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1

Adverse reactions to orthodontic appliances in nickel-allergic patients.  

PubMed

Nickel allergy (NA) is common and causes more cases of allergic contact dermatitis (ACD) than all other metals combined. Many orthodontic appliances (ODAs) contain nickel but their clinical relevance in nickel-allergic patients is unclear. We aimed to characterize the relationship between NA and ODAs because the medical literature investigating this is controversial. A survey concerning adverse reactions to ODAs in patients with NA was distributed to members of the Wisconsin Society of Orthodontics. Forty-three surveys were analyzed. The surveyed group was experienced, representing a mean of 21.2 years in practice and averaging 242 appliances placed per year per orthodontist. Most new patients with orthodontia were 10-18 years old. Most wires used were nickel-titanium alloy. Although 76% of orthodontists inquired about NA at initial evaluation, 37% still placed nickel-containing ODAs in known nickel-allergic patients. Fifty percent placed a single intraoral appliance, observing for reactions. Three orthodontists applied ODAs to the skin similar to patch testing. Only 8 patients with reactions to ODAs were described in detail, 6 were female patients and 6 were aged 13-14 years. Intraoral and extraoral reactions were mild; diffuse urticaria was reported in one patient. Treatment included removing the appliances or changing to nonnickel alternatives with favorable outcomes. These cases, which included >33,000 patients, suggest a prevalence of 0.03%. Adverse reactions to ODAs in patients with NA have been observed but are uncommon. Using suitable alternatives, patients usually can be accommodated. PMID:17883919

Volkman, Kristen K; Inda, Michael J; Reichl, Peter G; Zacharisen, Michael C

2007-01-01

2

Adverse drug reactions and debrisoquine\\/sparteine (P450IID6) polymorphism in patients with fibromyalgia  

Microsoft Academic Search

Summary  \\u000aObjective: To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions.\\u000aMethods: Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions.

K. J. Skeith; M. S. Hussain; R. T. Coutts; C. Ramos-Remus; J. A. Avina-Zubieta; A. S. Russell

1997-01-01

3

Who really knows their patients' penicillin adverse drug reaction status? A cross-sectional survey.  

PubMed

This cross-sectional survey of patients with adverse drug reactions (ADR) to penicillin and their treating doctor, nurse and pharmacist was undertaken to identify the extent of healthcare workers (HCW) awareness of their patients' ADR, and antibiotic use in hospital. There were 23 (38%) doctors, 53 (87%) nurses and 40 (66%) pharmacists who were aware of their patient's penicillin ADR, despite more than half of their patients receiving antibiotics. Interventions encouraging 'double checking' may improve antibiovigilance. PMID:25582941

Fehily, S R; Stuart, R L; Horne, K; Korman, T M; Dendle, C

2015-01-01

4

Adverse drug reactions in veterinary patients associated with drug transporters.  

PubMed

For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

Mealey, Katrina L

2013-09-01

5

Adverse reactions to gentamycin in patients with ear, nose or throat infections.  

PubMed

Eighty four patients requiring treatment with Gentamycin were selected from Otorhinolaryngology outpatient and those admitted to the hospital. Patients suffering from hepatic or renal disorders, pregnant women and children were excluded from the study. Seventy three were administered gentamycin 40 mg BD intramuscularly for 7-10 days and in 11 the drug was applied topically as ear drops for 6-12 weeks. Adverse reactions were observed in 9 (13.3%) and 11 (100%) patients given the drug parenterally and topically respectively. In parenteral group incidence was higher in females as compared to males and profile included nausea and vomiting, headache, cough, tinnitis, albuminuria, diminition of hearing and vertigo. Whereas diminition of hearing acuity was observed in all those who had topical application as evidenced by pure tone audiometry. PMID:1473850

Singhal, S; Sharma, S C; Singhal, K C

1992-07-01

6

Postmarketing adverse drug reactions  

PubMed Central

Summary Physicians play an important role in recognizing and reporting suspected adverse drug reactions (ADRs) to the Food and Drug Administration (FDA). Physicians can report suspected ADRs directly to the FDA via its MedWatch program, by contacting the manufacturer of the drug, and by publishing case reports. While this takes time, physicians have an ethical obligation to participate in recognizing and reporting ADR. PMID:24195018

Bourdette, Dennis

2013-01-01

7

[Cutaneous adverse drug reactions.  

PubMed

Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

Lebrun-Vignes, B; Valeyrie-Allanore, L

2014-11-01

8

Adverse reaction to intravenous gadoteridol.  

PubMed

Moderate and severe anaphylactoid reactions--while extremely rare--have been reported in association with intravenous administration of gadopentetate dimeglumine. There has been no similar experience related to use of the newly released magnetic resonance (MR) imaging contrast agent gadoteridol. The authors describe a case of vasovagal response and anaphylactoid reaction during intravenous administration of gadoteridol. MR users should be aware of the potential for adverse effects to occur in association with use of gadoteridol and be prepared by implementing appropriate observation procedures for patients receiving this as well as other MR contrast agents. In addition, physiologic monitoring devices and resuscitation equipment should be readily available in the clinical MR setting for proper treatment of patients who may experience moderate to severe adverse reactions. PMID:8372186

Shellock, F G; Hahn, H P; Mink, J H; Itskovich, E

1993-10-01

9

HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods.  

PubMed

The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including "in vivo" and "in vitro" allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H2 breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance. PMID:21614464

Erminia, Ridolo; Ilaria, Baiardini; Tiziana, Meschi; Silvia, Peveri; Antonio, Nouvenne; Pierpaolo, Dall'Aglio; Loris, Borghi

2013-09-01

10

Impact of levofloxacin dose adjustments by dispensing pharmacists on adverse reactions and costs in the treatment of elderly patients.  

PubMed

Ensuring an appropriate dosage of renally eliminated drugs for patients with renal insufficiency is important for preventing adverse drug reactions. We investigated the effectiveness of interventions by pharmacists in a hospital pharmaceutical department. The comparative study was performed at Gifu Municipal Hospital in Japan from March to August 2011, and included an intervention (142 patients) and a control group (98 patients). Upon receiving a prescription of levofloxacin for patients aged > or = 75 years, pharmacists evaluated the patients' kidney function and adjusted the appropriate dosage at the time of dispensation. In the intervention and control groups, levofloxacin-induced adverse reactions developed in 6 of 142 (4.2%) and 13 of 98 (13.3%) patients, respectively (p < 0.05). The cost of reducing levofloxacin per patient was yen 191.1 and yen 0 in the intervention and control groups, respectively. The cost per patient for adverse reaction treatments and examinations was yen 15.5 and yen 290.0 in the intervention and control groups, respectively. The intergroup difference in the total cost per patient was yen 465.6. Dose adjustment of levofloxacin at the time of dispensation by the pharmacist for patients aged > or = 75 years resulted in a decrease in the incidence of adverse reactions and cost. These findings can be applied not only to hospitals, but also to community pharmacies, because the intervention, which is a manual system, is simply performed when pharmacists are dispensing drugs. PMID:24400446

Tachi, T; Teramachi, H; Asano, S; Tanaka, K; Fukuta, M; Osawa, T; Aoyama, S; Yasuda, M; Mizui, T; Goto, C; Tsuchiya, T

2013-12-01

11

Adverse Drug Reactions of Long-term Intravenous Antibiotics in Patients with Pyogenic Spondylitis  

PubMed Central

Objective The purpose of this study was to investigate the incidence, cause, and influence of the adverse drug reactions (ADRs) associated with long-term intravenous antibiotics in patients with pyogenic spondylitis (PS). Methods We retrospectively reviewed the medical records of 84 patients with PS who underwent intravenous antibiotic therapy in our hospital from January 2001 to December 2012. ADRs were categorized to drug eruption, acute renal failure (ARF), hematologic toxicity, toxic hepatitis, pseudomembranous colitis (PMC), drug fever, and neuronal toxicity. Incidence and onset time of each ADR after antibiotic therapy were analyzed with the incidence of ADRs according to types of antibiotics. Results ADRs occurred in 38 of the 84 patients (incidence: 45.2%). The use of antibiotics was longer in the patients with ADRs (62.7 days) than in the patients without ADRs (44.3 day). The incidence of drug eruption, ARF, hematologic toxicity, toxic hepatitis, PMC, drug fever, and neuronal toxicity were 22.6, 11.9, 11.9, 10.7, 7.1, 3.6%, and 1.2%, respectively. The duration of antibiotics administration was related to the occurrence of PMC (p=0.001). ADRs were more common in patients treated by glycopeptides including vacomycin and teicoplanin. Conclusion The incidence of ADRs due to long-term intravenous antibiotics was as high as 45.2% in patients with PS. Therefore, we speculate that the possibility of delayed ADRs should be considered after long-term use of the antibiotics. Furthermore, close observation is mandatory to identify and treat ADRs promptly, even though PS revealed the improvement after antibiotic therapy. PMID:25346755

Kim, Dong Hwan; Kim, Hwan Soo; Nam, Kyoung Hyup; Choi, Byung Kwan

2014-01-01

12

ISMP Adverse Drug Reactions  

PubMed Central

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421518

2013-01-01

13

ISMP Adverse Drug Reactions  

PubMed Central

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

2013-01-01

14

ISMP Adverse Drug Reactions  

PubMed Central

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24474829

2013-01-01

15

Biomarkers for cancer-related fatigue and adverse reactions to chemotherapy in lung cancer patients.  

PubMed

This study was conducted to investigate the biomarkers that appear to be correlated with cancer-related fatigue (CRF) and the adverse reactions (ADRs) to chemotherapy. A total of 100 lung cancer patients were selected and CRF prior to and following chemotherapy was evaluated. The plasma levels of tumor necrosis factor (TNF)-? and interleukin (IL)-1 and the level of 17-hydroxycorticosteroid (17-OHCS) in the urine were analyzed and correlated with CRF and the ADRs associated with chemotherapy. The incidence of CRF was found to be 88.0% and ADRs following chemotherapy occurred in 15.0% of the patients. An increase in the TNF-? and IL-1 levels was detected in patients with CRF. The level of 17-OHCS in the urine was found to be elevated in cases that experienced ADRs following chemotherapy. In conclusion, CRF is closely correlated with increased plasma levels of TNF-? and IL-1. Furthermore, an abnormally elevated 17-OHCS level in the urine may be an important indicator predicting ADR development following chemotherapy. PMID:25469288

Sha, Fei; Zhuang, Shanshan; Zhou, Li; Zhang, Liqun; Yang, Yuxian; Zhang, Shengqi; Jiang, Yi; Qiu, Guodong; Chen, Chen; Zheng, Jieting; Zhang, Shuyao

2015-01-01

16

Adverse drug reactions in dermatology.  

PubMed

Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

Ferner, R E

2015-03-01

17

Adverse Reactions to Hallucinogenic Drugs.  

ERIC Educational Resources Information Center

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…

Meyer, Roger E. , Ed.

18

Evaluation of adverse drug reactions in HIV positive patients in a tertiary care hospital  

PubMed Central

Context: The advancement and development of new drugs and treatment strategies increase the risk of unusual Adverse Events (AEs) in HIV patients. Aims: The objective of our study was to assess the incidence, types and nature of AEs in HIV positive subjects. Settings and Design: Patients with WHO stage IV disease irrespective of the CD4 cell count, or WHO stage III disease with a CD4 cell count <350 cell/cu. Mm, or, WHO stage I or II disease with a CD4 cell count of <200 cells/cu. mm, and on prior anti-retroviral therapy for not more than six months preceding the observation date, were included in the study. After initiation of therapy, the patients were examined for the occurrence any adverse events including the type and severity, or any other abnormal laboratory findings. Causality assessment of the adverse events was done using the Naranjo's scale. Results: Out of 327 patients studied prospectively, 43 patients developed AEs. Out of these, 23 (53.5%) were males and 20 (46.5%) were females. A total of 53 (16.21%) AEs were reported. Antitubercular drugs caused the maximum AEs (28.3%) followed by zidovudine (20.7%), nevirapine (15.0%) and efavirenz (5.6%). Stavudine, ethambutol, sulfamethoxazole and trimethoprim, and atazanavir were also responsible for 3.7% of AEs individually. Causality assessment done according to the Naranjo's scale revealed that 66.04% AEs were ‘probable’ and 33.96% were ‘possible’. Conclusions: Anemia, hepatitis and dermatological adverse effects are the most common AEs. Antitubercular drugs contributed significantly for the incidence of AEs in these patients. Frequency of AEs was slightly more in males compared to females. PMID:25657900

Jha, Anshu Kumar; Gadgade, Akash; Shenoy, Ashok K.; Chowta, Mukta N.; Ramapuram, John T.

2015-01-01

19

Nurses must report adverse drug reactions.  

PubMed

There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

Griffith, Richard

20

Pharmacogenomics of adverse drug reactions  

PubMed Central

Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed. PMID:23360680

2013-01-01

21

Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients.  

PubMed

Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5?cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe. PMID:24672577

Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2014-01-01

22

Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients  

PubMed Central

Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5?cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe. PMID:24672577

Steele, Megan L.; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2014-01-01

23

Consequences, measurement, and evaluation of the costs associated with adverse drug reactions among hospitalized patients in China  

PubMed Central

Background Adverse drug reactions (ADRs) are a leading cause of morbidity in developed countries and represent a substantial burden on health-care resources. Many countries spent 15% to 20% of their hospital budgets to treat drug complications. However, few studies have measured the pharmacoeconomic effects of ADRs on hospitalized patients in China. The study estimates the costs of ADRs as identified from the spontaneous voluntary reports completed from healthcare professionals. To do so, we calculate these costs, determine the sum of Medicare payments and their proportion of total healthcare spending, and evaluate the incidence of ADRs, characteristics of hospitalized ADR patients, and outcomes of ADRs in China. Methods This retrospective survey studied patients who experienced ADRs during their hospitalization at a Chinese tertiary-care teaching hospital. The patients were divided into group A and group B according to general ADRs and serious ADRs in Provisions for Adverse Drug Reaction Monitoring and Reporting. The direct costs included treatment fees, inspection fees, laboratory fees, materials fees, bed charges, drug charges, nursing care, meals, and other expenses and the sunk-cost losses were calculated according to the hospital information system (HIS). Indirect costs of ADR treatment were calculated according to the human capital approach. The epidemiological characteristics of ADRs were evaluated. Results 2739 were diagnosed with ADR during the study period, which translates to an ADR rate of 0.81%. The total socioeconomic loss from 2739 cases of ADR was estimated at ¥817401.69, consisting of direct costs of ¥603252.81 and indirect costs of ¥214148.88. On average, the costs per patient amounted to ¥196.10 in group A, ¥7032.29 in group B. The sum of medicare payment and proportion were ¥219061.13 (65.23%) and ¥105422.02 (39.42%) in group A and B. The ADR incidence in old-age patients was significantly higher than in other age groups (P?patients, 34.94%). Conclusions The costs of especially severe ADRs could not be ignored, and in this hospital 0.13% of patients were diagnosed with ADRs associated with relatively higher direct costs than who suffered from mild ADRs, largely due to extended hospitalization. PMID:24533894

2014-01-01

24

Patients views and experiences in online reporting adverse drug reactions: findings of a national pilot study in Japan  

PubMed Central

Background Patients have been allowed to report adverse drug reactions (ADRs) directly to the government in some countries, which would contribute to pharmacovigilance. Objective We started a pilot study to determine whether web-based patient ADR reporting would work in Japan. This article aims to describe the characteristics of the patient reporters, and to clarify patient views and experiences of reporting. Methods Patients who submitted online ADR reports were contacted to respond to an ADR reporting questionnaire; only consenting reporters were included. Subjects with multiple responses were excluded from analysis. The questionnaire consisted of both closed and open questions. Questionnaire responses were examined using Pearson’s chi-squared test. Results A total of 220 web-based ADR reports were collected from January to December 2011; questionnaires were sent to 190 reporters, excluding those who gave multiple reports and those that refused to be contacted. Responses were obtained from 94 individuals (effective response rate: 49.5%). The median respondent age was 46.0 years. Sixty-three respondents found out about this pilot study on the Internet (67.0%). The numbers of respondents claiming that they had difficulty recalling the time/date of ADR occurrence were 16 patient reporters and three non-patient reporters. The number of reporters who found it difficult to complete the online reporting form was 22 patients (26.2%) and one non-patient (10%). Fifty-seven respondents (60.6%) expected feedback after reporting and many respondents wanted to know the process of ADR data collection and related information. Seventy-three respondents (77.7%) stated that they would report ADRs again in future. Conclusion Throughout the entire questionnaire, online patient ADR reporting was received with a forward-looking, positive approach. To facilitate smoother web-based reporting experiences in future, some improvements may be required in online ADR reporting forms, particularly with regard to respondent feedback.

Yamamoto, Michiko; Kubota, Kiyoshi; Okazaki, Mitsuhiro; Dobashi, Akira; Hashiguchi, Masayuki; Doi, Hirohisa; Suka, Machi; Mochizuki, Mayumi

2015-01-01

25

Adverse drug reaction-related hospitalisations among patients with heart failure at two hospitals in the United Arab Emirates.  

PubMed

Background Little is known about the adverse drug reaction (ADR) related admissions among heart failure (HF) patients. Objective The aim of this study was to determine the rate, factors, and medications associated with ADR-related hospitalisations among HF patients. Setting Two government hospitals in Dubai, United Arab Emirates. Methods This was a prospective, observational study. Consecutive adult HF patients who were admitted between December 2011 and November 2012 to the cardiology units were included in this study. The circumstances of their admission were analysed. Main outcome measures ADRs-related admissions of HF patients to cardiology units were identified and further assessed for their nature, causality, and preventability. Results Of 511 admissions, 34 were due to ADR-related hospitalisation (6.65, 95 % confidence interval 4.8-8.5 %). Number of medications taken by HF patients was the only predictors of ADR-related hospitalisations, where higher number of medications was associated with the odd ratio of 1.11 (95 % CI, 1.03-1.20, P = 0.005). More than one-third of ADR-related hospitalisations (35 %) were preventable The most frequent drugs causing ADR-related hospitalisation were diuretics (32 %), followed by non-steroidal anti-inflammatory drugs (15 %), thiazolidinediones (9 %), anticoagulants (9 %), antiplatelets (6 %), and aldosterone blockers (6 %). Conclusion ADR-related hospitalisations account for 6.7 % of admissions of HF patients to cardiac units, one-third of which are preventable. Number of medications taken by HF patients is the only predictors of ADR-related hospitalisations. Diuretic induced volume depletion, and sodium and water retention caused by thiazolidinediones and NSAIDs medications are the major causes of ADR-related hospitalisations of HF patients. PMID:25488317

Saheb Sharif-Askari, Narjes; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Fatemeh; Hussain, Ali Al Sayed

2015-02-01

26

Mechanisms of Adverse Drug Reactions to Biologics  

Microsoft Academic Search

Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although\\u000a the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce\\u000a significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and\\/or long\\u000a stays in intensive care units.

Janet B. Clarke

27

The pharmacist and adverse drug reaction reporting.  

PubMed

During premarketing trials, the number of patients exposed to a drug and the length of exposure to a drug are both limited. After marketing, many thousands, frequently millions, of patients are exposed to the drug over considerably longer periods of time, and adverse drug reactions not previously recognized appear. Because of these factors, postmarketing surveillance is extremely important. Pharmacists can contribute to drug safety and improved patient care by understanding and actively participating in the Food and Drug Administration's Spontaneous Reporting Program. PMID:10256700

Pearson, K

1982-08-01

28

Adverse Drug Reactions in Dental Practice  

PubMed Central

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

Becker, Daniel E.

2014-01-01

29

Adverse reactions of ferric carboxymaltose.  

PubMed

The author reports a 55-year-old female diagnosed of chronic kidney disease grade-5 with associated co-morbidities like type 2 diabetes mellitus, diabetic retinopathy and hypothyroidism was admitted for arteriovenous fistula construction. She was started on ferric carboxymaltose for the treatment of anaemia. She was given a test dose before administering the drug intravenously and she did not develop any reaction. The drug ferric carboxymaltose was then administered over a period of one hour. About half an hour after drug administration, the patient developed breathlessness and myalgia. After half hour of the above episode of breathlessness and myalgia she also developed vomiting (one episode). Patient was managed with oxygen therapy, IV fluids and other drugs like corticosteroids, phenaramine maleate and nalbuphine which controlled the above symptoms. PMID:25478369

Thanusubramanian, Harish; Patil, Navin; Shenoy, Smita; Bairy, K L; Sarma, Yashdeep

2014-10-01

30

Adverse Reactions of Ferric Carboxymaltose  

PubMed Central

The author reports a 55-year-old female diagnosed of chronic kidney disease grade-5 with associated co-morbidities like type 2 diabetes mellitus, diabetic retinopathy and hypothyroidism was admitted for arteriovenous fistula construction. She was started on ferric carboxymaltose for the treatment of anaemia. She was given a test dose before administering the drug intravenously and she did not develop any reaction. The drug ferric carboxymaltose was then administered over a period of one hour. About half an hour after drug administration, the patient developed breathlessness and myalgia. After half hour of the above episode of breathlessness and myalgia she also developed vomiting (one episode). Patient was managed with oxygen therapy, IV fluids and other drugs like corticosteroids, phenaramine maleate and nalbuphine which controlled the above symptoms. PMID:25478369

Patil, Navin; Shenoy, Smita; Bairy, K L; Sarma, Yashdeep

2014-01-01

31

Benznidazole-Related Adverse Drug Reactions and Their Relationship to Serum Drug Concentrations in Patients with Chronic Chagas Disease  

PubMed Central

For treating Chagas disease (CD), a current worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronic Trypanosoma cruzi infection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up and evaluated according to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) ?g/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD. PMID:23114763

Guerrero, Laura; Posada, Elizabeth; Rodríguez, Elena; Soy, Dolors; Gascon, Joaquim

2013-01-01

32

Adverse reactions to sedative/hypnotics: three years' experience.  

PubMed

Reported adverse reactions to orally administered sedative/hypnotics were systematically recorded during a 3-year period in a 1,000-bed teaching hospital. Reported cases were reviewed by a multidisciplinary committee and then by a pharmacist, and judgments were made as to type, severity, and outcome of adverse reactions. Probability that the reaction was caused by the medication was recorded in terms of both a global judgment and a systematic scale. The frequency of adverse reactions was calculated as a percentage of total doses of each agent dispensed by the pharmacy during the same time period. The assessment of benzodiazepine sedative/hypnotics indicated that adverse reactions were rare, ranging from frequencies of 0.05% of doses administered (lorazepam) to none (chlorazepate). The median frequency of reported adverse reactions was 0.01%, or 1 in 10,000 doses. The vast majority of reactions could be viewed as extensions of the therapeutic effect, were considered mild, and were without sequelae. All adverse reactions occurred in patients over 55 years old except for four patients under age 50 who received lorazepam. There were no reported cases of violent behavior or global amnesia. PMID:9122556

Mendelson, W B; Thompson, C; Franko, T

1996-11-01

33

Idiosyncratic Adverse Drug Reactions: Current Concepts  

PubMed Central

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

Naisbitt, Dean J.

2013-01-01

34

Life-threatening acute adverse cutaneous drug reactions  

Microsoft Academic Search

Adverse cutaneous reactions to drugs are frequent, affecting 2% to 3% of all hospitalized patients. Fortunately, only about 2% of adverse cutaneous reactions are severe and very few are fatal.Stevens-Johnson syndrome and toxic epidermal necrolysis are severe life-threatening diseases with a mortality rate reaching 30%, and only prompt recognition and diagnosis, withdrawal of the offensive drug, and referral to an

Ronni Wolf; Edith Orion; Batsheva Marcos; Hagit Matz

2005-01-01

35

Pharmacogenetics of Idiosyncratic Adverse Drug Reactions  

Microsoft Academic Search

Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion\\u000a of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented\\u000a capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock\\u000a to this is the lack of sufficient numbers of

Munir Pirmohamed

36

Glaucoma Eye Drops Adverse Skin Reactions.  

PubMed

The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

Carmen, Cantisani; Marina, Ambrifi; Federica, Frascani; Gilda, Fazia; Roberto, Lisi; Stefano, Calvieri

2014-12-01

37

Pharmacogenomics and adverse drug reactions in children  

PubMed Central

Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

Rieder, Michael J.; Carleton, Bruce

2014-01-01

38

Pharmacogenomics and adverse drug reactions in children.  

PubMed

Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

Rieder, Michael J; Carleton, Bruce

2014-01-01

39

Adverse reactions to sulfa drugs: implications for malaria chemotherapy.  

PubMed Central

National adverse drug reaction registers in Sweden and the United Kingdom provided data on the type, severity and frequency of reported adverse reactions attributed to sulfa drugs. Reactions to the ten principal drugs were examined in terms of their half-lives and usual indications for use. Of 8339 reactions reported between 1968 and 1988, 1272 (15%) were blood dyscrasias, 3737 (45%) were skin disorders, and 578 (7%) involved the liver. These side-effects occurred with all types of sulfa drugs investigated, although at different relative rates, and 3525 (42%) of them were classified as serious. The overall case fatality rate (CFR) was 1:15 serious reactions, and was highest in patients with white blood cell dyscrasias (1:7). Drugs with longer elimination half-lives had higher CFRs, particularly for fatalities after skin reactions. In Sweden, the estimated incidences of serious reactions were between 9 and 33 per 100,000 short-term users of sulfa drugs (two weeks), between 53 and 111 among those on malaria prophylaxis, and between 1744 and 2031 in patients on continuous therapy. For dapsone, the incidence appeared to increase with higher doses. Our results indicate that sulfa drugs with short elimination half-lives deserve to be considered for use in combination with proguanil or chlorproguanil for malaria chemotherapy and possibly prophylaxis. The smaller risk of adverse reactions associated with lower-dose dapsone suggests that it should also be evaluated as a potentially safe alternative. PMID:1893504

Björkman, A.; Phillips-Howard, P. A.

1991-01-01

40

Self-reported adverse drug reactions and their influence on highly active antiretroviral therapy in HIV infected patients: a cross sectional study  

PubMed Central

Background Patients on antiretroviral therapy have higher risk of developing adverse drug reactions (ADRs). The impact of ADRs on treatment adherence, treatment outcomes and future treatment options is quiet considerable. Thus, the purpose of this study was to describe the common self-reported ADRs and their impact on antiretroviral treatment. Methods Cross-sectional study was conducted at antiretroviral therapy (ART) clinic of Gondar University Hospital. Semi-structured interview questionnaire was used to extract self-reported ADRs, socio-demographic, and psycho-social variables. Variables related to antiretroviral medication, laboratory values and treatment changes were obtained from medical charts. Chi-square and odds ratio with 95% confidence interval were used to determine the associations of dependent variables. Result A total of 384 participants were enrolled. At least one adverse drug reaction was reported by 345 (89.8%) study participants and the mean number of ADRs reported was 3.7 (±0.2). The most frequently reported ADRs were nausea (56.5%) and headache (54.9%). About 114 (31.0%) participants considered antiretroviral therapy to be unsuccessful if ADRs occurred and only 10 (2.6%) decided to skip doses as ADRs were encountered. Based on chart review, treatment was changed for 78 (20.3%) patients and from which 79% were due to documented ADRs (p = 0.00). Among them, CNS symptoms (27.4%) and anemia (16.1%) were responsible for the majority of changes. Around four percent of patients were non-adherent to ART. Non-adhered participants and those on treatment changes were not statistically associated with self-reported ADRs. Only unemployment status (AOR = 1.76 (1.15 - 2.70), p = 0.01) and ADR duration of less than one month (AOR = 1.95 (1.28-2.98), p = 0.001) were significantly associated with self-reported adverse effects of three or more in the multivariate analysis. Conclusion Self-reported ADRs to antiretroviral therapy are quite common. More of the reactions were of short lasting and their impact on adherence and treatment change were less likely. However, documented ADRs were the most prevalent reasons for ART switch. Moreover, the level of unemployment was a strong predictor of self-reported ADRs. PMID:24957052

2014-01-01

41

Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study  

PubMed Central

Objectives: Toxicity of cancer chemotherapy may be affected by nutritional status of patients which is reflected in the body mass index (BMI). We sought to assess whether the adverse drug reaction (ADR) profile of platinum-based chemotherapy varies with BMI status. Materials and Methods: Adult patients of either sex, suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach, colon) and started on platinum-based chemotherapy as initial treatment were included. BMI at chemotherapy commencement was obtained from medical records. Events were recorded and graded as per Eastern Co-operative Oncology Group Common Toxicity Criteria-patients’ complaints; clinically evident signs and laboratory reports were considered. Frequencies of individual adverse events were compared between low BMI (<18.5 kg/m2) and satisfactory BMI groups. Similar comparisons were done for events with grades 2 or 3 severities. Results: A total of 50 patients were observed over a 3-month period of whom 17 (34%) belonged to the low BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and paresthesia were the commonly observed ADRs. The frequencies of anemia (P = 0.152) and vomiting (P = 0.140) and severity of grades of nausea (P = 0.066), anemia (P = 0.120) and paresthesia (P = 0.128) showed a higher trend in the low BMI group though differences were not statistically significant. The frequencies of tinnitus (P = 0.021) and paresthesia overall (P = 0.036) were significantly higher in the low BMI group. Conclusion: ADR profile of primary platinum-based chemotherapy appears to be partly influenced by BMI. This suggests the importance of maintaining adequate nutrition in patients and the need for greater vigilance in those with low BMI. PMID:24741198

Chatterjee, Dattatreyo; Roy, Somnath; Hazra, Avijit; Dasgupta, Partha; Ganguly, Subir; Das, Anup Kumar

2014-01-01

42

Application of the Apriori algorithm for adverse drug reaction detection.  

PubMed

The objective of this research is to assess the suitability of the Apriori association analysis algorithm for the detection of adverse drug reactions (ADR) in health care data. The Apriori algorithm is used to perform association analysis on the characteristics of patients, the drugs they are taking, their primary diagnosis, co-morbid conditions, and the ADRs or adverse events (AE) they experience. This analysis produces association rules that indicate what combinations of medications and patient characteristics lead to ADRs. A simple data set is used to demonstrate the feasibility and effectiveness of the algorithm. PMID:19745239

Kuo, M H; Kushniruk, A W; Borycki, E M; Greig, D

2009-01-01

43

A prospective open-label study evaluating the efficacy and adverse reactions of the use of Niferex-150 in ESRD patients receiving EPOGEN.  

PubMed

Iron supplementation is usually required in patients receiving epoetin alfa. Ferrous sulfate is commonly prescribed, however many patients experience adverse gastrointestinal effects. Adverse effects may limit the amount of iron that can be prescribed, and may lead to noncompliance. Polysaccharide-iron complex (PIC) is an iron supplement containing greater amounts of elemental iron, and may produce fewer adverse effects. This study compared the efficacy and adverse effects of PIC to a historical period of treatment with ferrous iron salts to 38 dialysis patients receiving epoetin alfa. All patients were switched to PIC, and were followed for six months. The following laboratory information was recorded: hematocrit, serum iron concentration, percent transferrin saturation, total iron-binding capacity, serum ferritin concentration. Patients were given an adverse experience questionnaire at four and six months of PIC treatment. No differences in laboratory values were noted between treatments. The amount of prescribed elemental iron increased, while iron dextran use decreased during PIC therapy. Epoetin alfa doses were unchanged. Patients reported fewer gastrointestinal adverse effects at four months, however differences at six months were less striking. PIC is as effective as ferrous sulfate in sustaining erythropoiesis in patients receiving epoetin alfa. It may produce fewer adverse effects. PMID:1361844

Johnson, C A; Rosowski, E; Zimmerman, S W

1992-01-01

44

Adverse drug reactions in the elderly.  

PubMed

Medications probably are the single most important health care technology in preventing illness, disability, and death in the geriatric population. Age-related changes in drug disposition and pharmacodynamic responses have significant clinical implications; increased use of a number of medications raises the risk that medicine-related problems may occur. The relationship between increased use of drugs including the prescription medication and elderly is well established. Majority of ADRs (80%) causing admission or occurring in hospital are type A reactions. Although less common occurring in elderly, type B ADRs may sometimes cause serious toxicity. Studies have correlated the integral association between old age and increased rate of adverse drug reactions arising out of confounding association between age and polypharmacy contributed by age-related changes in pharmacodynamics and pharmacokinetics at least for some medical conditions. A drug combination may sometimes cause synergistic toxicity which is greater than the sum of the risks of toxicity of either agent used alone. But, strategies to increase opportunities for identifying ADRs and related problems have not been emphasised in current international policy responses especially in India to the increase in elderly population and chronic conditions. Careful epidemiological studies that encompass large numbers of elderly drug users are required to obtain this information as increased knowledge of the frequency and cost of adverse drug reactions is important in enabling both more rational therapeutic decisions by individual clinicians and more optimal social policy. PMID:23761706

Brahma, Dhriti K; Wahlang, Julie B; Marak, Maxilline D; Ch Sangma, Marlina

2013-04-01

45

Adverse reactions to the sulphite additives  

PubMed Central

Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

Misso, Neil LA

2012-01-01

46

Low dose treatment with methotrexate-adverse drug reactions survey.  

PubMed

Antineoplastic drugs caused various and frequent adverse drug reactions (ADR) in connection with their pharmacodynamics. Methotrexate (MTX) ADRs are preferably gastrointestinal disorders and hepatotoxicity (hepatic enzyme abnormalities). The aim of this study was to detect and analyse ADR induced by low-dose MTX treatment in rheumatology. We observed 94 patients, 63 with rheumatoid arthritis and 31 with psoriatic arthritis. All patients were co-medicated with nonsteroidal anti-inflammatory drugs (NSAID) as Diclofenacum, Indomethacinum, Piroxicamum and 51% with glycocorticosteroides. During the follow-up study we collected 18 case-reports with ADR for 17% of the patients. From the patients with registered ADR, 11 was treated with standard dose of 7.5 mg MTX for a week and 7 patients received from 10 to 15 mg for a week. The distribution of the cases according patients' gender was 9 females and 7 males. Prevail individuals in age groups' 41-50 and over 61 years. The most frequent adverse drug reactions were leucopenia, trombocytopenia, skin reactions and gastrointestinal disorders as vomiting, melaena, epigastrial pain, etc. The primary risk connected with long therapy of low doses MTX is hepatotoxicity that diagnose and treatment are painful and expensive. As a result of the appearance of ADR in 5 patients the therapy with MTX was not changed, in two cases MTX is stopped timely or the dosage is changed and in the rest 11 patients MTX was excluded from the therapeutic scheme. PMID:11059096

Getov, I; Dimitrova, Z; Petkova, V

2000-01-01

47

Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study  

PubMed Central

Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR.

Sasidharanpillai, Sarita; Riyaz, Najeeba; Khader, Anza; Rajan, Uma; Binitha, Manikoth P; Sureshan, Deepthi N

2015-01-01

48

Smallpox vaccination and adverse reactions. Guidance for clinicians.  

PubMed

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or

Cono, Joanne; Casey, Christine G; Bell, David M

2003-02-21

49

Epidemiology Of Adverse Drug Reactions To Phenformin And Metformin  

Microsoft Academic Search

Adverse drug reactions (ADRs) to phenformin and metformin reported to the Swedish Adverse Drug Reaction Committee during 1965-77 were analysed in relation to sales and prescription data. The biguanides accounted for 0·6% of all reported adverse drug reactions but for 6% of the fatal cases (all phenformin). Sixty-four ADRs to phenformin and eight to metformin were classified as causal relation

Ulf Bergman; Gunnar Boman; Bengt-Erik Wiholm

1978-01-01

50

Adverse drug events in emergency department patients  

Microsoft Academic Search

Study Objective: Adverse drug events (ADEs) have been studied in hospitalized patients. Less is known about this common type of injury in emergency department patients. This study seeks to measure the risks, incidence, severity, and costs of ADEs in an ED population. Methods: ED charts of visits to a university-affiliated tertiary-care ED occurring between March 1 and May 31, 1997,

John W. Hafner; Steven M. Belknap; Marc D. Squillante; Kay A. Bucheit

2002-01-01

51

[Adverse skin reactions induced by BRAF inhibitors: a systematic review].  

PubMed

Recent developments and therapeutic use of selective BRAF inhibitors (e.g. dabrafenib and vemurafenib) have significantly improved overall survival and disease-free survival of patients with BRAF V600 mutation-positive metastatic melanoma. Despite their survival benefits, small-molecule inhibitors of BRAF are associated with significant and sometimes severe treatment-related dermatological toxicity. The most common adverse skin reactions include photosensitivity, induced malignant lesions of the skin such as keratoacanthomas, squamous cell carcinoma and new primary melanomas, as well as keratinocyte proliferation and differentiation dysfunctions that can manifest as skin papillomas, hand-foot skin reaction, keratosis pilaris-like rash, acantholytic dyskeratosis and cysts of the milia type. In this article, we describe the clinical and histological features of the cutaneous manifestations induced by vemurafenib and dabrafenib on the basis of our clinical experience and a literature review. The crucial role of dermatologists in patient management is also highlighted. PMID:24034635

Sibaud, V; Lamant, L; Maisongrosse, V; Delord, J-P

2013-01-01

52

Pharmacogenetic markers of severe cutaneous adverse drug reactions.  

PubMed

Different responses, in terms both of efficacy and toxicity, are commonly observed for any drug administered to apparently homogeneous groups of patients. It is estimated that adverse drug reactions (ADRs) cause 3-6% of all hospitalizations, accounting for 5% to 9% of hospital admission costs. The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis. SCARs are associated with significant mortality and require prompt diagnosis and adequate treatment. Pharmacogenetics studies individual variants in the DNA sequence associated with drug efficacy and toxicity, allowing prescription of a drug to patients expected to benefit from it, and excluding from treatment those who are at risk of developing ADRs. Pharmacogenetics already achieved several important results in the prevention of SCARs, and pharmacogenetic testing is now recommended by regulatory agencies before administration of abacavir and carbamazepine, leading to reduced incidence of SCARs. In this review, the pharmacogenetic associations of SCARs that have been validated in independent, case-control association studies will be presented. By familiarizing with principles of pharmacogenetics, dermatologists should be able to correlate specific cutaneous ADR phenotypes to the underlying genotype, thus contributing to better drug safety and facilitating drug discovery, development and approval. PMID:24819643

Borroni, R G

2014-04-01

53

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

PubMed Central

OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

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

2013-01-01

54

Use of a personal computer to monitor adverse drug reactions.  

PubMed

The Pharmacy department at Sewickley Valley Hospital, Sewickley, Pennsylvania, has developed an adverse drug reaction database using DBase III Plus software. The computer database allows instant, custom manipulation of large amounts of data, and aids in the analysis of adverse drug reaction reports for quality assurance purposes. PMID:10108661

Schlicht, J R; Fowler, T J

1991-01-01

55

Quinolones: review of psychiatric and neurological adverse reactions.  

PubMed

Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim of this article was to review the neurological and psychiatric adverse drug reaction (ADR) profile of quinolones, using a literature search strategy designed to identify case reports and case series. A literature search using PubMed/MEDLINE (from inception to 31 October 2010) was performed to identify case reports and case series related to quinolone-associated neurological and psychiatric ADRs. The search was conducted in two phases: the first phase was the literature search and in the second phase relevant articles were identified through review of the references of the selected articles. Relevant articles were defined as articles referring to adverse events/reactions associated with the use of any quinolone. Abstracts referring to animal studies, clinical trials and observational studies were excluded. Identified case reports were analysed by age group, sex, active substances, dosage, concomitant medication, ambulatory or hospital-based event and seriousness, after Medical Dictionary for Regulatory Activities (MedDRA®) coding. From a total of 828 articles, 83 were identified as referring to nervous system and/or psychiatric disorders induced by quinolones. 145 individual case reports were extracted from the 83 articles. 40.7% of the individual case reports belonged to psychiatric disorders only, whereas 46.9% related to neurological disorders only. Eight (5.5%) individual case reports presented both neurological and psychiatric ADRs. Ciprofloxacin, ofloxacin and pefloxacin were the quinolones with more neurological and psychiatric ADRs reported in the literature. Ciprofloxacin has been extensively used worldwide, which may explain the higher number of reports, while for ofloxacin and pefloxacin, the number of reports may be over-representative. A total of 232 ADRs were identified from the selected articles, with 206 of these related to psychiatric and/or neurological ADRs. The other 26 were related to other body systems but were reported together with the reactions of interest. Mania, insomnia, acute psychosis and delirium were the most frequently reported psychiatric adverse events; grand mal convulsion, confusional state, convulsions and myoclonus were the most frequently reported neurological adverse events. Several aspects should be taken into account in the development of CNS adverse effects, such as the pharmacokinetics of quinolones, chemical structure and quinolone uptake in the brain. These events may affect not only susceptible patients but also 'healthy' patients. PMID:21585220

Tomé, Ana M; Filipe, Augusto

2011-06-01

56

Factors affecting the development of adverse drug reactions (Review article)  

PubMed Central

Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

Alomar, Muaed Jamal

2013-01-01

57

A Clinical Study of Cutaneous Adverse Reactions to Nonionic Contrast Media in Korea  

PubMed Central

Background The use of intravenous contrast media (CM) has increased for the diagnosis of several diseases. The newly developed low osmolar nonionic contrast agents cause significantly decreased adverse reactions than the higher osmolar ones. However, adverse reactions may still occur, ranging in severity from minor side effects to severe complications. However, there have been few reports about cutaneous adverse reactions (CARs) to nonionic monomer CM. Objective The purpose of this study was to evaluate clinical features of CAR to intravenous nonionic monomer CM. Methods A total 47,338 examinees underwent intravenous iodinated contrast-enhanced computed tomography scan using nonionic monomer CM. Among the adverse reactions to the CM, we divided them into cutaneous or noncutaneous and immediate (<1 hr) or late (?1 hr) adverse reactions. Results Adverse reactions were noted in 62 cases out of the total 47,338 cases; 50 cases (80.7%) were categorized CARs. Among them, there were 24 male and 26 female patients. There was no significant difference between the sexes, and CARs occurred in all age groups. The highest occurrence was in the age range of 50~59 years. CARs included urticaria (78%), angioedema (10%), maculopapular rash (8%), erythema (2%), and pruritus without rash (2%). Immediate reactions were 92% (46 cases), while late reactions were 8% (4 cases). Conclusion CARs to nonionic monomer CM accounted for most of the adverse reactions (80.7%) and urticaria was the most common. PMID:22363151

Jung, Kyung Eun; Chung, Jimin; Park, Byung Cheol; Jee, Keum Nahn; Jee, Young Koo

2012-01-01

58

National differences in publishing papers on adverse drug reactions  

PubMed Central

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

Ferner, R E; Aronson, J K

2005-01-01

59

Getting under the skin of adverse drug reactions.  

PubMed

Cutaneous drug reactions are among the most commonly reported adverse drug reactions. Drugs prescribed by orthopedic surgeons, such as antibiotics, opiates, and nonsteroidal anti-inflammatory drugs, are common offenders. Cutaneous drug reactions can range from those that are common, mild nuisances to those that are rare, severe, and life-threatening. Medications should be considered part of a differential diagnosis for any dermatologic condition. It is important to recognize the different clinical features and common drugs that are related to each type of reaction. This review characterizes the different forms of cutaneous drug reactions and the clinical features, proposed mechanisms, and drugs frequently associated with each. PMID:23027476

Hempel, Carolyn; Martin, Craig

2012-10-01

60

[Adverse cutaneous reactions induced by exposure to woods].  

PubMed

Various adverse cutaneous reactions may occur as a result of exposure to wood dust or solid woods. These include allergic contact dermatitis, irritant contact dermatitis and, more rarely, contact urticaria, photoallergic and phototoxic reactions. Also cases of erythema multiforme-like reactions have been reported. Contact dermatitis, both allergic and irritant, is most frequently provoked by exotic woods, e.g. wood of the Dalbergia spp., Machaerium scleroxylon or Tectona grandis. Cutaneous reactions are usually associated with manual or machine woodworking, in occupational setting or as a hobby. As a result of exposure to wood dust, airborne contact dermatitis is often diagnosed. Cases of allergic contact dermatitis due to solid woods of finished articles as jewelry or musical instruments have also been reported. The aim of the paper is to present various adverse skin reactions related to exposure to woods, their causal factors and sources of exposure, based on the review of literature. PMID:23650772

Chomiczewska-Skóra, Dorota

2013-01-01

61

The severe adverse reaction to vitamin k1 injection is anaphylactoid reaction but not anaphylaxis.  

PubMed

The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and ?-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer. PMID:24594861

Mi, Yan-Ni; Ping, Na-Na; Xiao, Xue; Zhu, Yan-Bing; Liu, Jing; Cao, Yong-Xiao

2014-01-01

62

The Severe Adverse Reaction to Vitamin K1 Injection Is Anaphylactoid Reaction but Not Anaphylaxis  

PubMed Central

The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and ?-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer. PMID:24594861

Mi, Yan-Ni; Ping, Na-Na; Xiao, Xue; Zhu, Yan-Bing; Liu, Jing; Cao, Yong-Xiao

2014-01-01

63

Clinical and economic burden of adverse drug reactions.  

PubMed

Adverse drug reactions (ADRs) are unwanted drug effects that have considerable economic as well as clinical costs as they often lead to hospital admission, prolongation of hospital stay and emergency department visits. Randomized controlled trials (RCTs) are the main premarketing methods used to detect and quantify ADRs but these have several limitations, such as limited study sample size and limited heterogeneity due to the exclusion of the frailest patients. In addition, ADRs due to inappropriate medication use occur often in the real world of clinical practice but not in RCTs. Postmarketing drug safety monitoring through pharmacovigilance activities, including mining of spontaneous reporting and carrying out observational prospective cohort or retrospective database studies, allow longer follow-up periods of patients with a much wider range of characteristics, providing valuable means for ADR detection, quantification and where possible reduction, reducing healthcare costs in the process. Overall, pharmacovigilance is aimed at identifying drug safety signals as early as possible, thus minimizing potential clinical and economic consequences of ADRs. The goal of this review is to explore the epidemiology and the costs of ADRs in routine care. PMID:24347988

Sultana, Janet; Cutroneo, Paola; Trifirò, Gianluca

2013-12-01

64

Vertigo/dizziness as a Drugs’ adverse reaction  

PubMed Central

Introduction: Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. Materials and Methods: The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Results: Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Conclusions: Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs’ classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly in fragile patients. PMID:24347974

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

2013-01-01

65

Dietary aspects of adverse reactions to foods in adults.  

PubMed Central

Dietary considerations play an important role in the diagnosis, treatment and management of immunologic and nonimmunologic reactions to foods. Food diaries and trial elimination diets may prove helpful in identifying the responsible foods. Elimination diets must be monitored carefully for nutritional adequacy and should be used no longer than absolutely necessary; in some instances appropriate vitamin and mineral supplementation may be necessary. Ideally the identification of foods that provoke symptoms should be confirmed by means of double-blind challenge testing. Avoidance of some problem foods is unlikely to cause nutritional problems, but the practical and nutritional implications of allergies to staple foods such as cow's milk, eggs and wheat are far greater. Nonimmunologic adverse reactions that may mimic food allergic reactions include gastrointestinal disorders, sensitivity to food additives and psychologically based adverse reactions. There may be some degree of tolerance in metabolic disorders, which makes dietary management easier. Sensitivity to food additives necessitates careful scrutiny of food labels. In psychologic adverse reactions to foods, several foods are often involved, which increases the risk of nutritional problems. PMID:3048623

Parker, S L; Sussman, G L; Krondl, M

1988-01-01

66

iADRs: towards online adverse drug reaction analysis.  

PubMed

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. PMID:23420567

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

2012-12-01

67

Physician access to drug profiles to reduce adverse reactions  

NASA Astrophysics Data System (ADS)

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

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

1995-10-01

68

Prevalence of Adverse Food Reactions and Food Allergy among Thai Children  

Microsoft Academic Search

Introduction: Adverse food reactions are not uncommon among children. Several of these reactions are IgE-mediated. Prevalence of adverse food reactions among Thai children has not been fully explored. Objectives: The objectives of the study are (1) to determine prevalence of adverse food reactions and food allergy among Thai children, (2) to determine types of foods producing such reactions, (3) to

Sathit Santadusit

69

Cytotoxic Proteins and Therapeutic Targets in Severe Cutaneous Adverse Reactions  

PubMed Central

Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), are rare but life-threatening conditions induced mainly by a variety of drugs. Until now, an effective treatment for SJS/TEN still remains unavailable. Current studies have suggested that the pathobiology of drug-mediated SJS and TEN involves major histocompatibility class (MHC) I-restricted activation of cytotoxic T lymphocytes (CTLs) response. This CTLs response requires several cytotoxic signals or mediators, including granulysin, perforin/granzyme B, and Fas/Fas ligand, to trigger extensive keratinocyte death. In this article, we will discuss the cytotoxic mechanisms of severe cutaneous adverse reactions and their potential applications on therapeutics for this disease. PMID:24394640

Su, Shih-Chi; Chung, Wen-Hung

2014-01-01

70

ADVERSE REACTIONS OF NITROFURANTOIN, TRIMETHOPRIM AND SULFAMETHOXAZOLE IN CHILDREN  

Microsoft Academic Search

Purpose:Many children with urological disease require long-term treatment with antibiotics. In many cases the choice of medical instead of surgical management hinges on the implied safety of certain drugs. Recently some groups have advocated subureteral injection procedures to avoid long-term antibiotics for low grade reflux. We present a concise and relevant review on the use and adverse reactions of nitrofurantoin,

EDWARD KARPMAN; ERIC A. KURZROCK

2004-01-01

71

Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions.  

PubMed

Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean=15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ? 9 years (34.2%), 10-19 years (26.5%), and ? 20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%-2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p=0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p < 0.001). These results indicate that IVIG infusion can be considered a safe procedure. Low reaction incidence and few severe immediate infusion-related adverse reactions were observed. PMID:25257732

Bichuetti-Silva, Danielli C; Furlan, Fernanda P; Nobre, Fernanda A; Pereira, Camila T M; Gonçalves, Tessa R T; Gouveia-Pereira, Mariana; Rota, Rafael; Tavares, Lusinete; Mazzucchelli, Juliana T L; Costa-Carvalho, Beatriz T

2014-12-01

72

Potential Adverse and Allergic Reactions from Complementary and Alternative Medicine and Dietary Supplements  

PubMed Central

Complementary and alternative medicine and dietary supplements are often used by patients. A detailed examination of each preparation used by four patients was carried out. Seven such preparations with the potential to cause bleeding, cardiovascular and central nervous system side effects, and allergic food reactions are described. They were taken by both Asian and Caucasian patients, were purchased locally, and were used for allergic and nonallergic disorders. Inquiry into their use is important to prevent potential adverse and allergic reactions. There should be a higher standard of regulation for such products. PMID:20525159

2006-01-01

73

Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial  

Microsoft Academic Search

OBJECTIVE--To assess the frequency and type of side effects after influenza vaccination in elderly people. DESIGN--Randomised double blind placebo controlled study. SETTING--15 general practices in the southern Netherlands. SUBJECTS--1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo. MAIN OUTCOME MEASURES--Adverse reactions reported on postal questionnaire completed four weeks after vaccination. RESULTS--210 (23%) patients given

T M Govaert; G J Dinant; K Aretz; N Masurel; M J Sprenger; J A Knottnerus

1993-01-01

74

A CONTINUOUS GRASP TO DETERMINE THE RELATIONSHIP BETWEEN DRUGS AND ADVERSE REACTIONS  

E-print Network

A CONTINUOUS GRASP TO DETERMINE THE RELATIONSHIP BETWEEN DRUGS AND ADVERSE REACTIONS M. J. HIRSCH, C. N. MENESES, P. M. PARDALOS, M. A. RAGLE, AND M. G. C. RESENDE ABSTRACT. Adverse drug reactions drugs and adverse reac- tions that they cause. We formulate the drug-reaction relationship problem

Resende, Mauricio G. C.

75

Adverse reaction to metal debris is more common in patients following MoM total hip replacement with a 36 mm femoral head than previously thought: results from a modern MoM follow-up programme.  

PubMed

We conducted a retrospective study to assess the prevalence of adverse reactions to metal debris (ARMD) in patients operated on at our institution with metal-on-metal (MoM) total hip replacements with 36 mm heads using a Pinnacle acetabular shell. A total of 326 patients (150 males, 175 hips; 176 females, 203 hips) with a mean age of 62.7 years (28 to 85) and mean follow-up of 7.5 years (0.1 to 10.8) participating in our in-depth modern MoM follow-up programme were included in the study, which involved recording whole blood cobalt and chromium ion measurements, Oxford hip scores (OHS) and plain radiographs of the hip and targeted cross-sectional imaging. Elevated blood metal ion levels (> 5 parts per billion) were seen in 32 (16.1%) of the 199 patients who underwent unilateral replacement. At 23 months after the start of our modern MoM follow-up programme, 29 new cases of ARMD had been revealed. Hence, the nine-year survival of this cohort declined from 96% (95% CI 95 to 98) with the old surveillance routine to 86% (95% CI 82 to 90) following the new protocol. Although ARMD may not be as common in 36 mm MoM THRs as in those with larger heads, these results support the Medicines and Healthcare Products Regulatory Agency guidelines on regular reviews and further investigations, and emphasise the need for specific a follow-up programme for patients with MoM THRs. PMID:25452362

Lainiala, O; Eskelinen, A; Elo, P; Puolakka, T; Korhonen, J; Moilanen, T

2014-12-01

76

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

PubMed Central

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

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

2002-01-01

77

Oral adverse reactions due to cinnamon-flavoured chewing gums consumption.  

PubMed

Cinnamon-flavoured products (toothpaste, chewing gum, food, candy and mouthwash) can cause oral adverse reactions; among these, the most common is contact stomatitis (cinnamon contact stomatitis, CCS). Signs and symptoms of contact allergic reactions affecting the oral mucosa can mimic other common oral disorders, making diagnosis difficult. As CCS may be more prevalent than believed and its clinical features can frequently determine misdiagnosis, we reviewed case reports and case series of oral adverse reactions due to cinnamon-containing chewing gums, emphasizing clinical aspects, diagnostic and management procedures. We also proposed an algorithm to perform a diagnosis of CCS as in the previous published literature the diagnostic approach was not based on a harmonized and shared evidence-based procedure. Moreover, as patients can refer to different specialists as dentists, dermatologists and allergists, a multidisciplinary approach is suggested. PMID:24004186

Calapai, G; Miroddi, M; Mannucci, C; Minciullo, Pl; Gangemi, S

2014-10-01

78

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

PubMed Central

Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences. Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well. Results: We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities. Conclusions: We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences. PMID:25249979

Roitmann, Eva; Eriksson, Robert; Brunak, Søren

2014-01-01

79

Late-onset inflammatory adverse reactions related to soft tissue filler injections.  

PubMed

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein. PMID:23361999

Alijotas-Reig, Jaume; Fernández-Figueras, Maria Teresa; Puig, Lluís

2013-08-01

80

A time-indexed reference standard of adverse drug reactions  

PubMed Central

Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance.

Harpaz, Rave; Odgers, David; Gaskin, Greg; DuMouchel, William; Winnenburg, Rainer; Bodenreider, Olivier; Ripple, Anna; Szarfman, Ana; Sorbello, Alfred; Horvitz, Eric; White, Ryen W.; Shah, Nigam H.

2015-01-01

81

Adverse Drug Reactions in Children—A Systematic Review  

PubMed Central

Background Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided. Methods and Findings We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable. Conclusions There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented. PMID:22403604

Smyth, Rebecca Mary Diane; Gargon, Elizabeth; Kirkham, Jamie; Cresswell, Lynne; Golder, Su; Smyth, Rosalind; Williamson, Paula

2012-01-01

82

Detect adverse drug reactions for drug Simvastatin Yihui Liu1,2  

E-print Network

Detect adverse drug reactions for drug Simvastatin Yihui Liu1,2 1 Institute of Intelligent feature matrix and feature selection. The experiments are carried out on the drug Simvastatin. Major side- adverse drug reaction; feature matrix; feature selection; Simvastatin I. INTRODUCTION Adverse drug

Aickelin, Uwe

83

Adverse events in patients with return emergency department visits  

PubMed Central

Objectives This study describes the proportion of emergency department (ED) returns within 7?days due to adverse events, defined as adverse outcomes related to healthcare received. Design Prospective cohort study. Setting We used an electronically triggered adverse event surveillance system at a tertiary care ED from May to June 2010 to examine ED returns within 7?days of index visit. Participants One of three trained nurses determined whether the visit was related to index emergency care. For such records, one of three trained emergency physicians conducted adverse event determinations. Main outcome measure We determined adverse event type and severity and analysed the data with descriptive statistics, ?2 tests and logistic regression. Results Of 13?495 index ED visits, 923 (6.8%) were followed by ED returns within 7?days. The median age of all patients was 47?years and 52.8% were women. After nursing review, 211 cases required physician review. Of these, 53 visits were adverse events (positive predictive value (PPV)=5.7%, 95% CI 4.4% to 7.4%) and 30 (56.6%) were preventable. Common adverse event types involved management, diagnostic or medication issues. We observed one potentially preventable death and 58.5% of adverse events resulting in transient disability. The PPV of a modified trigger with a cut-off of return within 72?h, resulting in admission was 11.9% (95% CI 6.8% to 18.9%). Conclusions Our electronic trigger efficiently identified adverse events among 12% of patients with ED returns within 72?h, requiring hospital admission. Given the high degree of preventability of the identified adverse events, this trigger also holds promise as a performance measurement tool. PMID:25540424

Calder, Lisa; Pozgay, Anita; Riff, Shena; Rothwell, David; Youngson, Erik; Mojaverian, Naghmeh; Cwinn, Adam; Forster, Alan

2015-01-01

84

Cutaneous adverse drug reactions in Indian population: A systematic review  

PubMed Central

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%), ?-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/TEN, and exfoliative dermatitis were 1.71%, 16.39%, and 3.57%, respectively. “Definitely preventable”, “probably preventable” and “not preventable” categories CADRs were 15.64%, 63.14%, and 34.64%, respectively. Conclusion: Antimicrobials, NSAIDs and antiepileptic are common causative agents of CADRs in India. Antiepileptic agents show high rates of severe cutaneous reactions. PMID:25593813

Patel, Tejas K; Thakkar, Sejal H; Sharma, DC

2014-01-01

85

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

PubMed Central

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

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

2012-01-01

86

[Adverse events in patients from a pediatric hospital.  

PubMed

Background: detection of adverse events is part of the safety management in hospitalized patients. The objective of this study was to describe the incidence of adverse events that occurred in a pediatric hospital. Methods: cross-sectional study of the adverse events occurred in a pediatric hospital from 2007 to 2009. Factors associated with their developmental causes were identified. The statistical analysis was descriptive and bivariate, with contingency tables to estimate the relationship between those factors. A p value = 0.05 was considered significant. Results: a total of 177 adverse events were registered. When they began, human factor occurred in 23 cases (13 %, OR = 1.41, p = 0.001), organizational factor was present in 71 cases (40 %, OR = 1.91, p = 0.236) and technical factor in 46 cases (26 %, OR = 0.87, p = 0.01). Blows or bruises from falls as a result of adverse events occurred in 71 cases (40 %, 95 % CI = 64-78). Conclusions: we found 1.84 events per 100 hospital discharges during the study period. The fall of patients ranked first of the adverse events identified. PMID:24290022

Ornelas-Aguirre, José Manuel; Arriaga-Dávila, José de Jesús; Domínguez-Serrano, María Isabel; Guzmán-Bihouet, Beatriz Filomena; Navarrete-Navarro, Susana

2013-01-01

87

Salicylate intolerance: a masquerader of multiple adverse drug reactions  

PubMed Central

A female in her early 50s presented with a long-standing history of episodic urticaria and angioedema. She also reported urticarial reactions after ingestion of aspirin, prednisone and multiple antibiotics. These medications were all taken during upper respiratory tract infections. An elimination diet followed by a series of open challenges to food chemicals demonstrated an urticarial eruption following the ingestion of mints, which contain high levels of salicylates. A double-blinded placebo-controlled challenge to salicylate confirmed her sensitivity and explained her reaction to aspirin. The patient informed her treating physician of her copious ingestion of mints during upper respiratory tract infections. Drug hypersensitivity to antibiotics and prednisone was excluded on the basis of negative radioallergosorbent tests (RASTs) and/or absent skin-test responses and/or tolerance to oral challenges. This patient had a salicylate intolerance that caused her episodic urticaria and angioedema, and also masqueraded as a drug allergy due to the concurrent ingestion of mints. PMID:21918670

Fernando, Suran Loshana; Clarke, Lesley R

2009-01-01

88

Trends in Adverse Reactions to Trimethoprim-Sulfamethoxazole  

PubMed Central

OBJECTIVE: To examine temporal trends of adverse drug reactions (ADRs) associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in children. METHODS: We performed a retrospective observational study to characterize TMP-SMX ADRs in children between 2000 and 2009. We completed a chart review at our institution by identifying children diagnosed with TMP-SMX ADRs. To compare local trends to comparable institutions, we estimated the frequency of hospitalizations for TMP-SMX ADRs at 25 tertiary pediatric hospitals utilizing the Pediatric Health Information System database. To determine whether changes in outpatient prescribing rates occurred, we used the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey. RESULTS: At our institution, 109 children were diagnosed with a TMP-SMX ADR (5 cases from 2000 to 2004 as compared with 104 cases from 2005 to 2009). Fifty-eight percent had been treated for a skin and soft tissue infection (SSTI). A similar trend was observed nationally, where the incidence of TMP-SMX ADRs more than doubled from 2004 to 2009 at comparable pediatric hospitals (P < .001). Although national outpatient data revealed no change in overall TMP-SMX prescribing, the percentage of children prescribed TMP-SMX for SSTI sharply increased during the study period (0%–2% [2000-2004]; 9%–17% [2005–2009]). CONCLUSIONS: The majority of TMP-SMX ADRs at our institution occurred in conjunction with SSTI treatment. TMP-SMX ADRs have occurred more frequently coincident with increased prescribing for SSTI. Increased usage alone may explain the increasing trend of TMP-SMX ADRs in children; however drug–disease interaction may play a role and requires further investigation. PMID:23209098

Jackson, Mary Anne; Herigon, Joshua C.; Hersh, Adam L.; Shapiro, Daniel J.; Leeder, J. Steven

2013-01-01

89

Adverse Drug Events in Cognitively Impaired Elderly Patients  

Microsoft Academic Search

Background\\/Aims: Adverse drug events (ADEs) are a frequent problem encountered in the elderly. The aim of this study was to elucidate the factors that influence ADEs in an elderly population with cognitive impairment. Methods: 242 patients were recruited from dementia clinics and assessed after 6 months for ADEs. The use of natural health products (NHPs) was also documented. Results: Backward

Hooman Ganjavi; Nathan Herrmann; Paula A. Rochon; Papita Sharma; Monica Lee; Daniel Cassel; Morris Freedman; Sandra E. Black; Krista L. Lanctôt

2007-01-01

90

Adverse drug reactions during lymphatic mapping and sentinel lymph node biopsy for solid neoplasms.  

PubMed

Currently, 1 per cent isosulfan blue dye and technetium-99-labeled sulfur colloid (SC) are used in lymphatic mapping (LM). Several reports have suggested that the incidence of adverse drug reactions (ADRs) during LM is high. We report our experience with LM for solid neoplasms in order to determine the incidence and risk factors for development of ADRs. Seven hundred fifty-three patients (90% women, mean age 57) underwent LM with blue dye alone or in combination with SC from 1998 to 2004. The most common malignancy was breast cancer (83%). One hundred ten patients (14%) had injection of both mapping agents. Most patients (87%) underwent intraparenchymal injection of LM agent. Eight patients (1.1%) had an ADR during LM; none had prior exposure to LM. Of these, 7 had limited reactions (mostly blue hives) that quickly resolved. One patient (0.1%) developed anaphylaxis. The ADR incidence in patients with a sulfa allergy was not significantly different than that in patients without a sulfa allergy (3.4 vs 1%, P = 0.12). No risk factors for development of ADR were identified. Overall, the incidence of ADR during LM is low. Patients with sulfa allergies and prior exposure to LM did not demonstrate an increased incidence of ADR. Anaphylaxis, though rare, can occur during LM. PMID:16468505

Amr, Dena; Broderick-Villa, Gregory; Haigh, Philip I; Guenther, J Michael; DiFronzo, L Andrew

2005-09-01

91

Adverse reactions to tick-borne encephalitis vaccine: FSME-Immun®  

Microsoft Academic Search

Summary  Vaccination against tick-borne encephalitis with FSME-Immun® vaccine was started in the Department of Infectious Diseases,\\u000a University Medical School of Bia?ystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed.\\u000a Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n=2,135) and only in 14 patients (1.2%)\\u000a after the second one (n=1,183). These effects were

A. Grzeszczuk; E. Sokolewicz-Bobrowska; D. Prokopowicz

1998-01-01

92

Adverse reactions to nitrofurantoin in the United Kingdom, Sweden, and Holland  

Microsoft Academic Search

A study was carried out comparing the reporting of adverse reactions to nitrofurantoin in Sweden, Holland, and the United Kingdom. The Swedish drug regulatory authorities receive more reports of adverse reactions to nitrofurantoin than to any other drug, and the annual reporting rate is increasing despite a steady fall in the prescription of nitrofurantoin. In the United Kingdom the total

R G Penn; J P Griffin

1982-01-01

93

A U.S. Perspective on the Adverse Reactions from Traditional Chinese Medicines  

Microsoft Academic Search

Background. Traditional Chinese medicines (TCM) are popular in the United States and Asian and non-Asian consumers are using the product for disease treatment and health prevention. As more people are using TCM products, there are increased re- ports on adverse reactions. This review will focus on adverse reactions due to TCM as reported in the literature. Methods. The review is

Richard J. Ko

94

Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury.  

PubMed

Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings. PMID:23635947

Kaniwa, Nahoko; Saito, Yoshiro

2013-06-01

95

A Pharmaceutical Intelligent Information System to detect allergies and Adverse Drugs Reactions based on internet of things  

Microsoft Academic Search

The incidence of serious and fatal Adverse Drugs Reaction (ADR) and harmful effects of pharmaceutical excipients in worldwide hospitals is extremely high. Some studies show a rate of ADR appearance about 6.5% in worldwide hospitals. The consequences of these cases lead to a rate of 80% of ADR incidences that require the patient admission, a medium bed stay of eight

Antonio J. Jara; Francisco J. Belchi; Alberto F. Alcolea; Jose Santa; Miguel A. Zamora-Izquierdo; Antonio Fernando Gómez-Skarmeta

2010-01-01

96

Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms  

PubMed Central

Suspected adverse drug reactions first reported in 1963 in the “British Medical Journal,” the “Lancet,” the “Journal of the American Medical Association,” and the “New England Journal of Medicine” were reviewed 18 years later to assess their initial validity and subsequent verification. Of 52 first reports, five were deliberate investigations into potential or predictable reactions, and in each case causality was reasonably established; the other 47 reports were essentially anecdotal. Of these 47 reports, 14 related to categories of adverse reaction where false-positive reports were unlikely: immediate reactions, local reactions, and known reactions caused by a different mode of administration or a brand previously thought or claimed to be safe. The problem of false alarms rose in the remaining types of reactions: general reactions that did not occur immediately after administration and arose for the first time with a new chemical entity. Of 33 reports of such suspected adverse reactions, validity was satisfactorily established in 14 cases on the basis of rechallenge, predictability from known pharmacology, or the unique nature of the reaction. Of the remaining 19 reports, further verification still has not been satisfactorily established in 12. Seven of these possible false alarms were haematological reactions. Although 35 of the 47 anecdotal reports were clearly correct, of the 19 reports that were not reasonably validated at the time of the report, only seven were subsequently verified. This suggests that agencies monitoring adverse drug reactions should adopt criteria for assessing the validity of first reports of suspected adverse reactions. Such criteria should include: reactions on rechallenge, a pharmacological basis for the adverse reaction, immediate acute reactions, local reactions at the site of administration, reactions with a new route of administration of a drug known to provoke such reactions by another route, and the repeated occurrence of very rare events. PMID:6799125

Venning, G R

1982-01-01

97

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

NASA Astrophysics Data System (ADS)

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

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

2007-11-01

98

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

PubMed

Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings. PMID:22512705

Mangoni, Arduino A

2012-05-01

99

Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model  

PubMed Central

Background 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. Methods 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). Results 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. Conclusions 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. PMID:25356898

Tangiisuran, Balamurugan; Scutt, Greg; Stevenson, Jennifer; Wright, Juliet; Onder, G.; Petrovic, M.; van der Cammen, T. J.; Rajkumar, Chakravarthi; Davies, Graham

2014-01-01

100

Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department  

Microsoft Academic Search

Study Objectives: We sought to document the degree of polypharmacy, the frequency of adverse drug-related events (ADREs) leading to emergency department presentation that were recognized by emergency physicians, and the frequency of potential adverse drug interactions (PADIs) in medication regimens of elderly patients in the ED. Methods: We conducted a retrospective chart review on 300 randomly selected ED visits made

Corinne Michèle Hohl; Jerrald Dankoff; Antoinette Colacone; Marc Afilalo

2001-01-01

101

Risk factors for the development of adverse drug events in hospitalized patients  

Microsoft Academic Search

Adverse drug events in hospitalized patients lead to increased morbidity, mortality and costs. Early detection of adverse drug events could aid in the prevention of these adverse outcomes. A cost-effective system for the early detection of adverse drug events should focus on high risk patients. A study was set up with the primary aim to identify characteristics that are associated

P. M. L. A. van den Bemt; A. C. G. Egberts; A. W. Lenderink; J. M. Verzijl; K. A. Simons; W. S. C. J. M. van der Pol; H. G. M. Leufkens

2000-01-01

102

A SNPshot of PubMed to associate genetic variants with drugs, diseases, and adverse reactions  

E-print Network

A SNPshot of PubMed to associate genetic variants with drugs, diseases, and adverse reactions Jörg, drug efficacy, and drug responses between individuals and sub-populations. Wrong dosages of drugs can lead to severe adverse drug reac- tions in individuals whose drug metabolism drastically differs from

Baral, Chitta

103

40 CFR 717.12 - Significant adverse reactions that must be recorded.  

Code of Federal Regulations, 2010 CFR

...physical environment, especially in the case of ground water, and surface water and soil resources that have limited self-cleansing capability. (d) Firms are not required to record a significant adverse reaction to the environment if the...

2010-07-01

104

40 CFR 717.12 - Significant adverse reactions that must be recorded.  

Code of Federal Regulations, 2014 CFR

...physical environment, especially in the case of ground water, and surface water and soil resources that have limited self-cleansing capability. (d) Firms are not required to record a significant adverse reaction to the environment if the...

2014-07-01

105

40 CFR 717.12 - Significant adverse reactions that must be recorded.  

Code of Federal Regulations, 2013 CFR

...physical environment, especially in the case of ground water, and surface water and soil resources that have limited self-cleansing capability. (d) Firms are not required to record a significant adverse reaction to the environment if the...

2013-07-01

106

40 CFR 717.12 - Significant adverse reactions that must be recorded.  

Code of Federal Regulations, 2012 CFR

...physical environment, especially in the case of ground water, and surface water and soil resources that have limited self-cleansing capability. (d) Firms are not required to record a significant adverse reaction to the environment if the...

2012-07-01

107

40 CFR 717.12 - Significant adverse reactions that must be recorded.  

Code of Federal Regulations, 2011 CFR

...physical environment, especially in the case of ground water, and surface water and soil resources that have limited self-cleansing capability. (d) Firms are not required to record a significant adverse reaction to the environment if the...

2011-07-01

108

The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada  

PubMed Central

Background Research into adverse events (AEs) has highlighted the need to improve patient safety. AEs are unintended injuries or complications resulting in death, disability or prolonged hospital stay that arise from health care management. We estimated the incidence of AEs among patients in Canadian acute care hospitals. Methods We randomly selected 1 teaching, 1 large community and 2 small community hospitals in each of 5 provinces (British Columbia, Alberta, Ontario, Quebec and Nova Scotia) and reviewed a random sample of charts for nonpsychiatric, nonobstetric adult patients in each hospital for the fiscal year 2000. Trained reviewers screened all eligible charts, and physicians reviewed the positively screened charts to identify AEs and determine their preventability. Results At least 1 screening criterion was identified in 1527 (40.8%) of 3745 charts. The physician reviewers identified AEs in 255 of the charts. After adjustment for the sampling strategy, the AE rate was 7.5 per 100 hospital admissions (95% confidence interval [CI] 5.7– 9.3). Among the patients with AEs, events judged to be preventable occurred in 36.9% (95% CI 32.0%–41.8%) and death in 20.8% (95% CI 7.8%–33.8%). Physician reviewers estimated that 1521 additional hospital days were associated with AEs. Although men and women experienced equal rates of AEs, patients who had AEs were significantly older than those who did not (mean age [and standard deviation] 64.9 [16.7] v. 62.0 [18.4] years; p = 0.016). Interpretation The overall incidence rate of AEs of 7.5% in our study suggests that, of the almost 2.5 million annual hospital admissions in Canada similar to the type studied, about 185 000 are associated with an AE and close to 70 000 of these are potentially preventable. PMID:15159366

Baker, G. Ross; Norton, Peter G.; Flintoft, Virginia; Blais, Régis; Brown, Adalsteinn; Cox, Jafna; Etchells, Ed; Ghali, William A.; Hébert, Philip; Majumdar, Sumit R.; O'Beirne, Maeve; Palacios-Derflingher, Luz; Reid, Robert J.; Sheps, Sam; Tamblyn, Robyn

2004-01-01

109

21 CFR 606.170 - Adverse reaction file.  

Code of Federal Regulations, 2012 CFR

...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports...reactions regarding each unit of blood or blood product arising as...

2012-04-01

110

Increasing the number of adverse drug reactions reporting: the role of clinical pharmacy residents.  

PubMed

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

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

2014-01-01

111

Increasing the Number of Adverse Drug Reactions Reporting: the Role of Clinical Pharmacy Residents  

PubMed Central

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

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

2014-01-01

112

Adverse reactions of Methylphenidate in children with attention deficit-hyperactivity disorder: Report from a referral center  

PubMed Central

Objective: The aim of the current study was to determine various aspects of methylphenidate adverse reactions in children with attention deficit-hyperactivity disorder (ADHD) in Iran. Methods: During the 6 months period, all children under methylphenidate treatment alone or along with other agents attending a university-affiliated psychology clinic were screened regarding all subjective and objective adverse drug reactions (ADRs) of methylphenidate. Causality and seriousness of detected ADRs were assessed by relevant World Health Organization definitions. The Schumock and Thornton questionnaire was used to determine preventability of ADRs. Findings: Seventy-one patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled within the study period. All (100%) ADHD children under methylphenidate treatment developed at least one ADR. Anorexia (74.3%), irritability (57.1%), and insomnia (47.2%) were the most frequent methylphenidate-related adverse reactions. Except for one, all other detected ADRs were determined to be mild. In addition, no ADR was considered to be preventable and serious. Conclusion: Our data suggested that although methylphenidate related adverse reactions were common in children with ADHD, but they were mainly mild and nonserious. PMID:25535621

Khajehpiri, Zahra; Mahmoudi-Gharaei, Javad; Faghihi, Toktam; Karimzadeh, Iman; Khalili, Hossein; Mohammadi, Mostafa

2014-01-01

113

[Diagnostic and therapeutic procedure for two popular but quite distinct adverse reactions to food - fructose malabsorption and histamine intolerance].  

PubMed

Claiming to suffer from adverse food reactions is popular. In contrast to the classical food allergy, there are some pathomechanisms which are evidently dose-dependent. Thus the procedure in diagnosis and therapy must undoubtedly differ from the practice when food allergy is suspected or proven. Nevertheless many patients suffering from dose-dependent adverse reactions to food are given strict elimination diets, which is neither necessary nor helpful and decreases their quality of life broadly. This holds especially true for fructose malabsorption and histamine intolerance. For the latter, the term adverse reaction to ingested histamine is preferred, because histamine intolerance implies that symptoms are caused entirely by an enzyme defect. Why this is not very likely to be the only reason is discussed in this article. Both adverse reactions require an individual approach especially with regard to nutrition therapy. Therefore the task of diagnosis should be to establish an individual profile of tolerated and not tolerated foods taking into account that tolerance can greatly vary by meal composition, frequency and individual triggering factors. In view of this, therapeutic recommendations should not be based on the absolute quantities of the eliciting substance to be eliminated but on a feasible transfer into daily life. Thereby food restriction can be minimized and a high quality of life will be maintained. PMID:22477662

Reese, I

2012-04-01

114

Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges  

PubMed Central

Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered. PMID:17971785

Wilke, Russell A.; Lin, Debbie W.; Roden, Dan M.; Watkins, Paul B.; Flockhart, David; Zineh, Issam; Giacomini, Kathleen M.; Krauss, Ronald M.

2009-01-01

115

Days lost due to disability of diclofenac-induced adverse drug reactions  

PubMed Central

Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. Objective DLD was measured for diclofenac tablets to prepare the ADR profile. Methods The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. Results About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even though few cases were reported. Conclusions Diclofenac has a complex adverse drug profile. Around 34 types of reactions were reported. Diclofenac was widely prescribed because of the experiential belief of comparative safety with other NSAIDs. The study shows the importance of pharmacovigilance even on the most prescribed medicine. Most disabling ADR for the study population was peptic ulcer with or without perforation. YLD or DLD are useful measures of calculating disability caused by ADRs. Future studies could focus on improving the usefulness & precision of DLD. PMID:24155815

Thomas, Dixon; Mathew, Molly; Raghavan, C. Vijaya; Mohanta, Guru P.; Reddy, Y. Padmanabha

116

Presentation and management of docetaxel-related adverse effects in patients with breast cancer  

PubMed Central

The taxane chemotherapeutic agent docetaxel has been utilized in the management of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although well tolerated by the majority of patients, docetaxel toxicity may limit the dose which can be administered. Adverse events include infusion reactions, febrile neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity, epiphora and lacrimal duct stenosis, gastrointestinal complications, and neuropathies. In this review, we explore these complications and how they can be effectively managed to improve patient quality of life during and following docetaxel therapy. PMID:24904223

Ho, Maria Y; Mackey, John R

2014-01-01

117

Adverse Drug Event Surveillance and Drug Withdrawals in the United States, 1969-2002: The Importance of Reporting Suspected Reactions  

Microsoft Academic Search

Results:During the 33-year period from 1969 when ad- verse drug event reporting was initiated through 2002, about 2.3 million case reports of adverse events for the cumulative number of approximately 6000 marketed drugs were entered in the database. Most reports were for female patients. During this period, numerous drug reactions have been identified and added to the product labeling as

Diane K. Wysowski; Lynette Swartz

2005-01-01

118

Implementation and evaluation of adverse drug reaction monitoring system in a tertiary care teaching hospital in Mumbai, India  

PubMed Central

Adverse drug reactions (ADR) are a significant cause of morbidity and mortality, often identified only post-marketingly. Improvement in current ADR reporting, including utility of underused or innovative methods, is crucial to improve patient safety and public health. Hospital-based monitoring is one of the methods used to collect data about drug prescriptions and adverse events. The aims of this study were to identify the most frequent ADRs recognized by the attending physicians, study their nature, and to target these ADRs in order to take future preventive measures. A prospective study was conducted over a 7-month period in an internal medicine department using stimulated spontaneous reporting for identifying ADRs. Out of the 254 admissions, 32 ADRs in 37 patients (14.56%) were validated from the total of 36 suspected ADRs in 41 patients. Female predominance was noted over males in case of ADRs. Fifty percent of total ADRs occurred due to multiple drug therapy. Dermatological ADRs were found to be the most frequent (68.75%), followed by respiratory, central nervous system and gastrointestinal ADRs. The drugs most frequently involved were antibiotics, anti-tubercular agents, antigout agents, and NSAIDs. The most commonly reported reactions were itching and rashes. Out of the 32 reported ADRs, 50% of the reactions were probable, 46.87% of the reactions were possible and 3.12% of the reactions were definite. The severity assessment done by using the Hartwig and Seigel scale indicated that the majority of ADRs were ‘Mild’ followed by ‘Moderate’ and ‘Severe’ reactions, respectively. Out of all, 75% of ADRs were recovered. The most potent management of ADRs was found to be drug withdrawal. Our study indicated that hospital based monitoring was a good method to detect links between drug exposure and adverse drug reactions. Adequate training regarding pharmacology and optimization of drug therapy might be helpful to reduce ADR morbidity and mortality. PMID:24170978

Rajput, Mithun S.; Nirmal, Nilesh P.; Savitri, Wenny

2013-01-01

119

Making Risks Visible: The Science & Politics of Adverse Drug Reactions  

Microsoft Academic Search

A popular statin used to lower cholesterol is associated with an unusual breakdown of muscle tissue. An analgesic prescribed for arthritic patients is linked to heart attacks. The scenarios involved in the recent cases of Baycol and Vioxx should be familiar. A novel drug passes intense regulatory scrutiny. The drug's makers heavily promote it. Following widespread use, a previously unnoticed

Harry M. Marks; Matthew Prior

120

Reporting hospitals’ antibiotic timing in pneumonia: adverse consequences for patients?  

PubMed Central

Objective In 2004, the Hospital Quality Alliance began nationwide public reporting of hospital quality performance. There has been concern that public reporting of the antibiotic timing measure (percentage of patients with pneumonia receiving antibiotics within 4 hours) has led to unintended adverse consequences for patients. In a nationally-representative hospital sample, we sought to determine whether public reporting has been associated with overdiagnosis of pneumonia, excessive antibiotic use, or inappropriate prioritization of patients with respiratory symptoms. Study Design Retrospective analyses of 13,042 emergency department (ED) visits by adult patients with respiratory symptoms in the National Hospital Ambulatory Medical Care Survey, 2001–2005. Methods Rates of pneumonia diagnosis, antibiotic use, and waiting times to see a physician were compared before and after public reporting. These outcomes were also compared between hospitals with different antibiotic timing scores. Results Comparing outcomes before and after antibiotic timing score reporting, there were no differences in rates of pneumonia diagnosis (10% vs. 11% of all ED visits, P = .72) or antibiotic administration (34% vs. 35%, P = .21). Mean waiting times to be seen by a physician increased similarly for patients with and without respiratory symptoms (11 vs. 6 minute increase, respectively; P = .29). After adjustment for confounders, hospitals with higher 2005 antibiotic timing scores had shorter mean waiting times for all patients, but there were no significant score-related trends for rates of pneumonia diagnosis or antibiotic use. Conclusions Despite concerns, public reporting of hospital antibiotic timing scores has not led to increased pneumonia diagnosis, antibiotic use, or a change in patient prioritization. PMID:19284811

Friedberg, Mark W.; Mehrotra, Ateev; Linder, Jeffrey A.

2009-01-01

121

A retrospective evaluation of adverse reactions to trimethoprim?sulphonamide combinations in dogs and cats  

Microsoft Academic Search

Adverse reactions to various trimethoprim?sulphonamide (T?S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985–1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1

C. Noli; J. P. Koeman; T. Willemse

1995-01-01

122

Adverse drug reactions to antiretroviral therapy during the early art period at a tertiary hospital in Ghana  

PubMed Central

Introduction Antiretroviral therapy (ART) has reduced HIV morbidity and mortality worldwide but has many adverse effects. These adverse drug reactions (ADRs) lead to discontinuations, disease progression or treatment failure. We explored the types and risk factors for ADRs in a cohort starting ART in a teaching hospital in Accra, Ghana where the main regimens used were a combination of nucleotide and non nucleotide reverse transcriptase inhibitors. Methods A Cross-sectional retrospective study was conducted reviewing data of 2042 patients initiated on HAART from 2003 to 2007. Univariate analysis was done for the dependent and independent variables. Stepwise logistic regression procedures were used to model the effect of gender on the development of ADRs controlling for other variables like age, marital status, weight at baseline and CD4 at baseline. Results The period prevalence of ADRs was 9.4%. The two most common adverse reactions were anaemia and diarrhoea. Female sex was a statistically significant independent predictor of an adverse drug reaction (AOR: 1.66, p = 0.01, CI: 1.16-2.36). CD4 counts 250 cells/mm3 or more was significantly associated with the occurrence of an ADR. The occurrence of anaemia in females was statistically significant compared to males. Conclusion Adverse drug reactions were less common than expected, anaemia was the commonest ADR. Female sex and high CD4 counts >250mm3 were predictors of ADRs whereas females were significantly more likely to develop anaemia than males. Recommendations were made for interventions to prevent and also mitigate the high levels of anaemia especially among women in the ART scale up. PMID:25368714

Lartey, Margaret; Asante-Quashie, Abena; Essel, Ama; Kenu, Ernest; Ganu, Vincent; Neequaye, Alfred

2014-01-01

123

Review of the pharmacokinetics, interactions and adverse reactions of cyclosporine in people, dogs and cats.  

PubMed

Cyclosporine is being increasingly used in veterinary medicine. Oral formulations of the drug have found many therapeutic uses, but topical formulations have met with only limited success, probably owing to their poor penetration through the stratum corneum. The concurrent use of ketoconazole to inhibit cyclosporine metabolism has been shown to reduce the required dose and hence the cost of cyclosporine therapy. In human medicine, adverse reactions to the drug, especially nephrotoxicity, are common but in dogs given the commonly used oral dose of 5 mg/kg per day there have been few adverse reactions. However, no toxicity studies lasting longer than 12 months have been carried out in this species. This paper reviews the pharmacokinetics, drug and procedural interactions, contraindications and the adverse reactions to cyclosporine, with particular reference to its use in the treatment of dermatological conditions in dogs, cats and people. PMID:12833934

Robson, D

2003-06-14

124

Identifying genomic and developmental causes of adverse drug reactions in children  

PubMed Central

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

Becker, Mara L; Leeder, J Steven

2011-01-01

125

Documentation and evaluation of adverse drug reactions (ADR)--contribution from a poison information center.  

PubMed

The Department of Clinical Pharmacology in Jena is a pharmacovigilance center in a study on intensified spontaneous adverse drug reaction reporting. Physicians specialized in clinical pharmacology screen admissions to the Department of Internal Medicine for possible adverse drug reactions. Because of the collaboration between the Pharmacology Department and the nearby Poison Information Center (PIC) in Erfurt the question occurred whether the latter might contribute to adverse drug reaction monitoring. We compared the ADR registered by the intensified spontaneous reporting system in 1999 with those of the PIC during the same period. Each symptom observed was regarded as 1 case. Every suspected drug was also treated separately. The symptoms were classified using adverse reaction terminology. The drugs were classified according to the WHO Anatomical Therapeutic Chemical (ATC) classification index. The causality assessment was based upon bibliographic data and the method of Bégaud et al. [1985]. Only possible, probable or very probable ADR were compared. The PIC registered mainly psychiatric and nervous system disorders sedation and extrapyramidal disorders were the most frequent reactions - unlike the pharmacovigilance study which registered primarily gastrointestinal and heart rate disorders. The PIC registered mainly drugs used in the therapy of disorders of the central nervous system, i.e. mostly psycholeptics and drugs acting on the alimentary tract, mostly anticholinergics. Drugs for the therapy of sensory organs disorders were frequent owing to the systemic and local adverse drug effects of anticholinergic mydriatics. The PIC and pharmacovigilance centers can benefit from co-operation. The PIC provides easy access to qualified drug information and is thus a useful tool in ADR evaluation. Although the number of adverse reactions assessed was small, their evaluation revealed problems in drug usage which would not otherwise be reported. The evaluation has enlarged the pool of ADR data which is the basis for signal detection. PMID:11911597

Mey, C; Hentschel, H; Hippius, M; Balogh, A

2002-03-01

126

Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial  

Microsoft Academic Search

Objective To assess the efficacy and safety of low dose adrenaline injected subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum in patients admitted to hospital after snake bite. Design Prospective, double blind, randomised, placebo controlled trial. Setting District general hospital in Sri Lanka. Subjects 105 patients with signs of envenomation after snake bite, randomised to receive either adrenaline

S B Gunatilake; de Silva

127

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011  

PubMed Central

Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

128

Are migraineurs at increased risk of adverse drug responses? A meta-analytic comparison of topiramate-related adverse drug reactions in epilepsy and migraine.  

PubMed

To compare adverse drug reactions (ADRs) to topiramate in patients with migraine and patients with epilepsy, we systematically reviewed all published randomized controlled trials (RCTs) that compare topiramate monotherapy in epilepsy and migraine. We included four epilepsy RCTs (N = 1,179 patients; vs. active comparators) and six migraine RCTs (N = 1,723 patients; vs. placebo). Behavioral ADRs and headache were found only in the case of epilepsy, whereas cognitive complaints and alteration of taste were found only in the case of migraine. The risk ratios (RRs) for paresthesia in migraine vs. epilepsy trials were 2.5 (99% confidence interval (CI): 1.66-3.77) for 50 mg, 2.7 (99% CI: 1.80-3.97) for 100 mg, and 3.0 (99% CI: 1.95-4.56) for 200 mg. For ADR-related dropouts, the RR was 2.5 (95% CI: 2.03-2.98) for 50 mg but no different for the other doses. We conclude that when treated with the same doses of topiramate, migraineurs show different ADRs than patients with epilepsy and are more likely to drop out because of ADRs. PMID:18987621

Luykx, J; Mason, M; Ferrari, M D; Carpay, J

2009-03-01

129

Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006)  

PubMed Central

Background Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost. Methods Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated. Results During the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. PMID:20942906

2010-01-01

130

Reported paediatric adverse drug reactions in the UK 2000–2009  

PubMed Central

AIMS The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card Scheme) to collect ‘suspected’ adverse drug reaction (ADR) data. MHRA advice is to report all suspected ADRs in paediatric (<17 years) patients. METHODS Data on all ADRs reported to the MHRA in patients <17 years from the years 2000–9 were supplied in two datasets, inclusive and exclusive of vaccines. RESULTS Of 222 755 ADR reports received by the MHRA from 2000–9, 31 726 (14.2%) were in children <17 years. The number of reports in 2000 was greater than in subsequent years (12 035) due to a national vaccination programme (Meningococcal Serogroup C conjugate vaccine). The median number of ADR reports per annum (2001–2009) for children was 2146 (95% CI 1801, 2575). Vaccines were included in 22 102 (66.5%) paediatric ADR reports, with Meningococcal Serogroup C conjugate vaccine reported most frequently (12 106 reports) and headache the commonest symptom (3163). Excluding vaccines, methylphenidate (653 reports) and atomoxetine (491) were the most commonly reported medications, and the most commonly reported symptom was vomiting (374). Reporting by nurses increased from 396 in 2001 to 1295 in 2009 (41.8% of all reports); reporting by doctors stayed constant. Reports from patients, parents or carers more than doubled but remained infrequent (1.5% in 2005, 4.0% in 2009). CONCLUSIONS Although under-reporting is probably common, the Yellow Card Scheme in the UK receives more than 2000 reports per year on patients <17 years. Nurses now report more suspected ADRs in children than any other healthcare professional. PMID:21988288

Hawcutt, Daniel B; Mainie, Pramod; Riordan, Andrew; Smyth, Rosalind L; Pirmohamed, Munir

2012-01-01

131

An exclusive causal-leverage measure for detecting adverse drug reactions from electronic medical records  

Microsoft Academic Search

Early detection of causal relationships between drugs and their associated adverse drug reactions (ADRs) can prevent harmful consequences or even deaths. Rare ADRs cannot be detected by pre-marketing clinical trials due to limitations in their size and duration. Existing postmarketing surveillance methods mainly rely on spontaneous reporting which is limited by severe underreporting (<10 percentage reporting rate), latency and inconsistency.

Yanqing Ji; Hao Ying; Peter Dews; John Tran; Ayman Mansour; Richard E. Miller; R. Michael Massanari

2011-01-01

132

Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir  

PubMed Central

SUMMARY Background Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients. Aim To investigate adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting. Methods Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected. Biopsy data and FIB-4 scores identified patients with advanced fibrosis. Multivariable fully adjusted models were built to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event. Results Patients with (n = 71) and without (n = 103) advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, haemoglobin and creatinine, but differed in race. Overall, 47% of patients completed treatment and 40% of patients achieved SVR. Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events; advanced fibrosis, however, was independently associated with ano-rectal discomfort (P = 0.03). Three patients decompensated and had advanced fibrosis. The discontinuation of all treatment medications due to an adverse event was significantly associated with older age (P = 0.01), female gender (P = 0.01) and lower platelets (P = 0.03). Conclusions Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis. More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations. PMID:24266536

Bichoupan, K.; Schwartz, J. M.; Martel-Laferriere, V.; Giannattasio, E. R.; Marfo, K.; Odin, J. A.; Liu, L. U.; Schiano, T. D.; Perumalswami, P.; Bansal, M.; Gaglio, P. J.; Kalia, H.; Dieterich, D. T.; Branch, A. D.; Reinus, J. F.

2014-01-01

133

An international comparison of case definition of severe adverse cutaneous reactions to medicines.  

PubMed

There is substantial intercountry variation in the proportion of cases of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) which are attributed to specific drugs. This study was undertaken to determine whether these differences might reflect biases in diagnosis of these conditions. A total of 138 reactions in 5 countries originally diagnosed as TEN or SJS were coded on to standardised forms. A single observer blind to the original diagnosis assessed each case according to specified criteria. This observer's diagnoses were compared with the original diagnoses. Overall, 111 of the 138 cases had information adequate for assessment. The blinded observer agreed with the diagnosis for 61% of cases where the original diagnosis was TEN and 58% of cases where the original diagnosis was SJS. There was no significant difference in rates of agreement when reactions attributed to sulphonamide antibiotics were compared with reactions attributed to other drugs. There were substantial and significant differences in percentage agreement between the blinded observer's diagnosis and the original diagnoses between countries. The lowest rates of agreement between the blinded observer and the original reports occurred in the US. Our results illustrate the difficulty in comparing reaction rates based on spontaneous reports between countries where the systems for gathering such reports vary. This illustrates the need for a minimum quantity of standard data and precise definitions of reactions if spontaneous reports of adverse reactions are to provide useful information about severe adverse skin reactions associated with drugs. PMID:8338525

Stern, R S; Albengres, E; Carlson, J; Chen, D; Kreft, C; Dai, W; Joseph, M; Tilson, H; Wiholm, B E; Kraft, C

1993-01-01

134

Corrosion at the Head-Neck Taper as a Cause for Adverse Local Tissue Reactions After Total Hip Arthroplasty  

PubMed Central

Background: Corrosion at the modular head-neck junction of the femoral component in total hip arthroplasty has been identified as a potential concern, although symptomatic adverse local tissue reactions secondary to corrosion have rarely been described. Methods: We retrospectively reviewed the records of ten patients with a metal-on-polyethylene total hip prosthesis, from three different manufacturers, who underwent revision surgery for corrosion at the modular head-neck junction. Results: All patients presented with pain or swelling around the hip, and two patients presented with recurrent instability. Serum cobalt levels were elevated prior to the revision arthroplasty and were typically more elevated than were serum chromium levels. Surgical findings included large soft-tissue masses and surrounding tissue damage with visible corrosion at the femoral head-neck junction; the two patients who presented with instability had severe damage to the hip abductor musculature. Pathology specimens consistently demonstrated areas of tissue necrosis. The patients were treated with debridement and a femoral head and liner exchange, with use of a ceramic femoral head with a titanium sleeve in eight cases. The mean Harris hip score improved from 58.1 points preoperatively to 89.7 points at a mean of 13.0 months after the revision surgery (p = 0.01). Repeat serum cobalt levels, measured in six patients at a mean of 8.0 months following revision, decreased to a mean of 1.61 ng/mL, and chromium levels were similar to prerevision levels. One patient with moderate hip abductor muscle necrosis developed recurrent instability after revision and required a second revision arthroplasty. Conclusions: Adverse local tissue reactions can occur in patients with a metal-on-polyethylene bearing secondary to corrosion at the modular femoral head-neck taper, and their presentation is similar to the adverse local tissue reactions seen in patients with a metal-on-metal bearing. Elevated serum metal levels, particularly a differential elevation of serum cobalt levels with respect to chromium levels, can be helpful in establishing this diagnosis. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID:23289127

John Cooper, H.; Della Valle, Craig J.; Berger, Richard A.; Tetreault, Matthew; Paprosky, Wayne G.; Sporer, Scott M.; Jacobs, Joshua J.

2012-01-01

135

[The history of adverse drug reactions, relief for these health damage and safety measures in Japan].  

PubMed

The first remarkable adverse drug reaction (ADR) reported in Japan was anaphylactic shock caused by penicillin. Although intradermal testing for antibiotics had been exercised as prediction method of anaphylactic shock for a long time, it was discontinued in 2004 because of no evidence for prediction. The malformation of limbs, etc. caused by thalidomide was a global problem, and thalidomide was withdrawn from the market. Teratogenicity testing during new drug development has been implemented since 1963. Chinoform (clioquinol)-iron chelate was detected from green tongue and green urine in patients with subacute myelo-optic neuropathy (SMON) and identified as a causal material of SMON in 1970. Chinoform was withdrawn from the market, and a fund for relief the health damage caused by ADR was established in 1979. The co-administration of sorivudine and fluorouracil anticancer agents induced fatal agranulocytosis, and sorivudine was withdrawn from the market after being on sale for one month in 1993. The guidelines for package inserts were corrected with this opportunity, and early phase pharmacovigilance of new drugs was introduced later. Since acquired immune deficiency syndrome, and hepatitis B and C were driven by virus-infected blood products, the Ministry of Health, Labor and Welfare tightened regulations regarding biological products in 2003, and a fund for relief of health damage caused by infections driven from biological products was established in 2004. The other remarkable ADRs were quadriceps contracture induced by the repeated administration of muscular injection products and Creutzfeldt-Jakob disease caused by the transplantation of human dry cranial dura matter, etc. The significance of safety measures for drugs based on experiences related to ADRs is worthy of notice. New drugs are approved based on a benefit-risk assessment, if the expected therapeutic benefits outweigh the possible risks associated with treatment. Since unexpected, rare and serious ADRs have been detected after administration to many patients in the post-marketing stage, risk management is required for product life-cycle management. PMID:20527311

Takahashi, Haruo

2009-01-01

136

[Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].  

PubMed

A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported. PMID:11227244

Tejos, S; Torrejón, N; Reyes, H; Meneses, M

2000-12-01

137

Incidence of hospital admissions due to adverse drug reactions in France: the EMIR study.  

PubMed

To assess the incidence of hospital admissions related to adverse drug reactions (ADRs) in France and the frequency of preventable ADRs in France, a prospective study was conducted among a representative randomly selected sample of medical wards in public hospitals between December 2006 and June 2007; all patients admitted during a 2-week period were included. An ADR-related hospitalization case was defined as a hospital admission because of an ADR, and an independent committee reviewed and validated all potential cases. Preventability was assessed using the French ADR preventability scale. Data were extrapolated to the population of France. Among 2692 admissions, 97 were related to an ADR (incidence 3.6%, 95% confidence interval, CI [2.8-4.4]). Patients admitted for an ADR were significantly older than those admitted for other reasons (P < 0.001). A third (32.0%) of ADR-related hospitalizations were 'preventable', 16.5% 'potentially preventable'. Drug interactions accounted for 29.9% of ADR-related hospitalizations. The most frequent causes of ADR-related hospitalizations were vascular disorders (20.6%), mainly bleeding complications, central nervous system disorders (11.3%), gastrointestinal disorders, and general disorders (9.3%). Antithrombotic and antineoplastic agents were the most frequently involved (12.6% each), followed by diuretics and analgesics (9.0% each). Vitamin-K-antagonists (VKAs) were the most common drugs associated with admission. The estimated annual number of ADR-related hospitalizations in France was 143 915 (95% CI [112 063-175 766]). ADRs were a significant cause of hospital admission in 2006-2007, in particular those due to VKAs. As new oral anticoagulants (NOACs) have been marketed, more attention needs to be paid to ensure a safe use of antithrombotic agents. PMID:24990220

Bénard-Laribière, Anne; Miremont-Salamé, Ghada; Pérault-Pochat, Marie-Christine; Noize, Pernelle; Haramburu, Françoise

2015-02-01

138

Knowledge discovery of drug data on the example of adverse reaction prediction  

PubMed Central

Background Antibiotics are the widely prescribed drugs for children and most likely to be related with adverse reactions. Record on adverse reactions and allergies from antibiotics considerably affect the prescription choices. We consider this a biomedical decision-making problem and explore hidden knowledge in survey results on data extracted from a big data pool of health records of children, from the Health Center of Osijek, Eastern Croatia. Results We applied and evaluated a k-means algorithm to the dataset to generate some clusters which have similar features. Our results highlight that some type of antibiotics form different clusters, which insight is most helpful for the clinician to support better decision-making. Conclusions Medical professionals can investigate the clusters which our study revealed, thus gaining useful knowledge and insight into this data for their clinical studies. PMID:25079450

2014-01-01

139

Adverse reactions to patent blue V dye – The NEW START and ALMANAC experience  

Microsoft Academic Search

BackgroundBlue dye with or without isotope has been widely used to identify the sentinel lymph node(s) in breast cancer. Patent blue V is used in the UK while its isomer isosulfan blue is used in the US. The allergic potential of isosulfan blue is well documented (1.4% adverse reactions) but that of patent blue V is less clearly defined.

L. Barthelmes; A. Goyal; R. G. Newcombe; F. McNeill; R. E. Mansel

2010-01-01

140

Validating administrative data for the detection of adverse events in older hospitalized patients  

PubMed Central

Older hospitalized patients are at risk of experiencing adverse events including, but not limited to, hospital-acquired pressure ulcers, fall-related injuries, and adverse drug events. A significant challenge in monitoring and managing adverse events is lack of readily accessible information on their occurrence. Purpose The objective of this retrospective cross-sectional study was to validate diagnostic codes for pressure ulcers, fall-related injuries, and adverse drug events found in routinely collected administrative hospitalization data. Methods All patients 65 years of age or older discharged between April 1, 2009 and March 31, 2011 from a provincial academic health sciences center in Canada were eligible for inclusion in the validation study. For each of the three types of adverse events, a random sample of 50 patients whose records were positive and 50 patients whose records were not positive for an adverse event was sought for review in the validation study (n=300 records in total). A structured health record review was performed independently by two health care providers with experience in geriatrics, both of whom were unaware of the patient’s status with respect to adverse event coding. A physician reviewed 40 records (20 reviewed by each health care provider) to establish interrater agreement. Results A total of 39 pressure ulcers, 56 fall-related injuries, and 69 adverse drug events were identified through health record review. Of these, 34 pressure ulcers, 54 fall-related injuries, and 47 adverse drug events were also identified in administrative data. Overall, the diagnostic codes for adverse events had a sensitivity and specificity exceeding 0.67 (95% confidence interval [CI]: 0.56–0.99) and 0.89 (95% CI: 0.72–0.99), respectively. Conclusion It is feasible and valid to identify pressure ulcers, fall-related injuries, and adverse drug events in older hospitalized patients using routinely collected administrative hospitalization data. The information is relatively inexpensive and easy to access with no impact on clinical staff. PMID:25143755

Ackroyd-Stolarz, Stacy; Bowles, Susan K; Giffin, Lorri

2014-01-01

141

Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management.  

PubMed

Sunscreen is a key component in the preventive measures recommended by dermatologists and public health campaigns aimed at reducing sunburn, early skin aging, and skin cancer. To maximize compliance, adverse reactions to sunscreens should be minimized. Although inactive ingredients cause many of these reactions, it is important for dermatologists to be aware of reactions to active ultraviolet filters. There are approximately 120 chemicals that can function as ultraviolet (UV) filters. This review focuses on the 36 most common filters in commercial and historical use. Of these, 16 are approved for use by the US Food and Drug Administration. The benzophenones and dibenzoylmethanes are the most commonly implicated UV filters causing allergic and photoallergic contact dermatitis (PACD) reactions; benzophenone-3 is the leading allergen and photoallergen within this class. When clinically indicated, patch and photopatch testing should be performed to common UV filters. PMID:25384223

Heurung, Ashley R; Raju, Srihari I; Warshaw, Erin M

2014-01-01

142

Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment  

PubMed Central

Aims In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l?1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. Methods Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. Results There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million). Conclusions The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning. PMID:24666324

Bateman, D Nicholas; Carroll, Robert; Pettie, Janice; Yamamoto, Takahiro; Elamin, Muhammad E M O; Peart, Lucy; Dow, Margaret; Coyle, Judy; Cranfield, Kristina R; Hook, Christopher; Sandilands, Euan A; Veiraiah, Aravindan; Webb, David; Gray, Alasdair; Dargan, Paul I; Wood, David M; Thomas, Simon H L; Dear, James W; Eddleston, Michael

2014-01-01

143

DNA repair capacity and acute radiotherapy adverse effects in Italian breast cancer patients.  

PubMed

Therapeutic exposure to ionising radiation can induce normal tissue side effects which consistently differ among individuals suggesting a possible genetic control. One approach to elucidate the underlying mechanisms is to analyse the relation between genetic traits, biomarkers of in vitro DNA damage and side toxicity in vivo. 43 breast cancer (BC) patients receiving radiotherapy after a breast-conserving surgery were recruited together with 34 age- and sex-matched healthy controls. Adverse tissue reactions were recorded as indicators of radiotherapy susceptibility. All blood samples from both patients (35) and controls (34) were irradiated in vitro and DNA primary damage and repair kinetic were measured through Comet assay. All study subjects were genotyped for XRCC1, OGG1 and XRCC3 gene polymorphisms. In our small groups we found a positive association between XRCC1 variant allele (399Gln) and the occurrence of breast cancer [p=0.01; OR=2.41, 95%CI (1.24-4.66)]. BC patients showed a higher degree of basal (p<0.001) and X-ray induced DNA damage (p<0.01) when compared to healthy controls. A reduced repair ability was found in BC patients showing high degrees of tissue side effects as classified by Radiation Morbidity Scoring Scheme. BC patients showed an impairment of their DNA repair capacity associated with the development of radiation sensitivity but not with polymorphisms in any of the considered genes. PMID:19962393

Sterpone, Silvia; Cornetta, Tommaso; Padua, Luca; Mastellone, Valeria; Giammarino, Daniela; Testa, Antonella; Tirindelli, Donatella; Cozzi, Renata; Donato, Vittorio

2010-02-01

144

Perioperative Hyperglycemia and Risk of Adverse Events Among Patients With and Without Diabetes  

PubMed Central

Objective To study the association between diabetes status, perioperative hyperglycemia, and adverse events in a statewide surgical cohort. Background Perioperative hyperglycemia may increase the risk of adverse events more significantly in patients without diabetes (NDM) than in those with diabetes (DM). Methods Using data from the Surgical Care and Outcomes Assessment Program, a cohort study (2010–2012) evaluated diabetes status, perioperative hyperglycemia, and composite adverse events in abdominal, vascular, and spine surgery at 53 hospitals in Washington State. Results Among 40,836 patients (mean age, 54 years; 53.6% women), 19% had diabetes; 47% underwent a perioperative blood glucose (BG) test, and of those, 18% had BG ?180 mg/dL. DM patients had a higher rate of adverse events (12% vs 9%, P < 0.001) than NDM patients. After adjustment, among NDM patients, those with hyperglycemia had an increased risk of adverse events compared with those with normal BG. Among NDM patients, there was a dose-response relationship between the level of BG and composite adverse events [odds ratio (OR), 1.3 for BG 125–180 (95% confidence interval (CI), 1.1–1.5); OR, 1.6 for BG ?180 (95% CI, 1.3–2.1)]. Conversely, hyperglycemic DM patients did not have an increased risk of adverse events, including those with a BG 180 or more (OR, 0.8; 95% CI, 0.6–1.0). NDM patients were less likely to receive insulin at each BG level. Conclusions For NDM patients, but not DM patients, the risk of adverse events was linked to hyperglycemia. Underlying this paradoxical effect may be the underuse of insulin, but also that hyperglycemia indicates higher levels of stress in NDM patients than in DM patients. PMID:25133932

Kotagal, Meera; Symons, Rebecca G.; Hirsch, Irl B.; Umpierrez, Guillermo E.; Dellinger, E. Patchen; Farrokhi, Ellen T.; Flum, David R.

2014-01-01

145

Impact of patient communication problems on the risk of preventable adverse events in acute care settings  

PubMed Central

Background Up to 50% of adverse events that occur in hospitals are preventable. Language barriers and disabilities that affect communication have been shown to decrease quality of care. We sought to assess whether communication problems are associated with an increased risk of preventable adverse events. Methods We randomly selected 20 general hospitals in the province of Quebec with at least 1500 annual admissions. Of the 145 672 admissions to the selected hospitals in 2000/01, we randomly selected and reviewed 2355 charts of patients aged 18 years or older. Reviewers abstracted patient characteristics, including communication problems, and details of hospital admission, and assessed the cause and preventability of identified adverse events. The primary outcome was adverse events. Results Of 217 adverse events, 63 (29%) were judged to be preventable, for an overall population rate of 2.7% (95% confidence interval [CI] 2.1%–3.4%). We found that patients with preventable adverse events were significantly more likely than those without such events to have a communication problem (odds ratio [OR] 3.00; 95% CI 1.43–6.27) or a psychiatric disorder (OR 2.35; 95% CI 1.09–5.05). Patients who were admitted urgently were significantly more likely than patients whose admissions were elective to experience an event (OR 1.64, 95% CI 1.07–2.52). Preventable adverse events were mainly due to drug errors (40%) or poor clinical management (32%). We found that patients with communication problems were more likely than patients without these problems to experience multiple preventable adverse events (46% v. 20%; p = 0.05). Interpretation Patients with communication problems appeared to be at highest risk for preventable adverse events. Interventions to reduce the risk for these patients need to be developed and evaluated. PMID:18519903

Bartlett, Gillian; Blais, Régis; Tamblyn, Robyn; Clermont, Richard J.; MacGibbon, Brenda

2008-01-01

146

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012].  

PubMed

197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats. PMID:24168771

Müntener, C R; Bruckner, L; Kupper, J; Althaus, F R; Schäublin, M

2013-11-01

147

Localized chronic fibrosing vasculitis in a tattoo: a unique adverse tattoo reaction.  

PubMed

Decorative tattoos are associated with a variety of adverse cutaneous reactions. We describe a unique fibrosing vasculitic reaction to red tattoo ink. The histopathology was similar to that in localized chronic fibrosing vasculitis (LCFV), but sharply limited to sites of red tattoo ink injection and associated with florid verrucoid epidermal hyperplasia. LCFV has been described in a broad variety of slowly progressive disorders with a firm consistency such as erythema elevatum diutinum, plasma cell granuloma, granuloma faciale, and IgG4-associated sclerosing diseases. It has been hypothesized that LCFV is the result of maladaptive immune reaction with failure to clear the causative antigen. To the best of our knowledge, this is the first case of LCFV associated with tattoo. We speculate on the implications our case holds for the pathogenesis of LCFV. PMID:24736671

Deeken, Audrey; Jefferson, Julie; Hawkinson, Dana; Fraga, Garth R

2014-04-01

148

Patient Safety, Potential Adverse Drug Events, and Medical Device Design: A Human Factors Engineering Approach  

Microsoft Academic Search

Adverse drug events are the single leading threat to patient safety. Human factors engineering has been repeatedly proposed, but largely untested, as the key to improving patient safety. The value of this approach was investigated in the context of a commercially available patient-controlled analgesia device that has been linked with several alleged patient injuries and deaths. Several reports have stated

Laura Lin; Kim J. Vicente; D. John Doyle

2001-01-01

149

Detecting adverse events for patient safety research: a review of current methodologies  

Microsoft Academic Search

Promoting patient safety is a national priority. To evaluate interventions for reducing medical errors and adverse event, effective methods for detecting such events are required. This paper reviews the current methodologies for detection of adverse events and discusses their relative advantages and limitations. It also presents a cognitive framework for error monitoring and detection. While manual chart review has been

Harvey J. Murff; Vimla L. Patel; George Hripcsak; David W. Bates

2003-01-01

150

Recognition and reporting of suspected adverse drug reactions by surveyed healthcare professionals in Uganda: key determinants  

PubMed Central

Objective To assess extent and determinants of past-month recognition of suspected adverse drug reactions (ADR) and past-year ADR reporting among healthcare professionals (HCPs) in Uganda. Setting Geographically diverse health facilities (public, private for-profit, private not-for-profit). Participants Of 2000 questionnaires distributed, 1345 were completed: return rate of 67%. Primary and secondary outcome measures Per cent HCPs who suspected ADR in the past month; reported ADR in the past year. Results Nurses were the majority (59%, 792/1345). Only half the respondents had heard about pharmacovigilance: 39% of nurses (295/763; 95% CI 35% to 42%), 70% otherwise (383/547; 95% CI 66% to 74%). One fifth (268/1289 or 21%; 95% CI 19% to 23%) had suspected an ADR in the previous 4?weeks, 111 of them were nurses; 15% (190/1296) had reported a suspected ADR in the past year, 103 of them were nurses. Past-month ADR suspicion was more likely by non-nurses (OR=1.7, 95% CI 1.16 to 2.40) and with medical research involvement (OR=1.5, 95% CI 1.05 to 2.15) but past-month receipt of patient ADR-complaint predominated (OR=19, 95% CI 14 to 28). Past-year ADR reporting was higher by hospital staff (OR=1.9, 95% CI 1.18 to 3.10), especially in medicine (OR=2.3, 95% CI 1.08 to 4.73); but lower from private for-profit health facilities (OR=0.5, 95% CI 0.28 to 0.77) and by older staff (OR=0.6, 95% CI 0.43 to 0.91); more likely by HCPs who had ever encountered a fatal ADR (OR=2.9, 95% CI 1.94 to 4.25), knew to whom to report (OR=1.7, 95% CI 1.18 to 2.46), or suggested how to improve ADR reporting (OR=1.6, 95% CI 1.04 to 2.49). Two attitudinal factors were important: diffidence and lethargy. Conclusions One in five HCPs suspected an ADR in the past-month and one in seven reported ADR in the previous year. Empowering patients could strengthen ADR detection and reporting in Africa. PMID:25421337

Kiguba, Ronald; Karamagi, Charles; Waako, Paul; Ndagije, Helen B; Bird, Sheila M

2014-01-01

151

A potential causal association mining algorithm for screening adverse drug reactions in postmarketing surveillance.  

PubMed

Early detection of unknown adverse drug reactions (ADRs) in postmarketing surveillance saves lives and prevents harmful consequences. We propose a novel data mining approach to signaling potential ADRs from electronic health databases. More specifically, we introduce potential causal association rules (PCARs) to represent the potential causal relationship between a drug and ICD-9 (CDC. (2010). International Classification of Diseases, Ninth Revision (ICD-9). [Online]. Available: http://www.cdc.gov/nchs/icd/icd9.html) coded signs or symptoms representing potential ADRs. Due to the infrequent nature of ADRs, the existing frequency-based data mining methods cannot effectively discover PCARs. We introduce a new interestingness measure, potential causal leverage, to quantify the degree of association of a PCAR. This measure is based on the computational, experience-based fuzzy recognition-primed decision (RPD) model that we developed previously (Y. Ji, R. M. Massanari, J. Ager, J. Yen, R. E. Miller, and H. Ying, "A fuzzy logic-based computational recognition-primed decision model," Inf. Sci., vol. 177, pp. 4338-4353, 2007) on the basis of the well-known, psychology-originated qualitative RPD model (G. A. Klein, "A recognition-primed decision making model of rapid decision making," in Decision Making in Action: Models and Methods, 1993, pp. 138-147). The potential causal leverage assesses the strength of the association of a drug-symptom pair given a collection of patient cases. To test our data mining approach, we retrieved electronic medical data for 16,206 patients treated by one or more than eight drugs of our interest at the Veterans Affairs Medical Center in Detroit between 2007 and 2009. We selected enalapril as the target drug for this ADR signal generation study. We used our algorithm to preliminarily evaluate the associations between enalapril and all the ICD-9 codes associated with it. The experimental results indicate that our approach has a potential to better signal potential ADRs than risk ratio and leverage, two traditional frequency-based measures. Among the top 50 signal pairs (i.e., enalapril versus symptoms) ranked by the potential causal-leverage measure, the physicians on the project determined that eight of them probably represent true causal associations. PMID:21435986

Ji, Yanqing; Ying, Hao; Dews, Peter; Mansour, Ayman; Tran, John; Miller, Richard E; Massanari, R Michael

2011-05-01

152

Adverse Reactions to Field Vaccination Against Lumpy Skin Disease in Jordan.  

PubMed

Lumpy skin disease (LSD) is an emerging disease in the Middle East region and has been recently reported in Jordan. The aim of this study was to investigate the adverse reactions that were reported after vaccine administration. Geographical areas enrolled in the study were free of the disease and away from the outbreak governorate. Sixty-three dairy cattle farms, with a total of 19,539 animals, were included in the study. Of those, 56 farms reported adverse clinical signs after vaccine administration. The duration between vaccine administration and appearance of adverse clinical signs ranged from 1 to 20 days (Mean = 10.3, SD ± 3.9). Clinical signs were similar to those observed with natural cases of lumpy skin disease. These were mainly fever, decreased feed intake, decreased milk production and variable sized cutaneous nodules (a few millimetres to around 2 cm in diameter) that could be seen anywhere on the body (head, neck, trunk, perineum), udder, and/or teats. Nodules were raised and firm initially and then formed dry scabs that could be peeled off the skin. The characteristic deep 'sit fast' appearance was rarely seen and most lesions were superficial. Some cattle had swollen lymph nodes, while a few pregnant animals aborted. The percentage of affected cattle ranged from 0.3 to 25% (Mean = 8, SD ± 5.1). Fever, decreased feed intake, and decreased milk production were seen in 83.9, 85.7, and 94.6% in cattle on the affected farms, respectively. All affected cattle displayed skin nodules over their entire bodies, while 33.9 and 7.1% of the affected farms reported nodular lesions present on the udders and teats, respectively. No mortalities were reported due to vaccine adverse reactions. Duration (course) of clinical signs ranged from 3 to 20 days (Mean = 13.7, SD ± 4.1). Two types of LSD vaccines were used by the farmers in this study. The first one was a sheep pox virus (SPPV) vaccine derived from the RM65 isolate [Jovivac(®) , manufactured by Jordan Bioindustries Centre (JOVAC)] and the other an unlabelled one, which was later identified using PCR as a strain of lumpy skin disease virus (LSDV). Blood and skin samples collected from cattle vaccinated with the LSDV vaccine were positive for LSDV using both general and species-specific PCR primers, whereas those from cattle vaccinated with the Jovivac(®) vaccine were negative. Adverse reactions observed in cattle after administration of the LSDV vaccine were reported to be more severe than those seen after Jovivac(®) vaccine administration and were comparable with clinical signs observed in natural infections. PMID:25098267

Abutarbush, S M; Hananeh, W M; Ramadan, W; Al Sheyab, O M; Alnajjar, A R; Al Zoubi, I G; Knowles, N J; Bachanek-Bankowska, K; Tuppurainen, E S M

2014-08-01

153

Adverse drug reactions and polypharmacy in the elderly in general practice  

Microsoft Academic Search

Objectives: The risk of adverse drug reactions (ADRs) increases with the number of drugs used. Most studies refer to potential interactions;\\u000a the results regarding the severity of occurring and registered ADRs are inconsistent. Therefore, we examined the relevance\\u000a of drug-induced problems in the elderly in general practice and their association with polypharmacy.\\u000a \\u000a \\u000a \\u000a Design: Retrospective cross-sectional analysis of prospectively collected data.

L. J. G. Veehof; R. E. Stewart; B. Meyboom-de Jong; F. M. Haaijer-Ruskamp

1999-01-01

154

Constipation and diarrhoea - common adverse drug reactions? A cross sectional study in the general population  

Microsoft Academic Search

Background  Constipation and diarrhoea are common complaints and often reported as adverse drug reactions. This study aimed at finding\\u000a associations between drugs and constipation and diarrhoea in a general population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A selection of inhabitants in Oppland County, Norway participated in a cross-sectional survey. Information about demographics,\\u000a diseases including gastrointestinal complaints classified according to the Rome II criteria and use of drugs

Gunvor S Fosnes; Stian Lydersen; Per G Farup

2011-01-01

155

Adverse reactions to vitamin E and aloe vera preparations after dermabrasion and chemical peel.  

PubMed

Three women and one man aged forty-one to sixty-five years experienced a severe burning sensation following the application of aloe vera or vitamin E preparations to a skin area that had been subjected to a chemical peel or dermabrasion. Subsequently, a severe dermatitis occurred that required hospitalization of one patient and intravenous administration of steroids. The dermatitis abated very slowly in all patients: full recovery took three months or more. One patient resumed the use of vitamin E creams two years after the episode of dermatitis and experienced no adverse effect. Patients undergoing dermabrasion or chemical peel procedures should be cautioned specifically against the use of aloe vera or vitamin E topically in the first weeks after surgery. PMID:2022130

Hunter, D; Frumkin, A

1991-03-01

156

Active surveillance of visual impairment due to adverse drug reactions: findings from a national study in the United Kingdom  

PubMed Central

As visual impairment (VI) due to adverse drug reactions (ADR) is rare in adults and children, there is an incomplete evidence base to inform guidance for screening and for counseling patients on the potential risks of medications. We report on suspected drugs and the eye conditions found in a national study of incidence of diagnosis of visual impairment due to suspected ADR. Case ascertainment was via the British Ophthalmological Surveillance Unit (BOSU), between March 2010 and February 2012, with follow-up after 6 months. Case definition: any child or adult with bilateral or unilateral visual impairment due to a suspected ADR, using distance acuity worse than Snellen 6/18 (logMAR 0.48) in the better eye (bilateral) or affected eye (unilateral). Anonymized patient information on potential cases was provided by managing ophthalmologists, comprising visual status before and after suspected ADR, ophthalmic condition attributable to the ADR, preexisting eye disease and prescribed medications at the time of the ADR. Permanency and causality of the visual impairment were confirmed by the managing clinician, after 6 months, using the WHO Uppsala Monitoring Committee criteria. Over 2 years, 36 eligible cases were reported of whom 23 had permanent VI. While most cases were due to drugs known to have adverse side-effects, some were unanticipated sporadic cases. Visual impairment due to ADRs is rare. However, with for example, increasing polypharmacy in the elderly, monitoring of ocular ADRs, although challenging, is necessary. PMID:25692024

Cumberland, Phillippa M; Russell-Eggitt, Isabelle; Rahi, Jugnoo S

2015-01-01

157

Which adverse effects influence the dropout rate in selective serotonin reuptake inhibitor (SSRI) treatment? Results for 50,824 patients  

PubMed Central

Background: Nowadays, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants due to their superior clinical efficacy, effectiveness, tolerability, and safety as compared to tricyclic antidepressants or monoamino oxidase inhibitors. However, despite these advantages SSRIs are still associated with a number of adverse drug reactions, especially in the early stages of treatment, which may lead to premature discontinuation of therapy in some cases. The aim of the present study was to assess the most common adverse drug reactions of SSRIs as well as their impact on dropout rate in a large study population. Patients and methods: Data for 50,824 patients treated for major depressive disorder with SSRIs for the first time was accessed via the Disease Analyzer database (IMS Health, Germany), providing information on SSRI adverse drug reactions and their influence on premature treatment discontinuation calculated by regression analysis. The presence of certain co-morbidities was also registered. Results: The mean age was 54.5 ± 19 years, two-thirds of the study population being female. The adverse effects mentioned most frequently were: “discomfort” of the digestive system (10%), sleep disorders (8.6%), and heart rhythm disorders (4%); however, these were of tolerable severity as they did not significantly influence the dropout rate. Contrary to that, somnolence and younger age (?50 years) in particular increased the chance of premature treatment discontinuation, while patients suffering from cardiovascular risk factors or osteoporosis tended to adhere to the therapy. Conclusions: Overall, there is high tolerability for early SSRI treatment, whereas the occurrence of somnolence leads to discontinuation. PMID:25332703

Kostev, Karel; Rex, Juliana; Eith, Thilo; Heilmaier, Christina

2014-01-01

158

Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.  

PubMed

Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalizing the thyroid hormone status and optimizing of the concomitant medication may reduce the risk of statin induced adverse effects. PMID:24974574

Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

2014-06-01

159

Adverse outcomes among Aboriginal patients receiving peritoneal dialysis  

PubMed Central

Background The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural). Methods We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997–2007 (n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan–Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal. Results One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073–2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352–2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients. Interpretation Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban. PMID:20660579

Sood, Manish M.; Komenda, Paul; Sood, Amy R.; Reslerova, Martina; Verrelli, Mauro; Sathianathan, Chris; Eng, Loretta; Eng, Amanda; Rigatto, Claudio

2010-01-01

160

Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*  

PubMed Central

Objective Myelodysplastic syndrome (MDS) treatment can initially worsen patients’ clinical condition and they may discontinue therapy before achieving benefit. We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them. Methods In the Cancer and Leukemia Group B (CALGB) 9221 study, patients with any French-American-British (FAB) subtype of MDS were randomized to azacitidine or best supportive care (BSC). After 56 d, patients randomized to BSC with disease progression could cross over to receive azacitidine. In the AZA-001 study, patients with higher-risk MDS (FAB-defined refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocitic leukaemia and IPSS int-2 or high) were randomized to azacitidine or to conventional care regimens (CCR), which included low-dose ara-C, BSC, or intensive chemotherapy. In both studies, azacitidine dose was 75 mg/m2/d SC for 7 d every 28 d. AEs were graded per National Cancer Institute’s Common Toxicity Criteria version 2.0 (AZA-001) or CALGB Expanded CTC (CALGB 9221). Results In safety-evaluable patients in AZA-001 (N = 175) or CALGB 9221 (N = 150), the most common AEs with azacitidine included hematologic (eg, cytopenias) and non-hematologic administration-related events (eg, injection-site reactions and gastrointestinal disorders). Most AEs were transient and resolved during ongoing therapy (> 83%). Hematologic AEs, most frequently observed during early treatment cycles, decreased during subsequent cycles and were usually managed with dosing delays (23–29%). Gastrointestinal symptoms were primarily managed with anti-emetics and laxatives. Conclusion Hematologic and non-hematologic AEs with azacitidine decreased in frequency as treatment continued. Awareness of the onset, duration and management of AEs can facilitate treatment, permitting patients to continue therapy for maximum benefit. PMID:20394651

Santini, Valeria; Fenaux, Pierre; Mufti, Ghulam J.; Hellström-Lindberg, Eva; Silverman, Lewis R.; List, Alan; Gore, Steven D.; Seymour, John F.; Backstrom, Jay; Beach, Charles L.

2013-01-01

161

Adverse Outcomes After Noncardiac Surgery in Patients With Diabetes  

PubMed Central

OBJECTIVE To investigate whether diabetes affects perioperative complications or mortality and to gauge its impact on medical expenditures for noncardiac surgeries. RESEARCH DESIGN AND METHODS With the use of reimbursement claims from the Taiwan National Health Insurance system, we performed a population-based cohort study of patients with and without diabetes undergoing noncardiac surgeries. Outcomes of postoperative complications, mortality, hospital stay, and medical expenditures were compared between patients with and without diabetes. RESULTS Diabetes increased 30-day postoperative mortality (odds ratio 1.84 [95% CI 1.46–2.32]), particularly among patients with type 1 diabetes or uncontrolled diabetes and patients with preoperative diabetes-related comorbidities, such as eye involvement, peripheral circulatory disorders, ketoacidosis, renal manifestations, and coma. Compared with nondiabetic control patients, coexisting medical conditions, such as renal dialysis (5.17 [3.68–7.28]), liver cirrhosis (3.59 [2.19–5.88]), stroke (2.87 [1.95–4.22]), mental disorders (2.35 [1.71–3.24]), ischemic heart disease (2.08 [1.45–2.99]), chronic obstructive pulmonary disease (1.96 [1.29–2.97]), and hyperlipidemia (1.94 [1.01–3.76]) were associated with mortality for patients with diabetes undergoing noncardiac surgery. Patients with diabetes faced a higher risk of postoperative acute renal failure (3.59 [2.88–4.48]) and acute myocardial infarction (3.65 [2.43–5.49]). Furthermore, diabetes was associated with prolonged hospital stay (2.30 [2.16–2.44]) and increased medical expenditures (1.32 [1.25–1.40]). CONCLUSIONS Diabetes increases postoperative 30-day mortality, complications, and medical expenditures in patients undergoing in-hospital noncardiac surgeries. PMID:23990518

Yeh, Chun-Chieh; Liao, Chien-Chang; Chang, Yi-Cheng; Jeng, Long-Bin; Yang, Horng-Ren; Shih, Chun-Chuan; Chen, Ta-Liang

2013-01-01

162

Outcomes Research Branch | Collecting Patient Reports of Symptoms and Symptomatic Adverse Events During Cancer Treatment  

Cancer.gov

There is growing awareness that collecting symptom data directly from patients using patient-reported outcome (PRO) tools can improve the precision and efficiency of symptomatic adverse event (AE) data collection. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a system that provides a library of validated questions and a web-based platform for collecting patient reports of the symptoms they are experiencing while undergoing treatment, for the purpose of enhancing AE reporting.

163

Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial  

PubMed Central

Background Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1?1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized. Trial registration www.ClinicalTrials.gov NCT00270777 Please see later in the article for the Editors' Summary PMID:21572992

de Silva, H. Asita; Pathmeswaran, Arunasalam; Ranasinha, Channa D.; Jayamanne, Shaluka; Samarakoon, Senarath B.; Hittharage, Ariyasena; Kalupahana, Ranjith; Ratnatilaka, G. Asoka; Uluwatthage, Wimalasiri; Aronson, Jeffrey K.; Armitage, Jane M.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

164

Teaching dental students about patient communication following an adverse event: a pilot educational module.  

PubMed

Adverse events are an important but understudied area in dentistry. Most dentists will face the issue of an adverse event several times in their clinical careers. The authors implemented a six-hour pilot educational module at one dental school to improve fourth-year dental students' knowledge and confidence in communicating with patients about adverse events. Based on results from the twenty-nine students who completed both the pre- and posttests, the module significantly increased the students' knowledge of the key concepts involved in adverse events. However, the module did not improve the students' confidence that they would be able to implement these communication skills in clinical situations. Based on these results, this article discusses how future educational efforts can be modified to better prepare students for the communication challenges associated with adverse events. PMID:24789835

Raja, Sheela; Rajagopalan, Chelsea F; Patel, Janki; Van Kanegan, Kevin

2014-05-01

165

Health care costs for prostate cancer patients receiving androgen deprivation therapy: treatment and adverse events  

PubMed Central

Background Serious adverse events have been associated with androgen deprivation therapy (adt) for prostate cancer (pca), but few studies address the costs of those events. Methods All pca patients (ICD-9-CM 185) in Ontario who started 90 days or more of adt or had orchiectomy at the age of 66 or older during 1995–2005 (n = 26,809) were identified using the Ontario Cancer Registry and drug and hospital data. Diagnosis dates of adverse events—myocardial infarction, acute coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or pulmonary embolism, any diabetes, and fracture or osteoporosis—before and after adt initiation were determined from administrative data. We excluded patients with the same diagnosis before and after adt, and we allocated each patient’s time from adt initiation to death or December 31, 2007, into health states: adt (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event), and Final (?180 days before death). We used methods for Canadian health administrative data to estimate annual total health care costs during each state, and we examined monthly trends. Results Approximately 50% of 21,811 patients with no pre-adt adverse event developed 1 or more events after adt. The costliest adverse event state was stroke ($26,432/year). Multiple was the most frequent (n = 2,336) and the second most costly health state ($24,374/year). Costs were highest in the first month after diagnosis (from $1,714 for diabetes to $14,068 for myocardial infarction). Costs declined within 18 months, ranging from $784 per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased the costs of adt by 100% to 265%. Conclusions The economic burden of adverse events is relevant to programs and policies from clinic to government, and that burden merits consideration in the risks and benefits of adt. PMID:24940106

Krahn, M.D.; Bremner, K.E.; Luo, J.; Alibhai, S.M.H.

2014-01-01

166

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

PubMed Central

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

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

2012-01-01

167

Adverse drug events in hospitalized patientsA comparison of doctors, nurses and patients as sources of reports  

Microsoft Academic Search

Objective: This study investigated the relative value of adverse drug events reported by doctors, nurses and patients.\\u000a \\u000a \\u000a \\u000a Methods: The study was conducted on a total of four wards: the paediatric and internal medicine wards (including geriatric patients)\\u000a of two peripheral hospitals in the Netherlands. Adverse drug events were collected by spontaneous reporting (doctor and nurse\\u000a reports) and by daily ward

P. M. L. A. van den Bemt; A. C. G. Egberts; A. W. Lenderink; J. M. Verzijl; K. A. Simons; W. S. C. J. M. van der Pol; H. G. M. Leufkens

1999-01-01

168

Identifying plausible adverse drug reactions using knowledge extracted from the literature.  

PubMed

Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to "rediscover" these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831

Shang, Ning; Xu, Hua; Rindflesch, Thomas C; Cohen, Trevor

2014-12-01

169

Cumulative Adverse Financial Circumstances: Associations with Patient Health Status and Behaviors  

ERIC Educational Resources Information Center

This article examines associations between cumulative adverse financial circumstances and patient health in a sample of 1,506 urban emergency department (ED) patients. Study participants completed a previously validated Social Health Survey between May and October 2009. Five categories of economic deprivation were studied: food insecurity, housing…

Bisgaier, Joanna; Rhodes, Karin V.

2011-01-01

170

Predictive Factors of Herpes Zoster HIV-Infected Patients: Another Adverse Effect of Crack Cocaine  

E-print Network

Predictive Factors of Herpes Zoster HIV-Infected Patients: Another Adverse Effect of Crack Cocaine.001; and in patients previously reported to use crack cocaine AHR=5.9, (95%CI=1.4-25), P=0.02. Herpes zoster incidence inhibitors on herpes zoster incidence. The present study is the first to suggest that crack cocaine

Boyer, Edmond

171

Trunnionosis: the latest culprit in adverse reactions to metal debris following hip arthroplasty.  

PubMed

The imaging findings of periprosthetic soft tissue lesions (pseudotumours) have been typically defined in the context of newer second-generation metal-on-metal hip arthroplasty. More recently, similar findings have been described in the setting of non-metal-on-metal prostheses. Although uncommon, wear and corrosion between the metal surfaces at the head-neck ('trunnionosis') and neck-stem interfaces are the potential culprits. With modular junctions containing at least one cobalt chromium component frequently present in hip arthroplasty prostheses, the incidence of this mode of adverse wear may be higher than previously thought (irrespective of the specific bearing couple used). In the present report, we described a case of a severe adverse local tissue reaction secondary to suspected corrosion at the head-neck taper in a metal-on-polyethylene total hip arthroplasty and reviewed the literature. Knowledge of this topical entity should help radiologists facilitate early diagnosis and ensure early management of this potentially serious complication. PMID:25109382

Shulman, Ryan M; Zywiel, Michael G; Gandhi, Rajiv; Davey, J Roderick; Salonen, David C

2015-03-01

172

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol  

PubMed Central

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol–SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol–SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol–SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) (P < 10–7). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol–SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4–9780.9); corrected P value = 4.7 × 10–24] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23–6665.26); corrected P value = 8.1 × 10–18]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol–SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition. PMID:15743917

Hung, Shuen-Iu; Chung, Wen-Hung; Liou, Lieh-Bang; Chu, Chen-Chung; Lin, Marie; Huang, Hsien-Ping; Lin, Yen-Ling; Lan, Joung-Liang; Yang, Li-Cheng; Hong, Hong-Shang; Chen, Ming-Jing; Lai, Ping-Chin; Wu, Mai-Szu; Chu, Chia-Yu; Wang, Kuo-Hsien; Chen, Chien-Hsiun; Fann, Cathy S. J.; Wu, Jer-Yuarn; Chen, Yuan-Tsong

2005-01-01

173

Ci4SeR--curation interface for semantic resources--evaluation with adverse drug reactions.  

PubMed

Evaluation and validation have become a crucial problem for the development of semantic resources. We developed Ci4SeR, a Graphical User Interface to optimize the curation work (not taking into account structural aspects), suitable for any type of resource with lightweight description logic. We tested it on OntoADR, an ontology of adverse drug reactions. A single curator has reviewed 326 terms (1020 axioms) in an estimated time of 120 hours (2.71 concepts and 8.5 axioms reviewed per hour) and added 1874 new axioms (15.6 axioms per hour). Compared with previous manual endeavours, the interface allows increasing the speed-rate of reviewed concepts by 68% and axiom addition by 486%. A wider use of Ci4SeR would help semantic resources curation and improve completeness of knowledge modelling. PMID:25160157

Souvignet, Julien; Asfari, Hadyl; Declerck, Gunnar; Lardon, Jérémy; Trombert-Paviot, Béatrice; Jaulent, Marie-Christine; Bousquet, Cédric

2014-01-01

174

Titanium alloy stem as a cause for adverse reaction to metal debris after bipolar hemiarthroplasty.  

PubMed

A 68-year-old male with failure of bipolar hemiarthroplasty consistent with adverse reaction to metal debris (ARMD) who presented with a painful cystic lesion and lower extremity swelling was encountered. However, revision surgical findings showed no apparent cause of ARMD previously described in the literature, such as corrosion at the head-neck junction and articular abrasion. Therefore, it was difficult to make a definite diagnosis of failure secondary to ARMD, which consequently led to the decision to perform two-stage revision procedure, though the stem was firmly fixed. Postoperative analysis in the retrieval tissues showed that the metal debris mainly originated from the titanium alloy stem itself. Although this is a very rare case, one should be aware that even the well-fixed femoral components themselves have the potential to be the cause of ARMD. PMID:24716061

Sakamoto, Masaaki; Watanabe, Hitoshi; Higashi, Hidetaka; Kubosawa, Hitoshi

2014-01-01

175

Titanium Alloy Stem as a Cause for Adverse Reaction to Metal Debris after Bipolar Hemiarthroplasty  

PubMed Central

A 68-year-old male with failure of bipolar hemiarthroplasty consistent with adverse reaction to metal debris (ARMD) who presented with a painful cystic lesion and lower extremity swelling was encountered. However, revision surgical findings showed no apparent cause of ARMD previously described in the literature, such as corrosion at the head-neck junction and articular abrasion. Therefore, it was difficult to make a definite diagnosis of failure secondary to ARMD, which consequently led to the decision to perform two-stage revision procedure, though the stem was firmly fixed. Postoperative analysis in the retrieval tissues showed that the metal debris mainly originated from the titanium alloy stem itself. Although this is a very rare case, one should be aware that even the well-fixed femoral components themselves have the potential to be the cause of ARMD. PMID:24716061

Watanabe, Hitoshi; Kubosawa, Hitoshi

2014-01-01

176

Constipation and diarrhoea - common adverse drug reactions? A cross sectional study in the general population  

PubMed Central

Background Constipation and diarrhoea are common complaints and often reported as adverse drug reactions. This study aimed at finding associations between drugs and constipation and diarrhoea in a general population. Methods A selection of inhabitants in Oppland County, Norway participated in a cross-sectional survey. Information about demographics, diseases including gastrointestinal complaints classified according to the Rome II criteria and use of drugs were collected on questionnaires. Constipation was defined as functional constipation and constipation predominant Irritable Bowel Syndrome (IBS), and diarrhoea as functional diarrhoea and diarrhoea predominant IBS. Associations between drugs and constipation and diarrhoea were examined with multivariable logistic regression models. Based on the multivariable model, the changes in prevalence (risk difference) of the abdominal complaints for non-users and users of drugs were calculated. Results In total 11078 subjects were invited, 4622 completed the questionnaires, 640 (13.8%) had constipation and 407 (8.8%) had diarrhoea. To start using drugs increased the prevalence of constipation and diarrhoea with 2.5% and 2.3% respectively. Polypharmacy was an additional risk factor for diarrhoea. Use of furosemide, levothyroxine sodium and ibuprofen was associated with constipation, and lithium and carbamazepine with diarrhoea. The excess drug related prevalence varied from 5.3% for the association between ibuprofen and constipation to 27.5% for the association between lithium and diarrhoea. Conclusions Use of drugs was associated with constipation and diarrhoea in the general population. The associations are most likely adverse drug reactions and show that drug-induced symptoms need to be considered in subjects with these complaints. PMID:21332973

2011-01-01

177

Revised National Tuberculosis Control Program regimens with and without directly observed treatment, short-course: A comparative study of therapeutic cure rate and adverse reactions  

PubMed Central

Objective: To compare the therapeutic cure rate and adverse reactions in the regimens of the Revised National Tuberculosis Control Program (RNTCP) with directly observed treatment, short-course (DOTS) and without DOTS. Materials and Methods: Fifty patients in the DOTS regimen and 50 patients in the non-DOTS regimen were enrolled in the study. All the participants were asked to come regularly for 3 consecutive days for sputum collection, and the sputum samples were examined for acid-fast bacilli. If tuberculosis (TB) was confirmed, the disease status was confirmed through a chest X-ray (PA view). The participants were monitored for adverse events arising from the use of anti-TB drugs for the next 6 months. Results: The TB cure rates for RNTCP with DOTS and RNTCP with non-DOTS were 80% and 66%, respectively. The DOTS therapy had a better cure rate for radiologically positive, sputum-positive cases compared with the non-DOTS regimen group. The non-DOTS treatment regimen had significantly increased numbers of adverse events in the hepatic and hematinic systems. Conclusion: The DOTS regimen has higher cure rates and a lower incidence of adverse reactions compared with the non-DOTS regimen. PMID:24551582

Sivaraj, Rengaraj; Umarani, Sivaraj; Parasuraman, Subramani; Muralidhar, Pyapti

2014-01-01

178

A Prospective, Observational Study of Adverse Reactions to Drug Regimen for Multi-Drug Resistant Pulmonary Tuberculosis in Central India  

PubMed Central

Objective 1) To assess the adverse drug reactions (ADRs) 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 investigate the relationship of MDR-TB (primary or secondary) and the 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 2012 to December 2012 with a follow-up of nine months. Encountered ADRs were noted along with the time of sputum conversion. Results Total 64 ADRs were reported in 55 patients out of total 110 patients (n=110). As per the Naranjo causality assessment of ADRs, seven patients had definite, 45 had probable, and 3 had possible causal relation with drugs of DOTS-Plus regimen. 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 three not evaluable. Mean sputum smear conversion time was significantly higher in patients with a secondary type than that of primary type of MDR TB and in patients with DM than those without DM. Conclusion ADRs were common in patients of MDR-TB on DOTs-Plus drug regimen. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regimen compared to DOTS regimen 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 clinical parameters and instituting appropriate measures. PMID:25237474

Hire, Rohan; Kale, A. S.; Dakhale, G. N.; Gaikwad, Nilesh

2014-01-01

179

Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient's Perceptions of Over-the-Counter Medications and Their Adverse Effects.  

PubMed

We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient's perception of over-the-counter (OTC) medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them. PMID:24829833

Salter, Mark D

2013-01-01

180

In Vitro Release of Interferon-Gamma from Peripheral Blood Lymphocytes in Cutaneous Adverse Drug Reactions  

PubMed Central

Background. Cutaneous drug reactions are common but diagnostically challenging due to phenotypic heterogeneity and simultaneous exposure to multiple drugs. These limitations prompted the development of diagnostic tests. Aims. To evaluate the performance of an in vitro assay measuring interferon-gamma release from patients' lymphocytes in the presence of causative drugs for the diagnosis of drug reactions. Methods. Mononuclear cells derived from patients were incubated with and without suspected drugs, and increment of interferon-gamma levels was measured by ELISA. We performed a telephonic survey to evaluate the effect of stopping the drugs incriminated by the assay on cutaneous manifestations. Results. We assessed 272 patients who used 1035 medications. When assessed against the questionnaire data collected at least 6 months after stopping the causative drug, sensitivity was found to be 83.61% and specificity 92.67%. Likelihood ratio for a positive test is 11.40 and for a negative test 0.18. Positive predictive value is 75.37% and negative predictive value is 95.47%. The test was found to perform significantly better in females and in older patients. Conclusions. Interferon-gamma release test is a useful adjunct tool in the diagnosis of cutaneous drug reactions. PMID:22719779

Goldberg, Ilan; Hanson, Meital; Chodick, Gabriel; Shirazi, Idit; Brenner, Sarah

2012-01-01

181

Adverse events during rotary-wing transport of mechanically ventilated patients: a retrospective cohort study  

Microsoft Academic Search

Introduction  Patients triaged to tertiary care centers frequently undergo rotary-wing transport and may be exposed to additional risk for\\u000a adverse events. The incidence of physiologic adverse events and their predisposing factors in mechanically ventilated patients\\u000a undergoing aeromedical transport are unknown.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We performed a retrospective review of flight records of all interfacility, rotary-wing transports to a tertiary care, university\\u000a hospital during 2001

Christopher W Seymour; Jeremy M Kahn; C William Schwab; Barry D Fuchs

2008-01-01

182

Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy  

PubMed Central

Background Oral immunotherapy (OIT) has shown promise in inducing desensitization for food allergy. However, there are safety concerns regarding the frequency and severity of adverse events during food OIT. Objective To evaluate the effect of Ketotifen premedication on adverse reactions during peanut OIT. Methods A randomized single blind placebo controlled pilot study was performed. Peanut OIT was performed using a previously published protocol. Ketotifen was up-titrated to 2 mg twice daily over two weeks (week -2 to 0), followed by a peanut OIT initial escalation day (day 1). Ketotifen was administered from week 0–4 of peanut OIT; reactions to peanut OIT doses were recorded by clinic staff and subject diary. Results Six subjects (median age 10 years, peanut IgE >100kUA/L) were enrolled, 4 randomized to Ketotifen, 2 to placebo. The most common side effect of Ketotifen was fatigue (9% during up-titration). The rate of reaction per peanut OIT dose was lower for subjects on ketotifen (K) compared to placebo (P) during initial escalation on day 1 (K: 22% (8/36) vs. P: 67% (12/18)); week 0–4 build-up doses (K: 75% (3/4) vs. P: 100% (2/2)); and week 0–4 home doses (K: 50% (54/108) vs. P: 82% (27/33)). The rate of gastrointestinal symptoms per peanut OIT dose was also lower for subjects on ketotifen during initial escalation on day 1 (K: 17% (6/36) vs. P: 61% (11/18)); week 0–4 build-up doses (K: 75% (3/4) vs P: 100% (2/2)); and week 0–4 home doses (K: 46% (50/108) vs. P: 82% (27/33)). Conclusions Ketotifen premedication is well tolerated and reduces the rate of gastrointestinal symptoms during peanut OIT. These findings require confirmation in a larger study of Ketotifen premedication used throughout peanut OIT. Trial registration Clinical Trials number: NCT0162515 PMID:25031584

2014-01-01

183

Adverse tissue reaction to corrosion at the neck-stem junction after modular primary total hip arthroplasty.  

PubMed

Complications related to the neck-stem junction of modular stems used for total hip arthroplasty (THA) are generating increasing concern. A 74-year-old male had increasing pain and a cutaneous reaction around the scar 1 year after THA with a modular neck-stem. Imaging revealed osteolysis of the calcar and a pseudo-tumour adjacent to the neck-stem junction. Serum cobalt levels were elevated. Revision surgery to exchange the stem and liner and to resect the pseudo-tumour was performed. Analysis of the stem by scanning electron microscopy and by energy dispersive X-ray and white light interferometry showed fretting corrosion at the neck-stem junction contrasting with minimal changes at the head-neck junction. Thus, despite dry assembly of the neck and stem on the back table at primary THA, full neck-stem contact was not achieved, and the resulting micromotion at the interface led to fretting corrosion. This case highlights the mechanism of fretting corrosion at the neck-stem interface responsible for adverse local tissue reactions. Clinical and radiological follow-up is mandatory in patients with dual-modular stems. PMID:25620029

Gkagkalis, G; Mettraux, P; Omoumi, P; Mischler, S; Rüdiger, H A

2015-02-01

184

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

SciTech Connect

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.

Keating, Christopher, E-mail: C.Keating@sheffield.ac.u [Department of Biomedical Sciences, University of Sheffield, Sheffield (United Kingdom); Martinez, Vicente; Ewart, Lorna [Department of Safety Pharmacology, Safety Assessment UK, AstraZeneca, Alderley Park (United Kingdom); Gibbons, Stephen; Grundy, Luke [Department of Biomedical Sciences, University of Sheffield, Sheffield (United Kingdom); Valentin, Jean-Pierre [Department of Safety Pharmacology, Safety Assessment UK, AstraZeneca, Alderley Park (United Kingdom); Grundy, David [Department of Biomedical Sciences, University of Sheffield, Sheffield (United Kingdom)

2010-06-15

185

Features of portal hypertension are associated with major adverse events in Fontan patients: The VAST study  

PubMed Central

Background Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events. Methods A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001-2011 was performed. The relationship between features of portal hypertension (VAST score ?2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression. Results 73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24 ±11 years, mean interval from Fontan 17 ±6 years) were included in analysis. Features of portal hypertension (VAST score ?2) were present in 26 (36%), and there were 19 major adverse events: death (n=12), transplant (n=6), HCC (n=1). A significant relationship was found between VAST score ?2 and major adverse events (OR=9.8, 95% CI [2.9-32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ?2 remained significant (OR=9.1, 95% CI [1.4-57.6]). Conclusion Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings. PMID:23849105

Elder, Robert W.; McCabe, Nancy M.; Hebson, Camden; Veledar, Emir; Romero, Rene; Ford, Ryan M.; Mahle, William T.; Kogon, Brian E.; Sahu, Anurag; Jokhadar, Maan; McConnell, Michael E.; Book, Wendy M.

2013-01-01

186

Cumulative adverse financial circumstances: associations with patient health status and behaviors.  

PubMed

This article examines associations between cumulative adverse financial circumstances and patient health in a sample of 1,506 urban emergency department (ED) patients. Study participants completed a previously validated Social Health Survey between May and October 2009. Five categories of economic deprivation were studied: food insecurity, housing concerns, employment concerns, cost-related medication nonadherence, and cost barriers to accessing physician care. Logistic regression that adjusted for the effects of demographics (age, gender, race, education) tested the association between the cumulative number of adverse financial circumstances (range: 0 to 5) and patients' health status (self-rated health, stress level, depressed mood) and health behaviors (smoking and substance abuse). Approximately 48 percent of respondents reported one or more financial concern, and 31 percent reported two or more financial concerns. A significant graded relationship was found between the number of adverse financial circumstances and patients' poor/fair self-rated health, depressed mood, high stress, smoking, and illicit drug use. Findings suggest that in today's acute health safety net, patients' concerns related to financial insecurity are very relevant to patient health.This underscores the imperative for hospital-based social workers to design models of routine social health risk screening and system interventions that address patient financial well-being in the ED. PMID:21661302

Bisgaier, Joanna; Rhodes, Karin V

2011-05-01

187

Suspected iron dextran-related adverse drug events in hemodialysis patients  

Microsoft Academic Search

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with

Rafael Fletes; J. Michael Lazarus; John Gage; Glenn M. Chertow

2001-01-01

188

Cost of Opioid-Related Adverse Drug Events in Surgical Patients  

Microsoft Academic Search

Opioids have demonstrated efficacy and often are drugs of choice in the management of postoperative pain. However, their use is often limited by adverse drug events (ADEs). The objective of this study was to determine the ADE rate in adult surgical patients who received opioids and the impact of opioid ADEs on length of stay (LOS), costs, and mortality. A

Gary M Oderda; R. Scott Evans; James Lloyd; Arthur Lipman; Connie Chen; Michael Ashburn; John Burke; Matthew Samore

2003-01-01

189

FREQUENCY, SEVERITY, AND COSTS OF ADVERSE REACTIONS FOLLOWING MASS TREATMENT FOR LYMPHATIC FILARIASIS USING DIETHYLCARBAMAZINE AND ALBENDAZOLE IN LEOGANE, HAITI, 2000  

Microsoft Academic Search

In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcar- bamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%)

STEVEN I. MCLAUGHLIN; JEANNE RADDAY; MARIE CARMEL MICHEL; DAVID G. ADDISS; MICHAEL J. BEACH; PATRICK J. LAMMIE; JOHN LAMMIE; RICHARD RHEINGANS; JACK LAFONTANT

2003-01-01

190

Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)  

Cancer.gov

The purpose of the PRO-CTCAE project is to develop an electronic-based system for patient self-reporting of symptom adverse events (AEs) listed in the CTCAE in an effort to improve the accuracy and precision of grading of this class of AEs. The accurate reporting of AEs that occur to patients on clinical trials is a federal requirement that facilitates evaluation of new therapies.

191

Parental Satisfaction, Efficacy, and Adverse Events in 54 Patients Treated With Cantharidin for Molluscum Contagiosum Infection  

Microsoft Academic Search

Objective To study the efficacy, tolerability, and parental satisfaction of cantharidin in a patient population at a pediatric dermatology referral center.Methods Chart review was completed for 110 patients who presented with molluscum infection and were treated with cantharidin. A total of 54 were available for follow-up by telephone interview regarding adverse effects, parental satisfaction, and overall clearance of the infection.Results

Shelley Cathcart; Jacqueline Coloe; Dean S. Morrell

2009-01-01

192

Determinants of signal selection in a spontaneous reporting system for adverse drug reactions  

PubMed Central

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 this study is to gain insight into factors contributing to the selection and dissemination of possible signals originating from the SRS maintained by the Netherlands Pharmacovigilance Foundation. Methods In a case control design, all signals (n = 42) disseminated to the Medicines Evaluation Board from the second quarter of 1997 until the third quarter of 2000, which could be expressed as a combination of a single ATC code and a single WHO preferred term, were included. For each case, four controls were matched in time. Logistic regression analysis was used to investigate the influence of various factors, such as the fact whether the ADR or drug is new, the strength of the association, the seriousness of the reaction and the documentation of the reports. Results Multivariate analysis showed that the presence of a ‘serious report’ (Odds Ratio 3.8, 95% CI 1.3, 11.0), a WHO ‘critical term’ (OR 4.7, 95% CI 1.8, 13), the ADR being unlabelled (OR 6.1, 95% CI 2.3, 16) and the presence of a disproportionate association (OR 3.5, 95% CI 1.4, 8) were all independently associated with signal selection. The number of reports and the time after marketing of the drug had no influence. Conclusions This study showed that selection of signals is based on both qualitative and quantitative aspects. Knowledge of these factors may improve the efficiency of the underlying signal selection process. PMID:11736867

van Puijenbroek, Eugène P; van Grootheest, Kees; Diemont, Willem L; Leufkens, Hubert G M; Egberts, Antoine C G

2001-01-01

193

Analysis of the adverse reactions induced by natural product-derived drugs  

PubMed Central

Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209

Zeng, Zhi-Ping; Jiang, Jian-Guo

2010-01-01

194

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

PubMed

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. PMID:23130230

Tognetti, Linda; Giorgini, Simonetta; Lotti, Torello

2011-07-01

195

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

PubMed Central

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. PMID:23130230

Tognetti, Linda; Giorgini, Simonetta; Lotti, Torello

2011-01-01

196

The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety  

PubMed Central

The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary healthcare. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications, and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity-related issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety. PMID:24454289

Ekor, Martins

2014-01-01

197

A Systematic Investigation of Computation Models for Predicting Adverse Drug Reactions (ADRs)  

PubMed Central

Background Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. Principal Findings In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Conclusion Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms. PMID:25180585

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

2014-01-01

198

Psychotropic drugs in Bulgaria-frequency and risk of adverse drug reactions.  

PubMed

The aim of the study is to determine the frequency and risk of appearance of adverse drug reactions/ADRs/during the treatment with psychotropic drugs. The first part of the study is an analysis of the use of the psychotropic drugs for one-year period of time in our country, performed by DDD methodology. An attempt is made to equalize the Bulgarian list of the psychotropic drugs with the ATC classification and to estimate the DDD/1000/day. The data for Bulgaria is compared with that of the other countries. The collected data for the psychotropic drug use is divided into 2 groups: Psycholeptics and Psychoanaleptics. It is made an attempt to explain the main differences between them. The number of the standard therapeutic courses/NT/is used for assessment of the frequency and risk of ADRs. The results from the study show that the determined frequency of appearance of ADR for the different drugs is within "rare" and "very rare' for 100,000 inhabitants, according to the WHO terminology. Only for the drug Tardyl (EGIS Pharmaceuticals, Hungary) with INN Aminobarbitalum + Glutethimidum + Promethazini hydrochloridum the frequency is above 1%. That fact makes us to recommend a limitation of the prescription and usage of this drug to the Bulgarian Ministry of Health and to the National Drug Agency. PMID:12064062

Dimitrova, Z; Doma, A; Petkova, V; Getov, I; Verkkunen, E

2002-01-01

199

Adverse reactions associated with studying persons recently exposed to mass urban disaster.  

PubMed

This study assesses the psychological consequences of participation in a mental health study among people recently exposed to the September 11 attacks. Using cross-sectional telephone surveys, we interviewed random samples of English-speaking or Spanish-speaking adults living in New York City during the attacks 1 year after this event. Altogether, 2,368 people completed the surveys, including a random sample of 1,173 respondents who received mental health services after the attacks. Results indicated that 15% of New Yorkers found some of the survey questions stressful, whereas 28% of those who sought treatment found this to be the case. However, less than 2% reported being upset at survey completion, and among these persons, only four people consented to speak to the study's mental health consultant. Although the majority of those expressing adverse reactions had sought postdisaster treatment, even among these subjects, only 3% were still upset at survey completion, and 2% wanted more information about counseling services. In addition, more than 70% of participants expressed positive sentiments about survey participation. Predictive models indicated that respondents who met study criteria for posttraumatic stress disorder, depression, or anxiety were more likely to find questions stressful, with people having posttraumatic stress disorder or depression the most likely to be upset and to consent to psychiatric consultation at completion. We suggest that, with the proper safeguards, research with persons exposed to a resent mass urban disaster generally can be conducted safely and effectively. PMID:15387153

Boscarino, Joseph A; Figley, Charles R; Adams, Richard E; Galea, Sandro; Resnick, Heidi; Fleischman, Alan R; Bucuvalas, Michael; Gold, Joel

2004-08-01

200

Adverse Reactions to Foods and Food Allergy: Development and Reproducibility of a Questionnaire for Clinical Diagnosis  

PubMed Central

Objective. To develop a questionnaire as a screening tool for adverse reactions to foods in children and to assess the technical reproducibility by test-retest. Methods. Reproducibility of the questionnaire was performed by the literature review, preparing the preliminary questionnaire, peer review, pretest, and retest analysis. The study of the test-retest reproducibility was cross-sectional and descriptive. Kappa coefficient was used to study the reproducibility of the questionnaire. The sample consisted of 125 2–4 year-old children from 15 daycare centers in Recife, Brazil, and interviews with parents or caregivers were used to collect data. Results. From the total children, sixty-three were boys (50.4%), forty-six were two years old (36.8%), forty-seven were three years old (37.6%), and thirty-two were four years old (25.6%). Forty caregivers reported that their child had health problems with food. Most frequently reported offending foods were milk, peanuts, shrimp, and chocolate. Nine questions showed a good Kappa index (?0,6). Conclusions. The questionnaire used needs to be resized and reshaped on the basis of the issues with good internal consistency and reproducibility. The use of a validated and reproducible questionnaire in the children represents an important contribution towards assessing an eventual rise in overt food allergy. PMID:24198840

Lyra, Nilza R. S.; Motta, Maria E. F. A.; Rocha, Luiz A. R.; Solé, Dirceu; Peixoto, Décio M.; Rizzo, José A.; Taborda-Barata, Luis; Sarinho, Emanuel S. C.

2013-01-01

201

Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.  

PubMed

Although MedDRA has obvious advantages over previous terminologies for coding adverse drug reactions and discovering potential signals using data mining techniques, its terminological organization constrains users to search terms according to predefined categories. Adding formal definitions to MedDRA would allow retrieval of terms according to a case definition that may correspond to novel categories that are not currently available in the terminology. To achieve semantic reasoning with MedDRA, we have associated formal definitions to MedDRA terms in an OWL file named OntoADR that is the result of our first step for providing an "ontologized" version of MedDRA. MedDRA five-levels original hierarchy was converted into a subsumption tree and formal definitions of MedDRA terms were designed using several methods: mappings to SNOMED-CT, semi-automatic definition algorithms or a fully manual way. This article presents the main steps of OntoADR conception process, its structure and content, and discusses problems and limits raised by this attempt to "ontologize" MedDRA. PMID:24680984

Bousquet, Cédric; Sadou, Éric; Souvignet, Julien; Jaulent, Marie-Christine; Declerck, Gunnar

2014-06-01

202

A Structure-Based Approach for Mapping Adverse Drug Reactions to the Perturbation of Underlying Biological Pathways  

Microsoft Academic Search

Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and

Izhar Wallach; Navdeep Jaitly; Ryan Lilien; Ulrich Zanger

2010-01-01

203

Radiogenomics: Using Genetics to Identify Cancer Patients at Risk for Development of Adverse Effects Following Radiotherapy  

PubMed Central

Normal tissue adverse effects following radiotherapy are common and significantly affect quality of life. These effects cannot be accounted for by dosimetric, treatment or demographic factors alone, and evidence suggests that common genetic variants are associated with radiotherapy adverse effects. The field of radiogenomics has evolved to identify such genetic risk factors. Radiogenomics has two goals: 1) develop an assay to predict which cancer patients are most likely to develop radiation injuries resulting from radiotherapy, and 2) obtain information about the molecular pathways responsible for radiation-induced normal tissue toxicities. This review summarizes the history of the field and current research. PMID:24441285

Kerns, Sarah L; Ostrer, Harry; Rosenstein, Barry S

2013-01-01

204

Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation  

PubMed Central

Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

2013-01-01

205

Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions.  

PubMed

High cholesterol levels are an established risk factor for cardiovascular disease (CVD), the world's leading cause of death. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) are prescribed to lower serum cholesterol levels and reduce the risk of CVD. Despite the success of statins, many patients abandon treatment owing to neuromuscular adverse drug reactions (ADRs). Genome-wide association studies have identified the single-nucleotide polymorphism (SNP) rs4149056 in the SLCO1B1 gene as being associated with an increased risk for statin-induced ADRs. By studying slow-channel syndrome transgenic mouse models, we determined that statins trigger ADRs in mice expressing the mutant allele of the rs137852808 SNP in the nicotinic acetylcholine receptor (nAChR) ?-subunit gene CHRNA1. Mice expressing this allele show a remarkable contamination of end-plates with caveolin-1 and develop early signs of neuromuscular degeneration upon statin treatment. This study demonstrates that genes coding for nAChR subunits may contain variants associated with statin-induced ADRs. PMID:22688219

Grajales-Reyes, G E; Báez-Pagán, C A; Zhu, H; Grajales-Reyes, J G; Delgado-Vélez, M; García-Beltrán, W F; Luciano, C A; Quesada, O; Ramírez, R; Gómez, C M; Lasalde-Dominicci, J A

2013-08-01

206

Adverse reactions to suxamethonium and other muscle relaxants under general anesthesia  

SciTech Connect

The mechanisms of anaphylactic reactions to muscle relaxants under general anesthesia are not completely understood. Extending an earlier study, we report 41 cases of anaphylactic shock investigated by intradermal skin tests with muscle relaxants (suxamethonium, pancuronium, gallamine, nortoxiferine), in vitro leukocyte histamine release, and Prausnitz-Kuestner tests. Intradermal tests were significantly positive at concentrations ranging from 10 to 10(5) times less than those in controls. Reproducibility tested for suxamethonium at a 1-year interval in five patients was good. Histamine release induced by muscle relaxants in Tris-albumin-Ca++-Mg++ buffer showed positive results in 8/25 instances and was inhibited by antigen excess in seven cases. Addition of 50% deuterium oxide (D2O) caused significant increase of histamine release in positive cases and induced release in all five negative cases studied. Muscle relaxant-induced histamine release was inhibited by in vitro anti-IgE leukocyte desensitization. The mean maximal histamine release dropped from 58.2% +/- 9.7 to 5.8% +/- 2 (p less than 0.01). Similarly, leukocyte desensitization also inhibited histamine release induced by anti-IgE but not by formyl-L-methionyl-L-leucyl-L-phenylalanine or poly-L-arginine. Prausnitz-Kuestner tests were positive in five out of 21 cases studied and became negative after heat inactivation. These results confirm the usefulness of intradermal skin tests in diagnosis of patients' reaction to muscle relaxants and suggest an IgE-mediated rather than an idiosyncratic mechanism.

Vervloet, D.; Nizankowska, E.; Arnaud, A.; Senft, M.; Alazia, M.; Charpin, J.

1983-06-01

207

A Prediction Model for Adverse Outcome in Hospitalized Patients With Diabetes  

PubMed Central

OBJECTIVE There are no formal prognostic models predicting adverse outcomes (excessive length of stay or mortality) in hospitalized patients with diabetes. In this study, we aimed to develop a prediction model that will help identify patients with diabetes who are most likely to have an adverse event during their hospital stay. RESEARCH DESIGN AND METHODS Analysis was based on 25,118 admissions with diabetes to University Hospital Birmingham, Birmingham, U.K., over 4 years (2007–2010). Adverse events are defined as either excessive length of stay or inpatient mortality. Key predictors were variables that are often available in the first 72 h of admission and included demographic characteristics, clinical pathological test results, and use of insulin. Models were constructed using logistic regression, discrimination and calibration was assessed, and internal validation was carried out. RESULTS The model performed well with an area under the curve (AUC) of 0.802 with only a mild reduction being noted in the internal validation (AUC 0.798). At a cutoff value of 25% probability of having an adverse outcome the sensitivity was 76%, specificity was 70%, and the positive predictive value was 49%. If it is used for a case-finding approach limiting to noncritical care settings, then at the same cutoff value, two-thirds (sensitivity 69%) of the admissions with adverse outcomes could potentially be identified. CONCLUSIONS Once externally validated, we suggest that our model will be a useful tool for identifying diabetic patients who are at risk for poor outcomes when admitted to hospital. PMID:24026555

Nirantharakumar, Krishnarajah; Hemming, Karla; Narendran, Parth; Marshall, Tom; Coleman, Jamie J.

2013-01-01

208

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

PubMed Central

Background Reporting of adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. In the European Union, more countries have allowed consumers to report ADRs directly to the regulatory agencies. The aim of this study was to characterize ADRs reported by European consumer for nervous system medications. Methods ADRs reported by consumers for nervous system medications (ATC group N) from 2007 to 2011 and located in the European ADR database, EudraVigilance, were analysed. Data were categorized with respect to age and sex, category and seriousness of reported ADRs and medications. The unit of analysis was one ADR. Results We located 4766 ADRs reported for nervous system medications, and one half of these were serious including 19 deaths. Less than 5% of ADRs were reported in children. Totally, 58% of ADRs were reported for women, 42% for men. The majority of reported ADRs were of the types “nervous system disorders” (18% of total ADRs) followed by “psychiatric disorders” (18% of total ADRs) and “general disorders” (15% of total ADRs) which also were the system organ classes in which the majority of serious ADRs were found. ADR reports encompassed medicines from the therapeutic groups: antiepileptics (ATC group N03) (36% of total ADRs), parasympathomimetics (ATC group N07) (22% of total ADRs) and antidepressants ATC group N06A (9% of total ADRs). Antiepileptics were the therapeutic group with the highest share of serious ADRs (60%) followed by antidepressants (15%). Many serious ADRs were reported for pregabalin and varenicline. Conclusions The majority of ADRs from nervous system mediations reported by consumers that were identified from the EudraVigilance database were serious. The value of consumer reports in pharmacovigilance still remains unclarified. PMID:23763896

2013-01-01

209

Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients.  

PubMed

In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations. PMID:24759150

Kuragano, Takahiro; Matsumura, Osamu; Matsuda, Akihiko; Hara, Taiga; Kiyomoto, Hideyasu; Murata, Toshiaki; Kitamura, Kenichiro; Fujimoto, Shouichi; Hase, Hiroki; Joki, Nobuhiko; Fukatsu, Atushi; Inoue, Toru; Itakura, Ikuhiro; Nakanishi, Takeshi

2014-10-01

210

Oral bisphosphonate adverse effects in 849 patients with metabolic bone diseases  

Microsoft Academic Search

OBjeCTive: Bisphosphonates are potent antiresorptive agents used for a spectrum of metabolic bone diseases. The aim of this study was to compare the adverse effects (Aes) of alendronate, etidronate and risedronate prescribed in a non-selected population, attending a single insti - tution on an outpatient basis. DeSign: 849 patients receiving either alendronate (n=710), etidronate (n=181) or risedronate (n=130) were studied

Athanasios D. Anastasilakis; Dimitrios G. Goulis; Marina Kita; Avraam Avramidis

2007-01-01

211

ATM SEQUENCE VARIANTS ARE PREDICTIVE OF ADVERSE RADIOTHERAPY RESPONSE AMONG PATIENTS TREATED FOR PROSTATE CANCER  

Microsoft Academic Search

Purpose: To examine whether the presence of sequence variants in the ATM (mutated in ataxia-telangiectasia) gene is predictive for the development of radiation-induced adverse responses resulting from 125I prostate brachytherapy for early-stage prostate cancer. Materials and Methods: Thirty-seven patients with a minimum of 1-year follow-up who underwent 125I prostate brachytherapy of early-stage prostate cancer were screened for DNA sequence variations

JAMIE A. CESARETTI; RICHARD G. STOCK; STEVEN LEHRER; DAVID A. ATENCIO; JONINE L. BERNSTEIN; NELSON N. STONE; SYLVAN WALLENSTEIN; SHERYL GREEN; KAREN LOEB; MARISA KOLLMEIER; MICHAEL SMITH; BARRY S. ROSENSTEIN

2005-01-01

212

The effect of patient sex on the incidence of early adverse effects in a population of elderly patients.  

PubMed

Patient sex is known to influence the response to general and regional anaesthesia and recovery after surgery. However, most studies come from analyses carried out on middle-aged patients. As most of the patients admitted to the post-anaesthesia recovery room in our institution are elderly, we took the opportunity to investigate the association between sex and incidence of early adverse events in this older population of patients after major surgery. Consecutive patients undergoing general, orthopaedic, urological and gynaecological surgery, admitted to the recovery room of our institution over a 15-month period, were retrospectively studied. The following adverse events were considered in the analysis: shivering, postoperative nausea and vomiting, hypotension and hypertensive responses, new arrhythmias requiring treatment, acute respiratory failure and desaturation. A total of 1347 patients (mean age 73.3±15.1 years, 61.4% women) were included. Women showed a higher incidence of shivering (relative difference +48%, P=0.0003), postoperative nausea and vomiting (+91%, P<0.0001), hypotension (+32%, P=0.044) and desaturation (+60%, P=0.0030) than men. The incidence of hypertensive response, arrhythmias and acute respiratory failure were not statistically significantly different. The findings of this exploratory study suggest that women have a higher risk of early postoperative adverse events even in a more elderly population. PMID:24967759

Conti, D; Ballo, P; Boccalini, R; Boccherini, A; Cantini, S; Venni, A; Pezzati, S; Gori, S; Franconi, F; Zuppiroli, A; Pedullà, A

2014-07-01

213

Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study  

PubMed Central

Background Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes. Methods Consecutive patients presenting with ALTR from two major hip implant classes (N?=?54 patients with Dual-Modular Neck implant; N?=?14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry. Results Length of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p?reaction in both implants, with increased ratios of perivascular T-cell relative to B-cell markers in the DMN relative to the MoM group (p?=?0.032). Conclusion Our results demonstrate that both implant classes display common features of neo-synovial proliferation and necrosis with a CD4 and GATA-3 rich inflammatory infiltrate. Qualitative differences in corrosion product appearance, macrophage morphology, and lymphocyte distributions were seen between the two implant types. Our data suggests that ALTR represents a histological spectrum with implant-based features. PMID:25242891

2014-01-01

214

Photoselective vaporization of the prostate: outcomes and adverse events of 220 consecutive patients  

NASA Astrophysics Data System (ADS)

Purpose: To evaluate the short term outcomes of 220 consecutive patients who underwent the 532 nm KTP photoselective vaporization of the prostate (PVP) procedure and to evaluate and categorize the complications of the procedure. Materials and Methods: A total of 220 patients with symptomatic benign prostatic obstruction were treated with KTP photoselective vaporization of the prostate. Evaluation measures included the AUA Symptom Score (AUASS)/Quality of Life Score (QOL), peak urinary flow rate (Qmax), post void residual urine (PVR) and adverse events. Results: Symptoms were evaluated at 3 months and adverse events at 1 and 3 months. 181 patients returned for their 1 month visit and 152 returned for their 3 month visit. The American Urological Association Symptom Score (AUASS) decreased from 21.8 to 6.7. The Quality of Life Score (QOL) decreased from 3.8 to 0.7. The peak urinary flow rate (Qmax) increased from 10.7 cc/sec to 22.7 cc/sec. And the post void residual urine (PVR) decreased from 262 cc to 105 cc. Most common adverse events lasting more than 10 days were mild hematuria in 45%, dysuria in 32%, and urgency/frequency in31%. Conclusion: These results confirm that photoselective vaporization of the prostate (PVP) is a safe and effective therapy for benign prostatic obstruction. However, there is frequent, but mild, hematuria and irritative voiding symptoms during the early postoperative period.

Robson, C.; Mueller, E. J.

2010-02-01

215

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.  

PubMed

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the ?(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects. PMID:22806578

Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

216

Seriousness, preventability, and burden impact of reported adverse drug reactions in Lombardy emergency departments: a retrospective 2-year characterization  

PubMed Central

Objective The purpose of this study was to determine the prevalence of adverse drug reactions (ADRs) reported in emergency departments (EDs) and carry out a thorough characterization of these to assess preventability, seriousness that required hospitalization, subsequent 30-day mortality, and economic burden. Methods This was a retrospective cohort study of data from an active pharmacovigilance project at 32 EDs in the Lombardy region collected between January 1, 2010 and December 31, 2011. Demographic, clinical, and pharmacological data on patients admitted to EDs were collected by trained and qualified monitors, and deterministic record linkage was performed to estimate hospitalizations. Pharmacoeconomic analyses were based on Diagnosis-Related Group reimbursement. Results 8,862 ADRs collected with an overall prevalence rate of 3.5 per 1,000 visits. Of all ADRs, 42% were probably/definitely preventable and 46.4% were serious, 15% required hospitalization, and 1.5% resulted in death. The System Organ Classes most frequently associated with ADRs were: skin and subcutaneous tissue, gastrointestinal, respiratory thoracic and mediastinal, and nervous system disorders. The most common Anatomical Therapeutic Chemical classes involved in admissions were J (anti-infectives and immunomodulating agents), B (blood and blood-forming organs), and N (nervous system). Older age, yellow and red triage, higher number of concomitantly taken drugs, and previous attendance in ED for the same ADR were significantly associated with an increased risk of hospitalization. The total cost associated with ADR management was €5,184,270, with a mean cost per patient of €585. Fifty-eight percent of the economic burden was defined as probably/definitely preventable. Conclusion ADRs are a serious health/economic issue in EDs. This assessment provides a thorough estimation of their seriousness, preventability, and burden impact in a large population from a representative European region. PMID:25506231

Perrone, Valentina; Conti, Valentino; Venegoni, Mauro; Scotto, Stefania; Degli Esposti, Luca; Sangiorgi, Diego; Prestini, Lucia; Radice, Sonia; Clementi, Emilio; Vighi, Giuseppe

2014-01-01

217

The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis  

PubMed Central

OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-? therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-? blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-? blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

2013-01-01

218

Identifying and managing an adverse food reaction in a polar bear (Ursus maritimus) by an elimination diet trial.  

PubMed

A 16-yr-old polar bear (Ursus maritimus) presented with severe diarrhea shortly following transfer to the North Carolina Zoological Park. Multiple diagnostic procedures were performed over several months and the cause of the chronic diarrhea was inconclusive. Histologically, colonic mucosal biopsies were consistent with severe chronic eosinophilic and lymphoplasmacytic colitis with no evidence of etiologic agents present. A dietary elimination trial was conducted and an adverse food reaction to the dog chow in the diet was confirmed. PMID:25000711

Monson, Sara; Minter, Larry J; Krouse, Marissa; De Voe, Ryan S

2014-06-01

219

ADVERSE DRUG REACTIONS TO ANTIBIOTICS OBSERVED IN TWO PULMONOLOGY DIVISIONS OF CATANZARO, ITALY: A SIX-YEAR RETROSPECTIVE STUDY  

Microsoft Academic Search

We retrospectively analysed adverse drug reactions (ADRs) associated with antibiotic therapy and reported over a 6-year period, from January 1995 to December 2000, in clinical notes of two Pulmonology Units of “Mater Domini” University Hospital and “Pugliese-Ciaccio” Hospital, both located in Catanzaro, Italy.Antibiotics were responsible for 92 (44.9%) out of 205 episodes of ADRs. In particular, 22 episodes (23.9%) were

L. GALLELLI; G. FERRERI; M. COLOSIMO; D. PIRRITANO; L. GUADAGNINO; G. PELAIA; R. MASELLI; G. B. DE SARRO

2002-01-01

220

In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for Pathophysiology.  

PubMed

Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug's known pharmacology and have no clear dose-effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible without the aid of a reliable diagnostic test. Drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential ham to patients; however, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here. PMID:25199801

Elzagallaai, Abdelbaset A; Rieder, Michael J

2014-09-01

221

[Medication adverse events: Impact of pharmaceutical consultations during the hospitalization of patients].  

PubMed

The medication iatrogenic events are responsible for nearly one iatrogenic event in five. The main purpose of this prospective multicenter study is to determine the effect of pharmaceutical consultations on the occurrence of medication adverse events during hospitalization (MAE). The other objectives are to study the impact of age, of the number of medications and pharmaceutical consultations on the risk of MAE. The pharmaceutical consultation is associated to a complete reassessment done by both a physician and a pharmacist for the home medication, the hospital treatment (3days after admission), the treatment during chemotherapy, and/or, the treatment when the patient goes back home. All MAE are subject to an advice for the patient, additional clinical-biological monitoring and/or prescription changes. Among the 318 patients, 217 (68%) had 1 or more clinically important MAE (89% drug-drug interaction, 8% dosing error, 2% indication error, 1% risk behavior). The patients have had 1121 pharmaceutical consultations (3.2±1.4/patient). Thus, the pharmaceutical consultations divided by 2.34 the risk of MAE (unadjusted incidence ratio, P?0.05). Each consultation decreased by 24% the risk of MAE. Moreover, adding one medication increases from 14 to 30% as a risk of MAE on the population. Pharmaceutical consultations during the hospital stay could reduce significantly the number of medication adverse effects. PMID:25438655

Santucci, R; Levêque, D; Herbrecht, R; Fischbach, M; Gérout, A C; Untereiner, C; Bouayad-Agha, K; Couturier, F

2014-11-01

222

Adverse Local Tissue Reaction Arising from Corrosion at the Femoral Neck-Body Junction in a Dual-Taper Stem with a Cobalt-Chromium Modular Neck  

PubMed Central

Background: Femoral stems with dual-taper modularity were introduced to allow additional options for hip-center restoration independent of femoral fixation in total hip arthroplasty. Despite the increasing availability and use of these femoral stems, concerns exist about potential complications arising from the modular neck-body junction. Methods: This was a multicenter retrospective case series of twelve hips (eleven patients) with adverse local tissue reactions secondary to corrosion at the modular neck-body junction. The cohort included eight women and three men who together had an average age of 60.1 years (range, forty-three to seventy-seven years); all hips were implanted with a titanium-alloy stem and cobalt-chromium-alloy neck. Patients presented with new-onset and increasing pain at a mean of 7.9 months (range, five to thirteen months) following total hip arthroplasty. After serum metal-ion studies and metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) revealed abnormal results, the patients underwent hip revision at a mean of 15.2 months (range, ten to twenty-three months). Tissue specimens were examined by a single histopathologist, and the retrieved implants were studied with use of light and scanning electron microscopy. Results: Serum metal levels demonstrated greater elevation of cobalt (mean, 6.0 ng/mL) than chromium (mean, 0.6 ng/mL) or titanium (mean, 3.4 ng/mL). MRI with use of MARS demonstrated adverse tissue reactions in eight of nine patients in which it was performed. All hips showed large soft-tissue masses and surrounding tissue damage with visible corrosion at the modular femoral neck-body junction. Available histology demonstrated large areas of tissue necrosis in seven of ten cases, while remaining viable capsular tissue showed a dense lymphocytic infiltrate. Microscopic analysis was consistent with fretting and crevice corrosion at the modular neck-body interface. Conclusions: Corrosion at the modular neck-body junction in dual-tapered stems with a modular cobalt-chromium-alloy femoral neck can lead to release of metal ions and debris resulting in local soft-tissue destruction. Adverse local tissue reaction should be considered as a potential cause for new-onset pain in patients with these components, and early revision should be considered given the potentially destructive nature of these reactions. A workup including serologic studies (erythrocyte sedimentation rate and C-reactive protein), serum metal levels, and MARS MRI can be helpful in establishing this diagnosis. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:23677352

Cooper, H. John; Urban, Robert M.; Wixson, Richard L.; Meneghini, R. Michael; Jacobs, Joshua J.

2013-01-01

223

Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment.  

PubMed

Adverse drug reactions account for between 2 to 5% of all hospital admissions and can prevent the administration of an otherwise effective therapeutic agent. Hypersensitivity or immune-mediated reactions, although less common, tend to be proportionately more serious. There is convincing evidence to implicate the immune system in the pathogenesis of hypersensitivity reactions. Our understanding of the way in which the immune system recognises drugs is based on the hapten hypothesis; the onset of hypersensitivity involves drug bioactivation, covalent binding to proteins, followed by uptake, antigen processing and T cell proliferation. Central to this hypothesis is the critical role of drug metabolism, with the balance between metabolic bioactivation and detoxification being one important component of individual susceptibility. The purpose of this review is to classify drug hypersensitivity reactions in terms of their clinical presentation, and also to consider recent advances in our understanding of the chemical, biochemical and, in particular, cellular immunological mechanisms of hypersensitivity. The following topics are reviewed: (i) drug disposition and cellular metabolism; (ii) mechanisms of antigen processing and presentation; (iii) the role of cytokines and co-stimulatory molecules in the induction and maintenance of a polarised immune response; and (iv) the application of the hapten hypothesis, danger hypothesis and serial triggering model to drug hypersensitivity. A greater understanding of the mechanism(s) of hypersensitivity may identify novel therapeutic strategies and help to combat one of the more severe forms of adverse reactions to drugs. PMID:11144658

Naisbitt, D J; Gordon, S F; Pirmohamed, M; Park, B K

2000-12-01

224

Evaluating Predictive Pharmacogenetic Signatures of Adverse Events in Colorectal Cancer Patients Treated with Fluoropyrimidines  

PubMed Central

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers. PMID:24167597

Skinner, Jane; Keane, Melanie; Chu, Gavin S.; Turner, Richard; Epurescu, Daniel; Barrett, Ann; Willis, Gavin

2013-01-01

225

Role of Erythrocytes as a Reservoir for Ribavirin and Relationship with Adverse Reactions in the Early Phase of Interferon Combination Therapy for Chronic Hepatitis C Virus Infections  

PubMed Central

We investigated the relationship between serum ribavirin concentrations and clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese patients with chronic hepatitis C virus infections treated with a 6-month course of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800 mg/day) combination therapy. This randomized trial showed that the saturation of ribavirin uptake after taking ribavirin capsules does not occur within a dose range of 600 to 800 mg/day, which is a standard dosage used clinically in Japan. Serum ribavirin concentrations and clearance did not correlate with sustained virological response rates. Fourteen patients discontinued therapy because of adverse reactions, and sustained virological response rates were significantly reduced by discontinuation of therapy, while dose reduction of ribavirin did not alter the therapeutic effects. Ribavirin concentrations after 1 week and ribavirin clearance were significantly correlated with discontinuation of ribavirin; however, a multiple-regression analysis revealed that only hemoglobin concentration, but not ribavirin clearance, was a significant factor for discontinuation of therapy (odds ratio, 0.514; 95% confidence interval, 0.311 to 0.85; P = 0.0095). It appears that peripheral erythrocytes may act as a reservoir for ribavirin and regulate serum ribavirin levels in the very early phase of treatment. PMID:17021083

Saito, Hidetsugu; Tada, Shinichiro; Ebinuma, Hirotoshi; Ishii, Hiromasa; Kashiwazaki, Kazuo; Takahashi, Masahiko; Tsukada, Nobuhiro; Nishida, Jiro; Tanaka, Shin; Shiozaki, Hiroshi; Hibi, Toshifumi

2006-01-01

226

Patient Suicide: A Survey of Therapists' Reactions  

ERIC Educational Resources Information Center

A substantial proportion of therapists will at some point in their professional life experience the loss of a patient to suicide. Our aims were to assess how therapists react to patient's suicide over time and which factors contribute to the reaction. One third of the therapists, mostly women, suffer from severe distress. The impact is not…

Wurst, Friedrich Martin; Mueller, Sandra; Petitjean, Sylvie; Euler, Sebastian; Thon, Natasha; Wiesbeck, Gerhard; Wolfersdorf, Manfred

2010-01-01

227

Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study  

PubMed Central

Background: Underreporting of spontaneous adverse drug reaction (ADR) is a threat to pharmacovigilance. Various factors related with the knowledge and attitudes are responsible for underreporting of ADRs. Aims: The study was aimed at investigating the knowledge and attitudes of doctors to ADR reporting. Materials and Methods: It was a questionnaire-based cross-sectional study. One hundred and eight questionnaires were administered to doctors working in a teaching hospital with an ADR monitoring center. Statistical Analysis Used: The descriptive statistics were used for responses to evaluate the knowledge and attitudes toward ADR reporting. Pearson's Chi-square test was used to observe the association of knowledge and attitude with experience and position. Results: The response rate was 62.9%. Spontaneous reporting rate was found to be 19.1%. The major factors found to be responsible for underreporting of ADR include inadequate risk perception about newly marketed drugs (77.9%), fear factor (73.5%), diffidence (67.7%), lack of clarity of information on ADR form about reporting (52.9%), lethargy (42.7%), insufficient training to identify ADRs (41.2%), lack of awareness about existence of pharmacovigilance program (30.9%) and ADR monitoring center in the institute (19.1%), and inadequate risk perception of over-the-counter (OTC) product (20.6%) and herbal medicines (13.2%). Experience and position did not influence the knowledge and attitudes of doctors. Conclusion: The deficiencies in knowledge and attitudes require urgent attention not only to improve the rate of spontaneous reporting, but also for enhanced safety of the patients and society at large. PMID:23633861

Khan, Sarfaraz Alam; Goyal, Chhaya; Chandel, Nitibhushansingh; Rafi, Mohammed

2013-01-01

228

Potentially inappropriate prescribing and adverse health outcomes in community dwelling older patients  

PubMed Central

Aims This study aimed to determine the association between potentially inappropriate prescribing (PIP) and health related outcomes [adverse drug events (ADEs), health related quality of life (HRQOL) and hospital accident and emergency (A&E) visits] in older community dwelling patients. Methods A retrospective cohort study of 931 community dwelling patients aged ?70 years in 15 general practices in Ireland in 2010. PIP was defined by the Screening Tool of Older Person's Prescriptions (STOPP). ADEs were measured by patient self-report and medical record for the previous 6 months and reviewed by two independent clinicians. HRQOL was measured by the EQ-5D. A&E visits were measured by patients’ medical records and self-report. Multilevel logistic, linear and Poisson regression examined how ADEs, HRQOL and A&E visits varied by PIP after adjusting for patient and practice level covariates: socioeconomic status, co-morbidity, number of drug classes and adherence. Results The overall prevalence of PIP was 42% (n = 377). Patients with ?2 PIP indicators were twice as likely to have an ADE (adjusted OR 2.21; 95% CI 1.02, 4.83, P < 0.05), have a significantly lower mean HRQOL utility (adjusted coefficient ?0.09, SE 0.02, P < 0.001) and nearly a two-fold increased risk in the expected rate of A&E visits (adjusted IRR 1.85; 95% CI 1.32, 2.58, P < 0.001). The number of drug classes and adherence were also significantly associated with these same adverse health outcomes. Conclusions Reducing PIP in primary care may help lower the burden of ADEs, its associated health care use and costs and enhance quality of life in older patients. PMID:23711082

Cahir, Caitriona; Bennett, Kathleen; Teljeur, Conor; Fahey, Tom

2014-01-01

229

Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant Patients Treated with mTOR Inhibitors  

PubMed Central

The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications. PMID:24151517

Zaza, Gianluigi; Tomei, Paola; Ria, Paolo; Granata, Simona; Boschiero, Luigino; Lupo, Antonio

2013-01-01

230

Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.  

PubMed

The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications. PMID:24151517

Zaza, Gianluigi; Tomei, Paola; Ria, Paolo; Granata, Simona; Boschiero, Luigino; Lupo, Antonio

2013-01-01

231

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

PubMed

Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan. PMID:23243990

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

2012-01-01

232

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

PubMed Central

Background The new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication. Methods All reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN’s Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments. Results Three main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them attempt to discontinue their antidepressant treatment on their own. Conclusions The present study indicates that free text comments as often contained in case reports directly submitted by patients can be of value in pharmacovigilance and provide important information on how a drug may affect the person using it and influence his or her personal life. PMID:23259410

2012-01-01

233

Study of adverse whole blood donor reactions in normal healthy blood donors: experience of tertiary health care centre in jammu region.  

PubMed

Whole blood donation is generally a safe procedure, but sometimes adverse reactions of varying severity may occur during or at completion of blood donation process. The aim of the present study was to estimate the frequency and type of adverse events during blood donation. This retrospective study conducted from November 2011 to December 2012 at Department of Blood Transfusion Medicine GMC Jammu. All whole blood donations at our Department was analyzed. All adverse events occurring during or at end of donation were noted using standardized format. Overall 108 adverse events were reported in relation to 29,524 donations, resulting in overall adverse event rate of 0.365 %. Presyncopal reactions in other words vasovagal reactions of mild intensity, were the most commonly observed adverse reactions and accounted for approximately 58/108 (53.70 %) of all adverse reactions noted. Only 0.365 % of blood donations were complicated by adverse events and most of these events were presyncopal symptoms. Our study reinforces that blood donation is a very safe procedure which could be made even more event free by following certain friendly, reassuring and tactful practices. PMID:25548461

Dogra, Ashu; Sidhu, Meena; Dogra, Mitu; Raina, Tilak Raj

2015-03-01

234

A systematic review of the prevalence and risk factors for adverse drug reactions in the elderly in the acute care setting  

PubMed Central

Adverse drug reactions (ADRs) are an important health issue. While prevalence and risk factors associated with ADRs in the general adult population have been well documented, much less is known about ADRs in the elderly population. The aim of this study was to review the published literature to estimate the prevalence of ADRs in the elderly in the acute care setting and identify factors associated with an increased risk of an ADR in the elderly. A systematic review of studies published between 2003 and 2013 was conducted in the Cochrane Database of Systematic Reviews, EMBASE, Google Scholar and MEDLINE. Key search terms included: “adverse drug reactions”, “adverse effects”, “elderly patients and hospital admission”, “drug therapy”, “drug adverse effects”, “drug related”, “aged”, “older patients”, “geriatric”, “hospitalization”, and “emergency admissions”. For inclusion in the review, studies had to focus on ADRs in the elderly and had to include an explicit definition of what was considered an ADR and/or an explicit assessment of causality, and a clear description of the method used for ADR identification, and had to describe factors associated with an increased risk of an ADR. Fourteen hospital-based observational studies exploring ADRs in the elderly in the acute care setting were eligible for inclusion in this review. The mean prevalence of ADRs in the elderly in the studies included in this review was 11.0% (95% confidence interval [CI]: 5.1%–16.8%). The median prevalence of ADRs leading to hospitalization was 10.0% (95% CI: 7.2%–12.8%), while the prevalence of ADRs occurring during hospitalization was 11.5% (95% CI: 0%–27.7%). There was wide variation in the overall ADR prevalence, from 5.8% to 46.3%. Female sex, increased comorbid complexity, and increased number of medications were all significantly associated with an increased risk of an ADR. Retrospective studies and those relying on identification by the usual treating team reported lower prevalence rates. From this review, we can conclude that ADRs constitute a significant health issue for the elderly in the acute care setting. While there was wide variation in the prevalence of ADRs in the elderly, based on the findings of this study, at least one in ten elderly patients will experience an ADR leading to or during their hospital stay. Older female patients and those with multiple comorbidities and medications appear to be at the highest risk of an ADR in the acute care setting. PMID:25489239

Alhawassi, Tariq M; Krass, Ines; Bajorek, Beata V; Pont, Lisa G

2014-01-01

235

Role of inflammation and platelet activation in the adverse cardiovascular outcomes of patients undergoing surgery for critical limb ischaemia   

E-print Network

Increased platelet activation and inflammation play a key role in atherothrombosis. Patients with peripheral arterial disease are at increased risk of adverse cardiovascular events, particularly at the time of surgery. ...

Burdess, Anne

2014-07-05

236

Managing adverse effects of glaucoma medications  

PubMed Central

Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, ?-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

Inoue, Kenji

2014-01-01

237

Nonalcoholic fatty liver disease (NAFLD): a new risk factor for adverse cardiovascular events in dialysis patients.  

PubMed

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Today it is believed that NAFLD is a hepatic manifestation of metabolic syndrome, and thus it is closely related to the cardiovascular morbidity and mortality. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in patients with end-stage-renal disease (ESRD). NAFLD and ESRD share some important cardiometabolic risk factors and possible common pathophyisiological mechanisms, and are linked to an increased risk of incident CVD events. We hypothesize that the coexistence of these two conditions could lead to much faster progress of the aterogenic process. Furthermore, patients with ESRD who suffer from NAFLD have a much higher risk for the development of adverse CVD events. Given the high prevalence of NAFLD, and its tight association with other manifestations of the metabolic syndrome and thus cardiovascular complications, it is important to recognize and aggressively treat this condition in ESRD patients. To evaluate this hypothesis, we propose the use of non-invasive methods such as transient elastography (TE) (Fibroscan-CAP) for the detection and quantification of liver steatosis and fibrosis, as well as an abdominal ultrasound for detecting liver steatosis. We focus on their correlation with carotid intima-media thickness (IMT) and plaque as surrogate measures of increased cardiovascular risk in HD patients in order to investigate the association of NAFLD and increase risk of adverse CVD events. This evaluation will prove useful in assessing the risk in HD patients with NAFLD for increase CVD mortality. PMID:24365277

Mikolasevic, I; Racki, S; Zaputovic, L; Lukenda, V; Milic, S; Orlic, L

2014-02-01

238

Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel.  

PubMed Central

OBJECTIVE: To compare the adverse effects, particularly generalized aching, of a trivalent, inactivated whole-virion vaccine (WVV) and split-virion vaccine (SVV) for influenza in hospital personnel. DESIGN: Recipient-blinded study; first-time vaccinees were randomly assigned to receive either of the vaccines from one manufacturer in the 1989-90 influenza season. Subjects were asked to complete a symptom questionnaire during the 48 hours after immunization. SETTING: Annual influenza program for staff of a tertiary care children's hospital. PARTICIPANTS: Volunteers were sought among approximately 2200 members of the hospital staff. Of the 358 vaccinated for the first time, 333 (93%) returned the questionnaire. RESULTS: During the 48 hours after vaccination 13% of the SVV recipients reported generalized aching, as compared with 26% of the WVV recipients (p less than 0.01). Also, the SVV group reported fewer visible local reactions and more transient arm soreness, but the actual differences between the two groups were small. The occurrence of mild symptoms was equally common in the two groups (local reactions in at least 70% of cases, systemic reactions in at least 33%). In each group 1% of the subjects reported missing work because of the vaccination. CONCLUSIONS: The use of SVV reduces the rate of the most objectionable of the common adverse effects of influenza vaccination. Therefore, as with children, it might be more acceptable to health care workers than the current use of WVV. PMID:2070311

al-Mazrou, A; Scheifele, D W; Soong, T; Bjornson, G

1991-01-01

239

Postoperative Adverse Outcomes in Intellectually Disabled Surgical Patients: A Nationwide Population-Based Study  

PubMed Central

Background Intellectually disabled patients have various comorbidities, but their risks of adverse surgical outcomes have not been examined. This study assesses pre-existing comorbidities, adjusted risks of postoperative major morbidities and mortality in intellectually disabled surgical patients. Methods A nationwide population-based study was conducted in patients who underwent inpatient major surgery in Taiwan between 2004 and 2007. Four controls for each patient were randomly selected from the National Health Insurance Research Database. Preoperative major comorbidities, postoperative major complications and 30-day in-hospital mortality were compared between patients with and without intellectual disability. Use of medical services also was analyzed. Adjusted odds ratios using multivariate logistic regression analyses with 95% confidence intervals were applied to verify intellectual disability's impact. Results Controls were compared with 3983 surgical patients with intellectual disability. Risks for postoperative major complications were increased in patients with intellectual disability, including acute renal failure (odds ratio 3.81, 95% confidence interval 2.28 to 6.37), pneumonia (odds ratio 2.01, 1.61 to 2.49), postoperative bleeding (odds ratio 1.35, 1.09 to 1.68) and septicemia (odds ratio 2.43, 1.85 to 3.21) without significant differences in overall mortality. Disability severity was positively correlated with postoperative septicemia risk. Medical service use was also significantly higher in surgical patients with intellectual disability. Conclusion Intellectual disability significantly increases the risk of overall major complications after major surgery. Our findings show a need for integrated and revised protocols for postoperative management to improve care for intellectually disabled surgical patients. PMID:22046425

Lin, Jui-An; Liao, Chien-Chang; Chang, Chuen-Chau; Chang, Hang; Chen, Ta-Liang

2011-01-01

240

An Updated Meta-Analysis of Fatal Adverse Events Caused by Bevacizumab Therapy in Cancer Patients  

PubMed Central

Background The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue. Methods An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab. Results Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05–1.57). This association varied significantly with tumor types (P?=?0.002) and chemotherapeutic agents (P?=?0.005) but not with bevacizumab dose (P?=?0.90). Increased risk was seen in patients with non–small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum. Conclusion Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum. PMID:24599121

Zhu, Jianhong; Zhang, Jingjing; Chen, Huapu; Chen, Xinggui

2014-01-01

241

Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study  

PubMed Central

Background Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years. Methods Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients’ markers. Results 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events. Conclusions After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen. PMID:23145925

2012-01-01

242

To what extent are adverse events found in patient records reported by patients and healthcare professionals via complaints, claims and incident reports?  

PubMed Central

Background Patient record review is believed to be the most useful method for estimating the rate of adverse events among hospitalised patients. However, the method has some practical and financial disadvantages. Some of these disadvantages might be overcome by using existing reporting systems in which patient safety issues are already reported, such as incidents reported by healthcare professionals and complaints and medico-legal claims filled by patients or their relatives. The aim of the study is to examine to what extent the hospital reporting systems cover the adverse events identified by patient record review. Methods We conducted a retrospective study using a database from a record review study of 5375 patient records in 14 hospitals in the Netherlands. Trained nurses and physicians using a method based on the protocol of The Harvard Medical Practice Study previously reviewed the records. Four reporting systems were linked with the database of reviewed records: 1) informal and 2) formal complaints by patients/relatives, 3) medico-legal claims by patients/relatives and 4) incident reports by healthcare professionals. For each adverse event identified in patient records the equivalent was sought in these reporting systems by comparing dates and descriptions of the events. The study focussed on the number of adverse event matches, overlap of adverse events detected by different sources, preventability and severity of consequences of reported and non-reported events and sensitivity and specificity of reports. Results In the sample of 5375 patient records, 498 adverse events were identified. Only 18 of the 498 (3.6%) adverse events identified by record review were found in one or more of the four reporting systems. There was some overlap: one adverse event had an equivalent in both a complaint and incident report and in three cases a patient/relative used two or three systems to complain about an adverse event. Healthcare professionals reported relatively more preventable adverse events than patients. Reports are not sensitive for adverse events nor do reports have a positive predictive value. Conclusions In order to detect the same adverse events as identified by patient record review, one cannot rely on the existing reporting systems within hospitals. PMID:21356056

2011-01-01

243

Palliative effects and adverse events of strontium-89 for prostate cancer patients with bone metastasis.  

PubMed

The aim of the present study was to evaluate the palliative effects and adverse events of strontium-89 (Sr-89) in patients with bone metastasis from prostate cancer. A total of 18 patients with prostate cancer and painful bone metastases, as diagnosed on bone scintigraphy, who were treated with Sr-89 at the National Kyushu Cancer Center between February, 2008 and April, 2014 were reviewed. Of the 18 subjects, 13 (72.2%) achieved a pain response, whereas 5 were classified as pain non-responders (27.8%). According to a logistic regression analysis, the pre-administration characteristics, including age, prostate-specific antigen (PSA), alkaline phosphatase (ALP), history of bone-modifying agent administration, opioid use or palliative radiation therapy, time after the combined androgen blockade nadir and time since the pain onset, were not found to be significant predictors of the pain response. Similarly, the post-administration characteristics, including pain flares and the PSA and ALP response, were not found to be significant predictors of the pain response. Although no patients exhibited leukocyte toxicities, 2 patients experienced myelosuppression, involving anemia and thrombocytopenia, requiring transfusion of red cell or platelet concentrate following Sr-89 treatment. Of the 18 patients, 5 (27.8%) reported pain flares, all of whom were successfully treated with rescue drugs alone. According to the logistic regression analysis, of the pre-administration characteristics, only ALP was identified as a significant predictor of bone marrow suppression in the univariate and multivariate analyses (P=0.006). Therefore, Sr-89 treatment was found to be effective in ameliorating bone pain associated with metastasis from prostate cancer. Although it is difficult to identify the patients who will receive pain relief prior to Sr-89 administration, this drug should be administered during the early stages due to the potential for bone marrow suppression in patients with high ALP levels. PMID:25469306

Furubayashi, Nobuki; Negishi, Takahito; Ura, Shintaro; Hirai, Yoshiki; Nakamura, Motonobu

2015-01-01

244

Palliative effects and adverse events of strontium-89 for prostate cancer patients with bone metastasis  

PubMed Central

The aim of the present study was to evaluate the palliative effects and adverse events of strontium-89 (Sr-89) in patients with bone metastasis from prostate cancer. A total of 18 patients with prostate cancer and painful bone metastases, as diagnosed on bone scintigraphy, who were treated with Sr-89 at the National Kyushu Cancer Center between February, 2008 and April, 2014 were reviewed. Of the 18 subjects, 13 (72.2%) achieved a pain response, whereas 5 were classified as pain non-responders (27.8%). According to a logistic regression analysis, the pre-administration characteristics, including age, prostate-specific antigen (PSA), alkaline phosphatase (ALP), history of bone-modifying agent administration, opioid use or palliative radiation therapy, time after the combined androgen blockade nadir and time since the pain onset, were not found to be significant predictors of the pain response. Similarly, the post-administration characteristics, including pain flares and the PSA and ALP response, were not found to be significant predictors of the pain response. Although no patients exhibited leukocyte toxicities, 2 patients experienced myelosuppression, involving anemia and thrombocytopenia, requiring transfusion of red cell or platelet concentrate following Sr-89 treatment. Of the 18 patients, 5 (27.8%) reported pain flares, all of whom were successfully treated with rescue drugs alone. According to the logistic regression analysis, of the pre-administration characteristics, only ALP was identified as a significant predictor of bone marrow suppression in the univariate and multivariate analyses (P=0.006). Therefore, Sr-89 treatment was found to be effective in ameliorating bone pain associated with metastasis from prostate cancer. Although it is difficult to identify the patients who will receive pain relief prior to Sr-89 administration, this drug should be administered during the early stages due to the potential for bone marrow suppression in patients with high ALP levels. PMID:25469306

FURUBAYASHI, NOBUKI; NEGISHI, TAKAHITO; URA, SHINTARO; HIRAI, YOSHIKI; NAKAMURA, MOTONOBU

2015-01-01

245

No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and Hodgkin's disease.  

PubMed

There is insufficient information on the effects of chemotherapy protocols for Hodgkin's disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HD who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HD is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD. PMID:15941081

Pejsa, Vlatko; Grgurevi?, Ivica; Kujundzi?, Milan; Martinovi?, Marko; Stanci?, Vladimir; Donley, Kyle; Pavletic, Steven

2004-10-30

246

A Novel System to Diagnose Cutaneous Adverse Drug Reactions Employing the Cellscan—Comparison with Histamine Releasing Test and Inf-? Releasing Test  

PubMed Central

Background: There are several mechanisms to describe allergic drug reactions yet the methods to diagnose them are limited. Objective: To compare several conventional clinical and laboratory methods to diagnose skin reactions to drugs to a new method of diagnosing drug reactions by the CellScan system. Methods: The study entailed 21 patients who were diagnosed as suffering from drug eruptions, and 105 healthy controls with no history of drug allergy. The drugs were classified into two groups according to suspicion of causing drug allergy: high and low. Most of the patients were on more than one drug, leading to 41 patient-drug interactions (assays). Histamine releasing test (HRT), interferon (INF)-? releasing test and CellScan examination were performed on lymphocytes of the patients and controls. Results: The HRT was interpreted as positive in 9 out of 18 (50%) patients and in 13 out of 35 (37%) assays. Based on the INF-? releasing test, positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41 (59%) assays. In the CellScan test (CST), positive results were observed in 17 out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%) assays in the HRT, 20 out of 24 (83%) assays in the INF-? releasing test, and 21 out of 24 (87%) studies with the CellScan method. The rate of determining of the drug that caused the eruption in the low suspicion level drugs was 4 out of 13 (31%) in the HRT, 4 out of 17 (24%) assays in the INF-? releasing test, and 8 out of 17 (47%) analyses in the CST. When examined in the CellScan, 99 out of 105 (94%) controls were interpreted as negative. Conclusion: This preliminary study indicates that the CellScan seems to be an easy and promising method for the detection of drugs responsible for adverse skin reactions. In contrast to the HRT and to the Interferon-? secretion test, the CellScan method is characterized by its ability to track and monitor the reaction of individual cells. By measuring the kinetic parameters of selected cells before and after adding the suspected drug, we were able to identify the culprit drug. The CellScan method had the highest sensitivity, and the interferon-? secretion test had the highest specificity for detection of the culprit drug. In contrast, the analysis of 105 normal control sera disclosed a high specificity of 94% for the CellScan method. PMID:15712603

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

2005-01-01

247

ADReCS: an ontology database for aiding standardization and hierarchical classification of adverse drug reaction terms.  

PubMed

Adverse drug reactions (ADRs) are noxious and unexpected effects during normal drug therapy. They have caused significant clinical burden and been responsible for a large portion of new drug development failure. Molecular understanding and in silico evaluation of drug (or candidate) safety in laboratory is thus so desired, and unfortunately has been largely hindered by misuse of ADR terms. The growing impact of bioinformatics and systems biology in toxicological research also requires a specialized ADR term system that works beyond a simple glossary. Adverse Drug Reaction Classification System (ADReCS; http://bioinf.xmu.edu.cn/ADReCS) is a comprehensive ADR ontology database that provides not only ADR standardization but also hierarchical classification of ADR terms. The ADR terms were pre-assigned with unique digital IDs and at the same time were well organized into a four-level ADR hierarchy tree for building an ADR-ADR relation. Currently, the database covers 6544 standard ADR terms and 34 796 synonyms. It also incorporates information of 1355 single active ingredient drugs and 134 022 drug-ADR pairs. In summary, ADReCS offers an opportunity for direct computation on ADR terms and also provides clues to mining common features underlying ADRs. PMID:25361966

Cai, Mei-Chun; Xu, Quan; Pan, Yan-Jing; Pan, Wen; Ji, Nan; Li, Yin-Bo; Jin, Hai-Jing; Liu, Ke; Ji, Zhi-Liang

2015-01-28

248

Severe Infusion Reactions to Cetuximab Occur within 1 h in Patients with Metastatic Colorectal Cancer: Results of a Nationwide, Multicenter, Prospective Registry Study of 2126 Patients in Japan  

PubMed Central

Objective Infusion reactions are common adverse reactions associated with antibody preparations. However, no studies have examined the time to onset of serious infusion reactions after administering cetuximab. We aimed to investigate the timing and severity of IRs affecting Japanese patients after administration of cetuximab. Methods Study subjects were identified from a nationwide prospective registry of 2126 metastatic colorectal cancer patients scheduled to receive cetuximab. Infusion reactions were examined in 2006 patients with adequate safety data. Results Infusion reactions of any grade occurred in 114 patients (5.7%), including Grade 3–4 infusion reactions in 22 patients (1.1%). Premedications were antihistamine plus corticosteroid (88.9% of patients with infusion reactions), antihistamine alone (9.2%) or corticosteroid alone (1.1%). In 95 patients (83.3%), infusion reactions occurred after the first dose. Twenty of the 22 Grade 3–4 infusion reactions occurred within 1 h of the first dose (the timing of the infusion reaction was unknown in one patient while another infusion reaction occurred after the fourth dose). Infusion reactions resolved in 111/114 patients (97.4%) while one patient recovered with sequelae, one patient died and one patient failed to recover within the follow-up period. Thirteen patients (15.7% of patients with infusion reactions) with Grade 1–2 infusion reactions showed recurrence after readministration of cetuximab; the recurrent infusion reactions were less severe than the initial reactions. Conclusions Grade 3–4 infusion reactions occurred in 1.1% of colorectal cancer patients, and most occurred within 1 h of receiving the first dose of cetuximab. Therefore, patients should be carefully observed following cetuximab infusion, especially during the first hour after the first infusion. PMID:24771864

Yamaguchi, Kensei; Watanabe, Toshiaki; Satoh, Taroh; Ishiguro, Megumi; Izawa, Makiko; Inoshiri, Shogo; Sugihara, Kenichi; Sakata, Yuh

2014-01-01

249

[Cutaneous drug reactions in HIV-infected patients in the HAART era].  

PubMed

The introduction of highly active antiretroviral treatment (HAART) in 1996 radically changed the clinical course of human immunodeficiency virus (HIV) infection as it led to a dramatic reduction in mortality in these patients. However, these treatments have their limitations, including adverse effects, therapeutic failure, pharmacokinetic interactions, the development of resistance, and abnormal immune responses. In this article we review the current situation of cutaneous drug reactions in HIV-infected patients. PMID:19463228

Blanes, M; Belinchón, I; Portilla, J

2009-05-01

250

Adverse Reactions to Metal Debris in Metal-On-Polyethylene Total Hip Arthroplasty Using a Titanium-Molybdenum-Zirconium-Iron Alloy Stem.  

PubMed

We report a series of three patients who underwent uncemented total hip arthroplasty with a modular titanium-molybdenum-zirconium-iron stem and a cobalt-chrome-molybdenum head on an ultra-high molecular weight highly cross-linked polyethylene liner bearing. All three cases subsequently developed pain and adverse reaction to metal debris, leading to revision of the implants within thirty-six months. They were subsequently found to have hypersensitivity to cobalt or chromium. However where tested, blood metal ion levels were within MHRA guideline limits. Corrosion was noted at the taper-trunnion junction. It is possible, that the multi alloy head-neck combination may lead to corrosion. Hypersensitivity to metal ions may result to ARMD at lower metal ion levels. The use of ceramic heads may help avoid this risk. PMID:25466166

Kiran, Manish; Boscainos, Petros J

2014-10-30

251

Prevalence and Predictors of Adverse Events in Older Surgical Patients: Impact of the Present on Admission Indicator  

ERIC Educational Resources Information Center

Purpose of the Study: To examine the effects of the present on admission (POA) indicator on the prevalence of and factors associated with postsurgical adverse events in older patients. Design and Methods: This is a secondary data analysis of 82,898 surgical patients aged 65 years or older in 252 acute care hospitals in California in 2004. Four…

Kim, Hongsoo; Capezuti, Elizabeth; Kovner, Christine; Zhao, Zhonglin; Boockvar, Kenneth

2010-01-01

252

The JCAHO patient safety event taxonomy: a standardized terminology and classification schema for near misses and adverse events  

Microsoft Academic Search

Background. The current US national discussions on patient safety are not based on a common language. This hinders system- atic application of data obtained from incident reports, and learning from near misses and adverse events. Objective. To develop a common terminology and classification schema (taxonomy) for collecting and organizing patient safety data. Methods. The project comprised a systematic literature review;

ANDREW CHANG; PAUL M. SCHYVE; RICHARD J. CROTEAU; DENNIS S. O'LEARY; JEROD M. LOEB

2005-01-01

253

Vascular injury following accidental intra-arterial injection of clindamycin: adverse drug reaction report.  

PubMed

Clindamycin in a commonly used antibiotic, considered safe for oral, intravenous and intra-arterial use. We present a case of a patient that received an inadvertent injection clindamycin 600 mg in 4 mL through a radial arterial line. The patient presented signs and symptoms of vascular occlusion and despite aggressive pharmacological and medical treatment developed massive and severe tissue injury. PMID:21483392

Lehavi, A; Sandler, A; Netzer, A; Katz, Y Shai

2011-04-01

254

Informed Consent — A Reappraisal of Patients' Reactions  

PubMed Central

In response to the November 1972 ruling of the California Supreme Court requiring complete, detailed disclosure of risks for procedures and treatments, a survey was made of the reactions of one hundred patients to this decision. A fictional man was described with a clinical diagnosis of brain tumor, and then the procedure for cerebral angiography and all of that procedure's potential complications were described. The majority of the patients surveyed responded that this complete disclosure of risks helped them in making an intelligent decision about giving consent for the procedure. However, 50 percent of these patients would have withheld consent for the procedure on learning of the complications. Although physicians would have reacted differently, it is certainly the patients' right to make the choices they did. PMID:4755699

Rosenberg, Sidney H.

1973-01-01

255

Pharmacokinetics and adverse reactions of a new liposomal cisplatin (Lipoplatin): phase I study.  

PubMed

Lipoplatin, a new liposomal cisplatin formulation, is formed from cisplatin and liposomes composed of dipalmitoyl phosphatidyl glycerol (DPPG), soy phosphatidyl choline (SPC-3), cholesterol and methoxy-polyethylene glycol-distearoyl phosphatidylethanolamine (mPEG2000-DSPE). Following intravenous infusion, the nanoparticles (110 nm) are distributed into tissues and concentrate preferentially at tumor sites supposedly via extravasation through the leaky tumor vasculature. This study was designed to investigate the pharmacokinetics and the toxicity of this new liposomal cisplatin in patients with pretreated advanced malignant tumors. The drug was infused for 8 h every 14 days at escalating doses. Twenty-seven patients were included and 3-5 patients were selected for each dosage level; levels started at 25 mg/m2 and were increased by 25 to 125 mg/m2. Three patients were also treated at higher dose levels, one each at 200, 250 and 300 mg/m2. Blood was taken at certain time intervals in order to estimate total platinum plasma levels. At level 5 (125 mg/m2), grades 1 and 2 GI tract and hematological toxicities were detected. No nephrotoxicity was observed. Seven additional patients were added at the 4th level (100 mg/m2) for further pharmacokinetic evaluation. Measurement of platinum levels in the plasma of patients as a function of time showed that a maximum platinum level is attained at 6-8 h. The half-life of Lipoplatin was 60-117 h depending on the dose. Urine excretion reached about 40% of the infused dose in 3 days. The data demonstrate that Lipoplatin up to a dose of 125 mg/m2 every 14 days has no nephrotoxicity and it lacks the serious side effects of cisplatin. PMID:15756428

Stathopoulos, George P; Boulikas, Teni; Vougiouka, Maria; Deliconstantinos, George; Rigatos, Sotirios; Darli, Eleftheria; Viliotou, Vasiliki; Stathopoulos, John G

2005-04-01

256

Malaria chemoprophylaxis among European tourists in tropical Africa: use, adverse reactions, and efficacy.  

PubMed Central

In order to determine knowledge, attitudes and practices towards malaria prophylaxis, as well as its side-effects and efficacy, a self-administered questionnaire was distributed to European travellers on return flights from tropical Africa to Europe. Between 1985 and 1988 the questionnaire was completed by 44,472 passengers (80.1% of those on board) on 242 flights. A follow-up questionnaire was completed by 42,202 (94.9%) of the same travellers 3 months later. Almost all knew about the risk of malaria, but 10% relied solely on advice from nonmedical sources. While 55.6% had taken at least one measure against mosquito bites, only 4.5% adopted three such measures (used repellents and insecticides and wore long clothing after dusk). Compliance with chemoprophylaxis use was reported by 57.0% of travellers who spent less than 3 months in Africa, compared with 29.2% who stayed 3-12 months. Depending on the antimalaria regimen taken, 11-44% of the travellers experienced adverse effects, while four deaths were attributed to the chemoprophylaxis. The incidence of malaria per month of exposure for travellers who took no chemoprophylaxis was 15.2 per 1000 in East Africa and 24.2 per 1000 in West Africa. In East Africa, the prophylactic efficacy of the currently recommended antimalaria regimens (relative to that of no chemoprophylaxis) was zero for a chloroquine dosage of 300 mg base per week (4 malaria fatalities), 64.1% for a chloroquine dosage of 600 mg base per week (P = 0.03), and 94.0% for mefloquine (P = 0.003). PMID:2393977

Steffen, R.; Heusser, R.; Mächler, R.; Bruppacher, R.; Naef, U.; Chen, D.; Hofmann, A. M.; Somaini, B.

1990-01-01

257

Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study  

PubMed Central

Background: To assist physicians with difficult decisions about hospital admission for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) presenting in the emergency department, we sought to identify clinical characteristics associated with serious adverse events. Methods: We conducted this prospective cohort study in 6 large Canadian academic emergency departments. Patients were assessed for standardized clinical variables and then followed for serious adverse events, defined as death, intubation, admission to a monitored unit or new visit to the emergency department requiring admission. Results: We enrolled 945 patients, of whom 354 (37.5%) were admitted to hospital. Of 74 (7.8%) patients with a subsequent serious adverse event, 36 (49%) had not been admitted after the initial emergency visit. Multivariable modelling identified 5 variables that were independently associated with adverse events: prior intubation, initial heart rate ? 110/minute, being too ill to do a walk test, hemoglobin < 100 g/L and urea ? 12 mmol/L. A preliminary risk scale incorporating these and 5 other clinical variables produced risk categories ranging from 2.2% for a score of 0 to 91.4% for a score of 10. Using a risk score of 2 or higher as a threshold for admission would capture all patients with a predicted risk of adverse events of 7.2% or higher, while only slightly increasing admission rates, from 37.5% to 43.2%. Interpretation: In Canada, many patients with COPD suffer a serious adverse event or death after being discharged home from the emergency department. We identified high-risk characteristics and developed a preliminary risk scale that, once validated, could be used to stratify the likelihood of poor outcomes and to enable rational and safe admission decisions. PMID:24549125

Stiell, Ian G.; Clement, Catherine M.; Aaron, Shawn D.; Rowe, Brian H.; Perry, Jeffrey J.; Brison, Robert J.; Calder, Lisa A.; Lang, Eddy; Borgundvaag, Bjug; Forster, Alan J.; Wells, George A.

2014-01-01

258

Evaluating the risk of patient re-identification from adverse drug event reports  

PubMed Central

Background Our objective was to develop a model for measuring re-identification risk that more closely mimics the behaviour of an adversary by accounting for repeated attempts at matching and verification of matches, and apply it to evaluate the risk of re-identification for Canada’s post-marketing adverse drug event database (ADE).Re-identification is only demonstrably plausible for deaths in ADE. A matching experiment between ADE records and virtual obituaries constructed from Statistics Canada vital statistics was simulated. A new re-identification risk is considered, it assumes that after gathering all the potential matches for a patient record (all records in the obituaries that are potential matches for an ADE record), an adversary tries to verify these potential matches. Two adversary scenarios were considered: (a) a mildly motivated adversary who will stop after one verification attempt, and (b) a highly motivated adversary who will attempt to verify all the potential matches and is only limited by practical or financial considerations. Methods The mean percentage of records in ADE that had a high probability of being re-identified was computed. Results Under scenario (a), the risk of re-identification from disclosing the province, age at death, gender, and exact date of the report is quite high, but the removal of province brings down the risk significantly. By only generalizing the date of reporting to month and year and including all other variables, the risk is always low. All ADE records have a high risk of re-identification under scenario (b), but the plausibility of that scenario is limited because of the financial and practical deterrent even for highly motivated adversaries. Conclusions It is possible to disclose Canada’s adverse drug event database while ensuring that plausible re-identification risks are acceptably low. Our new re-identification risk model is suitable for such risk assessments. PMID:24094134

2013-01-01

259

Do adverse histopathologic findings in colorectal cancer patients explain disparate outcomes?  

PubMed Central

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist. PMID:16573297

Gray, Keith D.; Ballard, Billy R.; Washington, M. Kay; Belue, Rhonda; Grady, William M.; Chapman, William C.; Stain, Steven C.

2006-01-01

260

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

PubMed

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. PMID:25576362

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

2015-02-13

261

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients  

PubMed Central

Background The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity. Methods Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts. Results Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 × 10-5). SEMA3A knockdown enhanced radiation resistance. Conclusions This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity. PMID:20701746

2010-01-01

262

Bullous pemphigoid: corticosteroid treatment and adverse effects in long-term care patients.  

PubMed

Bullous pemphigoid (BP) is the most common autoimmune bullous disease. It primarily presents in elderly patients older than 70 years of age. The presentation can vary with localized or generalized disease that variably affects mucosal tissue. Therapy primarily consists of administration of topical and systemic corticosteroids. Topical corticosteroids are effective with less adverse effects compared with systemic steroids. Other therapies, such as steroid-sparing agents and plasma exchanges, have been recommended and studied to some degree, but these require more evidence before they can be routinely recommended. A 68-year-old African-American female resident of a nursing facility develops a rash and is evaluated at a dermatology clinic. Since the resident has many medications and concomitant diseases, the physician at first suspected a drug rash. On subsequent visits, the resident undergoes multiple punch biopsies and is diagnosed with BP. Treatment is initiated with topical steroids, systemic steroids, and oral minocycline. On a follow-up visit, the resident is showing improvement of her BP. However, the resident's hypertension and hyperglycemia are now uncontrolled as a result of the discontinuation of hydrochlorothiazide and the initiation of steroid therapy. This case highlights the dangers of corticosteroids in patients, especially the elderly, who have multiple comorbidities. PMID:23835463

Spivey, Justin; Nye, Ann Marie

2013-07-01

263

The Effect of Prophylactic Antipyretic Administration on Post-Vaccination Adverse Reactions and Antibody Response in Children: A Systematic Review  

PubMed Central

Background Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children. Methods A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs) comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ?6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717]. Results Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (?38.0°C) after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term) of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations. Conclusions Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at assessing the effectiveness of programs where prophylactic administration of PCM is given. The timing of administration of antipyretics should be discussed with the parents after explaining the benefits & risks. PMID:25180516

Das, Rashmi Ranjan; Panigrahi, Inusha; Naik, Sushree Samiksha

2014-01-01

264

Adverse reaction to metal debris after ReCap-M2A-Magnum large-diameter-head metal-on-metal total hip arthroplasty  

PubMed Central

Background and purpose The clinical findings of adverse reaction to metal debris (ARMD) following large-diameter-head metal-on-metal total hip arthroplasty (LDH MoM THA) may include periarticular fluid collections, soft tissue masses, and gluteal muscle necrosis. The ReCap-M2a-Magnum LDH MoM THA was the most commonly used hip device at our institution from 2005 to 2012. We assessed the prevalence of and risk factors for ARMD with this device. Methods 74 patients (80 hips) had a ReCap-M2a-Magnum LDH MoM THA during the period August 2005 to December 2006. These patients were studied with hip MRI, serum chromium and cobalt ion measurements, the Oxford hip score questionnaire, and by clinical examination. The prevalence of ARMD was recorded and risk factors for ARMD were assessed using logistic regression models. The mean follow-up time was 6.0 (5.5–6.7) years. Results A revision operation due to ARMD was needed by 3 of 74 patients (3 of 80 hips). 8 additional patients (8 hips) had definite ARMD, but revision was not performed. 29 patients (32 hips) were considered to have a probable or possible ARMD. Altogether, 43 of 80 hips had a definite, probable, or possible ARMD and 34 patients (37 hips) were considered not to have ARMD. In 46 of 78 hips, MRI revealed a soft tissue mass or a collection of fluid (of any size). The symptoms clicking in the hip, local hip swelling, and a feeling of subluxation were associated with ARMD. Interpretation ARMD is common after ReCap-M2a-Magnum total hip arthroplasty, and we discourage the use of this device. Asymptomatic patients with a small fluid collection on MRI may not need instant revision surgery but must be followed up closely. PMID:24171688

2013-01-01

265

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression  

PubMed Central

Background Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes. Methods Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography. Results Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts. Limitations Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used. Conclusion Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive–emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies. PMID:22008179

Frodl, Thomas; Carballedo, Angela; Fagan, Andrew J.; Lisiecka, Danuta; Ferguson, Yolande; Meaney, James F.

2012-01-01

266

General adverse response to cyclophosphamide in Chinese patients with systemic autoimmune diseases in recent decade - a single-center retrospective study.  

PubMed

This study was conducted to investigate the adverse reaction to cyclophosphamide (CYC) in Chinese patients with systemic autoimmune diseases. Patients with systemic autoimmune diseases who were exposed to CYC and followed up regularly for at least 2 years in Rheumatology Department during June 2003 to June 2013 were enrolled into this study. Participants were divided into per oral (PO) group and intravenous (IV) group. The adverse effects to CYC were recorded and analyzed. A total of 419 patients were enrolled in this study. The occurrence rates of gastrointestinal discomfort, alopecia, myelosuppression, secondary infection, abnormal liver function, dizziness/headache, menstrual disturbance and reversal to normal menstruation after discontinuation of CYC were 21.5 %, 12.4 %, 7.4 %, 3.6 %, 3.1 %, 3.1 %, 30.3 % and 31.0 %, respectively. None of the patients had hemorrhagic cystitis. The significant risk factors for gastrointestinal discomfort were female, exposure to CYC for a long time and intravenous route. Risk factors for mylosuppression were female and combination with other immunosuppressants. Risk factors were female gender for alopecia and older age for menstrual disturbance. Female patients were much more likely to have gastrointestinal discomfort, mylosuppression and alopecia when CYC was administrated intravenously. Risk factors were older age for menstrual disturbance and the combination with other immunosuppressants for myelosuppression. Hemorrhagic cystitis did not appear in our series for the possible reason of prophylactic hydration before intravenous injection and maybe racial difference. PMID:25053381

Li, Juan; Dai, Guowei; Zhang, Zhuoli

2015-02-01

267

FGF-23 Levels in Patients with AKI and Risk of Adverse Outcomes  

PubMed Central

Summary Background and objectives Fibroblast growth factor 23 plays an important role in regulating phosphate and vitamin D homeostasis. Elevated levels of fibroblast growth factor 23 are independently associated with mortality in patients with CKD and ESRD. Whether fibroblast growth factor 23 levels are elevated and associated with adverse outcomes in patients with AKI has not been studied. Design, setting, participants, & measurements This study had 30 participants with AKI, which was defined as an increase in serum creatinine?0.3 mg/dl or ?50% from baseline, and 30 controls from the general hospital wards and intensive care units. Plasma levels of C-terminal fibroblast growth factor 23 and vitamin D metabolites were measured within 24 hours of AKI onset and 5 days later. The composite endpoint was death or need for renal replacement therapy. Results Enrollment fibroblast growth factor 23 levels were significantly higher among participants with AKI than controls (median [interquartile range]=1471 [224–2534] versus 263 [96–574] RU/ml, P=0.003). Enrollment fibroblast growth factor 23 correlated negatively with 25-hydroxyvitamin D (r=?0.43, P<0.001) and 1,25-dihydroxyvitamin D (r=?0.39, P=0.003) and positively with phosphate (r=0.32, P=0.02) and parathyroid hormone (r=0.37, P=0.005). Among participants with AKI, enrollment fibroblast growth factor 23 (but not other serum parameters) was significantly associated with the composite endpoint, even after adjusting for age and enrollment serum creatinine (11 events; adjusted odds ratio per 1 SD higher ln[fibroblast growth factor 23]=13.73, 95% confidence interval=1.75–107.50). Conclusions Among patients with AKI, fibroblast growth factor 23 levels are elevated and associated with greater risk of death or need for renal replacement therapy. PMID:22700885

Wolf, Myles; Waikar, Sushrut S.; Chase, Herbert; Christov, Marta; Cremers, Serge; Stern, Leonard

2012-01-01

268

Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects.  

PubMed

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT. PMID:23283457

Gonçalves, Heitor de Sá; Pontes, Maria Araci de Andrade; Bührer-Sékula, Samira; Cruz, Rossilene; Almeida, Paulo Cesar; Moraes, Maria Elisabete Amaral de; Penna, Gerson Oliveira

2012-12-01

269

Cutaneous adverse reactions after intra-articular injection of triamcinolone acetonide.  

PubMed

A patient is described with a disseminated morbilliform and partially persistent urticarial dermatitis following intra-articular injections of triamcinolone acetonide. A delayed-type hypersensitivity to triamcinolone acetonide was observed after patch and intradermal testing. However, an immediate-type hypersensitivity to this drug was not observed. A delayed-type sensitization to betamethasone, dexamethasone and prednisolone, but not to hydrocortisone was also observed after patch testing. Intradermal tests with these representatives of corticosteroids were all negative. Although little is known yet about the relationship between immediate and delayed-type hypersensitivity and the side-effects of oral use of corticosteroids, the absence of positive skin tests to corticosteroids other than triamcinolone acetonide may indicate a safe use of these drugs orally or via injection. PMID:7747537

Ijsselmuiden, O E; Knegt-Junk, K J; van Wijk, R G; van Joost, T

1995-01-01

270

Reactions to a bovine collagen implant. Clinical and immunologic study in 705 patients.  

PubMed

A small percentage of patients treated with bovine collagen implants have adverse reactions involving both the cellular and humoral types of immune response. We report a clinical follow-up of 705 subjects treated with a new bovine collagen implant, Atelocollagen (Koken Co. Ltd., Tokyo, Japan). Sensitization to the implant was evaluated in all subjects by skin testing, and humoral response was monitored in 166 subjects by measuring the level of circulating antibodies directed against bovine collagen. Twenty-seven patients (3.8%) exhibited a positive response to a skin test, and of the remaining 656 patients, an adverse reaction to the implant developed in 2.3%. We found a strong correlation between the presence of antibodies to collagen and a positive response to skin testing (92%) or an adverse reaction (100%). In the case of a borderline clinical response to bovine collagen implantation, anticollagen serologic tests appeared to be a useful tool for the identification of clinically reactive patients. PMID:2584456

Charriere, G; Bejot, M; Schnitzler, L; Ville, G; Hartmann, D J

1989-12-01

271

Does Mental Illness Stigma Contribute to Adolescent Standardized Patients' Discomfort With Simulations of Mental Illness and Adverse Psychosocial Experiences?  

ERIC Educational Resources Information Center

Objective: Adolescent mental illness stigma-related factors may contribute to adolescent standardized patients' (ASP) discomfort with simulations of psychiatric conditions/adverse psychosocial experiences. Paradoxically, however, ASP involvement may provide a stigma-reduction strategy. This article reports an investigation of this hypothetical…

Hanson, Mark D.; Johnson, Samantha; Niec, Anne; Pietrantonio, Anna Marie; High, Bradley; MacMillan, Harriet; Eva, Kevin W.

2008-01-01

272

Effects of Video Games on the Adverse Corollaries of Chemotherapy in Pediatric Oncology Patients: A Single-Case Analysis.  

ERIC Educational Resources Information Center

Assessed effects of video games on adverse corollaries of chemotherapy in three pediatric oncology patients. Results indicated that access to video games resulted in reduction in the number of anticipatory symptoms experienced and observed, as well as a diminution in the aversiveness of chemotherapy side effects. (Author/NRB)

Kolko, David J.; Rickard-Figueroa, Jorge L.

1985-01-01

273

Imagery special issue: Intrusive images and memories of earlier adverse events in patients with obsessive compulsive disorder  

Microsoft Academic Search

Mental imagery is increasingly considered to be an important feature in anxiety disorders. The aim of this study was to investigate the prevalence and characteristics of mental images in obsessive compulsive disorder (OCD) and their possible association with earlier adverse events. A consecutive sample of 37 patients with OCD admitted to a specialist unit was interviewed using a semi-structured interview.

Anne E. M. Speckens; Ann Hackmann; Anke Ehlers; Bea Cuthbert

2007-01-01

274

Dysregulated Mineral Metabolism in Patients with Acute Kidney Injury and Risk of Adverse Outcomes  

PubMed Central

Objective Numerous studies have evaluated the prevalence and importance of vitamin D deficiency among patients with chronic kidney disease and end-stage renal disease, however, little is known about vitamin D levels in acute kidney injury (AKI). We evaluated the association between vitamin D metabolites and clinical outcomes among patients with AKI. Design Prospective cohort study. Patients 30 participants with AKI and 30 controls from general hospital wards and intensive care units at a tertiary care hospital. Measurements Plasma levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24R,25-dihydroxyvitamin D3, vitamin D binding protein (VDBP), and fibroblast growth factor 23 (FGF23) were measured within 24 hours of AKI onset and 5 days later. Bioavailable 25(OH)D and 1,25(OH)2D levels, defined as the sum of free- and albumin-bound 25(OH)D and 1,25(OH)2D, were estimated using equations. Results Compared to controls, participants with AKI had lower levels of 1,25(OH)2D [17 (10-22) versus 25 (15-35) pg/ml, p=0.01], lower levels of VDBP [23 (15-31) versus 29 (25-36) mg/dl, p=0.003], and similar levels of bioavailable 25(OH)D and 1,25(OH)2D at enrollment. Levels of bioavailable 25(OH)D were inversely associated with severity of sepsis in the overall sample (p<0.001). Among participants with AKI, bioavailable 25(OH)D, but not other vitamin D metabolites, was significantly associated with mortality after adjusting for age and serum creatinine (adjusted odds ratio per 1 SD ln [bioavailable 25(OH)D]=0.16, 95% confidence interval=0.03 to 0.85). Conclusions Bioavailable 25(OH)D could have a role as a biomarker or mediator of adverse outcomes among patients with established AKI. PMID:23414198

Leaf, David E.; Waikar, Sushrut S.; Wolf, Myles; Cremers, Serge; Bhan, Ishir; Stern, Leonard

2013-01-01

275

Potentials and limitations of nonclinical safety assessment for predicting clinical adverse drug reactions: correlation analysis of 142 approved drugs in Japan.  

PubMed

The objective of this study was to elucidate the range of abilities of nonclinical safety assessment for predicting adverse drug reactions (ADRs) in humans. The dataset included 1256 ADRs with an incidence rate of 5% or more collected from 142 drugs approved in Japan from 2001 to 2010 (excluding anticancer agents and vaccines). Gastrointestinal, neurological and hepatobiliary ADRs were relatively common, followed by hematological, cutaneous, systemic and cardiovascular ADRs in the dataset. The analysis revealed that 48% of ADRs were predictable based on a comprehensive nonclinical safety assessment considering animal toxicity. Hematological and ocular ADRs, infection, and application site reactions showed a correlation of more than 70%, while musculoskeletal, respiratory and neurological ADRs showed a correlation of less than 30%. In addition to subjective patient perceptions, several laboratory parameters routinely monitored both in animals and humans showed a lower correlation, e.g., abnormalities in hepatobiliary and metabolic parameters, and blood pressure increase. Large molecule drugs showed lower correlation than small molecule drugs; ADRs were observed in various organs and consideration of pharmacological action did not significantly contribute to the prediction. It was also confirmed that the current standard of toxicology testing regarding dosing duration and dose level is adequate to detect concordant animal toxicity. This study collectively demonstrated a significant value of nonclinical safety assessment in predicting ADRs in humans. It also identified the subset of ADRs with poor predictability, highlighting the need for advanced testing that enables successful translation of animal toxicity to clinical settings with better accuracy and sensitivity. PMID:23824014

Tamaki, Chihiro; Nagayama, Takashi; Hashiba, Masamichi; Fujiyoshi, Masato; Hizue, Masanori; Kodaira, Hiroshi; Nishida, Minoru; Suzuki, Kazuhiko; Takashima, Yoshiharu; Ogino, Yamato; Yasugi, Daisaku; Yoneta, Yasuo; Hisada, Shigeru; Ohkura, Takako; Nakamura, Kazuichi

2013-01-01

276

Shortening reaction in patients with cerebellar ataxia.  

PubMed

During passive extension of the elbow, the triceps muscle normally shows a burst of electromyographic activity. This shortening reaction (SR) is known to be exaggerated in extrapyramidal disease states, but the effects of cerebellar disease are unknown. The SR was measured in both arms of a patient with hemiataxia, the unaffected arm serving as a matched control. In the ataxic arm, the SR was significantly larger and did not show the normal increase during "reinforcement." In a patient with bilateral ataxia, the SR was grossly exaggerated as compared with the SRs in a group of normal subjects. The present findings indicate an unexpected point of similarity between cerebellar and extrapyramidal disease states, which is discussed in terms of the anatomical connections of the cerebellum and basal ganglia. The techniques used in this work provide a quantitative approach to disorders of movement and muscle tone. PMID:7092180

Angel, R W

1982-03-01

277

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study  

PubMed Central

Background Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India Methods A prospective, observational study of adult patients carried out over a 6 week period in 2005. The prevalence of ADRs, their economic burden from the hospital perspective, severity, and preventability were assessed using standard criteria. Results A total 6899 patients presented during the study period. Of these, 2046 were admitted for various reasons. A total of 265/6899 patients had ADRs (3.84 %). A total of 141/265 was admitted due to ADsR, and thus ADRs as a cause of admissions were 6.89% of total admissions. A majority (74.71%) were found to be of moderate severity. The most common ADRs were anti-tubercular drug induced hepatotoxicity, warfarin toxicity and chloroquine induced gastritis. The median duration of hospitalization was 5 days [95% CI 5.37, 7.11], and the average hospitalization cost incurred per patient was INR 6197/- (USD 150). Of total ADRs, 59.62% (158/265) were found to be either definitely or potentially avoidable. Conclusion The study shows that ADRs leading to hospitalization are frequent and constitute a significant economic burden. Training of patients and prescribers may lead to a reduction in hospitalization due to avoidable ADRs and thus lessen their economic burden. PMID:17662147

Patel, KJ; Kedia, MS; Bajpai, D; Mehta, SS; Kshirsagar, NA; Gogtay, NJ

2007-01-01

278

Serious adverse drug reaction in a woman with hyperemesis gravidarum after first exposure to vitamin B complex containing vitamins B1, B6 and B12.  

PubMed

We report the case of a pregnant woman who suffered from hypotension after first exposure to intravenous administration of a combination drug containing vitamins B1, B6 and B12 (Vitamedin; Daiichi-Sankyo, Tokyo, Japan). A 27-year-old Japanese woman received an intravenous infusion of fluid containing a vitamin B complex due to hyperemesis gravidarum. Thirty minutes after the start of infusion she was found to be in hypotension. The patient had stupor, general sweating, blood pressure of 82/50 mmHg, and low percutaneous oxygen saturation (SpO(2)) of 88%. We immediately stopped the infusion, lifted her legs and administered oxygen. Three minutes after these treatments, she quickly recovered to a good general condition. A skin prick test for vitamin B12 was positive, but tests for B1, B6, mannitol and saline were negative, indicating this adverse reaction was one of drug hypersensitivity due to the vitamin B12 in Vitamedin. Patients should be observed carefully immediately after the administration of Vitamedin. PMID:19751344

Kuwata, Yoshimine; Tsuruoka, Shuichi; Ohkuchi, Akihide; Matsubara, Shigeki; Izumi, Akio; Suzuki, Mitsuaki

2009-08-01

279

Imagery special issue: intrusive images and memories of earlier adverse events in patients with obsessive compulsive disorder.  

PubMed

Mental imagery is increasingly considered to be an important feature in anxiety disorders. The aim of this study was to investigate the prevalence and characteristics of mental images in obsessive compulsive disorder (OCD) and their possible association with earlier adverse events. A consecutive sample of 37 patients with OCD admitted to a specialist unit was interviewed using a semi-structured interview. Thirty (81%) patients with OCD reported mental images. Most images were either memories of earlier adverse events (n=10 or 34%) or were associated with them (n=13 or 45%). Patients with mental images had more obsessive compulsive symptoms, responsibility beliefs and anxiety than those without. Previous research has shown that patients with OCD and comorbid posttraumatic stress disorder might not benefit as much from standard behavioural treatment as those without. Consequently, additional therapeutic interventions such as imaginal reliving and restructuring of meaning or imagery modification of traumatic memories might be helpful in OCD patients with mental images that are linked to earlier adverse events. PMID:18005933

Speckens, Anne E M; Hackmann, Ann; Ehlers, Anke; Cuthbert, Bea

2007-12-01

280

Tamoxifen-associated skin reactions in breast cancer patients: from case report to literature review.  

PubMed

The purpose of this study was to firstly present the maiden case of tamoxifen-induced acute cutaneous lupus erythematosus (ACLE), and secondly, to broaden the discussion into a systematic review of the various tamoxifen-related skin changes documented in patients with breast cancer. We searched PubMed, Cochrane, Embase, CancerLit, Scopus, Web of Science, and Google Scholar databases using keywords to identify reported cases of tamoxifen-related cutaneous adverse events. Outcomes captured included type of cutaneous reaction, time to adverse event, pathologic mechanism, and possible treatment. From 17 clinical studies identified, over ten distinct types of adverse reactions of the skin were itemized. The character of these cutaneous events ranged from the relatively common hot flashes to the rare, but potentially life-threatening, Steven Johnson syndrome. Overall, tamoxifen is generally a well-tolerated hormone therapy with decades of supporting safety data. Based on current medical literature, we present the first case of tamoxifen-induced ACLE. Our clinical experience of managing this case revealed that despite its broad use and the frequency of associated skin reactions, there is a lack of concise information detailing the cutaneous adverse events associated with tamoxifen. The absence of summarized information concerning tamoxifen-related skin changes prompted us to perform a review herein. PMID:25292419

Andrew, Peter; Valiani, Sabira; MacIsaac, Jennifer; Mithoowani, Hamid; Verma, Shailendra

2014-11-01

281

Pharmacotherapy for Adverse Events Reduces the Length of Hospital Stay in Patients Admitted to Otolaryngology Ward: A Single Arm Intervention Study  

PubMed Central

Background To determine whether adverse events extend the duration of hospitalization, and to evaluate the effectiveness of medical intervention in ameliorating adverse events and reducing the prolonged hospital stay associated with adverse events. Methods A single arm intervention study was conducted from October 2012 to March 2014 in the otolaryngology ward of a 614-bed, university-affiliated hospital. Adverse events were monitored daily by physicians, pharmacists and nurses, and recorded in the electronic medical chart for each patient. Appropriate drug management of adverse events was performed by physicians in liaison with pharmacists. The Kaplan-Meier method was used to assess the length of hospitalization of patients who underwent medical intervention for adverse events. Results Of 571 patients admitted to the otolaryngology ward in a year, 219 patients (38.4%) experienced adverse events of grade ?2. The duration of hospitalization was affected by the grade of adverse events, with a mean duration of hospital stay of 9.2, 17.2, 28.3 and 47.0 days for grades 0, 1, 2, and 3–4, respectively. Medical intervention lowered the incidence of grade ?2 adverse events to 14.5%. The length of hospitalization was significantly shorter in patients who showed an improvement of adverse events after medical intervention than those who did not (26.4 days vs. 41.6 days, hazard ratio 1.687, 95% confidence interval: 1.260–2.259, P<0.001). A multivariate Cox proportional hazard analysis indicated that insomnia, constipation, nausea/vomiting, infection, non-cancer pain, oral mucositis, odynophagia and neutropenia were significant risk factors for prolongation of hospital stay. Conclusion Patients who experienced adverse events are at high risk of prolonged hospitalization. Medical intervention for adverse events was found to be effective in reducing the length of hospital stay associated with adverse events. PMID:25549093

Suzuki, Akio; Kobayashi, Ryo; Okayasu, Shinji; Kuze, Bunya; Aoki, Mitsuhiro; Mizuta, Keisuke; Itoh, Yoshinori

2014-01-01

282

Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials  

PubMed Central

Background Motility-related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development. Methods Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility-related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration-response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model. Key Results Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%. Conclusions & Inferences Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility. PMID:24813024

Keating, C; Ewart, L; Grundy, L; Valentin, JP; Grundy, D

2014-01-01

283

A Structure-Based Approach for Mapping Adverse Drug Reactions to the Perturbation of Underlying Biological Pathways  

PubMed Central

Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature. PMID:20808786

Wallach, Izhar; Jaitly, Navdeep; Lilien, Ryan

2010-01-01

284

Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations.  

PubMed

It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on 'HLA epitope' frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms-thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included. PMID:25414323

González-Galarza, Faviel F; Takeshita, Louise Y C; Santos, Eduardo J M; Kempson, Felicity; Maia, Maria Helena Thomaz; Silva, Andrea Luciana Soares da; Silva, André Luiz Teles E; Ghattaoraya, Gurpreet S; Alfirevic, Ana; Jones, Andrew R; Middleton, Derek

2015-01-28

285

Prescribing of medicines in the Danish paediatric population outwith the licensed age group: characteristics of adverse drug reactions  

PubMed Central

AIM To identify adverse drug reactions (ADRs) associated with off-label prescribing of medicines in a paediatric population. METHODS We analysed spontaneous ADR reports for children from ages 0 to 17 years submitted to the Danish national ADR database from 1998 to 2007. We defined off-label prescribing as prescriptions outside the licensed age group. Off-label ADRs were categorized by therapeutic group, age of child, type and severity. The unit of analysis was one ADR. RESULTS We analysed 4388 ADRs for children reported in the national database. Approximately 17% of reported ADRs were associated with off-label use, 60% of them serious. More than one half of off-label ADRs were reported in adolescents. Serious ADRs due to off-label prescribing are more likely to be reported for hormonal contraceptives (ATC group G), anti-acne preparations (ATC group D) and allergens (ATC group V). CONCLUSION One-fifth of all ADRs reported over a decade in Danish children was associated with off-label prescribing, and serious ADRs due to off-label prescribing were primarily present in three therapeutic groups: sex hormones, dermatologicals and allergens. There is a need for more research into the prescribing of these medicines in the teenage population, as well as tighter reporting and monitoring of ADRs for medicines prescribed off-label in the paediatric population. PMID:21241353

Aagaard, Lise; Hansen, Ebba Holme

2011-01-01

286

Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions  

PubMed Central

Introduction 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. Areas covered 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. Expert opinion 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. PMID:22280100

Clarke, John D; Cherrington, Nathan J

2013-01-01

287

Disclosure and adverse effects of complementary and alternative medicine used by hospitalized patients in the North East of England  

PubMed Central

Objective This study aimed to investigate the prevalence, disclosure and adverse effects of complementary and alternative medicine (CAM) use in hospitalised patients, and to explore the associations between patients' perceived side-effects and relevant factors. Methods Patients who were admitted to a district general hospital and met the eligibility criteria were interviewed using a semi-structured questionnaire. Their medications and pertinent details were verified from the medical notes. All quantitative and qualitative data were collated and analysed. A chi-squared test was performed to test the associations of the perceived CAM side-effects with the significance level determined at ?=0.05. Results A total of 240 in-patients completed the study. They were mostly white British (98.8%). The prevalence of CAM use within two years was 74.6% and one month 37.9%. Only 19 of 91 patients (20.9%) using CAM within one month disclosed their current CAM applications. Nearly half of patients (45.8%) who used CAM within two years experienced various CAM side-effects that tended to resolve after discontinuation. Slightly more than half (57.6%) perceived CAM side-effects and their perceptions were significantly associated with gender (P=0.048) and consideration for future CAM use (P=0.033). Potential interactions between herbal remedies/dietary supplements and prescribed drugs, such as garlic with lisinopril or aspirin, were assessed in 82 patients (45.8%). Conclusions Most in-patients used CAM and experienced some adverse effects. The disclosure of CAM use and its adverse outcomes should be encouraged by healthcare professionals. PMID:24155828

Bello, Nusirat; Winit-Watjana, Win; Baqir, Wasim; Mcgarry, Kenneth

288

Diagramming patients’ views of root causes of adverse drug events in ambulatory care: An online tool for planning education and research  

Microsoft Academic Search

ObjectiveDiagram patients’ views of the causes of adverse drug events (ADEs) in ambulatory care, examine characteristics of causes reported by patients, and identify those that have been studied in the medical and social science literatures.

Mary Brown; Rowan Frost; Yu Ko; Raymond Woosley

2006-01-01

289

Design and validation of an automated method to detect known adverse drug reactions in MEDLINE: a contribution from the EU–ADR project  

PubMed Central

Objectives The aim of this research was to automate the search of publications concerning adverse drug reactions (ADR) by defining the queries used to search MEDLINE and by determining the required threshold for the number of extracted publications to confirm the drug/event association in the literature. Methods We defined an approach based on the medical subject headings (MeSH) ‘descriptor records’ and ‘supplementary concept records’ thesaurus, using the subheadings ‘chemically induced’ and ‘adverse effects’ with the ‘pharmacological action’ knowledge. An expert-built validation set of true positive and true negative drug/adverse event associations (n=61) was used to validate our method. Results Using a threshold of three of more extracted publications, the automated search method presented a sensitivity of 90% and a specificity of 100%. For nine different drug/event pairs selected, the recall of the automated search ranged from 24% to 64% and the precision from 93% to 48%. Conclusions This work presents a method to find previously established relationships between drugs and adverse events in the literature. Using MEDLINE, following a MeSH approach to filter the signals, is a valid option. Our contribution is available as a web service that will be integrated in the final European EU–ADR project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) automated system. PMID:23195749

Avillach, Paul; Dufour, Jean-Charles; Diallo, Gayo; Salvo, Francesco; Joubert, Michel; Thiessard, Frantz; Mougin, Fleur; Trifirò, Gianluca; Fourrier-Réglat, Annie; Pariente, Antoine; Fieschi, Marius

2013-01-01

290

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.  

PubMed

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/?L. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge. PMID:25386460

Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

2014-09-01

291

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient – A Case Report  

PubMed Central

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/?L. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge. PMID:25386460

Janardhanan, Manju; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

2014-01-01

292

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

Microsoft Academic Search

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250

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

2012-01-01

293

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

Microsoft Academic Search

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250

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

2011-01-01

294

Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells.  

PubMed

Contact sensitizers induce phenotypic and functional changes in dendritic cells (DC) that enhance their antigen-presenting capacity and, ultimately, modulate the T cell response. To evaluate if there is a similar effect of drugs causing T-cell-mediated cutaneous adverse drug reactions (CADR), we studied the in vitro effect of drugs on THP-1 cells, a cell line widely used to evaluate the early molecular and cellular events triggered by contact sensitizers. The effect of allopurinol, oxypurinol, ampicillin, amoxicillin, carbamazepine and sodium valproate, at EC30 concentrations, was evaluated on p38 MAPK activation, by Western Blot, and on the expression of genes coding for DC maturation markers, pro-inflammatory cytokine/chemokines and hemeoxygenase 1 (HMOX1), by real-time RT-PCR. Results were compared with lipopolysaccharide (LPS), a DC maturation stimulus, and the strong contact sensitizer, 1-fluoro-2,4-dinitrobenzene (DNFB). All drugs studied significantly upregulated HMOX1 gene transcription and all, except the anticonvulsants, also upregulated IL8. Allopurinol and oxypurinol showed the most intense effect, in a magnitude similar to DNFB and superior to betalactams. Transcription of CD40, IL12B and CXCL10 genes by drugs was more irregular. Moreover, like DNFB, all drugs activated p38 MAPK, although significantly only for oxypurinol. Like contact sensitizers, drugs that cause non-immediate CADR activate THP-1 cells in vitro, using different signalling pathways and affecting gene transcription with an intensity that may reflect the frequency and severity of the CADR they cause. Direct activation of antigen-presenting DC by systemic drugs may be an important early step in the pathophysiology of non-immediate CADR. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25091725

Gonçalo, Margarida; Martins, João; Silva, Ana; Neves, Bruno; Figueiredo, Américo; Cruz, Teresa; Lopes, Celeste

2014-08-01

295

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene  

PubMed Central

Background: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. Objective: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. Design: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. Results: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. Conclusions: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis. PMID:15361376

Berkun, Y; Levartovsky, D; Rubinow, A; Orbach, H; Aamar, S; Grenader, T; Abou, A; Mevorach, D; Friedman, G; Ben-Yehuda, A

2004-01-01

296

Management of adverse events in patients with metastatic renal cell carcinoma treated with sunitinib and clinical outcomes.  

PubMed

Patients with progressive renal cell carcinoma who undergo sunitinib treatment, experience many adverse events (AEs), including thrombopenia and hypertension. Dose reduction or treatment discontinuation due to AEs makes it difficult to control the clinical condition. Therefore, patients' understanding regarding the basics of blood pressure (BP) measurement and how to deal with each AE are particularly important. Here we report whether or not pharmacist instructions help in order to increase patients' awareness of early AE management results in an improvement of treatment outcomes. The present study included 15 patients who were administered sunitinib. From the start of sunitinib treatment, pharmacists continuously provided drug administration guidance to the patients and confirmed their awareness and knowledge regarding AEs, symptom management, and drug adherence. The relative dose intensity (RDI) of 15 patients from week 1 to 24 after sunitinib treatment was calculated. Pharmaceutical interventions significantly improved patients' understanding of BP measurements and reference values, etc. Although the RDI was 67.3%-78.7%, there were no cases of discontinuation of administration or reduction of the dose caused by e.g. hypertension, hand and foot syndrome (HFS) and stomatitis. Pharmaceutical interventions improved patients' awareness of the management of AEs and adherence to sunitinib therapy. As a result, a high RDI was maintained, which may lead to prolonged survival. Therefore, our results suggest that early AE management provided by pharmacists is particularly important to assure the safety and efficacy of sunitinib therapy. PMID:24222148

Arakawa-Todo, Maki; Yoshizawa, Takahiko; Zennami, Kenji; Nishikawa, Genya; Kato, Yoshiharu; Kobayashi, Ikuo; Kajikawa, Keishi; Yamada, Yoshiaki; Matsuura, Katsuhiko; Tsukiyama, Ikuto; Saito, Hiroko; Hasegawa, Takaaki; Nakamura, Kogenta; Sumitomo, Makoto

2013-11-01

297

Models developed from the PLCO may help identify at-risk patients for adverse smoking outcomes  

Cancer.gov

Risk prediction models developed from an ancillary study of the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) may be useful in the public health sector for identifying individuals who are at risk for adverse smoking outcomes, such as relapse among former smokers and continued smoking among current smokers, and those who may benefit from relapse prevention and smoking cessation interventions, according to a study from the Lombardi Comprehensive Cancer Center at Georgetown University published October 26 in the Journal of the National Cancer Institute.

298

How to maintain patients on long-term therapy: understanding the profile and kinetics of adverse events.  

PubMed

Thalidomide, lenalidomide, and bortezomib have considerably improved the survival of patients with multiple myeloma. These agents have specific adverse event (AE) profiles, and it is especially important to consider severe AEs that may lead to premature discontinuation, negatively affecting outcomes. AEs of particular concern are peripheral neuropathy (associated with thalidomide and bortezomib), venous thromboembolism (associated with thalidomide and lenalidomide), and myelosuppression (associated with lenalidomide and bortezomib). AEs are usually predictable and easily managed with monitoring, appropriate dose adjustments, and supportive care. AEs are generally transient, occurring early in the course of treatment, providing evidence for the feasibility of continuous therapy. PMID:23176723

Mateos, María-Victoria

2012-11-01

299

Medication Monitoring in a Nurse-Led Respiratory Outpatient Clinic: Pragmatic Randomised Trial of the West Wales Adverse Drug Reaction Profile  

PubMed Central

Objective To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine. Design Single-site parallel-arm pragmatic trial using stratified randomisation. Setting Nurse-led respiratory outpatient clinic in general hospital in South Wales. Participants 54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists. Intervention Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care (‘intervention arm’ with 26 participants); or usual care alone (‘control arm’ with 28 participants). Main Outcome Measures Problems reported and actions taken. Results We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13–26], while that in the control arm was ?1 [?3 to +2] [Mann-Whitney U test: z?=?6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]–[4] while that in the control arm was 0 [?1.75 to +1] [Mann-Whitney U test: z?=?4.40, p<0.001]. Conclusion When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management. Trial Registration Controlled-trials.com ISRCTN10386209 PMID:24798210

Gabe, Marie E.; Murphy, Fiona; Davies, Gwyneth A.; Russell, Ian T.; Jordan, Susan

2014-01-01

300

Adverse Drug Events in Older Hospitalized Patients: Results and Reliability of a Comprehensive and Structured Identification Strategy  

PubMed Central

Background Older patients are at high risk for experiencing Adverse Drug Events (ADEs) during hospitalization. To be able to reduce ADEs in these vulnerable patients, hospitals first need to measure the occurrence of ADEs, especially those that are preventable. However, data on preventable ADEs (pADEs) occurring during hospitalization in older patients are scarce, and no ‘gold standard’ for the identification of ADEs exists. Methodology The study was conducted in three hospitals in the Netherlands in 2007. ADEs were retrospectively identified by a team of experts using a comprehensive and structured patient chart review (PCR) combined with a trigger-tool as an aid. This ADE identification strategy was applied to a cohort of 250 older hospitalized patients. To estimate the intra- and inter-rater reliabilities, Cohen’s kappa values were calculated. Principal Findings In total, 118 ADEs were detected which occurred in 62 patients. This ADE yield was 1.1 to 2.7 times higher in comparison to other ADE studies in older hospitalized patients. Of the 118 ADEs, 83 (70.3%) were pADEs; 51 pADEs (43.2% of all ADEs identified) caused serious patient harm. Patient harm caused by ADEs resulted in various events. The overall intra-rater agreement of the developed strategy was substantial (??=?0.74); the overall inter-rater agreement was only fair (??=?0.24). Conclusions/Significance The ADE identification strategy provided a detailed insight into the scope of ADEs occurring in older hospitalized patients, and showed that the majority of (serious) ADEs can be prevented. Several strategy related aspects, as well as setting/study specific aspects, may have contributed to the results gained. These aspects should be considered whenever ADE measurements need to be conducted. The results regarding pADEs can be used to design tailored interventions to effectively reduce harm caused by medication errors. Improvement of the inter-rater reliability of a PCR remains challenging. PMID:23940688

Klopotowska, Joanna E.; Wierenga, Peter C.; Stuijt, Clementine C. M.; Arisz, Lambertus; Dijkgraaf, Marcel G. W.; Kuks, Paul F. M.; Asscheman, Henk; de Rooij, Sophia E.; Lie-A-Huen, Loraine; Smorenburg, Susanne M.

2013-01-01

301

Sarcopenia Adversely Impacts Postoperative Complications Following Resection or Transplantation in Patients with Primary Liver Tumors  

PubMed Central

Background Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies. Methods Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed. Results Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm3/m) versus men (34.9 cm3/m) (P<0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia (P=0.01). Of note, all Clavien grade ?3 complications (n=11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR=3.06). Sarcopenia was not associated with long-term survival (HR=1.23; P=0.51). Conclusions Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies. PMID:25389056

Valero, Vicente; Amini, Neda; Spolverato, Gaya; Weiss, Matthew J.; Hirose, Kenzo; Dagher, Nabil N.; Wolfgang, Christopher L.; Cameron, Andrew A.; Philosophe, Benjamin; Kamel, Ihab R.

2015-01-01

302

What can we learn from patient claims? - A retrospective analysis of incidence and patterns of adverse events after orthopaedic procedures in Sweden  

PubMed Central

Background Objective data on the incidence and pattern of adverse events after orthopaedic surgical procedures remain scarce, secondary to the reluctance for encompassing reporting of surgical complications. The aim of this study was to analyze the nature of adverse events after orthopaedic surgery reported to a national database for patient claims in Sweden. Methods In this retrospective review data from two Swedish national databases during a 4-year period were analyzed. We used the "County Councils' Mutual Insurance Company", a national no-fault insurance system for patient claims, and the "National Patient Register at the National Board of Health and Welfare". Results A total of 6,029 patient claims filed after orthopaedic surgery were assessed during the study period. Of those, 3,336 (55%) were determined to be adverse events, which received financial compensation. Hospital-acquired infections and sepsis were the most common causes of adverse events (n = 741; 22%). The surgical procedure that caused the highest rate of adverse events was "decompression of spinal cord and nerve roots" (code ABC**), with 168 adverse events of 17,507 hospitals discharges (1%). One in five (36 of 168; 21.4%) injured patient was seriously disabled or died. Conclusions We conclude that patients undergoing spinal surgery run the highest risk of being severely injured and that these patients also experienced a high degree of serious disability. The most common adverse event was related to hospital acquired infections. Claims data obtained in a no-fault system have a high potential for identifying adverse events and learning from them. PMID:22264241

2012-01-01

303

Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events.  

PubMed

Abstract The effectiveness of aspirin and clopidogrel in patients with chronic kidney disease (CKD) suffering from acute cardiovascular events is unclear. High on treatment platelet reactivity (HTPR) has been associated with worse outcomes. Here, we assessed the association of dipstick proteinuria (DP) and renal function on HTPR and clinical outcomes. Retrospective cohort analysis of 261 consecutive, non-dialysis patients admitted for Major Adverse Cardiovascular Events (MACE) that had VerifyNow P2Y12 and VerifyNow Aspirin assays performed. HTPR was defined as P2Y12 reactivity unit (PRU)?>?208 for clopidogrel and aspirin reaction units (ARU)?>?550 for aspirin. Renal function was classified based on the estimated glomerular filtration rate (eGFR), and dipstick proteinuria was defined as ?30?mg/dl of albumin detected on a spot analysis. All cause mortality, readmissions, and cardiac catheterizations were reviewed over 520 days. In patients on clopidogrel (n?=?106), DP was associated with HTPR, independent of eGFR, diabetes mellitus, smoking or use of proton pump inhibitor (AOR?=?4.76, p?=?0.03). In patients with acute coronary syndromes, HTPR was associated with more cardiac catheterizations (p?=?0.009) and readmissions (p?=?0.032), but no differences in in-stent thrombosis or re-stenosis were noted in this cohort. In patients on aspirin (n?=?155), no associations were seen between DP and HTPR. However, all cause mortality was significantly higher with HTPR in this group (p?=?0.038). In this cohort, DP is an independent predictor of HTPR in patients on clopidogrel, but not aspirin, admitted to the hospital for MACE. PMID:25354134

Davila, Carlos D; Vargas, Fernando; Huang, Kuan-Hsiang Gary; Monaco, Thomas; Dimou, Anastasios; Rangaswami, Janani; Figueredo, Vincent M

2014-10-29

304

Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia  

PubMed Central

The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients. PMID:24649390

Khasawneh, Fadi T.; Shankar, Gollapudi S.

2014-01-01

305

Deficits in metacognitive capacity distinguish patients with schizophrenia from those with prolonged medical adversity.  

PubMed

Research has suggested that many with schizophrenia experience decrements in synthetic metacognition, or the abilities to form integrated representations of oneself and others and then utilize that knowledge to respond to problems. Although such deficits have been linked with functional impairments even after controlling for symptoms and neurocognition, it is unclear to what extent these deficits can distinguish persons with schizophrenia from others experiencing significant life adversity but without psychosis. To explore this issue we conducted logistic regression analysis to determine whether assessment of metacognition could distinguish between 166 participants with schizophrenia and 51 adults with HIV after controlling for social cognition and education. Metacognition was assessed with the Metacognitive Assessment Scale Abbreviated (MAS-A), and social cognition with the Bell Lysaker Emotion Recognition Test. We observed that the MAS-A total score was able to correctly classify 93.4% of the schizophrenia group, with higher levels of metacognition resulting in increased likelihood of accurate categorization. Additional exploratory analyses showed specific domains of metacognition measured by the MAS-A were equally able to predict membership in the schizophrenia group. Results support the assertion that deficits in the abilities to synthesize thoughts about oneself and others into larger representations are a unique feature of schizophrenia. PMID:24811777

Lysaker, Paul H; Vohs, Jenifer; Hamm, Jay A; Kukla, Marina; Minor, Kyle S; de Jong, Steven; van Donkersgoed, Rozanne; Pijnenborg, Marieke H M; Kent, Jerillyn S; Matthews, Sean C; Ringer, Jamie M; Leonhardt, Bethany L; Francis, Michael M; Buck, Kelly D; Dimaggio, Giancarlo

2014-08-01

306

Low impact of cardiovascular adverse events on anagrelide treatment discontinuation in a cohort of 232 patients with essential thrombocythemia.  

PubMed

This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs. PMID:21764130

Gugliotta, Luigi; Tieghi, Alessia; Tortorella, Giovanni; Scalzulli, Potito Rosario; Ciancia, Rosanna; Lunghi, Monia; Cacciola, Emma; Cacciola, Rossella; Candoni, Anna; Crugnola, Monica; Codeluppi, Katia; Usala, Emilio; Specchia, Giorgina; Martinelli, Vincenzo; Palmieri, Fausto; Pierri, Ivana; Liberati, Anna Marina; Iurlo, Alessandra; Grossi, Alberto; Vannucchi, Alessandro M; Vianelli, Nicola; Mazzucconi, Maria Gabriella

2011-12-01

307

Predictive factors of herpes zoster HIV-infected patients: another adverse effect of crack cocaine.  

PubMed

A retrospective cohort study was conducted on 1541 HIV-infected patients to determine variables associated with the incidence of herpes zoster. A single failure Cox model showed that herpes zoster incidence increased following the first 6 months of antiretroviral treatment adjusted hazard ratio (AHR)=5 (95%CI=2.6-9.2), P<0.001; in the >60 years age group AHR=2 (95%CI=1-4), P=0.04; in patients in the top CD8 quartile AHR=2.1 (95%CI=1.3-3.6), P<0.001; and in patients previously reported to use crack cocaine AHR=5.9, (95%CI=1.4-25), P=0.02. Herpes zoster incidence increased in patients with CD4 counts<500 per mm(3) and gradually declined since 1992-1996, with AHR=0.3 (95%CI=0.2-0.5), P<0.001 for the 1997-2002 period and AHR=0.24 (95%CI=0.14-0.4), P<0.001 for the 2002-2008 period. Contrary to what has been described elsewhere, there was no specific effect of protease inhibitors on herpes zoster incidence. The present study is the first to suggest that crack cocaine is associated with an increased incidence of herpes zoster. The neurological or immunological effects of crack are discussed. PMID:24244647

Nacher, Mathieu; Basurko, Celia; Adenis, Antoine; Gaubert-Marechal, Emilie; Mosnier, Emilie; Edouard, Sophie; Vantilcke, Vincent; Sivapregassam, Sindou; Tressières, Benoit; Cabié, André; Couppié, Pierre

2013-01-01

308

Drug Reactions  

MedlinePLUS

... version Drug Reactions Drug Reactions What is an adverse drug reaction? Medicines can treat or prevent illness and ... medicines can cause problems. These problems are called adverse drug reactions. You should know what to do if ...

309

PKPD Modeling of Predictors for Adverse Effects and Overall Survival in Sunitinib-Treated Patients With GIST  

PubMed Central

A modeling framework relating exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR)-2, -3, soluble stem cell factor receptor (sKIT)), and tumor growth to overall survival (OS) was extended to include adverse effects (myelosuppression, hypertension, fatigue, and hand–foot syndrome (HFS)). Longitudinal pharmacokinetic–pharmacodynamic models of sunitinib were developed based on data from 303 patients with gastrointestinal stromal tumor. Myelosuppression was characterized by a semiphysiological model and hypertension with an indirect response model. Proportional odds models with a first-order Markov model described the incidence and severity of fatigue and HFS. Relative change in sVEGFR-3 was the most effective predictor of the occurrence and severity of myelosuppression, fatigue, and HFS. Hypertension was correlated best with sunitinib exposure. Baseline tumor size, time courses of neutropenia, and relative increase of diastolic blood pressure were identified as predictors of OS. The framework has potential to be used for early monitoring of adverse effects and clinical response, thereby facilitating dose individualization to maximize OS. PMID:24304978

Hansson, E K; Ma, G; Amantea, M A; French, J; Milligan, P A; Friberg, L E; Karlsson, M O

2013-01-01

310

Severe infusion-related reactions are uncommon in rituximab-treated CLL patients in clinical practice: Results from a Swedish national observational study.  

PubMed

There have been concerns about serious infusion-related adverse drug reactions (ADR) with rituximab in chronic lymphocytic leukemia (CLL). We therefore conducted an observational trial in which CLL patients planned for rituximab-containing therapy were eligible. Ninety-six patients from 19 centers were enrolled. The most common regimen was rituximab, fludarabine and cyclophosphamide. Fifty-six patients experienced ADR during rituximab infusion. Reactions?grade 3 occurred in five patients and no cases of tumor lysis syndrome were recorded. Despite a high number of circulating tumor cells few severe ADR were noted. Thus, rituximab-containing regimens can be considered safe for CLL patients in general practice. PMID:25499233

Norin, Stefan; Björkstrand, Bo; Rommel, Franz; Timberg, Lars; Andersson, Per-Ola; Häggström, Johan; Aldrin, Anders; Hansson, Lotta

2015-01-01

311

Suspected adverse reactions associated with herbal products used for weight loss: a case series reported to the Italian National Institute of Health  

Microsoft Academic Search

Purpose  The aim of this study was to describe suspected adverse reactions (ARs) associated with herbal products used for weight control\\u000a in Italy.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Spontaneous reports of suspected ARs associated with herbal products used for weight control were collected by the Italian\\u000a National Institute of Health (April 2002 to June 2010), and the causality assessment was performed.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Forty-six of the suspected ARs

Annabella Vitalone; Francesca Menniti-Ippolito; Paola Angela Moro; Fabio Firenzuoli; Roberto Raschetti; Gabriela Mazzanti

2011-01-01

312

Matrix Metalloproteinase 7 Is Associated with Symptomatic Lesions and Adverse Events in Patients with Carotid Atherosclerosis  

PubMed Central

Background Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process. Methods Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (?70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined. Results Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-? in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality. Conclusion Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms. PMID:24400123

Abbas, Azhar; Aukrust, Pål; Russell, David; Krohg-Sørensen, Kirsten; Almås, Trine; Bundgaard, Dorte; Bjerkeli, Vigdis; Sagen, Ellen Lund; Michelsen, Annika E.; Dahl, Tuva B.; Holm, Sverre; Ueland, Thor

2014-01-01

313

Adverse Prognostic Impact of Intratumor Heterogeneous HER2 Gene Amplification in Patients With Esophageal Adenocarcinoma  

PubMed Central

Purpose There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. We determined the frequency and prognostic impact of heterogeneous HER2 gene amplification and polysomy 17 in patients with esophageal adenocarcinoma (EAC). Patients and Methods HER2 amplification (by fluorescence in situ hybridization) was examined in surgical EAC specimens (n = 675). HER2 heterogeneity was defined according to consensus guidelines as gene amplification (HER2/CEP17 ratio ? 2.0) in more than 5% but less than 50% of cancer cells. No patient received neoadjuvant or HER2-targeted therapy. Cox models were used to assess disease-specific survival (DSS) and overall survival (OS). Results Overall, 117 EACs (17%) demonstrated HER2 amplification, of which 20 (17%) showed HER2 heterogeneity. All HER2-heterogeneous tumors were amplified. Among HER2-amplified tumors, heterogeneous tumors had significantly higher frequency of poor histologic grade and polysomy 17. In multivariable models that included number of metastatic lymph nodes, grade, tumor stage, and polysomy 17, only HER2 heterogeneity and node number were prognostic among HER2-amplified tumors, with heterogeneity showing worse DSS (hazard ratio, 2.04; 95% CI, 1.09 to 3.79; P = .025) and OS (P = .026). Among HER2-nonamplified EACs, polysomy 17 was independently associated with worse DSS (P = .012) and OS (P = .023). Conclusion Among HER2-amplified EACs, 17% show HER2 heterogeneity, which independently predicts for worse cancer-specific death. Among HER2-nonamplified EACs, polysomy 17 is independently associated with worse survival. These novel findings demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that have important implications for HER2 analysis and determination of benefit from HER2-targeted therapy. PMID:22987085

Yoon, Harry H.; Shi, Qian; Sukov, William R.; Lewis, Mark A.; Sattler, Christopher A.; Wiktor, Anne E.; Wu, Tsung-Teh; Diasio, Robert B.; Jenkins, Robert B.; Sinicrope, Frank A.

2012-01-01

314

Venous thromboembolism is a relevant and underestimated adverse event in cancer patients treated in phase I studies  

PubMed Central

Background: To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies. Methods: Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered. Results: Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13–85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29–6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18–8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11–6.30, P=0.028), white blood cell >11?000??l?1 (HR: 2.59, 95% CI: 1.10–6.09, P=0.028) and haemoglobin<10?g?dl?1 (HR: 3.1, 95% CI: 1.07–8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02). Conclusion: Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs. PMID:22828607

Mandalà, M; Grosso, F; Vitalini, C; Corradino, I; Sanfilippo, R; Colombini, S; Clerici, M; Labianca, R; De Pascale, A; Marsoni, S

2012-01-01

315

The influence of a triclosan toothpaste on adverse events in patients with cardiovascular disease over 5-years.  

PubMed

Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown. We assessed the effect of long-term use of 0.3% triclosan-toothpaste on serious adverse events (SAEs) in patients with cardiovascular disease (CVD). 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital, Brisbane, Australia and randomised into test (triclosan) or placebo groups. There were no significant differences in demographics or clinical features between the groups. Patients were examined at baseline, and annually for 5-years. SAEs were classified according to the System Organ Classes defined by MedDRA (Medical Dictionary for Regulatory Activities). Results were analysed using chi square and Kaplan Meier analysis. Overall, 232 patients (123 in the triclosan group; 109 in the placebo group) experienced 569 SAEs (288 in the triclosan group and 281 in the placebo group). There was no significant difference between the groups in numbers of patients experiencing SAEs (p=0.35) or specific cardiovascular SAEs (p=0.82), nor in time to the first SAE or first cardiovascular SAE, irrespective of gender, age or BMI after adjusting for multiple comparisons (p>0.05). The adjusted odds of experiencing an SAE were estimated to increase by 2.7% for each year of age (p=0.02) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1% for each unit increase in BMI (p=0.02). Most cardiovascular events were related to unstable angina or myocardial infarcts, 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident. Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population. The long-term impact of triclosan on hormone-related disease, such as cancer, in humans remains to be determined. PMID:25442641

Cullinan, Mary P; Palmer, Janet E; Carle, Anne D; West, Malcolm J; Westerman, Bill; Seymour, Gregory J

2015-03-01

316

Prediction of adverse cardiac events in emergency department patients with chest pain using machine learning for variable selection  

PubMed Central

Background The key aim of triage in chest pain patients is to identify those with high risk of adverse cardiac events as they require intensive monitoring and early intervention. In this study, we aim to discover the most relevant variables for risk prediction of major adverse cardiac events (MACE) using clinical signs and heart rate variability. Methods A total of 702 chest pain patients at the Emergency Department (ED) of a tertiary hospital in Singapore were included in this study. The recruited patients were at least 30 years of age and who presented to the ED with a primary complaint of non-traumatic chest pain. The primary outcome was a composite of MACE such as death and cardiac arrest within 72 h of arrival at the ED. For each patient, eight clinical signs such as blood pressure and temperature were measured, and a 5-min ECG was recorded to derive heart rate variability parameters. A random forest-based novel method was developed to select the most relevant variables. A geometric distance-based machine learning scoring system was then implemented to derive a risk score from 0 to 100. Results Out of 702 patients, 29 (4.1%) met the primary outcome. We selected the 3 most relevant variables for predicting MACE, which were systolic blood pressure, the mean RR interval and the mean instantaneous heart rate. The scoring system with these 3 variables produced an area under the curve (AUC) of 0.812, and a cutoff score of 43 gave a sensitivity of 82.8% and specificity of 63.4%, while the scoring system with all the 23 variables had an AUC of 0.736, and a cutoff score of 49 gave a sensitivity of 72.4% and specificity of 63.0%. Conventional thrombolysis in myocardial infarction score and the modified early warning score achieved AUC values of 0.637 and 0.622, respectively. Conclusions It is observed that a few predictors outperformed the whole set of variables in predicting MACE within 72 h. We conclude that more predictors do not necessarily guarantee better prediction results. Furthermore, machine learning-based variable selection seems promising in discovering a few relevant and significant measures as predictors. PMID:25150702

2014-01-01

317

Alcoholism and other socio-demographic risk factors for adverse TB-drug reactions and unsuccessful tuberculosis treatment – data from ten years’ observation at the Regional Centre of Pulmonology, Bydgoszcz, Poland  

PubMed Central

Background Tuberculosis (TB) is one of the most dangerous infectious diseases and has one of the highest mortality rates. For decades a strong association has been evident between certain socio-economic factors and TB adverse events and failure of treatment, yet there is a limited quantity of literature available on this subject, especially in the Polish literature. Material/Methods We examined epidemiological data from 2025 TB patients treated at the Regional Centre of Pulmonology in Bydgoszcz, Poland between 2001 and 2010. This article focuses on the association between all forms of unsuccessful TB treatment outcomes or adverse drug reaction (ADR) and socio-demographic characteristics, condition on admission, and other biological, clinical, social, and healthcare access factors. Results The rate of TB-ADR during hospitalization was 38.9%. Multivariate logistic regression analysis showed that age (P<0.001) and alcohol abuse (P=0.007) were independently associated with the occurrence of TB-ADR. The rate of unsuccessful TB treatment was 10.5%. After adjusting for confounding variables, age (P<0.001), alcohol abuse (P=0.002), and education (P=0.01) were significantly associated with unsuccessful treatment. Smoking did not have any significant influence on occurrence of either TB-ADR during hospitalization or unsuccessful treatment. Conclusions Among our TB patients treated between 2001 and 2010, alcohol abuse significantly worsened the treatment outcome. This information will be crucial in developing strategies targeted at this demographic group. PMID:24643127

Przybylski, Grzegorz; D?browska, Anita; Trzci?ska, Hanna

2014-01-01

318

Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies.  

PubMed

High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption, are currently evaluated in phase III clinical trials in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton growth is a critical question in the context of patients with actively growing skeleton; in particular, in light of our previous studies evidencing that endochondral bone formation was transiently disturbed by high doses of ZOL. Two protocols adapted from pediatric treatments were developed for newborn mice (a total of 5 or 10 injections of ZOL 50?g/kg every two days). Their impact on skull bones and teeth growth was analyzed by X-rays, microCT and histology up to 3months after the last injection. ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption and root elongation. Other teeth were affected, but most were erupted by 3months. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in all mandibular incisors. High doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. These preclinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL. PMID:25193159

Lézot, Frédéric; Chesneau, Julie; Battaglia, Séverine; Brion, Régis; Castaneda, Beatriz; Farges, Jean-Christophe; Heymann, Dominique; Rédini, Françoise

2014-11-01

319

An Elevated Gap between Admission and A1C-Derived Average Glucose Levels Is Associated with Adverse Outcomes in Diabetic Patients with Pyogenic Liver Abscess  

PubMed Central

Objectives To assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA). Methods Clinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004–2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes. Results Diabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap<72 mg/dL. Multivariate analysis revealed that an elevated glycemic gap?72 mg/dL was important predictor of adverse outcomes. Conclusions A glycemic gap?72 mg/dL, rather than admission hyperglycemia or chronic glycemic control, was significantly correlated with adverse outcomes in diabetic PLA patients. Poorer chronic glycemic control in diabetic PLA patients is associated with high incidence of KP infection, hypoalbuminemia and longer hospital stay. PMID:23724053

Liao, Wen-I; Sheu, Wayne Huey-Herng; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Yu-Long; Tsai, Shih-Hung

2013-01-01

320

Predictors of time to revision and clinical outcomes following revision of metal-on-metal hip replacements for adverse reaction to metal debris.  

PubMed

We undertook a retrospective cohort study to determine clinical outcomes following the revision of metal-on-metal (MoM) hip replacements for adverse reaction to metal debris (ARMD), and to identify predictors of time to revision and outcomes following revision. Between 1998 and 2012 a total of 64 MoM hips (mean age at revision of 57.8 years; 46 (72%) female; 46 (72%) hip resurfacings and 18 (28%) total hip replacements) were revised for ARMD at one specialist centre. At a mean follow-up of 4.5 years (1.0 to 14.6) from revision for ARMD there were 13 hips (20.3%) with post-operative complications and eight (12.5%) requiring re-revision. The Kaplan-Meier five-year survival rate for ARMD revision was 87.9% (95% confidence interval 78.9 to 98.0; 19 hips at risk). Excluding re-revisions, the median absolute Oxford hip score (OHS) following ARMD revision using the percentage method (0% best outcome and 100% worst outcome) was 18.8% (interquartile range (IQR) 7.8% to 48.3%), which is equivalent to 39/48 (IQR 24.8/48 to 44.3/48) when using the modified OHS. Histopathological response did not affect time to revision for ARMD (p = 0.334) or the subsequent risk of re-revision (p = 0.879). Similarly, the presence or absence of a contralateral MoM hip bearing did not affect time to revision for ARMD (p = 0.066) or the subsequent risk of re-revision (p = 0.178). Patients revised to MoM bearings had higher rates of re-revision (five of 16 MoM hips re-revised; p = 0.046), but those not requiring re-revision had good functional results (median absolute OHS 14.6% or 41.0/48). Short-term morbidity following revision for ARMD was comparable with previous reports. Caution should be exercised when choosing bearing surfaces for ARMD revisions. PMID:25452361

Matharu, G S; Pynsent, P B; Sumathi, V P; Mittal, S; Buckley, C D; Dunlop, D J; Revell, P A; Revell, M P

2014-12-01

321

Caffeic acid phenethyl ester: A review of its antioxidant activity, protective effects against ischemia-reperfusion injury and drug adverse reactions.  

PubMed

Abstract Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions. PMID:25365228

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2014-11-01

322

Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study  

PubMed Central

Aim To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence. Methods In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them. Results HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n?=?4) was significantly higher (P?adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education. PMID:21990078

Miroševi? Skvrce, Nikica; Macoli? Šarini?, Viola; Mucalo, Iva; Krni?, Darko; Božina, Nada; Tomi?, Siniša

2011-01-01

323

Identifying and preventing adverse drug events in elderly hospitalised patients: A randomised trial of a program to reduce adverse drug effects  

Microsoft Academic Search

Objectives  Evaluate the impact of educational intervention in decreasing ADEs in elderly patients in a hospital setting.\\u000a \\u000a \\u000a \\u000a Design  Randomised prospective study.\\u000a \\u000a \\u000a \\u000a Setting  The study was performed in France in the Paris area, in 16 rehabilitation geriatric centres of APHP (Assistance Publique —\\u000a Höpitaux de Paris). Patient capacity per centre varied from 15 to 57 with a total of 526.\\u000a \\u000a \\u000a \\u000a \\u000a Participants  All the patients ?

Christophe Trivalle; T. Cartier; C. Verny; A.-M. Mathieu; P. Davrinche; H. Agostini; L. Becquemont; P. Demolis

2010-01-01

324

A pooled analysis of injection site-related adverse events in patients with schizophrenia treated with olanzapine long-acting injection  

PubMed Central

Background Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI). Methods Unsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p?patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with “pain” being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n?=?37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain. Conclusions Injection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics. Trial registration ClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489. PMID:24423017

2014-01-01

325

Simulations reveal adverse hemodynamics in patients with multiple systemic to pulmonary shunts.  

PubMed

For newborns diagnosed with pulmonary atresia or severe pulmonary stenosis leading to insufficient pulmonary blood flow, cyanosis can be mitigated with placement of a modified Blalock-Taussig shunt (MBTS) between the innominate and pulmonary arteries. In some clinical scenarios, patients receive two systemic-to-pulmonary connections, either by leaving the patent ductus arteriosus (PDA) open or by adding an additional central shunt (CS) in conjunction with the MBTS. This practice has been motivated by the thinking that an additional source of pulmonary blood flow could beneficially increase pulmonary flow and provide the security of an alternate pathway in case of thrombosis. However, there have been clinical reports of premature shunt occlusion when more than one shunt is employed, leading to speculation that multiple shunts may in fact lead to unfavorable hemodynamics and increased mortality. In this study, we hypothesize that multiple shunts may lead to undesirable flow competition, resulting in increased residence time (RT) and elevated risk of thrombosis, as well as pulmonary overcirculation. Computational fluid dynamics-based multiscale simulations were performed to compare a range of shunt configurations and systematically quantify flow competition, pulmonary circulation, and other clinically relevant parameters. In total, 23 cases were evaluated by systematically changing the PDA/CS diameter, pulmonary vascular resistance (PVR), and MBTS position and compared by quantifying oxygen delivery (OD) to the systemic and coronary beds, wall shear stress (WSS), oscillatory shear index (OSI), WSS gradient (WSSG), and RT in the pulmonary artery (PA), and MBTS. Results showed that smaller PDA/CS diameters can lead to flow conditions consistent with increased thrombus formation due to flow competition in the PA, and larger PDA/CS diameters can lead to insufficient OD due to pulmonary hyperfusion. In the worst case scenario, it was found that multiple shunts can lead to a 160% increase in RT and a 10% decrease in OD. Based on the simulation results presented in this study, clinical outcomes for patients receiving multiple shunts should be critically investigated, as this practice appears to provide no benefit in terms of OD and may actually increase thrombotic risk. PMID:25531794

Esmaily-Moghadam, Mahdi; Murtuza, Bari; Hsia, Tain-Yen; Marsden, Alison

2015-03-01

326

Adverse events analysis as an educational tool to improve patient safety culture in primary care: A randomized trial  

PubMed Central

Background Patient safety is a leading item on the policy agenda of both major international health organizations and advanced countries generally. The quantitative description of the phenomena has given rise to intense concern with the issue in institutions and organizations, leading to a number of initiatives and research projects and the promotion of patient safety culture, with training becoming a priority both in Spain and internationally. To date, most studies have been conducted in a hospital setting, even though primary care is the type most commonly used by the public, in our experience. Our study aims to achieve the following: - Assess the registry of adverse events as an education tool to improve patient safety culture in the Family and Community Teaching Units of Galicia. - Find and analyze educational tools to improve patient safety culture in primary care. - Evaluate the applicability of the Hospital Survey on Patient Safety Culture by the Agency for Healthcare Research and Quality, Spanish version, in the context of primary health care. Design and methods Design Experimental unifactorial study of two groups, control and intervention. Study population Tutors and residents in Family and Community Medicine in last year of studies in Galicia, Spain. Sample From the population universe through voluntary participation. Twenty-seven tutor-resident units in each group required, randomly assigned. Intervention Residents and their respective tutor (tutor-resident pair) in teaching units on Family and Community Medicine from throughout Galicia will be invited to participate. Tutor-resident pair that agrees to participate will be sent the Hospital Survey on Patient Safety Culture. Then, tutor-resident pair will be assigned to each group-either intervention or control-through simple random sampling. The intervention group will receive specific training to record the adverse effects found in patients under their care, with subsequent feedback, after receiving instruction on the process. No action will be taken in the control group. After the intervention has ended, the survey will once again be provided to all participants. Outcome measures Change in safety culture as measured by Hospital Survey on Patient Safety Culture CONSORT Extension for Non-Pharmacologic Treatments 2008 was applied. Discussion The most significant limitations on the project are related to selecting a tool to measure the safety environment, the training calendar of residents in Family and Community Medicine in last year of studies and the no-answer bias inherent to research conducted through self-administered surveys. The development and application of a safety culture in the health sector, specifically in primary care, is as yet limited. Thus, identifying the strengths and weaknesses in the safety environment may assist in designing strategies for improvement in the primary care health centers of our region. Trial registration ISRCTN: ISRCTN41911128 PMID:21672197

2011-01-01

327

Oversulfated chondroitin sulfate interaction with heparin-binding proteins: New insights into adverse reactions from contaminated heparins  

Microsoft Academic Search

An oversulfated chondroitin sulfate (OSCS) was identified as a contaminant to pharmaceutical heparin and severe anaphylactoid reactions were ascribed to this contaminant. An examination of the biochemistry underlying both the anticoagulant activity and the toxic effects of oversulfated chondroitin sulfate was undertaken. This study demonstrates that the anticoagulant activity of this oversulfated chondroitin sulfate is primarily dependent on heparin cofactor

Boyangzi Li; Jiraporn Suwan; Jeffrey G. Martin; Fuming Zhang; Zhenqing Zhang; Debra Hoppensteadt; Melanie Clark; Jawed Fareed; Robert J. Linhardt

2009-01-01

328

Adverse Events in the Long-Term Follow-Up of Patients Treated With Samarium Sm 153 Lexidronam for Osseous Metastases  

SciTech Connect

Purpose: To investigate adverse events after samarium Sm 153 lexidronam and the effect of pre- and post-samarium Sm 153 lexidronam external beam radiation therapy (EBRT) and/or chemotherapy on myelosuppression in patients who received samarium Sm 153 lexidronam for osseous metastases. Methods and Materials: We performed a single-institution retrospective review of 139 patients treated with samarium Sm 153 lexidronam between November 1997 and February 2008. New-onset adverse events after samarium Sm 153 lexidronam were reported. The effect of samarium Sm 153 lexidronam on platelet and peripheral white blood cell counts and the duration of myelosuppression after samarium Sm 153 lexidronam plus EBRT and/or chemotherapy were calculated. Differences in the prevalence of adverse events among patients with varying treatment histories were evaluated with the Pearson chi-square test. Results: Hematologic follow-up was available for 103 patients. Chemotherapy and/or EBRT had no effect on the magnitude or duration of myelosuppression. The most common nonhematologic adverse events were acute lower extremity edema (n = 27) and acute and transient neuropathy (n = 29). Patients treated with chemotherapy after samarium Sm 153 lexidronam had a higher prevalence of lower extremity edema (9 of 18 [50%]) than those who were not treated with chemotherapy after samarium Sm 153 lexidronam (18 of 85 [21.2%]) (p = 0.01, chi-square test). No adverse events were correlated with EBRT. Conclusions: Our observation of new-onset, acute and transient edema and neuropathy after samarium Sm 153 lexidronam and of a relationship between edema and post-samarium Sm 153 lexidronam chemotherapy suggests the need for re-examination of patients in past series or for a prospective investigation with nonhematologic adverse events as a primary endpoint.

Paravati, Anthony J., E-mail: Anthony.J.Paravati@dartmouth.edu [Dartmouth Medical School, Hanover, NH (United States); Russo, Andrea L. [Dartmouth Medical School, Hanover, NH (United States); Aitken, Candice [Dartmouth Medical School, Hanover, NH (United States); Department of Medicine, Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Lebanon)

2011-10-01

329

Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients  

PubMed Central

Background Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown. Methods In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF). Results Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003). Conclusion The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy. PMID:18366728

Wang, Lin-Fang; Fokas, Emmanouil; Juricko, Janko; You, An; Rose, Frank; Pagenstecher, Axel; Engenhart-Cabillic, Rita; An, Han-Xiang

2008-01-01

330

Stress-induced neuroplasticity: (mal)adaptation to adverse life events in patients with PTSD--a critical overview.  

PubMed

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and associated neurochemical reactions, following glucocorticoid release from the adrenal glands, accompanied by rapid physiological responses. Stimulation of this pathway results in the activation of specific brain regions, including the hippocampus, amygdala and prefrontal cortex which are enriched with glucocorticoid receptors (GRs). Recent findings indicate that the activation of GRs mediates the regulation of the brain-derived neurotrophic factor (BDNF). BDNF is crucial for neural plasticity, as it promotes cellular growth and synaptic changes. Hence stress-induced activation of these pathways leads to neuroplastic changes, including the formation of long-lasting memories of the experiences. As a consequence, organisms can learn from stressful events and respond in an adaptive manner to similar demands in the future. Whereas an optimal stress level leads to enhancement of memory performance, the exposure to extreme, traumatic or chronic stressors is a risk factor for psychopathologies which are associated with memory impairment and cognitive deficits such as posttraumatic stress disorder (PTSD). In this review article, we will outline the implications of stress exposure on memory formation involving the role of glucocorticoids and BDNF. Within this context, potential adverse effects of neuroplastic alterations will be discussed using the example of PTSD. PMID:25193848

Deppermann, S; Storchak, H; Fallgatter, A J; Ehlis, A-C

2014-12-26

331

Flare Up Reaction During Provocation Test to Glatiramer Acetate in a Patient With Allergy to Interferon Beta1a  

PubMed Central

Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-?1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test. PMID:25229006

Calapai, Gioacchino; Gangemi, Sebastiano

2014-01-01

332

Patient reactions to long-term outpatient treatment with continuous subcutaneous insulin infusion.  

PubMed Central

Fourteen of the first 15 insulin-dependent diabetics to be treated in our unit by three weeks or more of outpatient continuous subcutaneous insulin infusion with a portable syringe pump completed a questionnaire about their reactions to the system. Motivation was more important to a favourable response than occupation or intelligence. Most patients thought that diabetic control was better with the pump than conventional injection treatment and several felt subjectively better. Features such as the greater flexibility of diet and insulin delivery rates during continuous subcutaneous infusion were appreciated. The most consistent adverse criticism was about the size of the device used, nearly all patients thinking that smaller and lighter infusion systems should be developed. Psychological reactions to the infusion and difficulties with interpersonal relationships were identified; these must be clearly appreciated and discussed with patients and family before and during treatment. Nine of the 14 patients said they would undertake continuous subcutaneous infusion for one year and a further two said they would do so if the infuser was smaller. These results provide guidance on future technological development of continuous subcutaneous insulin infusion and indicate that the major constraint to long-term trials of the present system is the size of the pump. PMID:6783163

Pickup, J C; Keen, H; Viberti, G C; Bilous, R W

1981-01-01

333

Incidence and management of renal adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib.  

PubMed

Patients with multiple myeloma (MM) frequently experience renal dysfunction owing to patient-specific risk factors, the pathophysiology of MM, and treatment-related adverse events. The presence of renal complications in patients with MM may be associated with advanced disease and is a negative prognostic factor for survival. Frequently these patients receive reduced or modified dosing regimens, which can result in under-dosing and may adversely affect treatment efficacy. Consequently, there is a need for effective therapies with favorable renal safety profiles. Carfilzomib is a selective proteasome inhibitor approved in the United States as a single agent for the treatment of relapsed and refractory MM. Safety studies have demonstrated that single-agent carfilzomib is well tolerated in patients with relapsed and/or refractory MM and concomitant renal dysfunction. This article reviews the etiology and incidence of renal adverse events in patients with MM, the renal safety profile of single-agent carfilzomib from four phase II studies in patients with relapsed and/or refractory MM, and the management of patients with MM who receive carfilzomib and are at risk for renal complications. PMID:25184232

Shah, Jatin J

2013-12-01

334

Ticagrelor: An investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome  

PubMed Central

Acute coronary syndromes (ACS) are the leading cause of mortality and one of the main reasons for hospital admissions in the developed nations. Due to high rates of mortality and reinfarction, ACS represent a major public health concern. Platelets play a central role in atherothrombosis, the main pathologic substrate in ACS. Sufficient inhibition of platelet aggregation is therefore one of the key targets in the treatment of ACS. Blockade of the P2Y12 subtype of adenosine diphosphate (ADP) receptor on platelet cell membranes has been established as a key mechanism of platelet inhibition. Clopidogrel, an ADP receptor antagonist and a second-generation thienopyridine, has been demonstrated to be of clinical benefit in patients with ACS when added to aspirin. A delayed onset of action due to two-step conversion to the active metabolite, irreversible binding to P2Y12 receptors, and broad interindividual variability in levels of platelet response are the main limitations of clopidogrel. Prasugrel, a novel third-generation thienopyridine, provides faster and stronger inhibition of platelet aggregation than clopigodrel. However, like the active metabolite of clopidogrel, prasugrel binds irreversibly to the P2Y12 ADP receptor site, causing inhibition of platelet aggregation for the life of the platelet. Although in a randomized, double-blind trial prasugrel demonstrated superiority for multiple cardiovascular endpoints compared with standard-dose clopidogrel, it was also associated with an increased bleeding risk, including fatal bleeding. This review discusses the optimal antiplatelet regimens for management of patients with ACS, with special focus on ticagrelor, the first oral agent in a new chemical class of nonthienopyridine antiplatelet agents termed cyclopentyltriazolo-pyrimidines. Faster and greater platelet inhibition than clopidogrel, quick recovery of platelet function, and high efficacy regardless of clopidogrel response status, are the obvious advantages of ticagrelor as compared with thienopyridines. The prospective, randomized Platelet Inhibition and Patient Outcomes trial has established the clinical utility, enhanced efficacy, and similar safety of ticagrelor as compared with clopidogrel in a wide range of patients with ACS managed with contemporary antithrombotic therapies and invasive strategies when indicated. Dyspnea, ventricular pauses ?3 seconds, and elevation of serum creatinine and uric acid are the most common known adverse effects associated with ticagrelor, and require further comprehensive assessment. PMID:21057581

Abergel, Eitan; Nikolsky, Eugenia

2010-01-01

335

Relation between paradoxical decrease in high-density lipoprotein cholesterol levels after statin therapy and adverse cardiovascular events in patients with acute myocardial infarction.  

PubMed

Statin therapy moderately increases high-density lipoprotein cholesterol (HDL-C) levels. Contrary to this expectation, a paradoxical decrease in HDL-C levels after statin therapy is seen in some patients. We evaluated 724 patients who newly started treatment with statins after acute myocardial infarction (AMI). These patients were divided into 2 groups according to change in HDL-C levels between baseline and 6 to 9 months after initial AMI (?HDL). In total, 620 patients had increased HDL-C levels and 104 patients had decreased HDL-C levels. Both groups achieved follow-up low-density lipoprotein cholesterol levels <100 mg/dl. Adverse cardiovascular events (a composite of all-cause death, myocardial infarction, and stroke) have more frequently occurred in the decreased HDL group compared with the increased HDL group (15.4% vs 7.1%, p = 0.01). Multivariate analysis showed that decreased HDL, onset to balloon time, and multivessel disease were the independent predictors of adverse cardiovascular events (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.08 to 3.52; HR 1.05, 95% CI 1.01 to 1.09; and HR 2.08, 95% CI 1.22 to 3.56, respectively). In conclusion, a paradoxical decrease in serum HDL-C levels after statin therapy might be an independent predictor of long-term adverse cardiovascular events in patients with AMI. PMID:25555656

Ota, Tomoyuki; Ishii, Hideki; Suzuki, Susumu; Tanaka, Akihito; Shibata, Yohei; Tatami, Yosuke; Harata, Shingo; Shimbo, Yusaku; Takayama, Yohei; Kawamura, Yoshihiro; Osugi, Naohiro; Maeda, Kengo; Kondo, Takahisa; Murohara, Toyoaki

2015-02-15

336

Probability Analysis on Associations of Adverse Drug Events with Drug-Drug Interactions  

Microsoft Academic Search

Adverse drug reaction (ADR) may cost a lot of unnecessary medical resources and leads to extra suffering on patients. To provide the prompt information about ADR and avoid the rate of occurrence of ADR is an important task yet to be done. The US Food and Drug Administration (FDA) provides a Adverse Event Reporting System (AERS) which contains a lot

Yu-ting Huang; Shih-fang Lin; Chung-cheng Chiu; Hsiang-yuan Yeh; Von-wun Soo

2007-01-01

337

First Indian Study Evaluating Role of Biochemical Investigations and Diagnostic Tools in Detection of Adverse Drug Reactions  

PubMed Central

Aim of Study: To evaluate the role of biochemical investigations (BI) and diagnostic tools (DT) in ADR detection. Materials and Methods: An observational prospective cross-sectional study was done using suspected ADR data collection form. Results: A total of 2381 ADR related events were recorded in two years. Total number/percentage of biochemical abnormalities (BA) related ADR detection rate was 14.57% and of DT was 1.091% in contrast to 84.33% recorded with clinical presentation. Maximum cases were inward patients (87.13%), 67.02% were recorded by active surveillance. ADR detection rate at one point & detection on follow up was 56.31% Vs 46.38%. ADR detection rate of ECG, endoscopy, X-ray were 0.57%, 0.22%, 0.22% and of CT scan, MRI, DEXA scan, USG and biopsy was 0.04% each. Maximum ADRs were severe/serious, latent and Type-A in nature. Anemia (4.6%), followed by liver dysfunction (2.8%), renal dysfunction, electrolyte imbalance, hyperglycemia (1.1% each), abnormal coagulation profile (1%), decrease platelet count (0.8%), hypoglycemia (0.7%) were the most common BAs. Anti retroviral drugs (ART), tirofiban and methotrexate accounted for anemia, ART and anti tubercular drugs for liver & renal dysfunction, insulin for hypoglycemia, tirofiban, paclitaxel, capecipabine and ifosfamide for thrombocytopenia, hematuria by enoxaparin & dyslipidemia with ART were common ADRs. Conclusion: BI and DT can play very important role in ADR detection. PMID:25386459

Khajuria, Vijay; Raina, Kapila; Mahajan, Vivek; Sharma, Aman; Gillani, Zahid

2014-01-01

338

Management of hematologic adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib.  

PubMed

Hematologic adverse events (AEs) are commonly encountered in patients with multiple myeloma (MM) owing to the nature of the disease and the adverse effects related to myeloma treatment. Immunomodulatory drugs (eg, thalidomide, lenalidomide, and pomalidomide) and the proteasome inhibitor bortezomib have all been associated with increased rates of anemia, neutropenia, and thrombocytopenia, as well as greater incidences of infection caused by associated immunosuppression. The proteasome inhibitor carfilzomib was recently approved in the United States for the treatment of patients with relapsed and refractory MM. This article reviews the hematologic safety profile of carfilzomib in patients with relapsed/refractory MM, as assessed in a cross-trial safety analysis of four phase II studies, and makes recommendations for the appropriate management of hematologic AEs. PMID:25184231

Nooka, Ajay K

2013-12-01

339

Interplay between Genetic and Clinical Variables Affecting Platelet Reactivity and Cardiac Adverse Events in Patients Undergoing Percutaneous Coronary Intervention  

PubMed Central

Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1–6.8, p<0.001) for a score level of ?1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ?75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ?75 years and HTPR were the strongest predictors of MACE. PMID:25051347

Siller-Matula, Jolanta M.; Lang, Irene M.; Neunteufl, Thomas; Kozinski, Marek; Maurer, Gerald; Linkowska, Katarzyna; Grzybowski, Tomasz; Kubica, Jacek; Jilma, Bernd

2014-01-01

340

Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos  

PubMed Central

Background In a recent study one third of Lao patients presenting with uncomplicated Plasmodium falciparum malaria had biochemical evidence of thiamin deficiency, which was associated with a higher incidence of adverse events. Thiamin supplementation might, therefore, reduce adverse events in this population. Methods An exploratory, double-blind, parallel group, placebo-controlled, superiority trial of thiamin supplementation in patients of all ages with uncomplicated and severe falciparum malaria was conducted in Xepon District, Savannakhet Province, southern Laos. Patients were randomly assigned to either oral thiamin 10 mg/day for 7 days immediately after standard anti-malarial treatment then 5 mg daily until day 42, or identical oral placebo. Results After interim analyses when 630 patients (314 in thiamin and 316 in placebo groups) had been recruited, the trial was discontinued on the grounds of futility. On admission biochemical thiamin deficiency (alpha???25%) was present in 27% of patients and 9% had severe deficiency (alpha?>?31%). After 42 days of treatment, the frequency of thiamin deficiency was lower in the thiamin (2%, 1% severe) compared to the placebo (11%, 3% severe) groups (p?adverse events were not significantly different between the groups (p?>?0.05). Clinical, haematological, and parasitological responses to treatment did not differ significantly between the two groups. Conclusion Thiamin supplementation reduced biochemical thiamin deficiency among Lao malaria patients following anti-malarial drug treatment, but it did not reduce the frequency of adverse events after anti-malarial therapy or have any detected clinical or parasitological impact. Trial registration ISRCTN 85411059 PMID:25027701

2014-01-01

341

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis  

PubMed Central

Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug. PMID:24240528

Crowley, James J.; Kim, Yunjung; Lenarcic, Alan B.; Quackenbush, Corey R.; Barrick, Cordelia J.; Adkins, Daniel E.; Shaw, Ginger S.; Miller, Darla R.; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F.; Valdar, William

2014-01-01

342

Genetics of adverse reactions to haloperidol in a mouse diallel: a drug-placebo experiment and Bayesian causal analysis.  

PubMed

Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug-placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, "difference of models" and "multiple-impute matched pairs", are motivated by the Neyman-Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2-53.2%) but also strong effects of epistasis (10.64-25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug. PMID:24240528

Crowley, James J; Kim, Yunjung; Lenarcic, Alan B; Quackenbush, Corey R; Barrick, Cordelia J; Adkins, Daniel E; Shaw, Ginger S; Miller, Darla R; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F; Valdar, William

2014-01-01

343

Adverse drug reactions associated with the use of NSAIDs: a case/noncase analysis of spontaneous reports from the French pharmacovigilance database 2002-2006.  

PubMed

To evaluate the safety profile of eight oral nonsteroidal anti-inflammatory drugs (NSAIDs) available in France, using data reported through the French pharmacovigilance system. Data (from 2002 to 2006) were analysed for aceclofenac, diclofenac, ketoprofen, meloxicam, naproxen, nimesulide, piroxicam and tenoxicam, focusing on the reported rates of serious adverse drug reactions (ADRs) in the following system organ classes: gastrointestinal, hepatic, cutaneous, renal and cardiovascular. A total of 42 389 serious ADR reports were identified, and 38 506 were included in a case/noncase analysis. Ketoprofen was associated with the highest cumulative reported rate of serious ADRs (0.78 cases per million defined daily doses), followed by diclofenac (0.58), nimesulide (0.52), naproxen (0.50), piroxicam (0.47), tenoxicam (0.42), meloxicam (0.41) and aceclofenac (0.30). The most frequently reported serious ADRs were cutaneous, followed by gastrointestinal, hepatic, renal and rarely, cardiovascular events. In the case/noncase analysis, ketoprofen, piroxicam and naproxen were associated with the highest risk of serious gastrointestinal ADRs (odds ratios [ORs] of 6.87, 6.54 and 5.07, respectively). Nimesulide and aceclofenac were associated with the highest risk of liver ADRs (adjusted ORs of 4.53 and 3.67, respectively), as was meloxicam for cutaneous ADRs (adjusted OR of 3.15) and tenoxicam for renal ADRs (adjusted OR of 3.17). The most frequent serious ADRs reported with the selected oral NSAIDs are cutaneous, followed by gastrointestinal, hepatic and renal events. The highest risks for serious gastrointestinal, hepatic, cutaneous and renal adverse events were linked, respectively, with ketoprofen, nimesulide, meloxicam and tenoxicam compared with the other NSAIDs. PMID:21929527

Lapeyre-Mestre, Maryse; Grolleau, Sabrina; Montastruc, Jean-Louis

2013-04-01

344

The Threshold of Admission Glycemia as a Predictor of Adverse Events in Diabetic and Non-Diabetic Patients with Acute Coronary Syndrome  

PubMed Central

Recent studies indicated a high prevalence of hyperglycemia in non-diabetic patients presenting with acute coronary syndrome (ACS). However, the threshold of admission glucose (AG) as a predictor of adverse events in ACS is unclear. Objective: The aim of this study was to assess the threshold of admission glucose (AG) as a predictor of adverse events including Major Acute Cardiac Events (MACE) and mortality, during the first week of admitting patients presenting with ACS. Material and Methods: The data of 551 patients with ACS were extracted and evaluated. Patients were stratified according to their blood glucose on admission into three groups: group 1: ?7 mmol/L (n = 200, 36.3%) and group 2: >7 mmol/L and <15 mmol/L (n = 178, 32.3%) and group 3: ?15 mmol/L (n = 173, 31.4%). Stress hyperglycemia was arbitrarily defined as AG levels > 7 mmol/L (group 2 and 3). Patients with ACS were sub-divided into two groups: patients with unstable angina (UA, n = 285) and those with ST segment elevation myocardial Infarction (STEMI, n = 266) and data were analyzed separately using multiple regression analysis. Results: The mean age of patients was 59.7 ± 14.8 years and 63% were males. The overall mortality in the population was 8.5% (5.4% in STEMI and 3.1% in UA) patients. In STEMI patients, the odds ratio of stress hyperglycemia as predictor of mortality in group 3 compared with group 1 was 3.3 (CI 0.99–10.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.75–8.07, P = 0.065) after adjustment for age and sex. Similarly, in UA patients, the odds ratio of stress hyperglycemia in group 3 compared with group 1 was 2.7 (CI 0.37–18.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.4–15.2, P = 0.344) after adjustment for age and sex. The incidence of more than 2 MACE in both STEMI and UA patients was higher in group 3 compared with the other two groups. Regression analysis showed that history of DM, high level of LDL cholesterol, high level of HbA1c, and anterior infarction were significant predictors of adverse events while other risk factors such as BMI, history of hypertension and smoking were of no significance. Conclusion: This study indicates that the stress hyperglycemia on admission is a powerful predictor of increased major adverse events and hospital mortality in patients with acute coronary syndrome. PMID:20508764

Garadah, Taysir S.; Kassab, Salah; Al-Shboul, Qasim M.; Alawadi, Abdulhai

2009-01-01

345

Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile.  

PubMed

In 45, ? 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features. PMID:24314589

Mauro, Francesca R; Molica, Stefano; Laurenti, Luca; Cortelezzi, Agostino; Carella, Angelo M; Zaja, Francesco; Chiarenza, Annalisa; Angrilli, Francesco; Nobile, Francesco; Marasca, Roberto; Musolino, Caterina; Brugiatelli, Maura; Piciocchi, Alfonso; Vignetti, Marco; Fazi, Paola; Gentile, Giuseppe; De Propris, Maria S; Della Starza, Irene; Marinelli, Marilisa; Chiaretti, Sabina; Del Giudice, Ilaria; Nanni, Mauro; Albano, Francesco; Cuneo, Antonio; Guarini, Anna; Foà, Robin

2014-02-01

346

Symptomatic reactions, clinical outcomes and patient satisfaction associated with upper cervical chiropractic care: A prospective, multicenter, cohort study  

PubMed Central

Background Observational studies have previously shown that adverse events following manipulation to the neck and/or back are relatively common, although these reactions tend to be mild in intensity and self-limiting. However, no prospective study has examined the incidence of adverse reactions following spinal adjustments using upper cervical techniques, and the impact of this care on clinical outcomes. Methods Consecutive new patients from the offices of 83 chiropractors were recruited for this practice-based study. Clinical outcome measures included 1) Neck pain disability index (100-point scale), 2) Oswestry back pain index (100-point scale), 3) 11-point numerical rating scale (NRS) for neck, headache, midback, and low back pain, 4) treatment satisfaction, and 5) Symptomatic Reactions (SR). Data were collected at baseline, and after approximately 2 weeks of care. A patient reaching sub-clinical status for pain and disability was defined as a follow-up score <3 NRS and <10%, respectively. A SR is defined as a new complaint not present at baseline or a worsening of the presenting complaint by >30% based on an 11-point numeric rating scale occurring <24 hours after any upper cervical procedure. Results A total of 1,090 patients completed the study having 4,920 (4.5 per patient) office visits requiring 2,653 (2.4 per patient) upper cervical adjustments over 17 days. Three hundred thirty- eight (31.0%) patients had SRs meeting the accepted definition. Intense SR (NRS ?8) occurred in 56 patients (5.1%). Outcome assessments were significantly improved for neck pain and disability, headache, mid-back pain, as well as lower back pain and disability (p <0.001) following care with a high level (mean = 9.1/10) of patient satisfaction. The 83 chiropractors administered >5 million career upper cervical adjustments without a reported incidence of serious adverse event. Conclusions Upper cervical chiropractic care may have a fairly common occurrence of mild intensity SRs short in duration (<24 hours), and rarely severe in intensity; however, outcome assessments were significantly improved with less than 3 weeks of care with a high level of patient satisfaction. Although our findings need to be confirmed in subsequent randomized studies for definitive risk-benefit assessment, the preliminary data shows that the benefits of upper cervical chiropractic care may outweigh the potential risks. PMID:21974915

2011-01-01

347

Association between perceived unmet health care needs and risk of adverse health outcomes among patients with chronic medical conditions  

PubMed Central

Background Adults with chronic medical conditions are more likely to report unmet health care needs. Whether unmet health care needs are associated with an increased risk of adverse health outcomes is unclear. Methods Adults with at least one self-reported chronic condition (arthritis, chronic obstructive pulmonary disease, diabetes mellitus, heart disease, hypertension, mood disorder, stroke) from the 2001 and 2003 cycles of the Canadian Community Health Survey were linked to national hospitalization data. Participants were followed from the date of their survey until March 31, 2005, for the primary outcomes of all-cause and cause-specific admission to hospital. Secondary outcomes included length of stay, 30-day and 1-year all-cause readmission to hospital, and in-hospital death. Negative binomial regression models were used to estimate the association between unmet health care needs, admission to hospital, and length of stay, with adjustment for socio-demographic variables, health behaviours, and health status. Logistic regression was used to estimate the association between unmet needs, readmission, and in-hospital death. Further analyses were conducted by type of unmet need. Results Of the 51 932 adults with self-reported chronic disease, 15.5% reported an unmet health care need. Participants with unmet health care needs had a risk of all-cause admission to hospital similar to that of patients with no unmet needs (adjusted rate ratio [RR] 1.04, 95% confidence interval [CI] 0.94–1.15). When stratified by type of need, participants who reported issues of limited resource availability had a slightly higher risk of hospital admission (RR 1.18, 95% CI 1.09–1.28). There was no association between unmet needs and length of stay, readmission, or in-hospital death. Interpretation Overall, unmet health care needs were not associated with an increased risk of admission to hospital among those with chronic conditions. However, certain types of unmet needs may be associated with higher or lower risk. Whether unmet needs are associated with other measures of resource use remains to be determined. PMID:23687534

Ronksley, Paul E; Sanmartin, Claudia; Quan, Hude; Ravani, Pietro; Tonelli, Marcello; Manns, Braden; Hemmelgarn, Brenda R

2013-01-01

348

SePreSA: a server for the prediction of populations susceptible to serious adverse drug reactions implementing the methodology of a chemical-protein interactome.  

PubMed

Serious adverse drug reactions (SADRs) are caused by unexpected drug-human protein interactions, and some polymorphisms within binding pockets make the population carrying these polymorphisms susceptible to SADR. Predicting which populations are likely to be susceptible to SADR will not only strengthen drug safety, but will also assist enterprises to adjust R&D and marketing strategies. Making such predictions has recently been facilitated by the introduction of a web server named SePreSA. The server has a comprehensive collection of the structural models of nearly all the well known SADR targets. Once a drug molecule is submitted, the scale of its potential interaction with multi-SADR targets is calculated using the DOCK program. The server utilizes a 2-directional Z-transformation scoring algorithm, which computes the relative drug-protein interaction strength based on the docking-score matrix of a chemical-protein interactome, thus achieve greater accuracy in prioritizing SADR targets than simply using dock scoring functions. The server also suggests the binding pattern of the lowest docking score through 3D visualization, by highlighting and visualizing amino acid residues involved in the binding on the customer's browser. Polymorphism information for different populations for each of the interactive residues will be displayed, helping users to deduce the population-specific susceptibility of their drug molecule. The server is freely available at http://SePreSA.Bio-X.cn/. PMID:19417066

Yang, Lun; Luo, Heng; Chen, Jian; Xing, Qinghe; He, Lin

2009-07-01

349

[The feasibility of Erwinia asparaginase for pediatric patients who developed an allergic reaction to E.coli asparaginase during treatment of acute lymphoblastic leukemia].  

PubMed

Asparaginase (ASNase) is one of the most important key drugs in the treatment of acute lymphoblastic leukemia (ALL). However, clinical hypersensitivity reactions often occur and lead to the discontinuation of ASNase treatment. Here, we report a retrospective study of 68 Erwinia ASNase (Erw-ASNase) administrations in 11 patients with childhood ALL who developed allergic reactions to E.coli-ASNase in our hospital between 2006 and 2012. The median age of the patients was 6 (range, 0 to 14). Erw-ASNase purchased overseas by the patients' guardians had already been administered when we obtained informed consent from the guardians. In all patients, fibrinogen and/or anti-thrombin III levels were decreased, but thrombosis did not develop. There was only one mild adverse event (grade 2 urticaria) in one patient, in whom Erw-ASNase could be continued after increasing the doses of premedication with antihistamine and prednisolone. Erw-ASNase could be safely administered to all patients. PMID:23666219

Takahashi, Hiroyoshi; Koh, Katsuyoshi; Kato, Motohiro; Isobe, Kiyotaka; Yasui, Naoko; Mori, Makiko; Akiyama, Kosuke; Kikuchi, Akira; Hanada, Ryoji

2013-04-01

350

Ethnic minority patients not at increased risk of adverse events during hospitalisation in urban hospitals in the Netherlands: results of a prospective observational study  

PubMed Central

Objectives We analysed potential differences in incidence, type, nature, impact and preventability of adverse events (AEs) during hospitalisation between ethnic Dutch and ethnic minority patients, and the role of patient-related determinants. We hypothesised an increased AE incidence for ethnic minority patients. Setting We conducted a prospective cohort study in four urban hospitals. Participants 763 Dutch patients and 576 ethnic minority patients aged between 45 and 75, admitted for at least one night, were included in the study. All patients completed a questionnaire on patient-related determinants (eg, language proficiency). Outcome measures Incidence, type (eg, diagnostic AEs), impact and nature of AEs were assessed with a two-stage medical record review. Logistic regression analysis was used to adjust for patient and admission characteristics, and to investigate the contribution of patient-related determinants to AE risk. Results There was no significant difference in the incidence of AEs: 11% (95% CI 9% to 14%) in Dutch patients and 10% (95% CI 7% to 12%) in ethnic minority patients. Also, there was no significant difference in the incidence of preventable AEs: 3% (95% CI 1% to 4%) in Dutch patients and 1% (95% CI 0% to 2%) in ethnic minority patients. Low language proficiency, inadequate health literacy and low educational level did not increase the risk of an AE. Conclusions Compared with Dutch patients, ethnic minority patients were not at increased risk of AEs while receiving care in Dutch hospitals. Healthcare providers seem to have responded effectively to specific patient care needs, but we do not know whether this occurred in an ad hoc or in a systematic way. PMID:25550290

van Rosse, Floor; Essink-Bot, Marie-Louise; Stronks, Karien; de Bruijne, Martine; Wagner, Cordula

2014-01-01

351

Fc? receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with infusion reactions to infliximab in patients with rheumatoid arthritis  

PubMed Central

Objective Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fc? receptor (Fc?R) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined. Methods 96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for Fc?R were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis. Results An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions. Conclusion FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions. PMID:20980704

Okuyama, Ayumi; Nagasawa, Hayato; Suzuki, Katsuya; Kameda, Hideto; Kondo, Harumi; Amano, Kouichi; Takeuchi, Tsutomu

2011-01-01

352

Ocular adverse effects associated with systemic medications : recognition and management.  

PubMed

This article reviews several retrospective case series and reported adverse events regarding common ocular adverse effects related to systemic therapy. It is not intended as a comprehensive summary of these well described adverse drug reactions, nor is it intended to cover the complete spectrum of all ocular adverse effects of systemic therapy. Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications. For this review, the certainty of the adverse effect profile of each medication was evaluated according to the WHO Causality Assessment Guide.A certain relationship has been established for pamidronate and alendronate as causes of scleritis, uveitis, conjunctivitis and blurred vision. Topiramate has been established as adversely causing symptoms consistent with acute angle-closure glaucoma, typically bilateral. Vigabatrin has been shown to cause bilateral irreversible visual field defects attributed to underlying medication-induced retinal pathology. Isotretinoin should be considered in the differential diagnosis of any patient with pseudotumour cerebri. Patients taking amiodarone and hydroxychloroquine should be monitored and screened regularly for development of optic neuropathy and maculopathy, respectively. Sildenafil has been reported to cause several changes in visual perception and is a possible, not yet certain, cause of anterior ischaemic optic neuropathy. Patients taking tamoxifen should also be monitored for development of dose-dependent maculopathy and decreased colour vision. COX-2 inhibitors should be included in the differential diagnosis of reversible conjunctivitis. Several herbal medications including canthaxanthine, chamomile, datura, Echinacea purpurea, Ginkgo biloba and liquorice have also been associated with several ocular adverse effects. It is the role of all healthcare professionals to detect, treat and educate the public about adverse reactions to medications as they are an important health problem. PMID:17209665

Santaella, Ricardo M; Fraunfelder, Frederick W

2007-01-01

353

Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase  

PubMed Central

AIM To identify which drugs are associated with reports of suspected hepatic injury in children and adolescents. METHODS Using a worldwide pharmacovigilance database, VigiBase, we conducted a case/non-case study on suspected adverse drug reactions (ADRs) occurring in the population <18 years old. Cases were all the records with hepatic ADRs and non-cases were all the other ADR records. Records regarding topically administered drugs were excluded from both groups. The association between drug and suspected hepatic ADRs was calculated using the reporting odds ratio (ROR) as a measure of disproportionality while adjusting for gender, country, reporter and calendar year. Sub-analyses were performed within therapeutic class and by excluding vaccination-related reports to reduce confounding. RESULTS Overall, 6595 (1%) out of 624 673 ADR records in children and adolescents concerned hepatic injury. Most of the reported hepatic injuries concerned children 12–17 years of age. Drugs that were most frequently reported as suspected cause and were associated with hepatic injury comprised paracetamol, valproic acid, carbamazepine, methotrexate, minocycline, zidovudine, pemoline, ceftriaxone, bosentan, ciclosporin, atomoxetine, olanzapine, basiliximab, erythromycin and voriconazole. The association between hepatotoxicity and all these drugs, except for basiliximab, is already known. CONCLUSIONS Drug-induced hepatic injury is infrequently reported (only 1% of total) as a suspected ADR in children and adolescents. The drugs associated with reported hepatotoxicity (paracetamol, antiepileptic and anti-tuberculosis agents) are known to be hepatotoxic in adults as well, but age related changes in associations were observed. VigiBase is useful as a start to plan further drug safety studies in children. PMID:21039766

Ferrajolo, Carmen; Capuano, Annalisa; Verhamme, Katia M C; Schuemie, Martijn; Rossi, Francesco; Stricker, Bruno H; Sturkenboom, Miriam C J M

2010-01-01

354

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy.  

PubMed

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival. In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance. EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy. PMID:25216514

Aichler, Michaela; Motschmann, Martin; Jütting, Uta; Luber, Birgit; Becker, Karen; Ott, Katja; Lordick, Florian; Langer, Rupert; Feith, Marcus; Siewert, Jörg Rüdiger; Walch, Axel

2014-08-30

355

Clinical significance of acute phase reaction in stroke patients.  

PubMed

Acute cerebral ischemia triggers interleukin-6 (IL-6) release into cerebrospinal fluid and blood. IL-6 induces synthesis of the acute phase proteins (APPs) in the liver. Higher blood IL-6 level in stroke patients is associated with larger infarct size, greater neurological deficit on admission, early neurological worsening, and increased risk of death or poor functional outcome. The level of C-reactive protein (CRP), the major APP in man, rises in blood during acute stroke reaching maximal values between 5 and 7 day after stroke onset. Elevated CRP level in acute ischemic stroke predicts unfavorable outcome and is associated with increased risk of recurrent stroke or other cardiovascular events. Increased level of fibrinogen, another APP, is associated with worse outcome in patients with ischemic stroke. The acute phase reaction accompanies also intracerebral hemorrhage. Serum IL-6 and CRP level increases in the first days after intracerebral hemorrhage. Plasma IL-6 is independently associated with hematoma enlargement and fibrinogen level predicts early neurological deterioration and outcome in patients with intracerebral hemorrhage. PMID:17981765

Dziedzic, Tomasz

2008-01-01

356

Adverse Effects of Bisphosphonates  

Microsoft Academic Search

Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes,\\u000a the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have\\u000a a relatively good safety record and are tolerated by the majority of patients, but serious adverse events have been recorded\\u000a in some cases. Only the most

Bo Abrahamsen

2010-01-01

357

[Case report of gastric cancer patient who suffered life-threatening adverse events including severe myelosuppression during neoadjuvant chemotherapy with S-1 and CDDP combination].  

PubMed

Neoadjuvant chemotherapy has been a recent focus in the treatment for advanced gastric cancer. Although the preoperative chemotherapeutic regimen of S-1 and CDDP is regarded as effective, safe and well tolerable according to previous clinical study, we experienced a 74-year-old woman who suffered from life-threatening adverse events including severe myelosuppression during the neoadjuvant chemotherapy. Although the patient did not experience any severe adverse events during the first course of treatment, on day 18 of the second course of chemotherapy, she was hospitalized because of anorexia and severe dehydration, leading to following grade 4 leukopenia/neutropenia, bacteremia, and disseminated intravascular coagulation (DIC). She finally recovered from the life-threatening adverse events with intensive therapy and eventually had a distal gastrectomy. Clinicians need to be alert especially to renal dysfunction that induces severe myelosuppression during chemotherapy with S-1, which contains 5-chloro-2,4-dihydroxypyridine (CDHP), a renal excretory inhibitor of dihydropyrimidine dehydrogenase (DPD). PMID:18799915

Ueda, Shugo; Yoshida, Masahiro; Hashida, Hiroki; Tada, Masaharu; Takabayashi, Arimichi; Kanai, Michiyuki

2008-09-01

358

Reversible Ototoxicity: A Rare Adverse Reaction of Liposomal Amphotericin-B Used for the Treatment of Antimony-Resistant Visceral Leishmaniasis in an Elderly Male  

PubMed Central

Amphotericin-B, a broad spectrum antifungal agent, has been known to cause adverse effects such as nephrotoxicity and infusion-related side effects such as fever, chills, rigor, and arthralgias. However, ototoxicity as an adverse effect of Amphotericin-B has not yet been reported in medical literature. We here report a case of a reversible form of ototoxicity induced by liposomal Amphotericin-B (L-AmB). PMID:25093006

Das, PC; Kandel, Ramesh; Sikka, Kapil; Dey, AB

2014-01-01

359

The Risk of Anaphylactic Reactions to Rocuronium in the United States Is Comparable to That of Vecuronium: An Analysis of Food and Drug Administration Reporting of Adverse Events  

Microsoft Academic Search

PublishedreportsfromFranceandNorwaysuggestafre- quent incidence of anaphylaxis to rocuronium and have raisedconcernsaboutitssafety.Wehypothesizedthatthe FoodandDrugAdministrationAdverseEventReporting System could be used to confirm whether there has been an unusual incidence of anaphylactic events for rocuro- niumintheUnitedStates(U.S.)andwhetherthereporting patterns differ within and outside of the U.S.. We queried the Food and Drug Administration Adverse Event Re- porting System for 1999 through the first quarter of 2002 foralladverseeventsforthedrugsrocuroniumandvecu- roniumandthensearchedonthetermsconsideredtorep-

Sanjay M. Bhananker; John R. Salemi; Michael J. Bishop

2005-01-01

360

Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib.  

PubMed

Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2-10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m(2) for cycle 1 and a target dose of 27 mg/m(2) thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m(2) provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. In an integrated safety analysis of four Phase II studies, common adverse events (32.7%-55.5%) included fatigue, anemia, nausea, thrombocytopenia, dyspnea, and diarrhea. Grade 3/4 adverse events were generally hematologic and included thrombocytopenia (23.4%), anemia (22.4%), and lymphopenia (18.1%). Serious adverse events included pneumonia (9.9%), acute renal failure (4.2%), pyrexia (3.4%), and congestive heart failure (3.4%). New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods. PMID:24855395

Harvey, R Donald

2014-01-01

361

Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib  

PubMed Central

Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2–10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m2 for cycle 1 and a target dose of 27 mg/m2 thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m2 provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. In an integrated safety analysis of four Phase II studies, common adverse events (32.7%–55.5%) included fatigue, anemia, nausea, thrombocytopenia, dyspnea, and diarrhea. Grade 3/4 adverse events were generally hematologic and included thrombocytopenia (23.4%), anemia (22.4%), and lymphopenia (18.1%). Serious adverse events included pneumonia (9.9%), acute renal failure (4.2%), pyrexia (3.4%), and congestive heart failure (3.4%). New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods. PMID:24855395

Harvey, R Donald

2014-01-01

362

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions  

PubMed Central

Background Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. Methods We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. Results A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). Conclusions ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries. PMID:24228998

2013-01-01

363

Inhibitory effects of fluorinated pyrimidines, 5¢-DFUR, UFT and T-506, in a model of hepatic metastasis of mouse colon 26 adenocarcinoma - assessment of inhibitory activity and adverse reactions at the maximum tolerated dose  

Microsoft Academic Search

The effects of fluorinated pyrimidines, 5¢-DFUR, UFT and T-506, on a mouse model of hepatic metastasis were assessed in regard to inhibitory activity and adverse reactions at the maximum tolerated dose. The model was prepared by injecting the mouse colonic cancer cell line, colon 26, into the portal vein of CDF1 mice. At the treatment regimens employed for 5¢-DFUR (1.0mmol\\/kg\\/day,

Kenji Tazawa; Takashi Sakamoto; Yoshito Kuroki; Iwao Yamashita; Masahiro Okamoto; Shinnya Katuyama; Masao Fujimaki

1997-01-01

364

Hospital acquired blood stream infection as an adverse outcome for patients admitted to hospital with other principle diagnosis  

PubMed Central

Background: Hospital acquired infections (HAI) have emerged as an important public health problem and are a leading cause of morbidity and mortality worldwide. They affect both developed and resource-poor countries and constitute a significant burden both for the patient and for the health care system. Specific objectives in this study are assessment of HAI rate among patients admitted with other principle diagnosis, to identifying the causative agents of hospital acquired infections and to identify some possible risk factors associated with each type of infection, both health related and non-health related. Patients and Methods: The study was done on selected diagnosis groups during year 2010. The infections were found among 250 patients (43.6% males) have been exposed to episodes of infections. Median age of patients was 56. Data were abstracted from the archived patients’ files in medical record department using the annually infection control log-book prepared by the infection control department. The Data collected were demographic information about the patients (age and sex), clinical condition (diagnosis and the length of hospital stay) and possible risk factors for infection as smoking, diabetes mellitus, hypertension and exposure to invasive devices or exposure to surgical procedures. Results: Liver diseases 22.8%, cardiac diseases 22.8%, Gastro-Intestinal System diseases 20%, urinary system diseases 13.6%, and endocrinal disorder 13.6% Prostate gland diseases 7.2%. Episodes of infections caused by 9 types of organisms divided into 47.2% for blood stream infection and 52.8% for other types. 66% acquired blood stream infection were exposed to central venous line. Conclusion: Most common type of HAIs was blood stream infections. Liver, cardiac diseases and gastro-intestinal diseased patients show more proportion of HAIs while urinary system and prostate disease patients show less proportion of HAIs. Gram negative bacilli were the most common organisms found in our study (60%). PMID:25538530

Al-Hazmi, Hamdan H.; Al-Zahrani, Tariq; Elmalky, Ahmed M.

2014-01-01

365

Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study  

Microsoft Academic Search

In 1890 consecutive patients with documented CAD (1130 with stable angina (SAP) and 760 with acute coronary syndrome (ACS)) baseline concentrations of adiponectin were measured by enzyme-linked immuno assay. During a median follow-up of 2.5 years cardiovascular events were registered (cardiovascular deaths 70; non-fatal myocardial infarction 46). Baseline adiponectin concentrations were similar in patients presenting with SAP (9.03 mg\\/mL (6.7,

Renate Schnabel; Claudia M. Messow; Edith Lubos; Christine Espinola-Klein; Hans J. Rupprecht; Christoph Bickel; Christoph Sinning; Stergios Tzikas; Till Keller; Sabine Genth-Zotz; Karl J. Lackner; Thomas F. Munzel; Stefan Blankenberg

2008-01-01

366

Detecting Adverse Events Using Information Technology  

PubMed Central

Context: Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. Objective: To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. Design: Structured review. Methodology: English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. Main Outcome Measures: Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. Results: Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. Conclusion: Computerized detection of adverse events will soon be practical on a widespread basis. PMID:12595401

Bates, David W.; Evans, R. Scott; Murff, Harvey; Stetson, Peter D.; Pizziferri, Lisa; Hripcsak, George

2003-01-01

367

Overview and management of cardiac and pulmonary adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib.  

PubMed

Cardiac events and pulmonary complications are commonly seen in patients with multiple myeloma (MM), most of whom are over 60 years of age at the time of their diagnosis. These events and complications may be consequences of age-related comorbidities, or effects of the disease itself or current or previous treatment received. In this last category, patients who receive autologous stem cell transplant or treatment with anthracyclines, alkylating agents, immunomodulatory agents, or the proteasome inhibitor bortezomib have been found to be at increased risk for cardiovascular complications. In addition, treatment with an immunomodulatory agent or bortezomib has also been associated with pulmonary complications, which often manifest as dyspnea. An understanding of the cardiopulmonary adverse events associated with anti-MM treatment is, therefore, an important component of therapy selection. Carfilzomib is a selective proteasome inhibitor that was recently approved in the United States for the treatment of patients with relapsed and/or refractory MM who had received two or more prior therapies, including bortezomib and an immunomodulatory agent, and who demonstrated disease progression within 60 days of completion of the last therapy. This article presents an overview of the cardiac and pulmonary safety profile of single-agent carfilzomib therapy in patients with relapsed and/or refractory MM from an analysis of four phase II clinical studies, and provides practical recommendations for the management of patients at risk for cardiac events and pulmonary complications. PMID:25184233

Wang, Michael; Cheng, Jie

2013-12-01

368

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products?-?part 1: Achillea millefolium-Curcuma longa.  

PubMed

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 1: Achillea millefolium L.-Curcuma longa L. PMID:24621152

Calapai, Gioacchino; Miroddi, Marco; Minciullo, Paola L; Caputi, Achille P; Gangemi, Sebastiano; Schmidt, Richard J

2014-07-01