DRESS from 2000 to end of 2011. All files were analyzed through the RegiSCAR scoring system as "no," "possible," "probable," or "definite" DRESS. Patients were included only if they had a probable or definite DRESS. Demographic, hemodynamic, biological, and infectious data were recorded. Twenty-one patients were included. Hospital mortality was 10 (47%) of 21, and 16 of 21 patients had on admission a shock state necessitating vasopressor agents. Echocardiographic ejection fraction in shock patients was depressed (47% ± 13%). Mechanical ventilation was required in 13 of 21 cases. Hepatic failure was observed in 11 of 21 cases, acute renal failure in 18 of 20 cases, and lactic acidosis in 12 of 20 patients. Initial bacteriology was negative in all patients. Human herpesvirus reactivations were found in five of 15 cases. In conclusion, shock without bacteriological documentation associated with multiple organ failure is the most common presentation of DRESS at admission in ICU and is associated with a higher mortality than previously described.
Al Dweik, Rania; Stacey, Dawn; Kohen, Dafna; Yaya, Sanni
The aim of the present study was to determine the barriers and motives influencing consumer reporting of adverse drug reactions (ADRs). A systematic review, guided by the Cochrane Handbook, was conducted. Electronic searches included MEDLINE, EMBASE, PsycINFO, CINAHL, PubMed and the Cochrane Database of Systematic Reviews from 1964 to December 2014. Eligible studies addressed patients' perceptions and factors influencing ADR reporting. Studies about healthcare professional (HCP) reporting of ADRs were excluded. Studies were appraised for quality, and results were analysed descriptively. Of 1435 citations identified, 21 studies were eligible. Studies were primarily conducted in the UK, the Netherlands and Australia. The identified barriers to patient reporting of ADRs (n = 15 studies) included poor awareness, confusion about who should report the ADR, difficulties with reporting procedures, lack of feedback on submitted reports, mailing costs, ADRs resolved and prior negative reporting experiences. The identified motives for patients reporting ADRs (n = 10 studies) were: preventing others from having similar ADRs, wanting personal feedback, improving medication safety, informing regulatory agencies, improving HCP practices, responding to HCPs not reporting their ADRs and having been asked to report ADRs by HCPs. Most patients were not aware of reporting systems and others were confused about reporting. Patients were mainly motivated to make their ADRs known to prevent similar suffering in other patients. By increasing patient familiarity and providing clear reporting processes, reporting systems could better achieve patient reporting of ADRs. © 2016 The British Pharmacological Society.
Erdeljic, Viktorija; Francetic, Igor; Likic, Robert; Bakran, Ivan; Makar-Ausperger, Ksenija; Simic, Petra
Although no more than 1% of adverse reactions to local anesthetics (LA) are thought to be immunologically mediated, many patients continue to be referred to allergy clinics for allergy workup. We evaluated the impact of a history of drug hypersensitivity or atopy on results of allergy testing to LA, with the aim of determining the appropriateness of allergy testing to LA in such patients. We retrospectively analyzed medical records of 112 consecutive patients referred for allergy testing to LA in a 9-year period (1996-2005). Intradermal tests with diluted (1:10) LA were performed to identify patients at risk for immunoglobulin E (IgE)-mediated hypersensitivity reaction. The odds for being testpositive were calculated with regard to the defined risk factors (atopy, history of adverse reactions to LA or other drugs, underlying autoimmune disease). Eleven of 112 patients (9.8%) tested positive for allergy to LA. Atopy, history of adverse reactions to LA or other drugs and underlying autoimmune disease did not increase the odds for being test-positive. The prevalence of multiple drug hypersensitivity, IgE values and eosinophil count were not significantly higher among the patients who tested positive as compared to the patients who tested negative. According to our data, allergy testing to LA is not justified in patients with atopy or histories of adverse drug reactions other than to LA. Further studies using validated methods of allergy testing to LA coupled with analysis of defined risk factors are needed to definitively establish the indications for referral of patients for allergy testing to LA. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.
Sakai, Takamasa; Ohtsu, Fumiko; Sekiya, Yasuaki; Mori, Chiyo; Sakata, Hiroshi; Goto, Nobuyuki
Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.
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
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.
Zhu, F; Zhang, J; Feng, J; Yang, H
The epidemiology of cutaneous herpes simplex infection (CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear. To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir. The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score (AES). Safety was characterized as the proportion of patients with drug adverse reactions (DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference (SMD) and risk ratio (RR), respectively. Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = -0.73 (95% CI -0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002). Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored. © 2016 British Association of
Full Text Available Cutaneous tuberculosis continues to be a significant medical problem even with the advent of highly effective antituberculous drugs. It constitutes about 1.5% of all extra pulmonary tuberculosis. The prevalence in children varies from 18 to 54% in India. There is no gender predilection and the infection occurs with increased frequency in 10-14 year age group. Intrafamilial source of TB has been observed very frequently. A concomitant TB lymphadenitis is most common while involvement of other systemic organs like lung, bone and abdomen has also been observed. Protective efficacy of BCG is debatable and not yet fully defined. Of all the clinical types, scrofuloderma (SFD is the most commonly encountered variant followed by lupus vulgaris (LV and tuberculosis verrucosa cutis (TBVC. Lichen scrofulosorum (LS is generally found to be associated with systemic TB focus in about 72% of cases. The impact of HIV on childhood cutaneous TB seems to be minimal. Similar to adults, the diagnosis of cutaneous tuberculosis relies mainly on histopathology, culture on LJ medium or radiometric BACTEC 460 TB culture system and PCR. In addition Mantoux positivity and a positive therapeutic trial with anti-tubercular drugs may be a good pointer to tubercular infection. A thorough clinical evaluation and exhaustive investigations to pin-point associated systemic focus is advocated as the latter has an impact on the duration of treatment. Cutaneous TB in children is treated as per the recommendations of therapy for extrapulmonary TB.
Full Text Available OBJECTIVE: To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine that led to the withdrawal of licenses for these drugs for infants in France and then Italy. DESIGN: The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. SETTING: Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. PATIENTS: The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg and at least until the day before the first signs of the suspected ADR. RESULTS: The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old were increased bronchorrhea or mucus vomiting (n = 27, worsening of respiratory distress during respiratory tract infection (n = 35, dyspnoea (n = 18, cough aggravation or prolongation (n = 11, and bronchospasm (n = 1. Fifty-one (86% children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. CONCLUSION: Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.
Lorío, Marco; Colasanti, Jonathan; Moreira, Sumaya; Gutierrez, Gamaliel; Quant, Carlos
Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an important cause of hospitalization, treatment discontinuation, and regimen changes in both developed and developing countries. This study is the first to examine and understand ADRs in HIV-infected patients in Nicaragua. A retrospective descriptive study was conducted from May 2010 to March 2011, in a cohort of HIV-infected patients receiving ART at the largest public hospital in Managua, Nicaragua. Patients were identified based on ADRs reporting on a standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of these patients were performed in order to document the specific ADRs. Six hundred ninety-two patients on ART were included. The incidence of ADRs was 6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine (FTC)/tenofovir (TDF) had fewer ADRs (P reactions. Adverse drug reactions were classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs were preventable. Adverse drug reactions most frequently affected the central nervous system. No ADR was life threatening. The frequency of ADRs in this Nicaraguan patient population was less than that reported from other studies in resource-limited settings. © The Author(s) 2014.
Yang, Wei; Xie, Yan-Ming; Xiang, Yong-Yang
This research based on the analysis of spontaneous reporting system (SRS) data which the 9 601 case reports of Shuxuening injection adverse drug reactions (ADR) in national adverse drug reaction monitoring center during 2005-2012. Apply to the association rules to analysis of the relationship between Shuxuening injection's ADR and the characteristics of ADR reports were. We found that ADR commonly combination were "nausea + breath + chills + vomiting", "nausea + chills + vomiting + palpitations", and their confidence level were 100%. The ADR and the case reports information commonly combination were "itching, and glucose and sodium chloride Injection, and generally ADR report, and normal dosage", "palpitation, and glucose and sodium chloride injection, and normal dosage, and new report", "chills, and generally ADR report, and normal dosage, and 0.9% sodium chloride injection", and their confidence level were 100% too. The results showed that patients using Shuxuening injection occurred most of ADRs were systemic damage, skin and its accessories damage, digestive system damage, etc. And most of cases were generally and new reports, and patients with normal dosage. The ADR's occurred had little related with solvent. It is showed that the Shuxuening injection occurred of ADR mainly related to drug composition. So Shuxuening injection used in clinical need to closely observation, and focus on the ADR reaction, and to do a good job of drug risk management.
Conclusions: For correct diagnosis and intervention it is essential to identify the different clinical patterns of drug-induced skin reactions; DRESS syndrome in particular, is a drug-induced skin reaction that can endanger a patient's life, and therefore it is important that it is correctly identified and managed.
Krintel, Sophine B; Grunert, Veit Peter; Hetland, Merete L
To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.......To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure....
Paez Mildred; Neira, Myriam Consuelo; Latorre Pablo; Faisal, Michel
We present the case or a male, 28 year old that consulted for fever, weight loss and axillary ulcer. Clinically had two skin lesions where cutaneous tuberculosis was proven (lupus vulgaris-scrofuloderma). The skin lesions led to the diagnosis of lung tuberculosis and tuberculous adenitis. In this case all the diagnostic criteria for cutaneous tuberculosis were completed: active presence of tuberculosis in another place, positive reaction to tuberculin test, physical signs and appropriate answer to the treatment
Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna
Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.
Almandil, Noor B
To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods: This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia, between April 2015 and April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results: A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion: There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU.
Full Text Available Objectives: This study was conducted to evaluate knowledge, attitude and practice of Adverse Drug Reactions (ADR reporting among Healthcare Professionals.Methods: A cross-sectional study was done by survey using questionnaire. Questionnaire was distributed to 260 healthcare professionals working at M.R. Medical College and S Nijalingappa Institute of Dental Sciences, Kalaburagi, India.Results: Out 260 people 221 provided the response, giving a response rate of 85%. Among respondents 69.68% were Doctors, 23.53% were Nurses and 6.78% were Pharmacists. 71% of the healthcare professionals knew what are ADRs, 62.4% knew what is pharmacovigilance, 35.7% were aware of Pharmacovigilance Programme of India (PvPI and 21.7% knew nearest pharmacovigilance center. 50.2% had seen patients experiencing ADR out of which only 8.1% of them have reported ADR to the concerned unit. 72.4% feel that all the cases of ADR should be reported irrespective of seriousness. Concern that report may be wrong and fear of legal liability were the main factors discouraging them for reporting ADR. Local coordination, Financial Support, ADR reporting awareness programmes were the major expectations from respondents.Conclusion: Healthcare professionals working at HKE Society’s M.R. Medical College and S Nijalingappa Institute of Dental Sciences have positive attitudes towards ADR reporting. However knowledge regarding ADR reporting among Doctors is superior to that of Nurses and Pharmacists, awareness programmes can overcome this problem. But the practice of ADR reporting is poor among all Healthcare professionals.
Cocos, Anne; Fiks, Alexander G; Masino, Aaron J
Social media is an important pharmacovigilance data source for adverse drug reaction (ADR) identification. Human review of social media data is infeasible due to data quantity, thus natural language processing techniques are necessary. Social media includes informal vocabulary and irregular grammar, which challenge natural language processing methods. Our objective is to develop a scalable, deep-learning approach that exceeds state-of-the-art ADR detection performance in social media. We developed a recurrent neural network (RNN) model that labels words in an input sequence with ADR membership tags. The only input features are word-embedding vectors, which can be formed through task-independent pretraining or during ADR detection training. Our best-performing RNN model used pretrained word embeddings created from a large, non-domain-specific Twitter dataset. It achieved an approximate match F-measure of 0.755 for ADR identification on the dataset, compared to 0.631 for a baseline lexicon system and 0.65 for the state-of-the-art conditional random field model. Feature analysis indicated that semantic information in pretrained word embeddings boosted sensitivity and, combined with contextual awareness captured in the RNN, precision. Our model required no task-specific feature engineering, suggesting generalizability to additional sequence-labeling tasks. Learning curve analysis showed that our model reached optimal performance with fewer training examples than the other models. ADR detection performance in social media is significantly improved by using a contextually aware model and word embeddings formed from large, unlabeled datasets. The approach reduces manual data-labeling requirements and is scalable to large social media datasets. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: firstname.lastname@example.org
Full Text Available Introduction: Adverse drug reactions (ADRs are threat to the patient’s safety and the quality of life, and they increase the cost of health care. Spontaneous ADR reporting system mainly relies on physicians, but also pharmacists, nurses, and even patients. The aim of this study was to explore attitudes, barriers, and possible improvements to ADR reporting practices in Bosnia and Herzegovina.Methods: A self-reported questionnaire was developed to collect data on the perception of pharmacovigilance practice and ADR reporting. The survey was conducted in the period between September, 2014 and October, 2014.Results: The response rate was 73% (44 of 60 and 93% (148 of 160 among the pharmacist and family medicine physician groups, respectively. Regarding the attitudes to pharmacovigilance practice and reporting, both the pharmacists and physicians found the practices important. The majority of pharmacists and physicians in year 2014 did not report any ADR, while 18% of the pharmacists and 12% of the physicians, who participated in this study, reported one ADR. Reporting procedure, uncertainty, and their exposure were the main barriers to reporting ADRs for the pharmacists. The physicians claimed lack of knowledge to whom to report an ADR as the main barrier. A significant number of the respondents thought that additional education in ADR reporting would have a positive impact, and would increase the ADR reporting rate.Conclusions: Despite the overall positive attitude towards ADR reporting, the reporting rate in Bosnia and Herzegovina is still low. Different barriers to the ADR reporting have been identified, and there is also the need for improvements in the traditional education in this field.
Kiguba, Ronald; Ononge, Sam; Karamagi, Charles; Bird, Sheila M
Clinical history-taking can be employed as a standardized approach to elucidate the use of herbal medicines and their linked suspected adverse drug reactions (ADRs) among hospitalized patients. We sought to identify herbal medicines nominated by Ugandan inpatients; compare nomination rates by ward and gender; confirm the herbs' known pharmacological properties from published literature; and identify ADRs linked to pre-admission use of herbal medicines. Prospective cohort of consented adult inpatients designed to assess medication use and ADRs on one gynaecological and three medical wards of 1790-bed Mulago National Referral Hospital. Baseline and follow-up data were obtained on patients' characteristics, including pre-admission use of herbal medicines. Fourteen percent (26/191) of females in Gynaecology nominated at least one specific herbal medicine compared with 20 % (114/571) of inpatients on medical wards [20 % (69/343) of females; 20 % (45/228) of males]. Frequent nominations were Persea americana (30), Mumbwa/multiple-herb clay rods (23), Aloe barbadensis (22), Beta vulgaris (12), Vernonia amygdalina (11), Commelina africana (7), Bidens pilosa (7), Hoslundia opposita (6), Mangifera indica (4), and Dicliptera laxata (4). Four inpatients experienced 10 suspected ADRs linked to pre-admission herbal medicine use including Commelina africana (4), multiple-herb-mumbwa (1), or unspecified local-herbs (5): three ADR-cases were abortion-related and one kidney-related. The named herbal medicines and their nomination rates generally differed by specialized ward, probably guided by local folklore knowledge of their use. Clinical elicitation from inpatients can generate valuable safety data on herbal medicine use. However, larger routine studies might increase the utility of our method to assess herbal medicine use and detect herb-linked ADRs. Future studies should take testable samples of ADR-implicated herbal medicines for further analysis.
LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C
Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number
Montiago X LaBute
Full Text Available Late-stage or post-market identification of adverse drug reactions (ADRs is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409 of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively. Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with
Ruokolainen, Miina; Gul, Turan; Permentier, Hjalmar; Sikanen, Tiina; Kostiainen, Risto; Kotiaho, Tapio
The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off. Copyright © 2015 Elsevier B.V. All rights reserved.
Bigi, Caterina; Tuccori, Marco; Bocci, Guido
To analyze the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (FDA), investigating the characteristics of pediatric adverse drug reactions (ADRs) and describing the effective participation of healthcare professionals in the reporting activity. Reports of ADRs were obtained from the FDA website. Only ADRs in pediatric subjects (divided by age, by country and by professional category) were included into the analysis. The drugs suspected as primary cause of the ADRs in pediatric subjects and their principal anatomic group according to the Anatomical Therapeutic Chemical classification system were considered. To classify the ADRs, the Medical Dictionary for Regularity Activities terminology was adopted. Between 2008 and 2012, FDA collected 113,077 ADRs in pediatric patients. Of the total pediatric ADR reports, those performed by medical doctors were 32%, followed by consumers (26%) and healthcare professionals (25%). Most of the ADR reports were related to the adolescent group (39%). Healthcare professionals resulted the category with the highest rate of ADR reports in neonates and infants. Drugs acting on nervous system and antineoplastic/immunomodulating agents were the most involved the pediatric ADR reports. Pyrexia, convulsion, vomiting and accidental overdose were the reactions more reported both from healthcare professionals and medical doctors. The present study describes the pediatric ADR reports of the FDA database through healthcare professional's perspective, describing the various aspects of pediatric pharmacovigilance.
Full Text Available Purpose: Studies regarding pattern of adverse drug reactions (ADRs in cancer chemotherapy patients are scarce in India. This study was conducted to evaluate the pattern of occurrence of ADRs due to cancer chemotherapy in hospitalized patients and to assess the causality, severity, predictability, and preventability of these reactions. Materials and Methods: This was a retrospective, descriptive study and the occurrence and nature of ADR, suspected drug, duration of hospital stay and outcome were noted from case records. These ADRs were assessed for causality using both World Health Organization (WHO causality assessment scale and Naranjo′s algorithm. The severity and preventability of the reported reactions were assessed using modified Hartwig and Siegel scale and modified Schumock and Thornton scale respectively. Results: Five hundred ADRs were recorded from 195 patients. Most common ADRs were infections (22.4%, nausea/vomiting (21.6% and febrile neutropenia (13%. Platinum compounds, nitrogen mustards, taxanes, antibiotics and 5-fluorouracil were the most common drugs causing ADRs. WHO causality assessment scale showed 65% of the reactions to be "probable" and 35% to be "possible," while Naranjo′s algorithm indicated that 65.6% of ADRs were "probable" and 34.4% were "possible". Modified Hartwig and Siegel scale showed most reactions (41.4% to be of "moderate level 4(a" severity, while 30.6% of reactions were of "mild level 1" severity. About 30.8% of the ADRs were "definitely preventable" according to the modified Schumock and Thornton scale. Conclusion: ADRs are most important causes of morbidity and mortality and increase the economic burden on patient and society. By careful ADR monitoring, their incidence can be decreased.
Full Text Available Background: Cutaneous vasculitis presents as a mosaic of clinical and histological findings. Its pathogenic mechanisms and clinical manifestations are varied. Aims: To study the epidemiological spectrum of cutaneous vasculitides as seen in a dermatologic clinic and to determine the clinico-pathological correlation. Methods: A cohort study was conducted on 50 consecutive patients clinically diagnosed as cutaneous vasculitis in the dermatology outdoor; irrespective of age, sex and duration of the disease. Based on the clinical presentation, vasculitis was classified according to modified Gilliam′s classification. All patients were subjected to a baseline workup consisting of complete hemogram, serum-creatinine levels, serum-urea, liver function tests, chest X-ray, urine (routine and microscopic examination besides antistreptolysin O titer, Mantoux test, cryoglobulin levels, antineutrophilic cytoplasmic antibodies and hepatitis B and C. Histopathological examination was done in all patients while immunofluorescence was done in 23 patients. Results: Out of a total of 50 patients diagnosed clinically as cutaneous vasculitis, 41 were classified as leukocytoclastic vasculitis, 2 as Heinoch−Schonlein purpura, 2 as urticarial vasculitis and one each as nodular vasculitis, polyarteritis nodosa and pityriasis lichenoid et varioliforme acuta. Approximately 50% of the patients had a significant drug history, 10% were attributed to infection and 10% had positive collagen workup without any overt manifestations, while 2% each had Wegener granulomatosis and cryoglobulinemia. No cause was found in 26% cases. Histopathology showed features of vasculitis in 42 patients. Only 23 patients could undergo direct immunofluorescence (DIF, out of which 17 (73.9% were positive for vasculitis. Conclusions: Leukocytoclastic vasculitis was the commonest type of vaculitis presenting to the dermatology outpatient department. The workup of patients with cutaneous vasculitis
Full Text Available Three unusual clinical forms of sporotrichosis described in this paper will be a primer for the clinicians for an early diagnosis and treatment, especially in its unusual presentations. Case 1, a 52-year-old man, developed sporotrichosis over pre-existing facial nodulo-ulcerative basal cell carcinoma of seven-year duration, due to its contamination perhaps from topical herbal pastes and lymphocutaneous sporotrichosis over right hand/forearm from facial lesion/herbal paste. Case 2, a 25-year-old woman, presented with disseminated systemic-cutaneous, osteoarticular and possibly pleural (effusion sporotrichosis. There was no laboratory evidence of tuberculosis and treatment with anti-tuberculosis drugs (ATT did not benefit. Both these cases were diagnosed by histopathology/culture of S. schenckii from tissue specimens. Case 3, a 20-year-old girl, had multiple intensely pruritic, nodular lesions over/around left knee of two-year duration. She was diagnosed clinically as a case of prurigo nodularis and histologically as cutaneous tuberculosis, albeit, other laboratory investigations and treatment with ATT did not support the diagnosis. All the three patients responded well to saturated solution of potassium iodide (SSKI therapy. A high clinical suspicion is important in early diagnosis and treatment to prevent chronicity and morbidity in these patients. SSKI is fairly safe and effective when itraconazole is not affordable/ available.
Zegpi-Trueba, María Soledad; Hasbún-Acuña, Paula; Berroeta-Mauriziano, Daniela
Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G. M.; Dheda, Mukesh; Haaijer-Ruskamp, Flora M.; Taxis, Katja; Mol, Peter G. M.
OBJECTIVE: Identifying key features of cardiometabolic ADR reports in sub Saharan Africa (SSA) compared with reports from the rest of the world (RoW). METHODS: Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from
Sasani, F; Javanbakht, J; Samani, R; Shirani, D
Canine cutaneous leishmaniasis (CCL) is a significant veterinary problem. Infected dogs also serve as parasite reservoirs and contribute to human transmission of cutaneous leishmaniasis. Histologically, the lesions were nodular to diffuse interstitial granulomatous dermatitis with histiocytic pseudorosettes together with numerous amastigotes within macrophages and occasionally within the interstitium. Organisms were often contained within clear and intracellular vacuoles. The other inflammatory cells, which were present in the biopsies of the Leishmania-infected dog, were lymphocytes and plasma cells. The histopathology results emphasized the role of dog, particularly asymptomatic dog, as reservoirs for CCL because of the high cutaneous parasite loads. These results may help to explain the maintenance of high transmission rates and numbers of CCL cases in endemic urban regions.
Ramesh, V; Al Aboud, Khalid
It is important for dermatologists to be aware of cutaneous changes related to religious practices to help in their recognition and management. The anatomic location of cutaneous lesions associated with friction from praying varies based on religious practice. Allergic contact dermatitis from products and substances commonly used in worshipping also vary by religion. Some religious practices may render individuals prone to infections that manifest on the skin. Tattoos of godly figures also may adorn the body. Religious practices also have been implicated in cases of urticaria, köbnerization, and leukoderma. This article reviews the clinical presentation of some of the most common cutaneous changes that occur in individuals who practice the following religions: Christianity, Islam, Judaism, Hinduism, and Sikhism.
Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang
Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified
Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: email@example.com [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)
Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.
Full Text Available Introduction: Pharmacovigilance is an arm of patient care. No one wants to harm patients, but unfortunately any medicine will sometimes do just this. Underreporting of adverse drug reactions by healthcare professionals is a major problem in many countries. In order to determine whether our pharmacovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of health care professionals in adverse drug reaction (ADR reporting was performed.Methods: A pretested questionnaire comprising of 20 questions was designed for assessment of knowledge, perceptions, practice and barriers toward ADR reporting on a random sample of 1000 healthcare professionals in Bosnia and Herzegovina.Results: Of the 1000 respondents, 870 (87% completed the questionnaire. The survey showed that 62.9% health care professionals would report ADR to the Agency for Medicinal Products and Medical Device of Bosnia and Herzegovina (ALMBIH. Most of surveyed respondents has a positive perception towards ADR reporting, and believes that this is part of their professional and legal obligation, and they also recognize the importance of reporting adverse drug reactions. Only small percent (15.4% of surveyed health care professionals reported adverse drug reaction.Conclusions: The knowledge of ADRs and how to report them is inadequate among health care professionals. Perception toward ADR reporting was positive, but it is not reflected in the actual practice of ADRs, probably because of little experience and knowledge regarding pharmacovigilance. Interventions such as education and training, focusing on the aims of pharmacovigilance, completing the ADR form and clarifying the reporting criteria are strongly recommended.
Shubhangi Vinayak Agale
Full Text Available Primary cutaneous leiomyosarcoma of the skin is a rare soft tissue neoplasm, accounting for about 2-3% of all superficial soft tissue sarcomas. It arises between the ages of 50 and 70 years, and shows a greater predilection for the lower extremities. Clinically, it presents with solitary, well-circumscribed nodule and, microscopically, consists of fascicles of spindle-shaped cells with "cigar-shaped" nuclei. Local recurrence is known in this tumor. We document a case of primary cutaneous leiomyosarcoma in a 77-year-old man and discuss the histological features and immunohistochemical profile of this uncommon neoplasm.
Maria Edileuza Felinto de Brito
Full Text Available We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL: one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples and characterized as Leishmania (Viannia naiffi through an indirect immunofluorescence assay (IFA with species-specific monoclonal antibodies (mAbs and by multilocus enzyme electrophoresis (MLEE. Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis.
Poon, Samuel H; Baliog, Crisostomo R; Sams, Ralph N; Robinson-Bostom, Leslie; Telang, Gladys H; Reginato, Anthony M
We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy. Cases were seen and reviewed in both the inpatient consult service and the outpatient clinics at Rhode Island Hospital from August 2009 to August 2010. Clinical characteristics as well as pertinent laboratory parameters were also reviewed and corroborated with a review of the present literature. We describe 3 cases of cocaine-levamisole-related cutaneous vasculitis with or without associated neutropenia, and 1 case of severe neutropenia with oral mucosal ulceration. Further serologic studies revealed maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase tested negative or mildly elevated in our cohort. Three patients with neutropenia had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs were effective as first-line treatment for joint pain. The use of colchicine and systemic corticosteroid was employed to manage severe and persistent skin lesions. Cocaine-levamisole-related cutaneous vasculitis with leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of cutaneous manifestations consisting of palpable purpura or bullae with ear involvement, arthralgias, leukopenia, and positive ANCA in high titers and negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic entities have been excluded. Published by Elsevier Inc.
Sarker, Abeed; Gonzalez, Graciela
Automatic detection of adverse drug reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media-where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing (NLP) approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing benchmarks. Our experiments
Tuccori, Marco; Lapi, Francesco; Testi, Arianna; Ruggiero, Elisa; Moretti, Ugo; Vannacci, Alfredo; Bonaiuti, Roberto; Antonioli, Luca; Fornai, Matteo; Giustarini, Giulio; Scollo, Carla; Corona, Tiberio; Ferrazin, Fernanda; Sottosanti, Laura; Blandizzi, Corrado
The frequency and clinical features of drug-related taste and/or smell impairments are currently unclear. The aim of this study was to identify major drug classes associated with taste and smell alterations reported to the Italian spontaneous adverse drug reaction (ADR) reporting database. The association between drug and altered taste or smell was investigated by case/non-case methodology. The reporting odds ratio (ROR) was used as a measure of disproportionality. Cases were defined as patients with at least one ADR related to taste or smell impairments. The non-cases included all patients without any ADRs related to taste or smell alterations. According to the selection criteria, 52 166 reports were included in the analysis. Overall, 182 cases of drug-related taste and/or smell dysfunctions were identified. Statistically significant unadjusted RORs were reported for macrolides (n = 31; 7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n = 17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n = 15; 1.7; 95% CI 1.0, 2.8) and protein kinase inhibitors (n = 10; 4.0; 95% CI 2.1, 7.7). When RORs were adjusted for sex and age category, the disproportion remained statistically significant for all of the previously mentioned drug classes. Taste and/or smell abnormalities are common, sometimes unexpected and often persistent complaints of patients during pharmacological treatments. Physicians should be aware of the impact of these ADRs on patients' quality of life.
Tutubalina, Elena; Nikolenko, Sergey
Adverse drug reactions (ADRs) are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.
Full Text Available Adverse drug reactions (ADRs are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.
Acute radiation dermatitis were reported of iridium 172 under poor administration which radiated locally on the skin of hands and fingers of oil company workers. Atomic bomb over Hiroshima and Nagasaki killed many people by total body skin exposure. Many workers and firemen were radiated by beta and gamma rays in the Chernobyl' accident, where 19 of 28 death cases died by radiation burn. 8 patients with 60-100% burn area died in 15-24 days after the explosion. Of 12 patients with 30-60% burn area, 6 died by burn. 21 cases of 30% burn area did not die in spite of mild or severe bone marrow depression. In all these cases, areas of skin ulcers epithelized with dry and wet scales till 50-60 days after the explosion, except large area (20-25cm 2 ) transplanted. In this accident, severe radiation burn due to the beta ray irradiation occured with endogeneous intoxication, renal disturbance, blood biochemical changes and bleeding. Oral, pharyngeal and intestinal membrane were irradiated by beta ray and were ulcerated so they could hardly eat. The treatment of these cases with acute radiation dermatitis should be performed by the procedure of treatment of burn, locally and systematically. Local treatment should be performed by topical application of antibiotic ointment or adrenocortical steroid ointment with antibiotics. In severe burn, systemic treatment with plasma and other fluids for burn shock should be performed, corresponding to the area and depth of radiation burn. (A.Y.)