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1

Subjective adverse reactions to metronidazole in patients with amebiasis.  

PubMed

Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea. PMID:24929036

Ohnishi, Kenji; Sakamoto, Naoya; Kobayashi, Ken-Ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi; Ajisawa, Atsushi; Yamauchi, Yuko; Takeshita, Nozomi; Yamamoto, Yasuyuki; Tsunoda, Takafumi; Yoshimura, Yukihiro; Tachikawa, Natsuo; Uehira, Tomoko

2014-10-01

2

Adverse Reactions to Antituberculosis Drugs in Iranian Tuberculosis Patients  

PubMed Central

Background. Antituberculosis multidrug regimens have been associated with increased incidence of adverse drug reactions (ADRs). This study aimed to determine the incidence and associated factors of ADRs due to antituberculosis therapy. Methods. This is a retrospective cross-sectional study on tuberculosis patients who were treated in tuberculosis clinics in Markazi province in Iran. The information contained in the medical files was extracted and entered into the questionnaire. Data was descriptively analyzed by using statistical package for social sciences (SPSS 18). Results. A total of 940 TB patients of 1240 patients' medical records available in 10 medical offices were included in this study. Of the 563 ADRs found in this study, 82.4% were considered minor reactions and 17.6% were major reactions. No death from antituberculosis ADR was observed. We found that the risk of major ADRs was higher in females (P??value = 0.0241), age >50?y (P??value = 0.0223), coinfection with HIV (P??value = 0.0323), smoking (P??value = 0.002), retreatment TB (P??value = 0.0203), and comorbidities (P??value = 0.0005). Conclusions. This study showed that severe side effects of anti-TB drugs are common in patients who have risk factors of ADRs and they should be followed up by close monitoring. PMID:25506427

Sofian, Masoomeh; Keshavarz, Sara

2014-01-01

3

Fatal adverse reaction to ketorolac tromethamine in asthmatic patient.  

PubMed

A case of an asthmatic woman who collapsed within a few minutes after intramuscular ketorolac tromethamine (KT) injection is reported. Autopsy findings revealed anatomic evidence of a recent asthma attack. KT was found to be present in the blood at a concentration within the therapeutic range and consistent with the administered dose. Based on the timing of the collapse in relation to the KT administration, death was attributed to an adverse reaction to KT, resulting in acute bronchospasm and cardiac arrest, with asthma as an underlying contributing factor. In this case, asthma alone was not responsible for the death of the patient but only a contributing factor. Physicians have to be aware that in asthmatic patients bronchospasm can be induced by drugs among which aspirin or nonsteroidal anti-inflammatory drugs such as KT are the most common; therefore, death may have an iatrogenic cause. The paper also describes the pathogenic mechanism of an adverse reaction to such drugs and analytical methods for the isolation and detection of KT in postmortem blood. PMID:19259027

Campobasso, Carlo P; Procacci, Rossella; Caligara, Marina

2008-12-01

4

Adverse Drug Reactions amongst Adult Patients Admitted in Lagos State University Teaching Hospital Lagos, Nigeria.  

PubMed

Background: Adverse drug reaction (ADR) is a global drug therapy problem. It has been rated as one of the top leading causes of morbidity and mortality. In Nigeria, not much is known about ADRs especially with the existing weak post marketing surveillance for monitoring drug use, and its effect on the population. Objectives: The study is aimed to determining the incidence of ADRs, presentations of ADRs, classes of drugs that frequently cause ADRs and predictors of ADRs in adult medical in-patients in LASUTH. Method: A retrospective study of six hundred and twenty four (624) case notes of all patients admitted to the medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried out. Information obtained includes age, gender, and adverse drug reaction and drug details. The results obtained were analyzed using SPSS version 16 statistical software. Level of significance was set at p ? 0.05. Results: A total of 624 case notes consisting of 358 males and 266 females were assessed. The number of patients who experienced adverse drug reactions was 67 (n = 624, 10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100 patients' population. Most of the ADRs observed were type A reactions (97.8%). Mostly implicated classes of drugs are antidiabetics (26.7%) and NSAIDs (29.3%). Conclusion: The incidence rate of ADRs was 10.7%. ADRs which are predictable and preventable occur in hospitalized patients, such may be prevented or minimized by implementing measures to target specific drugs that are commonly suspected. PMID:24909574

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

2014-06-01

5

Cutaneous Adverse Reactions to Highly Antiretroviral Therapy in HIV-Positive Patients  

PubMed Central

Adverse drug reactions to highly antiretroviral therapy (HAART) are major obstacles in its success. Although overall mortality from HIV has dramatically declined owing to HAART, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. To optimize adherence and efficacy of antiretroviral treatment, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious. This paper presents the case of a serious cutaneous adverse reaction to Atripla in a HIV-positive 50-year-old Caucasian woman. PMID:24932169

Pistone, G.; Pistone, A.; Sorbello, D.; Viviano, E.; Bongiorno, M.R.

2014-01-01

6

Allergic adverse reactions to sulfonamides  

Microsoft Academic Search

Antimicrobial sulfonamides were the first antimicrobial agents used effectively to treat infectious diseases. However, because\\u000a they may cause severe adverse drug reactions (ADRs) and because more effective agents have since been developed, sulfonamides\\u000a now are used for only a few indications in specific groups, such as AIDS patients. Skin reactions, from benign rash to potentially\\u000a lethal toxidermias, are the most

Geneviève Choquet-Kastylevsky; Thierry Vial; Jacques Descotes

2002-01-01

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

2015-04-01

8

Adverse drug reactions in older patients: an Italian observational prospective hospital study  

PubMed Central

Background In adults over 65 years of age, the frequency of adverse drug reaction (ADRs) related hospital admissions is higher than in younger adults, and the frequency of ADRs occurring during hospital stay highly ranges. The review was designed to evaluate the frequency of ADRs, both resulting in hospital admission and occurring during the hospital stay of older patients, while identifying the types of reactions and the associated drugs. Methods Age, sex, date, and diagnosis of admission of all patients aged 65 and over admitted in three geriatric wards of University Hospital of Verona, Italy, from February to July 2009 were registered by nurses on a special form. In the specific cases of admissions caused by an ADR as well as in the cases of an ADR occurring during the hospital stay, the type of reactions and the suspected drugs were also registered by nurses and physicians involved in the study. Results During the six months of the study, 1023 patients matched the inclusion criteria and were included in the study. One hundred fourteen hospital admissions (11.1%) were caused by ADRs, while 256 patients (25.0%) had an ADR during their hospital stay. The duration of hospital stay was significantly longer in patients who developed an ADR during their time in hospital, 18.7 (95% CI: 17.2–20.1) days versus 12.6 (95% CI: 11.9–13.3) days. Electrolyte disorders, gastrointestinal disorders, anemia, and International Normalized Ratio increase were the more frequent observed ADRs, with diuretics, antithrombotic agents, and antibacterials as the main involved drugs. Our study confirms that ADRs are an important cause of hospitalization in older patients. In addition, the frequency of ADRs occurring during hospital stay is high and causes prolonged hospitalization. PMID:22888275

Conforti, Anita; Costantini, Davide; Zanetti, Francesca; Moretti, Ugo; Grezzana, Matteo; Leone, Roberto

2012-01-01

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

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

PubMed Central

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age. PMID:3263875

Castleden, C M; Pickles, H

1988-01-01

11

Development of an Adverse Drug Reaction Risk Assessment Score among Hospitalized Patients with Chronic Kidney Disease  

PubMed Central

Background Adverse drug reactions (ADRs) represent a major burden on the healthcare system. Chronic kidney disease (CKD) patients are particularly vulnerable to ADRs because they are usually on multiple drug regimens, have multiple comorbidities, and because of alteration in their pharmacokinetics and pharmacodynamic parameters. Therefore, one step towards reducing this burden is to identify patients who are at increased risk of an ADR. Objective To develop a method of identifying CKD patients who are at increased risk for experiencing ADRs during hospitalisation. Materials and Methods Factors associated with ADRs were identified by using demographic, clinical and laboratory variables of patients with CKD stages 3 to 5 (estimated glomerular filtration rate, 10–59 ml/min/1.73 m2) who were admitted between January 1, 2012, and December 31, 2012, to the renal unit of Dubai Hospital. An ADR risk score was developed by constructing a series of logistic regression models. The overall model performance for sequential models was evaluated using Akaike Information Criterion for goodness of fit. Odd ratios of the variables retained in the best model were used to compute the risk scores. Results Of 512 patients (mean [SD] age, 60 [16] years), 62 (12.1%) experienced an ADR during their hospitalisation. An ADR risk score included age 65 years or more, female sex, conservatively managed end-stage renal disease, vascular disease, serum level of C-reactive protein more than 10 mg/L, serum level of albumin less than 3.5 g/dL, and the use of 8 medications or more during hospitalization. The C statistic, which assesses the ability of the risk score to predict ADRs, was 0.838; 95% CI, 0.784–0.892). Conclusion A score using routinely available patient data can be used to identify CKD patients who are at increased risk of ADRs. PMID:24755778

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

2014-01-01

12

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

13

HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions.  

PubMed

Carbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse drug reactions (cADRs) that may range from mild to severe. It is reported recently that the human leukocyte antigen HLA-B*1502 is associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I in 15 Japanese patients who fulfilled the diagnostic criteria for CBZ-induced cADRs (mild in 10 and severe = SJS in 5). HLA-B*1518, HLA-B*5901 and HLA-C*0704 alleles showed higher relative risks (above 10.0) for severe cADRs. The haplotype (HLA-A*2402-B*5901-C*0102) had high relative risk (16.09) for severe cADRs. In patients with severe cADRs, frequencies of HLA-A*1101, HLA-A*3303, HLA-B*1501, HLA-B*4403, HLA-B*5101, HLA-B*5201, HLA-C*0702, and HLA-C*1202 alleles are relatively lower than in the Japanese population. These data may suggest that HLA-B*5901 is one of the candidate markers for CBZ-induced SJS in Japanese. PMID:19694795

Ikeda, Hiroko; Takahashi, Yukitoshi; Yamazaki, Etsuko; Fujiwara, Tateki; Kaniwa, Nahoko; Saito, Yoshiro; Aihara, Michiko; Kashiwagi, Mariko; Muramatsu, Masaaki

2010-02-01

14

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

15

Cutaneous Adverse Reactions of Amiodarone  

PubMed Central

Dermatological complications of amiodarone are commonly encountered problems in therapy. The incidence in the population of patients with prolonged use of amiodarone reaches nearly 75% according to various sources. Nevertheless, they are often misdiagnosed or overlooked. The aim of this review is to present the current state of knowledge about skin changes induced by amiodarone, including phototoxic and photoallergic reactions, as well as hyperpigmentation. In most cases, the adverse effects are reversible and disappear after discontinuation of the drug. Although the dermatological complications usually do not influence the outcome of the therapy and rarely cause discontinuation of treatment, they have a great impact on patient quality of life. PMID:25413691

Jaworski, Krzysztof; Walecka, Irena; Rudnicka, Lidia; Gnatowski, Maciej; Kosior, Dariusz A.

2014-01-01

16

Cutaneous adverse reactions of amiodarone.  

PubMed

Dermatological complications of amiodarone are commonly encountered problems in therapy. The incidence in the population of patients with prolonged use of amiodarone reaches nearly 75% according to various sources. Nevertheless, they are often misdiagnosed or overlooked. The aim of this review is to present the current state of knowledge about skin changes induced by amiodarone, including phototoxic and photoallergic reactions, as well as hyperpigmentation. In most cases, the adverse effects are reversible and disappear after discontinuation of the drug. Although the dermatological complications usually do not influence the outcome of the therapy and rarely cause discontinuation of treatment, they have a great impact on patient quality of life. PMID:25413691

Jaworski, Krzysztof; Walecka, Irena; Rudnicka, Lidia; Gnatowski, Maciej; Kosior, Dariusz A

2014-01-01

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

[Adverse reaction to not iodinated contrast].  

PubMed

Adverse reactions to drugs are relatively frequent in clinical practice, and some of them can be life threatening. Reactions to contrast material (CM) represent an important percentage of these adverse reactions. It has been found that 70% of reactions to contrast material happen within the first five minutes of their administration. Despite the fact that hypersensitivity reactions are traditionally classified as non-allergic, in recent years investigators have reported positive skin prick tests in patients with immediate and late reactions to contrast material. This paper reports the case of a female patient with non-Hodgkin lymphoma that has presented on two distinct occasions adverse reactions to contrast material. We discuss on the type of reaction, severity, suggested prophylaxis, prognosis and recommendations, keeping in mind the underlying disease and the need to have further image studies performed. PMID:25473874

Palma-Gómez, Samuel; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Macías-Weinmann, Alejandra; Amaro-Vivian, Laura Elizabeth; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; Yong-Rodríguez, Adrián

2014-01-01

20

Cutaneous adverse reactions to lenalidomide.  

PubMed

Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide. PMID:24998775

Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

2015-01-01

21

Monitoring for adverse drug reactions  

PubMed Central

Monitoring describes the prospective supervision, observation, and testing of an ongoing process. The result of monitoring provides reassurance that the goal has been or will be achieved, or suggests changes that will allow it to be achieved. In therapeutics, most thought has been given to Therapeutic Drug Monitoring, that is, monitoring of drug concentrations to achieve benefit or avoid harm, or both. Patients and their clinicians can also monitor the progress of a disease, and adjust treatment accordingly, for example, to achieve optimum glycaemic control. Very little consideration has been given to the development of effective schemes for monitoring for the occurrence of adverse effects, such as biochemical or haematological disturbance. Significant harm may go undetected in controlled clinical trials. Even where harm is detected, published details of trials are usually insufficient to allow a practical monitoring scheme to be introduced. The result is that information available to prescribers, such as the Summary of Product Characteristics, frequently provides advice that is incomplete or impossible to follow. We discuss here the elements of logical schemes for monitoring for adverse drug reactions, and the possible contributions that computerized decision support can make. We should require evidence that if a monitoring scheme is proposed, it can be put into practice, will prove effective, and is affordable. PMID:16542197

Coleman, J J; Ferner, R E; Evans, S J W

2006-01-01

22

Detecting Potential Adverse Reactions of Sulpiride in Schizophrenic Patients by Prescription Sequence Symmetry Analysis  

PubMed Central

Purpose Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects. Materials and Methods Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias. Results A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46–2.06) and hyperprolactinemia (12.04; 1.59–91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment. Conclusions We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia. PMID:24587038

Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Kao Yang, Yea-Huei; Lin, Swu-Jane

2014-01-01

23

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study  

PubMed Central

Objective: To monitor the adverse drug reactions (ADRs) associated with imatinib treatment in patients with chronic myeloid leukemia (CML) in a tertiary care hospital. Materials and Methods: The study was carried out by the Departments of Pharmacology and Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. The study was carried out from March 2012 to February 2014. The ADRs were reported in a suspected Adverse Drug Reaction Reporting form, provided by the Central Drugs Standard Control Organization (CDSCO), Ministry of Health and Family Welfare, Government of India. The ADRs were analyzed for their pattern, causality and severity. Results: A total of 326 ADRs from 81 patients were reported during the study period. The hematological toxicities were much more prominent than the non-hematological toxicities in this study. The prevalence of thrombocytopenia (21.17%) was higher compared with other reactions. Further analysis showed that most of the ADRs were mild to moderate in nature. The causality assessment revealed that the majority of the ADRs belonged to the possible category. Conclusion: The present study in a tertiary care hospital suggests that hematological toxicities are predominant in CML patients treated with imatinib mesylate. The blood and lymphatic system (38.96%) was the most affected, with imatinib therapy and thrombocytopenia (21.17%) being the most commonly encountered ADRs in the present study. Thorough monitoring of ADRs is warranted for better treatment outcomes. PMID:25709349

Francis, Jose; Palaniappan, Muthiah; Dubashi, Biswajit; Pradhan, Suresh Chandra; Chandrasekaran, Adithan

2015-01-01

24

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

25

Cutaneous adverse reaction to infliximab: report of psoriasis developing in 3 patients.  

PubMed

Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine that participates in both normal immune function and the pathogenesis of many autoimmune disorders. Treatment with infliximab reduces the biologic activities of TNF-alpha and thus is indicated in the treatment of rheumatoid arthritis, Crohn disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. To our knowledge, there have been 13 case reports of new-onset psoriasis, psoriasiform dermatitis, and palmoplantar pustular psoriasis that developed during treatment with infliximab. We report 3 additional cases of biopsy-proven new-onset psoriasis that developed while the patients underwent treatment with infliximab for inflammatory bowel disease. Although the mechanism for the development of psoriasis in these patients is unclear, several possible explanations are proposed. With increasing use of infliximab and other TNF-alpha inhibitors in clinical practice, more cases of similar reactions to these drugs probably will be reported and are necessary to determine the importance of this eruption. PMID:17956013

Severs, Gregg A; Lawlor, Tara H; Purcell, Stephen M; Adler, Donald J; Thompson, Robert

2007-09-01

26

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

27

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

28

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

29

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. PMID:25670886

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

2015-01-01

30

Pharmacogenetics of cutaneous adverse drug reactions.  

PubMed

Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS/TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS/TEN and DIHS/DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity. PMID:21342226

Aihara, Michiko

2011-03-01

31

Adverse Reactions: Structure, Philosophy, and Outcomes of the Patient Protection and Affordable Care Act  

Microsoft Academic Search

On March 24th, 2010, President Obama signed the Patient Protection and Affordable Care Act, declaring “everybody should have some basic security when it comes to their health care.” This Note provides legal scholarship’s first comprehensive examination of this complex legislation. Second, it reframes the bill by proposing that its miscellaneous-seeming provisions are designed to protect a single, central provision: the

Lee Michael A Jr

2010-01-01

32

Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness.  

PubMed Central

1. Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg-1 pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2. Maximum plasma drug concentrations varied between 713 and 2461 nmol 1-1. After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3. The 'terminal' elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) ml min-1 and 265 (107-446) h, respectively). The median apparent volume of distribution (Vss) was 11,850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4. Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5. The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day. PMID:7619671

Bronner, U; Gustafsson, L L; Doua, F; Ericsson, O; Miézan, T; Rais, M; Rombo, L

1995-01-01

33

Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness.  

PubMed

1. Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg-1 pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2. Maximum plasma drug concentrations varied between 713 and 2461 nmol 1-1. After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3. The 'terminal' elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) ml min-1 and 265 (107-446) h, respectively). The median apparent volume of distribution (Vss) was 11,850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4. Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5. The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day. PMID:7619671

Bronner, U; Gustafsson, L L; Doua, F; Ericsson, O; Miézan, T; Rais, M; Rombo, L

1995-03-01

34

Severe cutaneous adverse drug reactions  

PubMed Central

Severe cutaneous drug reactions are one of the commonest medical challenges presenting to an emergency room in any hospital. The manifestations range from maculopapular rash to severe systemic symptoms like renal failure and cardiovascular compromise. Toxic epidermal necrolysis, erythroderma, drug rash with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis and drug induced vasculitis are the common cutaneous drug reactions which can have severe morbidity and even mortality. Careful history taking of the lag period after drug intake and associated symptoms, along with detailed examination of the skin, mucosa and various systems, help in early diagnosis of these reactions. Early stoppage of the incriminating drug, specific therapy including corticosteroids, cyclosporine and intravenous immunoglobulin depending on the case along with supportive therapy and local measures help in salvaging most patients. An overview of these important cutaneous drug reactions along with their management is being reviewed in this article. PMID:24600147

Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran

2013-01-01

35

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

36

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

37

Clinical features of adverse reactions associated with telbivudine  

PubMed Central

AIM: To analyze the clinical features and risk factors of adverse reactions associated with telbivudine. METHODS: Clinical data were collected from cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis. RESULTS: Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high. CONCLUSION: The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions. PMID:18567085

Zhang, Xue-Song; Jin, Rui; Zhang, Shi-Bin; Tao, Ming-Ling

2008-01-01

38

Adverse cutaneous reactions to imatinib (STI571) in Philadelphia chromosome-positive leukemias: A prospective study of 54 patients  

Microsoft Academic Search

Background: Imatinib is a new major treatment in chronic myeloid leukemia. Objective: To study the cutaneous reactions induced by imatinib. Methods: All inpatients and outpatients with Philadelphia chromosome-positive leukemia treated by imatinib were included in this prospective study. Clinical features, pathologic findings, evolution of each case, and analysis of potential risk factors were recorded. Results: A total of 54 patients

Laurence Valeyrie; Sylvie Bastuji-Garin; Jean Revuz; Nicolas Bachot; Janine Wechsler; Patrice Berthaud; Michel Tulliez; Stéphane Giraudier

2003-01-01

39

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

40

Ranking Adverse Drug Reactions With Crowdsourcing  

PubMed Central

Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

2015-01-01

41

[Adverse reactions to food preservatives].  

PubMed

We relate our experiences about the number of exacerbations that certain food preservatives such as sorbic acid, benzoic acid, sodium benzoate, metabisulfite and sodium nitrate can provoke in 62 patients affected with ASA-triad in steroid dependent intrinsic asthma with nasal polyps and acute bronchospasm caused by aspirin ingestion, and in 80 patients with chronic urticaria (C.U.) as well as the first assays of the possible usefulness of the HRT (Histamine release test automatized using whole blood) for the etiologic diagnosis process. In the cases of ASA-triad, and after the ingestion of aspirin (alternating with lactose in identical capsule), we consider the result as positive when the reduction of FEV1 is superior to 20% from its baseline value. Regarding the cases of C.U., the symptoms always exacerbate twice as much with the same substance within 24 hours of its administration. We have performed the HRT on 59 patients (14 with ASA-triad, 11 with steroid dependent intrinsic asthma; 20 with C.U. were negative to oral intake of analgesics/additives and 14 with C.U. showed positive results). Successive dilutions were incubated for 30 minutes using: pyrazolones, acetylsalicylate of lysine, sodium salicylate, sodium benzoate and 4-hydroxybenzoic acid which did not produce liberation of histamine in 100 controlled individuals. All the determinations were done in duplicate, considering positive those superior to 20% of the difference between total and basal histamine. We have not observed any significant descent of the FEV1 with benzoate and salicylate in our group of 62 patients with ASA-triad, nor any manifestations presented with sodium metabisulfite, sodium nitrate and sorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2421566

Hernández García, J; Negro Alvarez, J M; García Sellés, F J; Pagán Alemán, J A

1986-01-01

42

Adverse skin reactions following intravitreal bevacizumab injection  

PubMed Central

The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

2011-01-01

43

Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China.  

PubMed

The aim of this study was to investigate the association between carbamazepine (CBZ)-induced cutaneous adverse drug reactions (cADRs) and the HLA-B*1502 allele among patients from central China. Eight patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), 28 with mild maculopapular eruptions (MPEs), 50 CBZ-tolerant controls, and 71 healthy volunteers were recruited. HLA genotyping was performed using the polymerase chain reaction sequence-based typing (SBT) method. As a result, the HLA-B*1502 allele was observed at the following rates: (1) 100% (8/8) among those with CBZ-induced SJS/TEN, (2) 10.7% (3/28) among those with CBZ-induced MPEs; (3) 8.0% (4/50) among CBZ-tolerant controls; (4) 8.5% (6/71) among healthy volunteers. The eight patients with SJS/TEN positive for the HLA-B*1502 allele had an odds ratio (OR) of 184 compared with CBZ-tolerant controls. There was no significant difference in frequency between patients with MPEs and CBZ-tolerant controls (P>0.05). Thus, CBZ-induced SJS/TEN, but not MPEs, is strongly associated with HLA-B*1502. Testing for HLA-B*1502 should be recommended for patients from central China prior to initial CBZ treatment. PMID:20833111

Wu, X T; Hu, F Y; An, D M; Yan, B; Jiang, X; Kwan, P; Stefan, H; Zhou, D

2010-11-01

44

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

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

2014-01-01

45

Adverse reactions and interactions with theophylline.  

PubMed

Despite the trend towards newer therapeutic agents, theophylline continues to play a major role in the treatment of reversible airway obstruction. Clinical use of the drug is complicated by a relatively narrow therapeutic range and a large pharmacokinetic variability between patients. Generally, however, theophylline toxicity is foreseeable and preventable. Most cases can be attributed to either inadvertent or intentional overdosing of the drug. Age, disease state and drug interactions are other factors which may contribute to its toxicity. Nausea, vomiting and tachycardia are common signs of mild theophylline toxicity; seizures, ventricular arrhythmias and hypotension are life-threatening manifestations of severe toxicity which may respond poorly to standard therapy. Although serum theophylline concentration correlates with toxicity in a general fashion, life-threatening adverse reactions are not readily predictable from the drug concentration alone. Treatment of theophylline toxicity primarily involves supportive care along with gastric lavage and administration of activated charcoal to facilitate drug removal. The early use of haemoperfusion may be life-saving in cases of severe toxicity. PMID:2198052

Skinner, M H

1990-01-01

46

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

47

[Exploratory study on biomarkers associated with severe cutaneous adverse reactions].  

PubMed

Most of adverse drug reactions (ADRs) occur as an extension of pharmacological effects. They occur dependently on their blood concentrations and can be potentially reduced by controlling their dose. On the other hand, ADRs categorized as Type B usually occur irrelevantly to their pharmacological effects at different organs from their target, and are often life-threatening and unpredictable. The incidences of Type B ADRs are very low. Severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are delayed allergic reactions in which T-cells are involved and categorized as Type B ADRs. Recent progress of pharmacogenomic studies has revealed that particular types of human leukocyte antigen (HLA) class I antigens have strong associations with severe cutaneous adverse reactions and that the associations are specific to causative drugs, phenotypes of adverse reactions and ethnic groups. We established a research group in 2006 with professionals of pharmacogenomics, dermatologists, ophthalmologists and psychiatrists to explore genetic biomarkers associated with Japanese SJS/TEN patients. To date, we have collected more than 100 Japanese SJS/TEN patients through participating institutes and a case-collecting system covering all over Japan constructed by us. No carriers of HLA-B*1502 which was reported to have extremely strong association with carbamazepine-induced SJS/TEN in Han Chinese and south Asians, although a moderate association between allopurinol-induced SJS/TEN and HLA-B*5801 detected in Han Chinese was observed. PMID:21297371

Kaniwa, Nahoko

2011-02-01

48

Adverse drug reactions in the elderly  

PubMed Central

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

2013-01-01

49

Revisiting cutaneous adverse reactions to pemetrexed  

PubMed Central

Pemetrexed (Alimta®) is a multitargeted antifolate drug approved as a single agent or in combination with cisplatin for the treatment of a small number of malignancies including advanced and metastatic non-squamous non-small cell lung cancer (NSCLC), and malignant pleural mesothelioma. This review reports the recent peer-reviewed publications and original findings regarding cutaneous adverse reactions (CARs) to pemetrexed. Pemetrexed-related CARs are frequently reported under the unspecific term ‘skin rash’. However, more specific diseases were tentatively identified as alopecias, urticarial vasculitis, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, radiation recall dermatitis and pityriasis lichenoides. Most of the skin reactions occur shortly after pemetrexed administration. As with methotrexate-related CARs, the cell cycle arrest in the S phase may be regarded as a direct and major cause of the cytotoxic pathobiology. An adverse immune reaction is unlikely. In conclusion, pemetrexed is responsible for CARs exhibiting a variety of clinical presentations. Their origin is likely attributed to direct cytotoxicity following the cell cycle arrest in the S phase and cell necrosis. PMID:22866124

Piérard-Franchimont, Claudine; Quatresooz, Pascale; Reginster, Marie?Annick; Piérard, Gérald E.

2011-01-01

50

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

51

Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: Survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).  

PubMed

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up. PMID:25623158

Kano, Yoko; Tohyama, Mikiko; Aihara, Michiko; Matsukura, Setsuko; Watanabe, Hideaki; Sueki, Hirohiko; Iijima, Masafumi; Morita, Eishin; Niihara, Hiroyuki; Asada, Hideo; Kabashima, Kenji; Azukizawa, Hiroaki; Hashizume, Hideo; Nagao, Keisuke; Takahashi, Hayato; Abe, Riichiro; Sotozono, Chie; Kurosawa, Michiko; Aoyama, Yumi; Chu, Chia-Yu; Chung, Wen-Hung; Shiohara, Tetsuo

2015-03-01

52

[Adverse effects and patient information].  

PubMed

Anti-D prophylaxis should be proposed to all RhD negative non-sensitized pregnant women, after delivering an information concerning both Rhesus disease and anti-D immunoglobulins. This information must be delivered as a written document and the patient's oral consent is required before administration of the anti-D immunoglobulins. Anti-D immunoglobulins currently used in France for prophylaxis are extracted from plasma of hyperimmunized paid donors. Even if all the conditions of viral safety are fulfilled in the preparation of anti-D immunoglobulins, they remain blood derived products. As such, prescription of anti-D immunoglobulins should follow legal rules concerning tracability and information. Refusal of rhesus prophylaxis can occur but should be transcribed and motivated in the patient's chart. Administration of anti-D immunoglobulins is usually well tolerated. Reactions to hemolysis of fetal Rhesus positive red cells can occur but remain rare and linked to important foeto-maternal hemorrhage. They can be easily prevented or treated by anti-inflammatory drugs. Patients can be vaccinated against rubella in the post-partum period even though they will receive a concomitant prophylaxis with Rh immunoglobulin. Persistence of passive anti-D in maternal circulation after injection lasts several weeks or months and could have various consequences. In the mother: it can interfere with diagnosis of active anti-D immunization. In most cases, it may be possible to differentiate passive and immune anti-D. When reliable information concerning date and dosage of antenatal anti-D prophylaxis are available. In the newborn: anti-D immunoglobulins can pass through the placenta and enter the fetal circulation, coat the D positive fetal red cells and give positive DAT. Positive DAT is reported in 5 to 15% of the newborns following rhesus prophylaxis in the third trimester but with no report of anemia or jaundice. In absence of ABO incompatibility, no additional investigation is needed in these newborns. PMID:16495836

Cortey, A; Brossard, Y

2006-02-01

53

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. PMID:25657416

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

2015-01-01

54

OBJECTIVE PSYCHOLOGICAL MEASUREMENT AND CLINICAL ASSESSMENT OF ANXIETY IN ADVERSE DRUG REACTIONS  

Microsoft Academic Search

Background A confounding factor in the diagnosis of adverse drug reactions (ADRs) is the psychological state of the patient. Patients with underlying anxiety and related disorders may present with psychogenic reactions, which involve physiologic responses originating from psychological, rather than organic factors. Objective To examine the contribution of anxiety and related disorders to adverse drug events. Methods Participants from an

Debra Ong; Sandra R. Knowles; Neil H. Shear; Karen E. Binkley

2004-01-01

55

Predictive genomic markers for severe adverse drug reactions.  

PubMed

  Severe adverse drug reactions are an important issue to be considered during proper drug usage in postmarketing period. Most severe adverse reactions are idiosyncratic and unrelated to their pharmacological actions via primary targets. Although these reactions were not predictable, recent developments in the field of genomics have revealed closely associated markers responsible for some severe adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This review demonstrates genomic biomarkers for SJS/TEN and drug-induced liver injury (DILI) that were found mainly in Japanese patients and reveal ethnic differences. We and other groups have found the following associations of SJS/TEN with susceptible drugs: 1) HLA-B*58:01 for allopurinol-related cases; 2) HLA-B*15:11 and HLA-A*31:01 for carbamazepine-related cases; 3) HLA-B*51:01 for phenobarbital-related cases; 4) HLA-A*02:07 for zonisamide-related cases; 5) CYP2C9*3 for phenytoin-related cases; and 6) HLA-A*02:06 for cold medicine-related cases. The allele frequencies of these related HLA types vary among Asian populations. In addition, direct (noncovalent) binding of carbamazepine or an allopurinol metabolite, oxypurinol, to the associated HLA-type proteins was suggested. Associated genomic biomarkers are also summarized for DILI in Japanese and Caucasian populations. The application of these genomic biomarkers to prevent the onset of a reaction has been utilized in a few countries. However, in Japan, the package inserts only contain precautions that cite the research findings. To overcome this limitation, the following points should be addressed: 1) factors responsible for the development of SJS/TEN should be identified in addition to the above-mentioned HLA alleles; and 2) an inexpensive genotyping strategy and assay methods should be developed to provide a pharmacoeconomical viewpoint. Further research on severe adverse reactions is warranted. PMID:25832839

Saito, Yoshiro; Kodama, Susumu; Sugiyama, Emiko; Nakamura, Ryosuke

2015-01-01

56

Association between Thiopurine S-methyltransferase Polymorphisms and Thiopurine-Induced Adverse Drug Reactions in Patients with Inflammatory Bowel Disease: A Meta-Analysis  

PubMed Central

Purpose Thiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between TPMT polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and thiopurine-induced ADRs using meta-analysis. Methods We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and thiopurine-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software. Results Fourteen published studies, with a total of 2,206 IBD patients, which investigated associations between TPMT polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82–6.19) and 6.67 (95%CI: 3.88–11.47), respectively. TPMT polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60–2.71), 0.97 (95%CI: 0.38–2.48), 1.82 (95%CI: 0.93–3.53), 1.28 (95%CI: 0.47–3.46) and 2.32 (95%CI: 0.86–6.25), respectively. Conclusions Our meta-analysis demonstrated an association of TPMT polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the TPMT genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up. PMID:25799415

Liu, Yue-Ping; Wu, Hai-Yan; Yang, Xiang; Xu, Han-Qing; Li, Yong-Chuan; Shi, Da-Chuan; Huang, Jun-Fu; Huang, Qing; Fu, Wei-Ling

2015-01-01

57

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

58

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

59

[Adverse drug reaction surveillance system in Korea].  

PubMed

Despite extensive researches and pre-market clinical trials, only limited information on the adverse drug reactions (ADRs) of a drug can be collected at the time of market approval from regulatory agency. ADRs constitute a major public health problem. Post-marketing surveillance of drugs is important to detect signals for ADR. In Korea, one of the main methods for monitoring the safety of marketed drugs is spontaneous reporting system of suspected ADRs. Re-examination and re-evaluation system are in force for monitoring safety of new market approval drugs and currently under marketing drugs, respectively. Recently, regional pharmacovigilance centers were designated from Korean Food and Drug Administration for facilitating ADR surveillance. Over recent years, with the development of information technology, there has been an increased interest in establishing data mining system for detecting signals from Health Insurance Review Agency database. The purpose of this paper is to review the current status of Korean ADR surveillance system and suggest the possible solutions for developing active pharmacovigilance system in Korea. PMID:17693730

Choi, Nam-Kyong; Park, Byung-Joo

2007-07-01

60

Nurse Staffing and Adverse Patient Outcomes  

Microsoft Academic Search

Knowledge regarding the influence of nurse staffing on patient outcomes provides information to nurse administrators for determining numbers of nurs- ing personnel in each units in order to promote a quality of care in nursing care. The purposes of this study is to identify the relationships between nurse staffing and adverse patient outcomes. Data were received from the documentation of

Bunpitcha Chitpakdee; Wipada Kunaviktikul; Wichit Srisuphan

2008-01-01

61

Quality check of spontaneous adverse drug reaction reporting forms of different countries.  

PubMed

Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge-rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. PMID:20845409

Bandekar, M S; Anwikar, S R; Kshirsagar, N A

2010-11-01

62

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

63

Evaluation of adverse reactions to contrast media in the hospital  

PubMed Central

Objective: To determine and analyse the characteristics of contrast media adverse reactions (CM-ARs) reported in a hospital. Methods: A retrospective review of CM-ARs from the electronic spontaneous adverse drug reaction (ADR) report system between January 2011 and August 2012 was conducted. CM-ARs were evaluated in terms of causality, severity, preventability and affected organs. Also, agreement and correlation among the tools used to evaluate CM-ARs were analysed. Results: The overall reaction rate was 1.5% (n?=?286). In total, 269 CM-ARs were identified. For ADR causality, 96.7% (n?=?260) and 98.5% (n?=?265) were evaluated as “probable” ADR using the Naranjo probability scale and the World Health Organization–Uppsala Monitoring Centre causality categories, whereas 98.1% (n?=?264) were evaluated as “certain” with Korean algorithm v. II. Of these, 91.4% (n?=?246) were mild in severity and 96.7% (n?=?260) were unpreventable. Most patients (n?=?233, 86.7%) could be managed with observation and/or simple treatment. The most frequent reaction (n?=?383, 79.5%) was dermatological. Spearman's correlation coefficient was 0.667 (p?patients undergoing CT procedures continues to increase, it is essential to identify and observe patients at risk for CM-ARs to prevent severe ADRs. Advances in knowledge: Continuous careful review of reporting and treatment protocols of CM-ARs is needed to prevent morbidity and mortality. PMID:24191123

Ryu, J-H; Kim, E-Y

2013-01-01

64

Toward the operational identification of adverse drug reactions.  

PubMed

The evaluation of adverse drug reactions in clinical practice is somewhat arbitrary and is characterized by considerable differences of opinion. This report presents a decision table algorithm approach toward the development of an operational system for the identification of adverse drug reactions. The algorithm incorporates an estimate of the certainty of the link between the untoward clinical event and the suspect drug, and examines the underlying causes of the identified drug reactions. Use of such a system is a first step toward reducing ambiguity in the evaluation of adverse drug reactions. PMID:837643

Karch, F E; Lasagna, L

1977-03-01

65

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

66

Adverse events in surgical patients in Australia  

Microsoft Academic Search

Objective. To determine the adverse event (AE) rate for surgical patients in Australia. Design. A two-stage retrospective medical record review was conducted to determine the occurrence of AEs in hospital admissions. Medical records were screened for 18 criteria and positive records were reviewed by two medical officers using a structured questionnaire. Setting. Admissions in 1992 to 28 randomly selected hospitals

A. K. KABLE; R. W. GIBBERD; A. D. SPIGELMAN

2002-01-01

67

Precautions and Adverse Reactions during Blood Transfusion  

MedlinePLUS

... leukocyte reduction), allergic reactions are less common. Fluid overload: Transfusion recipients can receive more fluid than their ... Special Blood Donation Procedures Next: Overview of Iron Overload

68

A prospective study of adverse drug reactions in hospitalized children  

PubMed Central

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

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

1999-01-01

69

Immunotoxicology of the liver: adverse reactions to drugs.  

PubMed

Liver is a frequent target for drug-induced hepatitis. They can be classified in two categories: the hepatitis in which the drug or a metabolite reach a vital target in the cell and the hepatitis in which the drug triggers an adverse immune response directed against the liver. We will discuss essentially this second kind of disease. They have key clinical features such as the low frequency, the dose independence, the delay between the beginning of drug intake and the triggering of the disease, the shortening of the delay upon rechallenge and very often the presence of autoantibodies in the serum of the patients. Such signs were found in hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine, anticonvulsants. They will be taken as examples to show the recent progress in the understanding of the mechanisms leading to the disease. It has been postulated that the drug is metabolised into a reactive metabolite binding to the enzyme which generated it; therefore the neoantigen might trigger an immune response characterised by the production of antibodies recognising the native and or the modified protein. Most of these steps were proven in the cases of halothane, tienilic acid and dihydralazine. Several points seem important in the development of the disease; the equilibrium between toxication and detoxication pathways, the nature and amount of neoantigen, the individual immune response. However, many points remain unclear: for instance, the reason for the very low frequency of this kind of disease; the precise mechanism of the adverse immune response; the risk factors for developing such adverse reactions. Efforts should be made to better understand the mechanisms of this kind of disease: for instance, an animal model, tests to identify drugs at risk for such reactions, the role of these drugs in the processing of P450s and the processing of the neoantigens for their presentation to the immune system. PMID:9204408

Beaune, P H; Lecoeur, S

1997-01-01

70

Severe cutaneous adverse reaction to telaprevir.  

PubMed

A 50-year-old woman presented with diffuse, intensely pruritic pink-red papules on her trunk and extremities three weeks after starting combination therapy with ribavirin, telaprevir, and interferon. She also had cervical lymphadenopathy, fever, eosinophilia, and transaminitis consistent with a severe drug reaction to telaprevir. She was started on high potency topical steroids under inpatient observation and recovered within two weeks. Severe cutaneous eruptions secondary to telaprevir have resulted in black-box warnings for potentially fatal skin reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN). Because these reactions carry acute mortality rates of 10%, prompt detection and treatment with steroids are important. As such, physicians should be aware of these potentially lethal side effects. PMID:25612120

Shuster, Marina; Do, Daihung; Nambudiri, Vinod

2015-01-01

71

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

Code of Federal Regulations, 2012 CFR

...false Significant adverse reactions that must be recorded...REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT...12 Significant adverse reactions that must be...

2012-07-01

72

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

Code of Federal Regulations, 2010 CFR

...false Significant adverse reactions that must be recorded...REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT...12 Significant adverse reactions that must be...

2010-07-01

73

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

Code of Federal Regulations, 2014 CFR

...false Significant adverse reactions that must be recorded...REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT...12 Significant adverse reactions that must be...

2014-07-01

74

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

Code of Federal Regulations, 2013 CFR

...false Significant adverse reactions that must be recorded...REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT...12 Significant adverse reactions that must be...

2013-07-01

75

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

Code of Federal Regulations, 2011 CFR

...false Significant adverse reactions that must be recorded...REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT...12 Significant adverse reactions that must be...

2011-07-01

76

Adverse reactions associated with systemic polymyxin therapy.  

PubMed

The systemic polymyxins, colistin and polymyxin B, are increasingly used for multidrug-resistant bacterial infections and have a long history of dose-limiting toxicity. This review summarizes the most recent available information about the mechanisms, incidence, risk factors, and minimization strategies for polymyxin toxicity. Nephrotoxicity is related to polymyxin exposure with both size of dose and length of therapy associated with frequency. Newer studies have questioned conventional thinking that the relative risk of nephrotoxicity is lower for colistin than polymyxin B, especially in light of evolving dosing practices. Neurotoxicities and hypersensitivity reactions are less common than nephrotoxicity. New techniques to minimize or avoid polymyxin toxicities are now emerging including a growing interest in clinical assays for therapeutic drug monitoring and the development of novel, less toxic agents (e.g., polymyxin derivatives) for the treatment of multidrug-resistant bacterial infections. PMID:25266910

Justo, Julie Ann; Bosso, John A

2015-01-01

77

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

78

Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.  

PubMed

CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case definitions presented in the report can be used in future vaccination programs to ensure uniform reporting guidelines and case classification. PMID:16456528

Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

2006-02-01

79

Energy drink use and adverse effects among emergency department patients.  

PubMed

Energy drink usage is common and contains caffeine or other stimulants. We evaluated demographics, prevalence, reasons and adverse effects with consuming energy beverages. Cross-sectional study of a convenience sample of patients recruited from two San Diego Emergency Departments from January to December 2009. One-thousand-two-hundred-ninety-eight subjects participated of which 52.6% were male. Ethnicity: Caucasian 48.3%, African American 17%, Hispanic 18%, Other 16.7%. Age ranges: 18-29 years (38.4%), 30-54 years (49.6%) and greater than 55 years (12%). Reasons for use: 57% to "increase energy", 9.5% for studying/work projects, 2.4% while prolonged driving, improve sports performance 2%, with ethanol 6.3%, "other" reasons 22.1%. Adverse reactions reported by 33.5% (429) patients. Two-hundred-eighty report feeling "shaky/jittery", insomnia 136, palpitations 150, gastrointestinal upset 82, headache 68, chest pain 39, and seizures in 6. Eighty-five patients reported co-ingestion with illicit "stimulants" including cocaine and methamphetamine. We identified one-third of patients reported at least one adverse effect. Whilst most were not severe, a small number were serious e.g., seizures. In addition, some report purposely ingesting with illicit drugs. PMID:22367607

Nordt, Sean Patrick; Vilke, Gary M; Clark, Richard F; Lee Cantrell, F; Chan, Theodore C; Galinato, Melissa; Nguyen, Vincent; Castillo, Edward M

2012-10-01

80

Frequency of adverse reactions to prochlorperazine in the ED  

Microsoft Academic Search

Prochlorperazine (Compazine, PCZ) is a frequently used medication in the emergency department (ED). Akathisia and dystonia are known adverse reactions to the use of this medication, but their incidence in the ED has not been well studied. We conducted a prospective, descriptive study to evaluate the frequency of akathisia and dystonia in the ED from the use of IV or

Jon C. Olsen; Jane A. Keng; James A. Clark

2000-01-01

81

Different Reactions to Adverse Neighborhoods in Games of Cooperation  

PubMed Central

In social dilemmas, cooperation among randomly interacting individuals is often difficult to achieve. The situation changes if interactions take place in a network where the network structure jointly evolves with the behavioral strategies of the interacting individuals. In particular, cooperation can be stabilized if individuals tend to cut interaction links when facing adverse neighborhoods. Here we consider two different types of reaction to adverse neighborhoods, and all possible mixtures between these reactions. When faced with a gloomy outlook, players can either choose to cut and rewire some of their links to other individuals, or they can migrate to another location and establish new links in the new local neighborhood. We find that in general local rewiring is more favorable for the evolution of cooperation than emigration from adverse neighborhoods. Rewiring helps to maintain the diversity in the degree distribution of players and favors the spontaneous emergence of cooperative clusters. Both properties are known to favor the evolution of cooperation on networks. Interestingly, a mixture of migration and rewiring is even more favorable for the evolution of cooperation than rewiring on its own. While most models only consider a single type of reaction to adverse neighborhoods, the coexistence of several such reactions may actually be an optimal setting for the evolution of cooperation. PMID:22539958

Zhang, Chunyan; Zhang, Jianlei; Weissing, Franz J.; Perc, Matjaž; Xie, Guangming; Wang, Long

2012-01-01

82

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

83

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

84

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

85

Risk factors associated with adverse reactions to antituberculosis drugs*  

PubMed Central

This review sought to identify the available scientific evidence on risk factors associated with adverse reactions to antituberculosis drugs. We performed a systematic review of studies published in the 1965-2012 period and indexed in the MEDLINE and LILACS databases. A total of 1,389 articles were initially selected. After reading their abstracts, we selected 85 studies. Of those 85 studies, 16 were included in the review. Risk factors for adverse reactions to antituberculosis drugs included age > 60 years, treatment regimens, alcoholism, anemia, and HIV co-infection, as well as sodium, iron, and albumin deficiency. Protective factors against hepatic adverse effects of antituberculosis drugs included being male (combined OR = 0.38; 95% CI: 0.20-0.72) and showing a rapid/intermediate N-acetyltransferase 2 acetylator phenotype (combined OR = 0.41; 95% CI: 0.18-0.90). There is evidence to support the need for management of adverse reactions to antituberculosis drugs at public health care facilities.

Resende, Laíse Soares Oliveira; dos Santos-Neto, Edson Theodoro

2015-01-01

86

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

E-print Network

Abstract Objective Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs...

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

2012-06-19

87

Genetic Variants of NPAT-ATM and AURKA are Associated With an Early Adverse Reaction in the Gastrointestinal Tract of Patients With Cervical Cancer Treated With Pelvic Radiation Therapy  

SciTech Connect

Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. Methods and Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade {<=}1, n = 150; Grade {>=}2, n = 58). Genomic DNA was genotyped, and association with the risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. Results: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). Conclusions: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.

Ishikawa, Atsuko; Suga, Tomo; Shoji, Yoshimi [RadGenomics Project, National Institute of Radiological Sciences, Chiba (Japan); Kato, Shingo; Ohno, Tatsuya; Ishikawa, Hitoshi [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yoshinaga, Shinji [Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Ohara, Kiyoshi [Tsukuba University Hospital, Tsukuba (Japan); Ariga, Hisanori [Tohoku University Hospital, Miyagi (Japan); Nomura, Kuninori [Toyama University Hospital, Toyama (Japan); Shibamoto, Yuta [Nagoya City University Hospital, Aichi (Japan); Ishikawa, Ken-Ichi; Moritake, Takashi; Michikawa, Yuichi; Iwakawa, Mayumi [RadGenomics Project, National Institute of Radiological Sciences, Chiba (Japan); Imai, Takashi, E-mail: imait@nirs.go.jp [RadGenomics Project, National Institute of Radiological Sciences, Chiba (Japan)

2011-11-15

88

Adverse drug reactions in children in Camagüey Province, Cuba  

Microsoft Academic Search

ObjectiveTo determine the incidence of adverse drug reactions (ADRs) in children in Camagüey Province, Cuba.MethodsA national pharmacovigilance programme has been established in Cuba and involves suspected ADRs being reported to provinces. All suspected ADRs reported to Camagüey Province during 2008 were analysed and classified in relation to causality and severity.ResultsOver a 12-month period, there were 124 reports of 152 suspected

Z Bárzaga Arencibia; D Novoa Sotomayor; N Caballero Mollinedo; I Choonara; E Fernández Manzano; A López Leyva

2010-01-01

89

[Herbal drug-drug interaction and adverse drug reactions].  

PubMed

Herbal medicines are used by many patients. Their known or potential adverse events should be taken into account during treatment with herbal medicines. In this article adverse effects of commonly used herbs are presented. St. John's wort is known to be a potent inducer of cytochrome P450 (CYP) 3A4 leading to reduced blood concentrations of a number of CYP3A4 substrates. For many other combinations evidence is sparse but due to a number of case reports of adverse interactions they should only cautiously be combined with certain critical dose drugs until their risk is fully assessed. Pertinent examples are the immunostimulant Echinacea which could decrease the effect of immunosuppressants. Ginseng and ginkgo should not be combined with anticoagulants. Excessive sedation may occur with concomitant use of valerian and barbiturates. PMID:21184395

Hafner-Blumenstiel, Verena

2011-01-01

90

Allergic Reactions After Egg-Free Recombinant Influenza Vaccine: Reports to the US Vaccine Adverse Event Reporting System.  

PubMed

The Vaccine Adverse Event Reporting System has received reports of allergic reactions following immunization with egg-free recombinant influenza vaccine, among patients with a self-reported egg allergy or previous allergic reaction to inactivated influenza vaccine. These results suggest that allergic reactions following influenza vaccination are not necessarily related to egg proteins. PMID:25428412

Woo, Emily Jane

2015-03-01

91

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

PubMed Central

Background There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children's symptoms to medicines could be a starting point for improved communication. PMID:23071535

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

2012-01-01

92

Adverse drug reactions and safety considerations of NSAIDs: clinical analysis.  

PubMed

NSAIDs are the most frequently used drugs for treatment, in Europe and the United States, accounting for approximately 5% of all prescriptions. Moreover, the use of NSAIDs is increasing because these constitute the first-line drug therapy for a wide range of rheumatic conditions. This increase is in part the result of the increasing population of elderly patients, who constitute the group of patients with greatest demand for these agents. There are many types of NSAIDs that vary in potency, action and potential side effects. Thus various efforts have been made to determine the safety considerations including adverse drug effects, duration of drug therapy, drug interactions, precautions and other drugs applied to reduce side effects. Researchers have introduced some novel techniques to diagnose NSAIDs related adverse effects on the gastrointestinal mucosa. The researchers dealing with the development of drug delivery system for these drugs should aim at designing a therapeutically efficacious dosage form with reduced side/adverse effects. Thus an effort has been made in this review to deal with the safety parameters of various NSAIDs with a special emphasis on preclinical and clinical safety analysis and various attempts to minimize the side effects by structural modification or by drug delivery system. PMID:22424538

Bahadur, Shiv; Keshri, Lav; Pathak, Kamla

2011-11-01

93

Nurse-perceived Patient Adverse Events and Nursing Practice Environment  

PubMed Central

Objectives: To evaluate the occurrence of patient adverse events in Korean hospitals as perceived by nurses and examine the correlation between patient adverse events with the nurse practice environment at nurse and hospital level. Methods: In total, 3096 nurses working in 60 general inpatient hospital units were included. A two-level logistic regression analysis was performed. Results: At the hospital level, patient adverse events included patient falls (60.5%), nosocomial infections (51.7%), pressure sores (42.6%) and medication errors (33.3%). Among the hospital-level explanatory variables associated with the nursing practice environment, ‘physician- nurse relationship’ correlated with medication errors while ‘education for improving quality of care’ affected patient falls. Conclusions: The doctor-nurse relationship and access to education that can improve the quality of care at the hospital level may help decrease the occurrence of patient adverse events. PMID:25284199

Kang, Jeong-Hee; Kim, Chul-Woung; Lee, Sang-Yi

2014-01-01

94

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.

95

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

Microsoft Academic Search

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 esti- mated the incidence of AEs among patients in Canadian acute care hospitals. Methods: We randomly selected 1 teaching, 1 large community and 2 small

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

2004-01-01

96

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

97

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

98

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

99

Nexavar®-related adverse reactions: Calabrian (Italy) experience for sorafenib exposition in 2012  

PubMed Central

Hepatocellular carcinoma (HCC) remains a major global health problem and Calabria in the south of Italy is not an exception. Sorafenib is the first and only Food and Drug Administration approved drug for the treatment of advanced HCC and it is currently under intensive monitoring by the Health Authorities in Italy Agenzia Italiana del Farmaco. This general report has been developed with the aim of briefly reviewing the data found in the reports of adverse reactions (ADRs) collected in Calabria in 2012 for sorafenib treated patients. Extrapolated data have highlighted some differences between the adverse drug reactions reported in patients younger or older than 70 years and other important differences with the current approved leaflet. Several limitations might be present in data analysis form spontaneous reporting, however, the relevance of reporting ADRs (dermatitis, asthenia, vomiting, etc.) for the early identification of drug related signals has to be underlined. PMID:24347990

Cilurzo, Felisa; Staltari, Orietta; Patanè, Marinella; Ammendola, Michele; Garaffo, Caterina; Di Paola, Eugenio Donato

2013-01-01

100

Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines  

Microsoft Academic Search

Background: 5-Aminosalicylates are extensively prescribed for the treatment of ulcerative colitis but have a wide range of described adverse effects.Aims: To determine whether serious adverse effect profiles differ for sulphasalazine and mesalazine.Methods: Analysis of suspected serious adverse reactions reported to the Committee on Safety of Medicines of the UK in 1991–1998. Adverse effect profiles were categorised for interstitial nephritis, pancreatitis,

R A J Ransford; M J S Langman

2002-01-01

101

Misuse of the Naranjo Adverse Drug Reaction Probability Scale in toxicology  

PubMed Central

Context When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo and colleagues developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients. Objective The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application. Methods A Medline search via PubMed without language limits, through September 2012, using the search terms “Naranjo” and “overdose” or “poisoning” yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients. Results From the 146 publications, we identified 17 case reports or series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Conclusion Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case reports or series of overdose patients, the Naranjo Scale has been applied to assess the probability an event was caused by the ingested drug or therapeutic modality. This application of the Naranjo Scale is not scientifically valid and may lead to erroneous conclusions. There is no evidence to support the application of the Naranjo scale to any events that occur in overdose patients. PMID:23777343

Seger, Donna; BARKER, Kimberly; McNAUGHTON, Candace D.

2014-01-01

102

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

103

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

104

Adverse effects of methotrexate in three psoriatic arthritis patients.  

PubMed

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed. PMID:23274445

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

105

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

PubMed Central

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

Gabrilovich, Evgeniy

2013-01-01

106

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

107

Severe cutaneous adverse reactions: emergency approach to non-burn epidermolytic syndromes  

Microsoft Academic Search

Introduction  Although severe cutaneous adverse reactions (SCARs), such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are\\u000a rare, they are associated with considerable morbidity and mortality.\\u000a \\u000a \\u000a \\u000a Methods  The current knowledge regarding background, differential diagnoses, critical care and implications for inter-hospital emergency\\u000a medical service (EMS) transport of these patients is discussed.\\u000a \\u000a \\u000a \\u000a Conclusion  SCAR patients will substantially benefit from early interdisciplinary care and thorough consideration of

Manuel Florian Struck; Peter Hilbert; Maja Mockenhaupt; Beate Reichelt; Michael Steen

2010-01-01

108

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

109

Identification of risk factors for carbamazepine-induced serious mucocutaneous adverse reactions: A case-control study using data from spontaneous adverse drug reaction reports  

PubMed Central

Objectives: To identify risk factors other than genetic for severe carbamazepine-induced mucocutaneous reactions, that is, SJS, TEN, and exfoliative dermatitis (ED). Materials and Methods: We did a case-control study using data from the Swedish national database of spontaneously reported adverse drug reactions (ADRs). We selected all patients who had been reported from January 1, 1965 to March 31, 2010 as having experienced SJS (n = 78), TEN (n = 6), or ED (n = 8), and assessed as at least possibly related to carbamazepine. We also included diagnoses possibly representative of early signs of these serious conditions, that is, erythema multiforme (EM, n = 34) and scaly rash (n = 13). We compared data on demographics, drug treatment, and clinical features for these patients (cases, n = 139) with those from patients who had experienced any other type of ADR from carbamazepine during the same time period (controls, n = 887). Results: After adjustment for multiple comparisons, alcohol abuse was statistically significantly more common among cases than controls (34.5% vs 8.7%, odds ratio 5.5 [95% confidence interval 3.6-8.4], P = 3.14 × 10-14 ). The same was seen for SJS and EM individually. Conclusion: Alcohol abuse is a possible risk factor for serious carbamazepine-induced mucocutaneous reactions. PMID:24799813

Bertulyte, Ilma; Schwan, Sofie; Hallberg, Pär

2014-01-01

110

Is inappropriate medication use a major cause of adverse drug reactions in the elderly?  

PubMed Central

What is already known about this subject Several studies have shown that inappropriate medications induce adverse health outcomes in the elderly. The hypothesis of Beers et al. that these inappropriate medications increase the likelihood of adverse drug reactions is debated and checked in patients admitted to hospital. What this study adds Inappropriate medications do not seem to be the major cause of adverse drug reactions in the elderly. More than the inappropriateness of the drugs themselves, it is the inappropriate use of drugs that is to be tackled when treating the elderly. The main preventable factor is the reduction in the number of drugs given. Aim To study the occurrence of adverse drug reactions (ADRs) linked to inappropriate medication (IM) use in elderly people admitted to an acute medical geriatric unit. Methods All the elderly people aged ? 70 years admitted to the acute medical geriatric unit of Limoges University hospital (France) over a 49-month period were included, whatever their medical condition. For all the patients, clinical pharmacologists listed the medications given before admission and identified the possible ADRs. The appropriateness of these medications and the causal relationship between drugs (either appropriate or not) and ADRs were evaluated. Results Two thousand and eighteen patients were included. The number of drugs taken was 7.3 ± 3.0 in the patients with ADRs and 6.0 ± 3.0 in those without ADRs (P < 0.0001). Sixty-six percent of the patients were given at least one IM prior to admission. ADR prevalence was 20.4% among the 1331 patients using IMs and 16.4% among those using only appropriate drugs (P < 0.03). In only 79 of the 1331 IM users (5.9%) were ADRs directly attributable to IMs. The IMs most often involved in patients with ADRs were: anticholinergic antidepressants, cerebral vasodilators, long-acting benzodiazepines and concomitant use of two or more psychotropic drugs from the same therapeutic class. Using multivariate analysis, after adjusting for confounding factors, IM use was not associated with a significant increased risk of ADRs (odds ratio 1.0, 95% confidence interval 0.8, 1.3). Conclusion Besides a reduction in the number of drugs given to the elderly, a good prescription should involve a reduction in the proportion of IMs and should take into consideration the frailty of these patients. PMID:17166186

Laroche, Marie-Laure; Charmes, Jean-Pierre; Nouaille, Yves; Picard, Nicolas; Merle, Louis

2007-01-01

111

Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.  

PubMed

The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism. PMID:25864225

Federico, Alessandro; Aitella, Ernesto; Sgambato, Dolores; Savoia, Alfonso; De Bartolomeis, Fabio; Dallio, Marcello; Ruocco, Eleonora; Pezone, Luciano; Abbondanza, Ciro; Loguercio, Carmela; Astarita, Corrado

2015-01-01

112

Adverse drug reaction profile of anti-snake venom in a rural tertiary care teaching hospital  

PubMed Central

Objectives The study was carried out with the aim of evaluation of the adverse drug reaction profile of anti-snake venom serum (ASV) in a rural tertiary care hospital. Methods An observational study was conducted in SRTR Medical College, Ambajogai, Maharashtra, India. A total number of 296 indoor case papers of snake bite from February to September 2011 and June to August 2012 were retrieved from the record section and the antivenom reactions were assessed. In addition, basic epidemiological data and prescribing practices of ASV were also analyzed. Results Vasculotoxic snake bites were more common (50.61%) than neuroparalytic ones (22.56%). Mild envenomation was the commonest presentation. A total of 92 (56.10%) patients who received ASV suffered from antivenom reactions. The most common nature of reaction was chills, rigors (69.56%) followed by nausea and vomiting (34.8%). 10-15% patients suffered from moderate to severe reactions like hypotension and sudden respiratory arrest. We did not find any dose response relationship of ASV to risk of reactions (odds ratio 0.37). Intradermal sensitivity test was performed in about 72% cases. Conclusion Our study showed a higher incidence of reactions to ASV at our institute. PMID:24396245

Deshpande, Rushikesh Prabhakar; Motghare, Vijay Motiram; Padwal, Sudhir Laxman; Pore, Rakesh Ramkrishna; Bhamare, Chetanraj Ghanshyam; Deshmukh, Vinod Shivaji; Pise, Harshal Nutan

2013-01-01

113

Adverse reaction to sublingual Parietaria vaccine following an ultra-rush induction.  

PubMed

In the treatment of respiratory allergies Sublingual Immunotherapy (SLIT) represents a valid alternative to Subcutaneous Immunotherapy (SCIT) for its better safety profile. We describe a case of acute severe asthma following the first maintenance dose of SLIT in a boy allergic to Parietaria pollen. At the initiation of therapy, the patient was in healthy condition and his asthma appeared to be under control. An ultra-rush induction had given no reaction. Despite the good safety profile of SLIT, clinicians should be aware of the risk of adverse effects when prescribing SLIT for respiratory allergies. PMID:24853571

Scala, G; Ciccarelli, A; Calabrò, C

2014-05-01

114

Adverse Reaction to Nicotine Gum in Malay Female Smoker: A Case Report  

ERIC Educational Resources Information Center

Nicotine replacement therapies (NRT) are prescribed in smoking cessation programmes to help smokers stop smoking. The ideal dosage of NRT should control cravings and withdrawal symptoms but avoid adverse reactions. This report describes a case of adverse reaction to nicotine gum in a female Malay smoker. Assays taken 2 h after the gum, showed that…

Noorzurani, Md Haris Robson; Bond, Alyson; Wolff, Kim

2008-01-01

115

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

116

Prevalence of adverse drug reactions at a private tertiary care hospital in south India  

PubMed Central

BACKGROUND: Adverse Drug Reactions (ADRs) constitute an enormous burden for the society. The aim of the present study was to detect, document, assess and report the suspected ADRs and preparation of guidelines to minimize the incidence of ADRs. METHODS: A prospective-observational study was conducted in the Department of General Medicine of a tertiary care hospital for 12 months from April 2008 to March 2009. Detected and suspected ADRs were analyzed for causality, severity and preventability using appropriate validated scales and were reported. ADR alert card was prepared and given to patients. Therapeutic guidelines were prepared and given to the relevant departments. RESULTS: A total of 57 ADRs were detected, documented, assessed and reported during the study period the incidence was found to be 1.8%. Assessment of severity of the suspected ADRs revealed that 12% of suspected ADRs were severe and 49% of ADRs were moderate in severity. Causality assessment was done which revealed 63% of ADRs were possibly drug-related. The majority of patients who had suffered from ADRs were above 60 years (56%). Gastrointestinal system was most commonly affected (37%) and the drug class mostly associated with ADRs was antibiotics (23%). Preventability of ADRs was assessed; and the results revealed that 28% of ADRs were definitely preventable. CONCLUSIONS: Measures to improve detection and reporting of adverse drug reactions by all health care professionals is recommended to be undertaken, to ensure, and improve patient's safety. In this way, hospital/clinical pharmacists play the cornerstone role. PMID:21448378

Sriram, Shanmugam; Ghasemi, Ali; Ramasamy, Rajeswari; Devi, Manjula; Balasubramanian, Rajalingam; Ravi, Thengungal Kochupapy; Sabzghabaee, Ali Mohammad

2011-01-01

117

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

118

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

Microsoft Academic Search

Objective: The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypo- tension (OH). Methods: In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Par- kinson's disease, pure autonomic failure, multiple sys- tem atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic

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

2005-01-01

119

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

Microsoft Academic Search

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics

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

2010-01-01

120

[Exploratory studies on genetic biomarkers related to serious drug adverse reactions].  

PubMed

Serious adverse events (SAEs) induced by drugs occur rarely, but the symptoms are very critical and generally not related to their pharmacological activities. Although SAEs should be avoided wherever possible, their occurrence is unpredictable at this time. In this article, we describe the clinical condition, figures on reported occurrence in Japan and studies on genetic markers related to serious cutaneous adverse reactions (SCARs), drug induced liver injury (DILI and rhabdomyolysis among SAEs. Then we introduce our last 3 years' approach of exploratory study on genetic markers for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), two of SCARs, useful for Japanese patients, including construction of a new case collection system, study methodology and progress. As the result at this moment, no Japanese SJS/TEN patients including 12 carbamazepine-related and 23 aromatic anti-epileptic agent-related ones carried HLA-B 1502 that was reported to have a strong association with carbamazepine-induced SJS/TEN in Han Chinese patients. On the other hand, 5 in 15 allopurinol-related SJS/TEN patients were found to have HLA-B 5801 that was detected as a genetic marker for allopurinol-induced SCARs in Han Chinese and Caucasians. Hereafter, we have a plan to begin the new exploratory studies on genetic markers for DILI and rhabdomyolysis, in addition to SJS/TEN patients. PMID:20306701

Kaniwa, Nahoko; Hasegawa, Ryuichi

2009-01-01

121

Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine  

PubMed Central

Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

Massot, Andreu; Gimenez-Arnau, Ana

2014-01-01

122

Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine.  

PubMed

Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

Massot, Andreu; Gimenez-Arnau, Ana

2014-10-01

123

Adverse skin reactions to infliximab in the treatment of intraocular inflammation  

Microsoft Academic Search

TNF? inhibitors are more widely used in the treatment of intraocular inflammation, thus ophthalmologists should become aware of possible adverse events, associated with this form of treatment. Herein we report two cases of cutaneous adverse events in uveitis patients treated with infliximab. In one patient, the primary outbreak of pustular psoriasis was observed after her third infusion. A second patient

B J Wegscheider; L El-Shabrawi; M Weger; N Ardjomand; J Hermann; E Aberer; Y El-Shabrawi

2007-01-01

124

Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program  

PubMed Central

Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

2012-01-01

125

Genetics and the potential for predictive tests in adverse drug reactions.  

PubMed

Drug hypersensitivity reactions are an immune-mediated reaction to otherwise innocuous antigens derived from drugs. These reactions can affect many different organs, with the skin being the commonest. Skin involvement can range in severity with hypersensitivity syndrome (or DRESS) and the blistering reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), also termed serious cutaneous adverse drug reactions, being the most severe and most feared. There is increasing evidence for the role of the immune system in the pathogenesis of these reactions, with drug-specific T cells having been identified in many patients. Until recently, very little was known about the predisposition to these reactions. However, the availability of more accurate molecular typing methods, and the ability to analyse the whole genome in an unbiased fashion, has led to some remarkable findings of the role of the HLA genes as genomic biomarkers of predisposition. The 'revolution' started with abacavir where the predisposition to hypersensitivity was linked to HLA-B*57:01, which was confirmed in a clinical trial, and where its implementation has shown to reduce the incidence of hypersensitivity in a cost-effective manner. Since then, associations have also been shown for allopurinol (HLA-B*58:01)- and carbamazepine (HLA-B*1502 and HLA-A*3101)-induced serious cutaneous adverse drug reactions. The latter is interesting since the association with HLA-B*1502 is present in certain South-Eastern Asian populations, and the predisposition is phenotype specific (only for SJS/TEN). The utility of this biomarker has been shown in a prospective cohort study performed in Taiwan. By contrast, the association with HLA-A*3101 is seen in more diverse ethnic groups, and predisposes to mild as well more severe cutaneous reactions associated with carbamazepine. It is important to note that strong HLA associations have also been shown with a number of drugs that cause liver injury including flucloxacillin, lumiracoxib, lapatinib and ximelagatran, indicating that the immune system is also important in the pathogenesis of other forms of drug-induced organ toxicity. The crucial question as to whether these HLA alleles are truly causative or acting as surrogate markers of predisposition, however, is still unclear, and will require further investigations in larger patient cohorts, through the use of bioinformatic techniques, fine mapping using next generation sequencing technologies and functional studies. PMID:22613851

Pirmohamed, Munir

2012-01-01

126

How to Discuss Errors and Adverse Events with Cancer Patients  

Microsoft Academic Search

Medical error has been increasingly recognized as a source of harm. The risk of harm can be even greater in cancer care with\\u000a its potentially life-limiting disease and toxic treatments. When errors and adverse events occur, patients have a right to\\u000a be informed and consistently report a desire to know about events in their care. Disclosure of errors is difficult

Iain E. Yardley; Sarah J. Yardley; Albert W. Wu

2010-01-01

127

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

PubMed Central

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 (cases) or placebo (controls) immediately before infusion of antivenom serum. Interventions Adrenaline 0.25?ml (1:1000). Main outcome measures Development of acute adverse reactions to serum and side effects attributable to adrenaline. Results 56 patients (cases) received adrenaline and 49 (controls) received placebo as pretreatment. Six (11%) adrenaline patients and 21 (43%) control patients developed acute adverse reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse reactions to serum were also seen in the adrenaline patients for each category of mild, moderate, and severe reactions. There were no significant adverse effects attributable to adrenaline. Conclusions Use of 0.25?ml of 1:1000 adrenaline given subcutaneously immediately before administration of antivenom serum to patients with envenomation after snake bite reduces the incidence of acute adverse reactions to serum. Key messagesAntivenom serum is the only effective treatment for envenomation after snake biteAcute adverse reactions to the serum are common and include anaphylactic shockThe prophylactic use of 1:1000 adrenaline in a dose of 0.25?ml given subcutaneously immediately before infusion of antivenom serum significantly reduces the risk of acute adverse reactions PMID:10205101

Premawardhena, A P; de Silva, C E; Fonseka, M M D; Gunatilake, S B; de Silva, H J

1999-01-01

128

Adverse Reaction Reporting Requirements: An Update for Manufacturers  

Microsoft Academic Search

The regulation governing postmarketing surveillance, Section 314.80 “Postmarketing reporting of adverse drug experience” is found under title 21 of the Code of Federal Regulations. This regulation was published on Feb 22, 1985, and became effective on Aug 22, 1985. Since that time, changes have been made that have been addressed in regulations, guidelines, and workshops. These adjustments have served the

Thomas H. Perez

1990-01-01

129

Adverse drug reactions in a complementary medicine hospital: a prospective, intensified surveillance study.  

PubMed

Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms. PMID:22315630

Süsskind, M; Thürmann, P A; Lüke, C; Jeschke, E; Tabali, M; Matthes, H; Ostermann, T

2012-01-01

130

Adverse Drug Reactions in a Complementary Medicine Hospital: A Prospective, Intensified Surveillance Study  

PubMed Central

Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms. PMID:22315630

Süsskind, M.; Thürmann, P. A.; Lüke, C.; Jeschke, E.; Tabali, M.; Matthes, H.; Ostermann, T.

2012-01-01

131

A review of pharmacogenetics of adverse drug reactions in elderly people.  

PubMed

Older adults are more susceptible to the prevalence of therapeutic failure and adverse drug reactions (ADRs). Recent advances in genomic research have shed light on the crucial role of genetic variants, mainly involving genes encoding drug-metabolizing enzymes, drug transporters and genes responsible for a compound's mechanism of action, in driving different treatment responses among individuals, in terms of therapeutic efficacy and safety. The interindividual variations of these genes may account for the differences observed in drug efficacy and the appearance of ADRs in elderly people. The advent of whole genome mapping techniques has allowed researchers to begin to characterize the genetic components underlying serious ADRs. The identification and validation of these genetic markers will enable the screening of patients at risk of serious ADRs and to establish personalized treatment regimens.The aim of this review was to provide an update on the recent developments in geriatric pharmacogenetics in clinical practice by reviewing the available evidence in the PubMed database to September 2012. A Pubmed search was performed (years 1999-2012) using the following two search strategies: ('pharmacogenomic' OR 'pharmacogenetic ') AND ('geriatric' or 'elderly ') AND 'adverse drug reactions'; [gene name] AND ('geriatric' or 'elderly ') AND 'adverse drug reactions', in which the gene names were those contained in the Table of Pharmacogenomic Biomarkers in Drug Labels published online by the US Food and Drug Administration ( http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm ). Reference lists of included original articles and relevant review articles were also screened. The search was limited to studies published in the English language. PMID:23446782

Cardelli, Maurizio; Marchegiani, Francesca; Corsonello, Andrea; Lattanzio, Fabrizia; Provinciali, Mauro

2012-01-01

132

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

133

Joint Symptoms, Aromatase Inhibitor-Related Adverse Reactions, Are Indirectly Associated with Decreased Serum Estradiol  

PubMed Central

Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested. Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level. Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of ?80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at ?5?pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old. Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS. PMID:22312534

Honda, Junko; Kanematsu, Miyuki; Nakagawa, Misako; Takahashi, Masako; Nagao, Taeko; Tangoku, Akira; Sasa, Mitsunori

2011-01-01

134

Morphological Pattern of Cutaneous Adverse Drug Reactions due to Antiepileptic Drugs in Eastern India  

PubMed Central

Introduction: Cutaneous manifestations of adverse drug reactions are a common occurrence and need to be differentiated from other causes of similar manifestations. Antiepileptic drugs (AED) usually are responsible for severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophillia and systemic symptoms (DRESS). There is paucity of published research regarding morphological pattern of CADR due to various antiepileptic drugs AED. Objective: To study the morphological patterns of CADR due to AED and common anticonvulsant drugs implicated particularly in severe CADR such as SJS/TEN and DRESS in a tertiary care teaching hospital in eastern India. Materials and Methods: A prospective, observational study was conducted over a period of 4 years from August 2009 to July 2013 after the approval of the Institutional Ethics Committee using self-reporting method for selection of cases. Settings: All patients with CADR after AED consumption for various conditions presenting to the Dermatology outpatient department (OPD) and Pediatric OPD and Indoor patients of a tertiary care teaching hospital located in Rohtas district of Bihar were included in this study. Results: During the study period, 64 cases of severe CADRs were included in this study. Out of 64 patients, 28 were male and 36 were female with mean age 36.1 years (range 6 years to 72 years). Most common AED implicated for CADR was Phenytoin. Maculopapular rash was the most common cutaneous manifestation of ADRs (42.85%). Serious CADR like TEN and SSJS were more likely in patients prescribed Phenytoin and Carbemazepine simultaneously. Conclusion: CADRs are a common occurrence and awareness about the same is essential for diagnosis and prevention. This study identified combined use of phenytoin and carbamezepine as a most important risk factor for serious CADR like SJS and TEN. PMID:25738068

Singh, Punit Kumar; Kumar, Dharmendra; Kumar, Prashant

2015-01-01

135

HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review.  

PubMed

Carbamazepine (CBZ) therapy is associated with cutaneous adverse reactions in up to 10% of patients. Predisposition to these hypersensitivity reactions has been linked to the human leukocyte antigen (HLA) genotype. This systematic review determines the strength of these associations and accuracy of proposed genetic screening. We determined that carriage of HLA-B*1502 in Asian patients was associated with a pooled odds ratio (OR) of 113.4 (95% confidence interval (CI) = 51.2-251.0, P < 1?×?10(-5)) for CBZ-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A total of 461 patients would need to be screened for HLA-B*1502 to prevent one episode of SJS/TEN. HLA-A*3101 is significantly associated with all phenotypes of CBZ hypersensitivity in multiple ethnicities with a pooled OR of 9.5 (95% CI = 6.4-13.9, P < 1?×?10(-5)). Between 47 and 67 patients would need to be tested for HLA-A*3101 to prevent one episode of hypersensitivity. Our findings suggest that HLA testing before carbamazepine therapy would be effective at identifying individuals at risk of hypersensitivity and applicable to multiple populations providing hope for prevention in the future. PMID:23132554

Yip, V L; Marson, A G; Jorgensen, A L; Pirmohamed, M; Alfirevic, A

2012-12-01

136

Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens.  

PubMed

The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ(®) Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy. PMID:25631061

Sastre, J; Rodríguez, F; Campo, P; Laffond, E; Marín, A; Alonso, M D

2015-05-01

137

Identifying adverse drug reactions and drug-induced diseases using network-based drug mapping.  

PubMed

Drugs are essential for the prevention and treatment of diseases. However, co-administration of multiple drugs may cause serious adverse drug reactions, which are usually known but sometimes unknown. Package inserts of prescription drugs are supposed to contain risks and side effects, but such information is not necessarily complete. At the core of efforts to improve prescription quality, there is reliance on the extent and quality of information used for decision of a medical doctor. To address this on-going need, GraphSAW provides users a comprehensive view on drug-related pharmacological and molecular information. The features of GraphSAW allow users to analyze drug cocktails for adverse drug reactions and drug-induced diseases. Network visualization by drug mapping enables exploring associative networks of drugs, pathways, and diseases to fully understand effects of drugs in an intuitive way. GraphSAW is meant to be a platform and starting point for health professionals and researchers for educational and scientific research in order to achieve substantial improvements in patient safety. PMID:25666653

Shoshi, Alban; Ogultarhan, Venus; Hoppe, Tobias; Kormeier, Benjamin; Müller, Ulrich; Hofestädt, Ralf

2015-02-01

138

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

139

The genetics of pro-arrhythmic adverse drug reactions.  

PubMed

Ventricular arrhythmia induced by drugs (pro-arrythmia) is an uncommon event, whose occurrence is unpredictable but potentially fatal. The ability of a variety of medications to induce these arrhythmias is a significant problem facing the pharmaceutical industry. Genetic variants have been shown to play a role in adverse events and are also known to influence an individual's optimal drug dose. This review provides an overview of the current understanding of the role of genetic variants in modulating the risk of drug induced arrhythmias. PMID:23834499

Petropoulou, Evmorfia; Jamshidi, Yalda; Behr, Elijah R

2014-04-01

140

The genetics of pro-arrhythmic adverse drug reactions  

PubMed Central

Ventricular arrhythmia induced by drugs (pro-arrythmia) is an uncommon event, whose occurrence is unpredictable but potentially fatal. The ability of a variety of medications to induce these arrhythmias is a significant problem facing the pharmaceutical industry. Genetic variants have been shown to play a role in adverse events and are also known to influence an individual's optimal drug dose. This review provides an overview of the current understanding of the role of genetic variants in modulating the risk of drug induced arrhythmias. PMID:23834499

Petropoulou, Evmorfia; Jamshidi, Yalda; Behr, Elijah R

2014-01-01

141

Adverse drug reaction monitoring in a secondary care hospital in South India  

PubMed Central

Aims To ascertain the current burden of ADRs at a Government hospital in Ooty and to assess the severity of reported ADRs and the additional financial burden associated with ADRs. Methods A prospective, spontaneous reporting study was conducted over a period of 9 months of inpatient admissions to the medical wards, co-ordinated by clinical pharmacists. The WHO definition of an ADR was adopted. The Naranjo algorithm scale was used for causality assessment. Confirmed ADRs were classified according to the Wills & Brown [7] method and assessed for severity and patient outcomes. The average cost incurred in treating the ADRs was calculated. Results Of the total of 187 adverse drug events (ADEs) reported, 164 reports from 121 patients were confirmed as ADRs, giving an overall incidence of 9.8%. This included 58 (3.4%) ADR related admissions and 63 (3.7%) ADRs occurring during the hospital stay. About two thirds of the reactions (102, 62.2%) were classified as probable. The majority of the reactions (88, 53.7%) were mild. Most patients (119, 72.6%) recovered from the incidence. The majority of the reactions were of type H (100, 61%) which indicates that they were not predictable and not potentially preventable. An average cost of 481 rupees (£6) was spent on each patient to manage ADRs. Conclusions The incidence and severity of ADRs documented in our study are lower than those reported in comparable populations in Western studies but more than those reported in India. What is already known about this subject The benefits of adverse drug reaction (ADR) monitoring are well-known.Poor awareness and nonavailability of a central co-ordinating body resulted in lack of ADR monitoring in India.The National Pharmacovigilance Programme was recently initiated, encouraging ADR monitoring in selected centres, including our centre. What this study adds This is the first study of its kind at GHQH, Ootacamund that has provided insight into the burden of ADRs here.The incidence and severity of ADRs documented in our study is lower than those reported in comparable populations in Western studies but more than those reported in India. PMID:17662089

Arulmani, R; Rajendran, SD; Suresh, B

2008-01-01

142

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

143

Patient-reported missed nursing care correlated with adverse events.  

PubMed

The aim of this study was to determine the extent and type of missed nursing care as reported by patients and the association with patient-reported adverse outcomes. A total of 729 inpatients on 20 units in 2 acute care hospitals were surveyed. The MISSCARE Survey-Patient was used to collect patient reports of missed care. Patients reported more missed nursing care in the domain of basic care (2.29 ± 1.06) than in communication (1.69 ± 0.71) and in time to respond (1.52 ± 0.64). The 5 most frequently reported elements of missed nursing care were the following: (a) mouth care (50.3%), (b) ambulation (41.3%), (c) getting out of bed into a chair (38.8%), (d) providing information about tests/procedures (27%), and (e) bathing (26.4%). Patients who reported skin breakdown/pressure ulcers, medication errors, new infections, IVs running dry, IVs infiltrating, and other problems during the current hospitalization reported significantly more overall missed nursing care. PMID:24006031

Kalisch, Beatrice J; Xie, Boqin; Dabney, Beverly Waller

2014-01-01

144

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

145

[Analysis of adverse reactions and pharmacovigilance research to parenterally administered shuxuening].  

PubMed

Parenterally administered Shuxuening is a commonly used Chinese medicine. There is a need to understand the characteristics of adverse drug reactions (ADRs) to it. 9 601 ADR cases reports were collected from the national adverse drug reaction monitoring center reported between January, 2005 and December, 2012. These included 326 serious ADR cases, accounting for 3.93% of the total. It was found that ADR reports increased annually from 2005, reaching a peak in the third quarter of 2009. The number of ADR cases reports were greatest in the third quarter of each year. ADRs in patients aged 60-74, accounted for 3 348 (34.87%) of all cases. 9 391(97.81%) cases were administered by intravenous infusion. In 8 431 cases, the dosage was in accordance with instructions. 61.61% ADR cases occurred on first administration. The ten most frequent symptoms were, rashes, itching, dizziness, palpitations, chills, allergic reactions, shortness of breath, nausea, phlebitis and vomiting. Systemic damage mainly affected the skin and its accessories damage, or the nervous system damage. Through the use of proportional reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) and propensity score applying generalized boosted models (GBM) to control for 17 confounding factors, analysis of the 10 kinds of ADRs found that for the ADR signals of dizziness, palpitations, phlebitis, and vomiting, BCPNN found that dizziness and phlebitis were early warning signals. This research found that in the 60-89 age group, higher dosages of parenterally administered Shuxuening gave rise to more phlebitis. This study provides important information for parenterally administered Shuxuening research, and guidance for its risk management. PMID:24471322

Yang, Wei; Xiang, Yong-Yang; Xie, Yan-Ming; Shen, Hao

2013-09-01

146

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

147

Adverse event prediction in patients with left ventricular assist devices.  

PubMed

This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment. PMID:24109937

Tsipouras, Markos G; Karvounis, Evaggelos C; Tzallas, Alexandros T; Katertsidis, Nikolaos S; Goletsis, Yorgos; Frigerio, Maria; Verde, Alessandro; Trivella, Maria G; Fotiadis, Dimitrios I

2013-01-01

148

Natural Inhibitors of Cholinesterases: Implications for Adverse Drug Reactions  

PubMed Central

Purpose Acetylcholinesterase and butyrylcholinesterase are two closely related enzymes important in the metabolism of acetylcholine and anaesthetic drugs, including succinylcholine, mivacurium, and cocaine. The solanaceous glycoalkaloids (SGAs) are naturally occurring steroids in potatoes and related plants that inhibit both acetylcholinesterase and butyrylcholinesterase. There are many clinical examples of direct SGA toxicity due to cholinesterase inhibition. The aim of this study was to review the hypotheses that (1) SGAs may be the evolutionary driving force for atypical butyrylcholinesterase alleles and that (2) SGAs may adversely influence the actions of anaesthetic drugs that metabolized by acetylcholinesterase and butyrylcholinesterase. Source The information was obtained by Medline search and consultation with experts in the study of SGAs and cholinesterases. Principal findings The SGAs inhibit both acetylcholinesterase and butyrylcholinesterase in numerous in vitro and in vivo experiments. Although accurate assays of SGA levels are difficult, published data indicate human serum SGA concentrations at least ten-fold lower than required to inhibit acetylcholinesterase and butyrylcholinesterase in vitro. However, we review evidence that suggests the dietary ingestion of SGAs can initiate a cholinergic syndrome in humans. This syndrome occurs at SGA levels lower than those which interfere with anaesthetic drug catabolism. The world distribution of solanaceous plants parallels the distribution of atypical alleles of butyrylcholinesterase and may explain the genetic diversity of the butyrylcholinesterase gene. Conclusion Correlative evidence suggests that dietary SGAs may be the driving force for atypical butyrylcholinesterase alleles. In addition, SGAs may influence the metabolism of anaesthetic drugs and this hypothesis warrants experimental investigation. PMID:9161749

Krasowski, Matthew D.; McGehee, Daniel S.

2010-01-01

149

[The associations between idiosyncratic adverse drug reactions and HLA alleles and their underlying mechanism].  

PubMed

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail. PMID:23984511

Wang, Qing; Mei, Hu; Zhang, Ya-Lan; Pan, Xian-Chao; Tan, Wen; Chao, Li

2013-06-01

150

Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland.  

PubMed

Previous studies have found a strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome in Asian areas including Taiwan, Hongkong and Thailand. This study explores the association between HLA-B*1502 allele and carbamazepine-induced cutaneous adverse reactions in Han Chinese of southern China mainland, and find the genetic marker that can predict carbamazepine-induced cutaneous adverse reactions. HLA-B*1502 allele genotyping was performed by a polymerase chain reaction-sequence specific primers (PCR-SSP) method in 48 Han Chinese subjects who had carbamazepine-induced cutaneous adverse reactions, including 9 severe cutaneous adverse reaction patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and 39 cutaneous adverse reaction patients with maculopapular eruption (MPE). Meanwhile 80 carbamazepine-tolerant controls and 62 healthy individuals were also tested. The frequency of HLA-B*1502 allele among SJS/TEN patients (100%) is significantly higher than carbamazepine-tolerant controls (13.75%, P<0.001) and healthy individuals (17.74%, P<0.001). But the frequency between MPE patients and carbamazepine-tolerant controls (25.64% vs.13.75%, P=0.110) did not have any significant difference. The data showed that HLA-B*1502 allele is strongly associated with carbamazepine-induced SJS/TEN but not MPE in Han Chinese of southern China mainland. PMID:21397523

Wang, Qian; Zhou, Jue-qian; Zhou, Lie-min; Chen, Zi-yi; Fang, Zi-yan; Chen, Shu-da; Yang, Li-bai; Cai, Xiao-dong; Dai, Qi-lin; Hong, Hua; Wang, Hong-xuan

2011-07-01

151

HLA-B*1502 allele is associated with a cross-reactivity pattern of cutaneous adverse reactions to antiepileptic drugs.  

PubMed

The US Food and Drug Administration has recommended genetic screening for the human leucocyte antigen-B (HLA-B)*1502 allele in patients of Asian ethnicity before starting carbamazepine therapy, to avoid the fatal adverse treatment-related events associated with this drug. The association between cross-reactivity to antiepileptic drugs (AEDs) and the HLA-B*1502 allele has been only rarely reported. Here, two cases of cross-reactivity to AEDs, where cutaneous adverse drug reactions (cADRs) developed in female Han Chinese patients with epilepsy who tested positive for the HLA-B*1502 allele, are described. If the genetic association could be confirmed in larger studies, the HLA-B*1502 allele should be tested for in any patient experiencing cADRs, to avoid crossreactivity to AEDs. PMID:22429379

Wang, J; Zhang, J; Wu, X; Yu, P; Hong, Z

2012-01-01

152

Adverse skin reactions to infliximab in the treatment of intraocular inflammation.  

PubMed

TNFalpha inhibitors are more widely used in the treatment of intraocular inflammation, thus ophthalmologists should become aware of possible adverse events, associated with this form of treatment. Herein we report two cases of cutaneous adverse events in uveitis patients treated with infliximab. In one patient, the primary outbreak of pustular psoriasis was observed after her third infusion. A second patient developed impetigo contagiosa induced by Staphylococcus aureus. Thus patients undergoing treatment with infliximab should be monitored carefully since dermal infections and pustular psoriasis, which may be triggered by streptococcal infection, may occur under this regime. PMID:16456589

Wegscheider, B J; El-Shabrawi, L; Weger, M; Ardjomand, N; Hermann, J; Aberer, E; El-Shabrawi, Y

2007-04-01

153

Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review.  

PubMed

Adverse drug reactions (ADRs) are common and are a major problem in drug therapy. Patients experience unnecessary morbidity and mortality whilst many effective drugs are withdrawn because of ADRs in a minority of patients. Recent studies have demonstrated significant associations between human leukocyte antigens (HLA) and predisposition to ADRs such as drug-induced skin injury (DISI) and drug-induced liver injury (DILI). HLA-B*58:01 has been significantly associated with allopurinol-induced hypersensitivity. Associations between HLA and carbamazepine hypersensitivity reactions demonstrate both ethnicity and phenotype specificity; with HLA-B*15:02 associated with Stevens-Johnson syndrome and toxic epidermal necrolysis in South East Asian patients only whilst HLA-A*31:01 is associated with all phenotypes of hypersensitivity in multiple ethnicities. Studies of ximelagatran, an oral direct thrombin inhibitor withdrawn because of hepatotoxicity, found associations between HLA-DRB1*07:01 and HLA-DQA1*02:01 and ximelagatran DILI. Interestingly, HLA-B*57:01 is associated with both abacavir DISI and flucloxacillin DILI but the reasons for the different phenotype of ADR remains unknown. Pharmacogenetic screening for HLA-B*57:01 prior to abacavir therapy has significantly reduced the incidence of abacavir hypersensitivity syndrome in clinical practice. No other HLA associations have been translated into clinical practice because of multiple reasons including failure to replicate, inadequate sample sizes, and our lack of understanding of pathophysiology of ADRs. Here, we review genetic associations that have been reported with ADRs and discuss the challenges that scientists, clinicians, pharmaceutical industry and regulatory agencies face when attempting to translate these associations into clinically valid and cost-effective tests to reduce the burden of ADRs in future. PMID:24777842

Yip, V L M; Alfirevic, A; Pirmohamed, M

2015-06-01

154

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

155

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

156

SideEffectPTM: An Unsupervised Topic Model to Mine Adverse Drug Reactions from Health Forums  

E-print Network

SideEffectPTM: An Unsupervised Topic Model to Mine Adverse Drug Reactions from Health Forums Sheng of drugs mentioned by forum users. Our approach is based on a novel probabilistic mixture model of symptoms models, and discovery of side ef- fect symptoms can be achieved in an unsupervised way through fit- ting

Zhai, ChengXiang

157

[Apply association rules to analysis adverse drug reactions of shuxuening injection based on spontaneous reporting system data].  

PubMed

This research based on the analysis of spontaneous reporting system (SRS) data which the 9 601 case reports of Shuxuening injection adverse drug reactions (ADR) in national adverse drug reaction monitoring center during 2005-2012. Apply to the association rules to analysis of the relationship between Shuxuening injection's ADR and the characteristics of ADR reports were. We found that ADR commonly combination were "nausea + breath + chills + vomiting", "nausea + chills + vomiting + palpitations", and their confidence level were 100%. The ADR and the case reports information commonly combination were "itching, and glucose and sodium chloride Injection, and generally ADR report, and normal dosage", "palpitation, and glucose and sodium chloride injection, and normal dosage, and new report", "chills, and generally ADR report, and normal dosage, and 0.9% sodium chloride injection", and their confidence level were 100% too. The results showed that patients using Shuxuening injection occurred most of ADRs were systemic damage, skin and its accessories damage, digestive system damage, etc. And most of cases were generally and new reports, and patients with normal dosage. The ADR's occurred had little related with solvent. It is showed that the Shuxuening injection occurred of ADR mainly related to drug composition. So Shuxuening injection used in clinical need to closely observation, and focus on the ADR reaction, and to do a good job of drug risk management. PMID:25532406

Yang, Wei; Xie, Yan-Ming; Xiang, Yong-Yang

2014-09-01

158

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

159

[Professionals' reactions to patient's suicide].  

PubMed

Physicians, nurses and social workers have a high risk of being confronted with the suicide of a patient during their career. After such an event they may react with sadness, anger or feelings of helplessness. Acute stress reactions are also observed, with irritability, disordered sleep and intrusive thoughts. Some professionals may fear to take care of suicidal patients. Reactions are particularly intense when there was a strong therapeutic relationship. Clinicians should recognize their need for support and look for help, particularly from colleagues. Such an experience may also help them to accept their limits and to become more vigilant and more sensitive to signs of suicidal risk. PMID:17939528

Kaufmann Didisheim, Nadine; Camus, Didier; Gulfi, Alida; Castelli Dransart, Angela

2007-09-19

160

Incidence and types of preventable adverse events in elderly patients: population based review of medical records  

Microsoft Academic Search

Objective To determine the incidence and types of preventable adverse events in elderly patients. Design Review of random sample of medical records in two stage process by nurses and physicians to detect adverse events. Two study investigators then judged preventability. Setting Hospitals in US states of Utah and Colorado, excluding psychiatric and Veterans Administration hospitals. Subjects 15 000 hospitalised patients

Eric J Thomas; Troyen A Brennan

2000-01-01

161

The drug efficacy and adverse reactions in a mouse model of oral squamous cell carcinoma treated with oxaliplatin at different time points during a day  

PubMed Central

Background Recent studies have shown that the growth and proliferation of cancer cells in vivo exhibit circadian rhythm, and the efficacy and adverse reactions of platinum-based anticancer drugs administered at different times of the day vary significantly on colon cancer. However, since the circadian rhythms of growth and proliferation of various cancer cells often differ, the question of whether the administration of platinum anticancer drugs at different times of the day exerts significantly different efficacy and adverse effects on oral cancers remains to be elucidated. This study has compared the efficacy and adverse effects of oxaliplatin (L-OHP) administration at different times during a day on oral squamous cell carcinoma in mice and has analyzed cellular circadian rhythms. Methods The mouse model for oral squamous cell carcinoma was established in 75 nude mice, housed in a 12 hour light/12 hour dark cycle environment. The mice were randomly divided into five groups; four experimental groups were intravenously injected with L-OHP at four time points within a 24-hour period (4, 10, 16, and 22 hours after lights on [HALO]). The control group was intravenously injected with the same volume of saline. Treatment efficacy and adverse reactions were compared on the seventh day after the injection, at 22 HALO. The existence of circadian rhythms was determined by cosine analysis. Results Only injections of L-OHP at 16 and 22 HALO significantly prolonged animal survival time. The adverse reactions in mice injected with L-OHP at 16 and 22 HALO were significantly less than those observed in mice administered L-OHP at 4 and 10 HALO. The cosine fitting curve showed that the survival time and adverse reactions exhibited circadian rhythm. Conclusion The time factor should be considered when treating patients with oral squamous cell carcinoma with L-OHP in order to achieve better efficacy, reduce the adverse reactions, and improve the patients’ survival time and quality of life. PMID:23818762

Yang, Kai; Zhao, Ningbo; Zhao, Dan; Chen, Dan; Li, Yadong

2013-01-01

162

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

163

Reported adverse food reactions overestimate true food allergy in the community  

Microsoft Academic Search

Objective: To determine the extent to which perceived adverse food reactions were associated with IgE mediated food allergy, as defined by skin prick testing (SPT).Design: A cohort epidemiological study. Participants underwent SPT to five common food allergens (cow's milk, peanut mix, egg white, shrimp and whole grain wheat mix) and were asked whether they had ever suffered any food ‘illness\\/trouble’,

RK Woods; RM Stoney; J Raven; EH Walters; M Abramson; FCK Thien

2002-01-01

164

The quality of information on monitoring for haematological adverse drug reactions  

PubMed Central

Aims To examine the adequacy of instructions to monitor for haematological adverse drug reactions in the Summary of Product Characteristics. Methods We searched the United Kingdom eMedicines Compendium to identify instructions to monitor for haematological adverse drug reactions, and selected 84 Summaries of Product Characteristics for nonhaematological drugs, which were then scored independently by five clinicians, using a scale we devised, the Systematic Instructions for Monitoring (SIM) score. A subset of comparable summaries from Australian and United States summaries was also examined. Results The SIM scores for the five clinicians agreed well: Kendall's coefficient of concordance = 0.937, P < 0.0001. The median SIM score for the 84 UK summaries was 13 [95% confidence interval (CI) for median 12, 15] out of a possible 31. Over 40% fell below a hypothetical minimally acceptable score of 12/31. SIM scores were on average 2.0 (95% CI 0.4, 3.8) higher for Australian summaries; US summaries had intermediate scores that did not significantly differ from those in Australia or the UK. Conclusions Instructions on monitoring for adverse drug reactions are often inadequate. Pharmaceutical companies and regulatory agencies should produce clear guidance on monitoring, and the data to support it. PMID:16187979

Ferner, R E; Coleman, Jamie; Pirmohamed, Munir; Constable, Simon A; Rouse, Andrew

2005-01-01

165

Interplay of Factors Leading to Adverse Drug Reactions in the Liver, A Personal Viewpoint 1  

PubMed Central

Adverse drug reactions in liver involve formation of a reactive metabolic intermediary of the drug, binding of the intermediary to macromolecules in the cell, notably proteins in the plasma membrane, immunological response to these altered proteins and attack against hepatocytes bearing these altered proteins by immune mechanisms. At each step in this complex process many factors act to enhance or depress drug metabolism, metabolite disposition, macromolecular binding, neoantigen formation, and the cell mediated and humoral immune attack. The extent and direction of each step may be dose dependent but the complexity of the overall mechanism is so immense that predictability of hepatic drug reactions is unlikely in most instances. PMID:602258

Schaffner, Fenton

1977-01-01

166

Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care hospital in South India  

PubMed Central

Purpose: Studies regarding pattern of adverse drug reactions (ADRs) in cancer chemotherapy patients are scarce in India. This study was conducted to evaluate the pattern of occurrence of ADRs due to cancer chemotherapy in hospitalized patients and to assess the causality, severity, predictability, and preventability of these reactions. Materials and Methods: This was a retrospective, descriptive study and the occurrence and nature of ADR, suspected drug, duration of hospital stay and outcome were noted from case records. These ADRs were assessed for causality using both World Health Organization (WHO) causality assessment scale and Naranjo's algorithm. The severity and preventability of the reported reactions were assessed using modified Hartwig and Siegel scale and modified Schumock and Thornton scale respectively. Results: Five hundred ADRs were recorded from 195 patients. Most common ADRs were infections (22.4%), nausea/vomiting (21.6%) and febrile neutropenia (13%). Platinum compounds, nitrogen mustards, taxanes, antibiotics and 5-fluorouracil were the most common drugs causing ADRs. WHO causality assessment scale showed 65% of the reactions to be “probable” and 35% to be “possible”, while Naranjo's algorithm indicated that 65.6% of ADRs were “probable” and 34.4% were “possible”. Modified Hartwig and Siegel scale showed most reactions (41.4%) to be of “moderate level 4(a)” severity, while 30.6% of reactions were of “mild level 1” severity. About 30.8% of the ADRs were “definitely preventable” according to the modified Schumock and Thornton scale. Conclusion: ADRs are most important causes of morbidity and mortality and increase the economic burden on patient and society. By careful ADR monitoring, their incidence can be decreased. PMID:25878957

Sharma, Ajitha; Kumari, K. Meena; Manohar, Hasitha Diana; Bairy, K. L.; Thomas, Joseph

2015-01-01

167

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

168

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

169

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

PubMed Central

Objective Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Methods Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. Results This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. Conclusion The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases. PMID:22718037

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

2012-01-01

170

Community pharmacists’ knowledge, behaviors and experiences about adverse drug reaction reporting in Saudi Arabia  

PubMed Central

Objective To assess community pharmacists’ knowledge, behaviors and experiences relating to Adverse Drug Reaction (ADR) reporting in Saudi Arabia. Methods A cross-sectional study was conducted using a validated self-administered questionnaire. A convenience sample of 147 community pharmacists working in community pharmacies in Riyadh, Saudi Arabia. Results The questionnaire was distributed to 147 pharmacists, of whom 104 responded to the survey, a 70.7% response rate. The mean age of participants was 29 years. The majority (n = 101, 98.1%) had graduated with a bachelorette degree and worked in chain pharmacies (n = 68, 66.7%). Only 23 (22.1%) said they were familiar with the ADR reporting process, and only 21 (20.2%) knew that pharmacists can submit ADR reports online. The majority of the participants (n = 90, 86.5%) had never reported ADRs. Reasons for not reporting ADRs most importantly included lack of awareness about the method of reporting (n = 22, 45.9%), misconception that reporting ADRs is the duty of physician and hospital pharmacist (n = 8, 16.6%) and ADRs in community pharmacies are simple and should not be reported (n = 8, 16.6%). The most common approach perceived by community pharmacists for managing patients suffering from ADRs was to refer him/her to a physician (n = 80, 76.9%). Conclusion The majority of community pharmacists in Riyadh have poor knowledge of the ADR reporting process. Pharmacovigilance authorities should take necessary steps to urgently design interventional programs in order to increase the knowledge and awareness of pharmacists regarding the ADR reporting process. PMID:25473329

Mahmoud, Mansour Adam; Alswaida, Yazeed; Alshammari, Thamir; Khan, Tahir Mehmood; Alrasheedy, Alian; Hassali, Mohamad Azmi; Aljadhey, Hisham

2013-01-01

171

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

172

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

173

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

174

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

175

Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists.  

PubMed

Biologic therapies targeting tumor necrosis factor (TNF)-alpha have become a mainstay in the management of a number of autoimmune diseases. We report a series of adverse skin eruptions in six patients (four females, two males, age: 21-58 years, mean: 39) receiving 4 months to 10 years (mean 3.1 years) of anti-TNF-alpha therapies (infliximab, n = 4; adalimumab, n = 1 or etanercept, n = 1). The following drug-associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between 3/2007 and 10/2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet's syndrome, lupus, vasculitis and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis-like and Sweet's-like hypersensitivity eruptions induced by anti-TNF-alpha therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved with switching to a different TNF-alpha inhibitor, discontinuation of the anti-TNF-alpha agent, and/or topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon withdrawal or steroid suppression of the anti-TNF-alpha agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The cutaneous adverse reaction profile of TNF-alpha inhibitors is broad and should be considered in the histopathologic differential in this clinical setting. PMID:22515220

Hawryluk, Elena B; Linskey, Katy R; Duncan, Lyn M; Nazarian, Rosalynn M

2012-05-01

176

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

177

Epidemiology and individual susceptibility to adverse drug reactions affecting the liver.  

PubMed

Adverse drug reactions affecting the liver represent an important challenge for safety in drug development. Drugs can reproduce practically the whole spectrum of liver diseases, but acute hepatitis is the most common syndrome. Drug hepatotoxicity is one of the most common causes of fulminant hepatitis. Most hepatic drug reactions occur in only a small proportion of individuals, making them difficult to detect at the time of drug development. Liver injury is principally recognized on the basis of spontaneous reports within the first 2 years of marketing a new drug. The prevalence of drug hepatotoxicity is poorly documented by a small number of retrospective studies. Despite the development of international analytical methods to allow standardized evaluation, the diagnosis remains indeterminate in many cases. Acquired and genetic factors influence the individual susceptibility to drug hepatotoxicity. Important directions for the future include prospective studies of the incidence of hepatic adverse drug reactions, finding specific markers that augment or replace causality assessment, and further elucidating the role of the genetic and environmental factors that contribute to individual susceptibility. PMID:12016546

Larrey, Dominique

2002-01-01

178

A risky business: the detection of adverse drug reactions in clinical trials and post-marketing exercises.  

PubMed

While it is widely acknowledged by epidemiologists, pharmacologists and physicians that adverse drug reactions (ADRs) occur with considerable frequency, within the realm of medical sociology, drug-induced risk currently receives little critical attention. This paper looks into this medical scientific 'black box' to present a comprehensive account of the epistemological and political processes at play in the detection of ADRs. By focusing on the literature generated by pharmacologists, epidemiologists and others working in the field, this paper examines the various techniques and methods used to identify and calculate ADRs both during clinical drug trials and beyond. Although risk associated with drug consumption is often presented as a scientifically calculable objective phenomenon, the attribution of causal mechanisms in determining whether the drug has caused an adverse event is a highly contingent social process, often involving complex clinical judgements. During clinical trials, variables are controlled and exclusions are imposed in order to fulfil scientific protocol requirements. These exclusionary practices mean that major patient population groups such as women and the elderly are often underrepresented during the trial process. At the time a drug product license is granted many uncertainties exist about the risk of ADRs. Once a drug is in widespread use, a more comprehensive profile of risk may begin to emerge. However, given that in everyday use drugs can interact with other drugs, alcohol and even certain foods and that drug reactions can mimic the disease they are supposed to be treating, differentiating between 'signal' and 'noise' is a messy, contingent complex process. PMID:12144155

Corrigan, Oonagh P

2002-08-01

179

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

PubMed Central

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

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

2013-01-01

180

Adverse effects of smoking on patients with ocular inflammation  

Microsoft Academic Search

BackgroundTo evaluate how smoking affects the time to disease quiescence and time to disease recurrence in patients with ocular inflammation.MethodsA retrospective cohort study of patients with ocular inflammation who were followed longitudinally and had smoking information available in the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study database.ResultsAmong 2676 patients with active ocular inflammation, smokers were more likely to have

Anat Galor; William Feuer; John H Kempen; R Oktay Kaçmaz; Teresa L Liesegang; Eric B Suhler; C Stephen Foster; Douglas A Jabs; Grace A Levy-Clarke; Robert B Nussenblatt; James T Rosenbaum; Jennifer E Thorne

2010-01-01

181

Optimising patient recall of adverse events over prolonged time periods  

E-print Network

an indication of the reduced level of exposure when comparing treat- ment duration in a non-inferiority trial. Optimal meth- ods of achieving accurate data are required. Methods PERSEPHONE is an investigator-led phase III trial of trastuzumab treatment duration... , the PERSEPHONE team have developed Patient Diary Sheets which list the common expected toxicities. For each trastuzumab cycle, patients are requested to record how much they are ‘troubled by each of the possible side-effects’ using patient-friendly severity...

2011-12-13

182

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

183

Perceived medication adverse effects and coping strategies reported by chronic heart failure patients  

Microsoft Academic Search

SUMMARY Background: Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these sub- jective AEs. Aims: To describe the scope and nature of perceived AEs of CHF patients, their coping strategies and the

R. H. E. De Smedt; P. Denig; F. M. Haaijer-Ruskamp; T. Jaarsma

2009-01-01

184

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

185

An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions.  

PubMed

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, cutaneous adverse drug reactions that are accompanied by keratinocyte cell death. Dead keratinocytes from SJS/TEN lesions exhibited necrosis, by morphological criteria. Supernatant from peripheral blood mononuclear cells (PBMCs) that had been exposed to the causative drug from patients with SJS/TEN induced the death of SJS/TEN keratinocytes, whereas supernatant from PBMCs of patients with ordinary drug skin reactions (ODSRs) exposed to the same drug did not. Keratinocytes from ODSR patients or from healthy controls were unaffected by supernatant from SJS/TEN or ODSR PBMCs. Mass spectrometric analysis identified annexin A1 as a key mediator of keratinocyte death; depletion of annexin A1 by a specific antibody diminished supernatant cytotoxicity. The necroptosis-mediating complex of RIP1 and RIP3 was indispensable for SJS/TEN supernatant-induced keratinocyte death, and SJS/TEN keratinocytes expressed abundant formyl peptide receptor 1 (FPR1), the receptor for annexin A1, whereas control keratinocytes did not. Inhibition of necroptosis completely prevented SJS/TEN-like responses in a mouse model of SJS/TEN. Our results demonstrate that a necroptosis pathway, likely mediated by annexin 1 acting through the FPR1 receptor, contributes to SJS/TEN. PMID:25031270

Saito, Nao; Qiao, Hongjiang; Yanagi, Teruki; Shinkuma, Satoru; Nishimura, Keiko; Suto, Asuka; Fujita, Yasuyuki; Suzuki, Shotaro; Nomura, Toshifumi; Nakamura, Hideki; Nagao, Koji; Obuse, Chikashi; Shimizu, Hiroshi; Abe, Riichiro

2014-07-16

186

Effects of an educational patient safety campaign on patients' safety behaviours and adverse events.  

PubMed

Rationale, aims and objectives? The study aims to investigate the effects of a patient safety advisory on patients' risk perceptions, perceived behavioural control, performance of safety behaviours and experience of adverse incidents. Method? Quasi-experimental intervention study with non-equivalent group comparison was used. Patients admitted to the surgical department of a Swiss large non-university hospital were included. Patients in the intervention group received a safety advisory at their first clinical encounter. Outcomes were assessed using a questionnaire at discharge. Odds ratios for control versus intervention group were calculated. Regression analysis was used to model the effects of the intervention and safety behaviours on the experience of safety incidents. Results? Two hundred eighteen patients in the control and 202 in the intervention group completed the survey (75 and 77% response rates, respectively). Patients in the intervention group were less likely to feel poorly informed about medical errors (OR?=?0.55, P?=?0.043). There were 73.1% in the intervention and 84.3% in the control group who underestimated the risk for infection (OR?=?0.51, CI 0.31-0.84, P?=?0.009). Perceived behavioural control was lower in the control group (meanCon ?=?3.2, meanInt ?=?3.5, P?=?0.010). Performance of safety-related behaviours was unaffected by the intervention. Patients in the intervention group were less likely to experience any safety-related incident or unsafe situation (OR for intervention group?=?0.57, CI 0.38-0.87, P?=?0.009). There were no differences in concerns for errors during hospitalization. There were 96% of patients (intervention) who would recommend other patients to read the advisory. Conclusions? The results suggest that the safety advisory decreases experiences of adverse events and unsafe situations. It renders awareness and perceived behavioural control without increasing concerns for safety and can thus serve as a useful instrument for communication about safety between health care workers and patients. PMID:22332730

Schwappach, David L B; Frank, Olga; Buschmann, Ute; Babst, Reto

2013-04-01

187

Variation in GNB3 predicts response and adverse reactions to antidepressants.  

PubMed

There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the ?3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response. PMID:20826553

Keers, Robert; Bonvicini, Cristian; Scassellati, Catia; Uher, Rudolf; Placentino, Anna; Giovannini, Caterina; Rietschel, Marcella; Henigsberg, Neven; Kozel, Dejan; Mors, Ole; Maier, Wolfgang; Hauser, Joanna; Souery, Daniel; Mendlewicz, Julien; Schmäl, Christine; Zobel, Astrid; Larsen, Erik R; Szczepankiewicz, Aleksandra; Kovacic, Zrnka; Elkin, Amanda; Craig, Ian; McGuffin, Peter; Farmer, Anne E; Aitchison, Katherine J; Gennarelli, Massimo

2011-07-01

188

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.

189

Early recognition of risk factors for adverse outcomes during hospitalization among Medicare patients: a prospective cohort study  

PubMed Central

Background There is a persistently high incidence of adverse events during hospitalization among Medicare beneficiaries. Attributes of vulnerability are prevalent, readily apparent, and therefore potentially useful for recognizing those at greatest risk for hospital adverse events who may benefit most from preventive measures. We sought to identify patient characteristics associated with adverse events that are present early in a hospital stay. Methods An interprofessional panel selected characteristics thought to confer risk of hospital adverse events and measurable within the setting of acute illness. A convenience sample of 214 Medicare beneficiaries admitted to a large, academic medical center were included in a quality improvement project to develop risk assessment protocols. The data were subsequently analyzed as a prospective cohort study to test the association of risk factors, assessed within 24 hours of hospital admission, with falls, hospital-acquired pressure ulcers (HAPU) and infections (HAI), adverse drug reactions (ADE) and 30-day readmissions. Results Mean age?=?75(±13.4) years. Risk factors with highest prevalence included >4 active comorbidities (73.8%), polypharmacy (51.7%), and anemia (48.1%). One or more adverse hospital outcomes occurred in 46 patients (21.5%); 56 patients (26.2%) were readmitted within 30 days. Cluster analysis described three adverse outcomes: 30-day readmission, and two groups of in-hospital outcomes. Distinct regression models were identified: Weight loss (OR?=?3.83; 95% CI?=?1.46, 10.08) and potentially inappropriate medications (OR?=?3.05; 95% CI?=?1.19, 7.83) were associated with falls, HAPU, procedural complications, or transfer to intensive care; cognitive impairment (OR?=?2.32; 95% CI?=?1.24, 4.37), anemia (OR?=?1.87; 95% CI?=?1.00, 3.51) and weight loss (OR?=?2.89; 95% CI?=?1.38, 6.07) were associated with HAI, ADE, or length of stay >7 days; hyponatremia (OR?=?3.49; 95% CI?=?1.30, 9.35), prior hospitalization within 30 days (OR?=?2.66; 95% CI?=?1.31, 5.43) and functional impairment (OR?=?2.05; 95% CI?=?1.02, 4.13) were associated with 30-day readmission. Conclusions Patient characteristics recognizable within 24 hours of admission can be used to identify increased risk for adverse events and 30-day readmission. PMID:23834816

2013-01-01

190

Needle phobia: etiology, adverse consequences, and patient management.  

PubMed

Needle phobia has profound health, dental, societal, and legal implications, and severe psychological, social, and physiologic consequences. There is genetic evidence for the physiologic response to needle puncture, and a significant familial psychological component, showing evidence of inheritance. Needle phobia is also a learned behavior. The dental practitioner must recognize patients with needle phobia before the administration of local anesthetics to identify patients who are potentially reactive and to prevent untoward sequelae. Needle phobia is highly associated with avoidance behavior, and the dentist must exhibit compassion and respect. To avoid bradycardia, hypotension, unconsciousness, convulsions, and possibly asystole, oral premedication with benzodiazepines or other antianxiety agents must be considered for patients who are needle phobic. Management of needle phobiaeinduced syncope includes perioperative monitoring, oxygen administration, positioning, atropine, and vasopressors. PMID:20831935

Sokolowski, Chester J; Giovannitti, Joseph A; Boynes, Sean G

2010-10-01

191

Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty  

PubMed Central

Purpose Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. Methods This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. Results Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. Conclusion Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP. PMID:25346917

Lee, Ji Woo; Kim, Hyung Jin; Choe, Yun Mee; Kang, Hee Suk; Kim, Soon Ki; Jun, Yong Hoon

2014-01-01

192

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study  

Microsoft Academic Search

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has

Lun Yang; Kejian Wang; Jian Chen; Anil G. Jegga; Heng Luo; Leming Shi; Chunling Wan; Xizhi Guo; Shengying Qin; Guang He; Guoyin Feng; Lin He

2011-01-01

193

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

194

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

Microsoft Academic Search

BackgroundIntellectually 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.MethodsA 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

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

2011-01-01

195

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

196

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

197

Age-adapted morphine titration produces equivalent analgesia and adverse effects in younger and older patients  

E-print Network

Age-adapted morphine titration produces equivalent analgesia and adverse effects in younger Summary Background To determine efficacy and safety of postoperative titrated morphine in elderly patients was titrated as 3 mg boluses for young (age 65 yrs) and 2 mg for elderly patients (> 65 yrs) respectively

Paris-Sud XI, Université de

198

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

199

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

200

Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions  

PubMed Central

Adverse drug reactions (ADRs) are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized. PMID:24734245

Chung, Wen-Hung

2014-01-01

201

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

202

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

203

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

204

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

205

[Psychopathologic reactions in orthopedic patients].  

PubMed

The idea to monitor and research psychopathological responses of physically injured persons in a more systematic manner has come from our observation of huge differences in patient behavior, whose psychological responses were noticeably changed and often inappropriate. The behavior aberrations were all the more striking because we treated war-time injuries in addition to peacetime ones. Our sample had 175 patient subjects, of both sexes, different ages, marital status and professions. A group of 70 patients treated in the Institute for Orthopedic Surgery and Traumatology were divided into two subgroups. The first experimental subgroup (E1) consisted of 26 (37.1%) patients physically injured in combat. The second subgroup (E2) had 44 (62.9%) patients physically injured in peacetime circumstances (car accidents, work accidents, etc). The physical injuries encompassed injuries to spinal column and extremities. The control (K) consisted of 105 subjects without physical injuries. The clinical picture and psychological reactions of the patients were examined by means of 4 instruments--PTSD-10 scale or posttraumatic symptoms scale [1], Family Homogeneity Index/FHI/with 19 variables, applied to measure the relation between the family system homogeneity and accident effects [2], Short Eysenck's Personality Inventory applied to investigate neuroticism and extroversion and introversion traits [3], Late Effects of Accidental Injury Questionnaire [4]. Our observations of psychological responses of patients in our ward (insomnia, sedatives intake) were mostly confirmed by tests conducted with the above instruments. In the group of the wartime injured (E1), as well as in the control (K), Eysenck's scale proved a significantly higher degree of neuroticism in comparison to the peacetime injured. Such results indicated that the wartime injured would most probably develop the picture of Posttraumatic Stress Disorder. Such a conclusion was related not only to the seriousness of injuries but also to the circumstances of their occurrence. The proneness to develop PTSD symptoms was not in correlation with the preparedness for accident, it being much poorer in peace-time injuries, as opposed to wartime patients, who had been prepared to the possibility of injury occurrence. The highest value of family homogeneity (FHI) was established in the wartime injured, which led us to conclude that the injury contributed to the cohesion of the family from which the patient came. By extracting some questions related to psychopathological entities such as insomnia, depression, somatization, anxiety, and cognitive disorders, the following results were obtained. Depression was the most frequent in both groups of injuries. Anxiety was also present in the control group; and insomnia and somatization, that is, conversion symptoms, were present in both groups of the injured. By examining narrower psychological characteristics of the wartime injured revealed dissociation problems--derangement to be the most frequent. Then follow the symptoms of depression, which occur significantly more frequently in the wartime injured in comparison to the peacetime injured. The phenomenological symptoms of derangement and depression proved to be reliable parameters of physical trauma. It is also significant that the three characteristics showed correlation to psychopathological responses: severity of surgery, paralysis, and acute injury. PMID:14692144

Lesi?, Aleksandar; Opali?, Petar

2003-01-01

206

Using a sibling design to compare childhood adversities in female patients with BPD and their sisters.  

PubMed

Abuse and neglect are well-established risk correlates of borderline personality disorder (BPD). The goal of this study was to examine whether BPD probands can be differentiated from their sisters with respect to a range of developmental adversity and maltreatment indicators, including retrospective self-reports of past experiences of childhood abuse and neglect, dysfunctional parent-child relationships and peer victimization and dysfunctional peer relationships. A total of 53 patients with BPD were compared to 53 sisters who were currently free of psychopathology on measures assessing childhood adversities. Both probands and sisters reported similar prevalence of intrafamilial abuse, although BPD patients reported more severe physical and emotional abuse. BPD patients reported higher prevalence of physical abuse by peers. These findings generally support the principle of multifinality, in which similar histories of adversities can be associated with a variety of outcomes, ranging from psychopathology to resilience. PMID:23076835

Laporte, Lise; Paris, Joel; Guttman, Herta; Russell, Jennifer; Correa, José A

2012-11-01

207

Genetic association studies to detect adverse drug reactions: abacavir hypersensitivity as an example.  

PubMed

Abacavir hypersensitivity (ABC HSR) is a treatment-limiting adverse event associated with the use of the antiretroviral medicine, abacavir. The objective of the ABC HSR pharmacogenetics program was to identify clinically useful genetic risk factors to predict an individual patient's risk for ABC HSR. The major histocompatibility complex allele, HLA-B*5701, was identified retrospectively and confirmed with independent sample sets. The clinical utility of prospective HLA-B*5701 screening was demonstrated in a blinded randomized clinical trial and in open-label cohorts. Screening has been incorporated into clinical practice and the ABC HSR pharmacogenetics program has been highlighted as a success by pharmacogenetics researchers. Important lessons from this pharmacogenetics program will be discussed in this paper. PMID:19207023

Hughes, Arlene R; Brothers, Cynthia H; Mosteller, Michael; Spreen, William R; Burns, Daniel K

2009-02-01

208

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

209

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

210

Use of Alternative Medicines by Patients with OA that Adversely Interact with Commonly Prescribed Medications  

Microsoft Academic Search

Owing to the increasing prevalence, patient interest, and high risk of adverse effects associated with use of complementary\\u000a and alternative medicine (CAM), investigation of this issue in an orthopaedic population is warranted. The objectives of this\\u000a study were to (1) identify the prevalence of CAM use, (2) assess the level of communication between patients and physicians\\u000a regarding CAMs, (3) uncover

Jacquelyn Marsh; Christine Hager; Tom Havey; Sheila Sprague; Mohit Bhandari; Dianne Bryant

2009-01-01

211

The Profile of Voluntary Reported Adverse Drug Reactions at a Tertiary Care Hospital: A Fifteen Month Prospective Study  

PubMed Central

Objectives: The present study was undertaken to provide the health professionals who were working at a tertiary care hospital, with a simple method to report Adverse Drug Reactions (ADRs) and to monitor, document and to evaluate them according to the set criteria. Method and materials: This study was conducted over a period of 15 months from 1st Jan’ 2008 to 31st March 2009 at Goa Medical College and Hospital (Goa, India). The evaluation of the data was done for various parameters, which included patient demographics and drug and reaction characteristics. An assessment was also done for the outcome, causality and the severity of the drug reactions. Results: A total of 265 ADRs were reported. Among the drugs, the ß-lactam antibiotics were implicated the maximum number of times (54, 20.37%), followed by fluoroquinolones (35, 13.20%), antiretrovirals (33, 12.45%) and antiepileptics (31, 11.69%). Females showed more ADRs (142, 54%) than males (123, 46%). The skin was involved in about 57.73% (153) of the ADRs, while the CNS and the vascular system were involved in 8.67% (23) and 8.30% (22) of the ADRs. Most of the ADRs were categorized as “Type II” (203, 77%) against “Type I” (62, 23%) by Rawlins and Thompson’s classification. The causality assessment was done by the Naranjo Algorithm and 62.26% (165) were seen to fall in the “probable category” as compared to 29.05% (77) in the “highly probable” one. Out of all the ADRs which were reported, 34.71% (148) were “severe”, in accordance with the Modified Hartwig and Siegel’s scale. Conclusion: The present work was a humble attempt to set up a well organized ADR reporting system at our government hospital. The systematic tracking and monitoring of ADRs can shed light on their extensiveness and their patterns of occurrence. PMID:23285441

Dang, Amit; Bhandare, P. N.

2012-01-01

212

Adverse events in older patients admitted to acute care: a preliminary cost description.  

PubMed

The financial costs associated with Adverse Events (AEs) for older patients (> or = 65 years) in Canadian hospitals are unknown. The objective of this paper is to describe and compare costs between patients who experienced an AE and those who did not during an acute hospital admission to a tertiary care facility. Patients with an AE had twice the hospital length of stay (20.2 versus 9.8 days, p < 0.00001), resulting in 1,400 extra days at a cost of approximately $7,500/patient. PMID:19999374

Ackroyd-Stolarz, Stacy; Guernsey, Judith Read; MacKinnon, Neil J; Kovacs, George

2009-01-01

213

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

214

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

215

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

216

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

PubMed

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

2014-01-10

217

Adverse drug reactions to dopamine agonists: a comparative study in the French Pharmacovigilance Database.  

PubMed

Pharmacodynamical differences between dopamine agonists (DAs) suggest differences in their adverse drug reactions (ADRs) profile. In this study, frequencies of ADR to DAs or levodopa reports in the French Pharmacovigilance Database were explored. Reports occurring between January 1, 1984 and December 31, 2008 were selected (2,189 for DAs and 1,315 for levodopa). The numbers of ADRs by system organ class were compared using ropinirole as a reference. Diurnal somnolence was less frequently reported with all DAs when compared with ropinirole (P < 0.001). Impulse control disorders (ICDs) were more frequently reported with pramipexole (P < 0.001). Significant difference was found among DAs in the frequency of confusion or disorientation (P < 0.001), nausea and vomiting (P < 0.05), or edemas (P < 0.001). No difference among DAs was observed in the frequency of hallucination or arterial hypotension ADR reports (P = 0.3 and P = 0.1). Pleural effusions were more frequently reported with pergolide or bromocriptine (P < 0.001). Somnolence or ICD reports were less frequent with levodopa, whereas confusion was more frequently reported. In summary, our data show significant differences in the kind of ADRs reported for each DA. PMID:20669320

Perez-Lloret, Santiago; Bondon-Guitton, Emmanuelle; Rascol, Olivier; Montastruc, Jean-Louis

2010-09-15

218

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

219

Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study  

PubMed Central

Introduction The aim was to investigate the frequency of neurological adverse events in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) treated with tumor necrosis factor (TNF) ? antagonists. Methods Seventy-seven patients eligible for anti-TNF? therapy were evaluated. There were 36 patients with RA, 41 with SpA [24 psoriatic arthritis (PsA) and 17 with ankylosing spondylitis (AS)]. All patients had a complete physical and neurological examination. Brain and cervical spine magnetic resonance imaging (MRI) and neurophysiological tests were performed in all patients before the initiation of anti-TNF? therapy and after a mean of 18 months or when clinical symptoms and signs indicated a neurological disease. Exclusion criteria included hypertension, diabetes mellitus, dyslipidemia, heart arrhythmias, atherothrombotic events, vitamin B12 and iron deficiency, head and neck trauma and neurological surgeries. Results Two patients did not receive anti-TNF? therapy because brain MRIs at baseline revealed lesions compatible with demyelinating diseases. Thus, 75 patients received anti-TNF? (38 infliximab, 19 adalimumab and 18 etanercept). Three patients developed neurological adverse events. A 35-year-old man with PsA after 8 months of infliximab therapy presented with paresis of the left facial nerve and brain MRI showed demyelinating lesions. Infliximab was discontinued and he was treated with pulses of corticosteroids recovering completely after two months. The second patient was a 45-year-old woman with RA who after 6 months of adalimumab therapy presented with optic neuritis. The third patient was a 50-year-old woman with AS, whom after 25 months of infliximab therapy, presented with tingling and numbness of the lower extremities and neurophysiological tests revealed peripheral neuropathy. In both patients anti-TNF were discontinued and they improved without treatment after 2 months. The rest of our patients showed no symptoms and MRIs showed no abnormalities. The estimated rate of neurological adverse events in patients treated with anti-TNF therapy is 4% (3/75). Conclusions Neurological adverse events after anti-TNF? therapy were observed in our patient. Brain MRI and neurophysiological tests are essential tools to discriminate neurological diseases. PMID:24938855

2014-01-01

220

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

221

Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities.  

PubMed

Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. PMID:24070880

Cavanna, Andrea E; Seri, Stefano

2013-11-01

222

Successful readministration of trastuzumab after severe immune reactions in two breast cancer patients.  

PubMed

Trastuzumab is a standard treatment in breast cancer overexpressing Her2 oncogene. However, its administration carries the risk of severe immune adverse events which often lead to the discontinuation of trastuzumab. There is no clear guideline on how patients experiencing trastuzumab-related reaction should be rechallenged with the monoclonal antibody. Here, we present two case reports of patients who have presented severe anaphylactic reactions during trastuzumab infusion. Both of them have been successfully rechallenged in intensive care units with premedication, lower rate of infusion and vitals monitoring. Thereafter, trastuzumab could be continued without any serious adverse reaction. Given the positive impact of trastuzumab on patients' survival, treatment rechallenge should be carefully considered in patients who presented anaphylactic reactions. PMID:24682736

Tanz, R; Meillan, N; Libert, N; Magne, N; Vedrine, L; Chargari, C

2014-06-01

223

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

224

Prevalence of cutaneous adverse events associated with long-term disease-modifying therapy and their impact on health-related quality of life in patients with multiple sclerosis: a cross-sectional study  

PubMed Central

Background Glatiramer acetate (GA) and interferon-beta (IFN-?) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient’s health-related quality of life (QoL). We aimed to determine the prevalence of cutaneous adverse events associated with long-term DMT use, and to assess the impact of cutaneous adverse events on QoL. Methods A cross-sectional study among patients with multiple sclerosis who had been treated with their first DMT for at least 2 years. Cutaneous events were assessed from photographs of injection-sites by dermatologists blinded for DMT. Generic and dermatology-specific health-related QoL were assessed using validated patient-reported questionnaires. Results A total of 229 patients were enrolled, of whom 156 (68%) had at least one skin reaction. The prevalence of cutaneous adverse events was higher for SC DMTs (75-82%) compared to IM DMT (41%) (P < 0.001). Erythema and lipoatrophy were the most common skin reactions, observed in 156 (68%) and 45 (20%) patients, respectively. Dermatology-specific, but not generic, QoL was significantly lower among patients with skin reactions compared to those without. Conclusions The prevalence of cutaneous adverse events was high in long-term DMT-treatment. Patients with cutaneous adverse events had a lower perceived dermatology-specific QoL. PMID:24131589

2013-01-01

225

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital  

PubMed Central

1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42). 5The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group. PMID:8877022

MARTÍNEZ-MIR, I.; GARCÍA-LÓPEZ, M.; PALOP, V.; FERRER, J. M.; ESTAÑ, L.; RUBIO, E.; MORALES-OLIVAS, F. J.

1996-01-01

226

Sex differences in cardiovascular drug-induced adverse reactions causing hospital admissions  

PubMed Central

AIMS Cardiovascular disease in women is often underestimated. The effects of cardiovascular drugs differ between the sexes because of pharmacokinetic and pharmacodynamic differences. Adverse drug reactions (ADRs) within these drug classes may have serious consequences, leading to hospital admission. We aimed to study differences between men and women in hospital admissions for ADRs due to cardiovascular drugs. METHODS We conducted a nationwide study of all hospital admissions between 2000 and 2005 with data from the Dutch National Medical Register. Relative risks were calculated of hospital admissions due to ADRs to the different cardiovascular drug groups for women compared with men. By an ecological design, risks were adjusted for the total number of Dutch inhabitants and the total number of prescriptions. RESULTS In total, 14 207 of the hospital admissions (34% of all ADR-related admissions) were attributed to cardiovascular drugs [7690 in women (54%; 95% confidence interval 53–55%)]. ‘Anticoagulants and salicylates’ (n= 8988), ‘high- and low-ceiling diuretics’ (n= 2242) and ‘cardiotonic glycosides’ (n= 932) were responsible for the majority of the ADR-related hospital admissions. The most pronounced sex differences were seen in users of low-ceiling diuretics (relative risk 4.02; 95% confidence interval 3.12–5.19), cardiotonic glycosides (relative risk 2.38; 95% confidence interval 2.06–2.74), high-ceiling diuretics (relative risk 2.10; 95% confidence interval 1.91–2.32) and coronary vasodilators (relative risk 0.77; 95% confidence interval 0.65–0.91). CONCLUSIONS Clear sex differences exist in ADRs requiring hospital admission for different cardiovascular drug groups. Sex differences should be taken into account in the prescription and evaluation of drugs. PMID:22533339

Rodenburg, Eline M; Stricker, Bruno H; Visser, Loes E

2012-01-01

227

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

228

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

229

A method for controlling complex confounding effects in the detection of adverse drug reactions using electronic health records  

PubMed Central

Objective Electronic health records (EHRs) contain information to detect adverse drug reactions (ADRs), as they contain comprehensive clinical information. A major challenge of using comprehensive information involves confounding. We propose a novel data-driven method to identify ADR signals accurately by adjusting for confounders. Materials and methods We focused on two serious ADRs, rhabdomyolysis and pancreatitis, and used information in 264?155 unique patient records. We identified an ADR using established criteria, selected potential confounders, and then used penalized logistic regressions to estimate confounder-adjusted ADR associations. A reference standard was created to evaluate and compare the precision of the proposed method and four others. Results Precision was 83.3% for rhabdomyolysis and 60.8% for pancreatitis when using the proposed method, and we identified several drug safety signals that are interesting for further clinical review. Discussion The proposed method effectively estimated ADR associations after adjusting for confounders. A main cause of error was probably due to the nature of the dataset in that a substantial number of patients had a single visit only and, therefore, it was not possible to determine correctly the appropriate sequence of events for them. It is likely that performance will be improved with use of EHR data that contain more longitudinal records. Conclusions This data-driven method is effective in controlling for confounding, resulting in either a higher or similar precision when compared with four comparators, has the unique ability to provide insight into confounders for each specific medication–ADR pair, and can be easily adapted to other EHR systems. PMID:23907285

Li, Ying; Salmasian, Hojjat; Vilar, Santiago; Chase, Herbert; Friedman, Carol; Wei, Ying

2014-01-01

230

Neurosyphilis presenting with dementia, chronic chorioretinitis and adverse reactions to treatment: a case report  

PubMed Central

Neurosyphilis results from infection of the brain, meninges or spinal cord by Treponema pallidum and develops in about 25%-40% of persons who are not treated for syphilis. This article reports a rare case of active neurosyphilis with mild dementia, chronic chorioretinitis, and hearing loss. During the treatment with Penicillin, a rare combination of complications such as Jarisch-Herxheimer and Hoigné reactions were observed. The clinical feature is characterized by a slow progressive cognitive decline and behavior changes for the last 2 years. Neuropsychological examination revealed mild dementia (MMSE = 23) with impaired memory and attention and executive function. Left sided chronic chorioretinitis and hearing loss were documented. High dose intravenous penicillin therapy was complicated by Jarisch-Herxheimer and Hoigne reactions. During the follow up examinations at 6 and 12 months, the clinical signs, neuropsychological examination, and cerebrospinal fluid (CFS) samples showed improvement of dementia, CSF findings, and hydrocephalus. In conclusion, this atypical presentation of neurosyphilis in combination with rare complications of treatment is worthy of attention. Neurosyphilis should be part of the differential diagnosis of each patient showing cognitive deterioration and behaviour disturbances. PMID:19918420

Raycheva, Margarita Radoslavova; Petrova, Elena Petrova; Tsankov, Nikolay Konstantinov; Traykov, Latchezar Dintchov

2009-01-01

231

Statin adverse effects: patients' experiences and laboratory monitoring of muscle and liver injuries.  

PubMed

Background Although statins have great benefit on the prevention of cardiovascular diseases with limited adverse effects (AEs), little is known about patients' contribution of AE reports in clinical practice. Objectives To explore patients' experiences of statin AEs and related laboratory monitoring in clinical practice. Setting Outpatient clinics of two University hospitals in northeast Thailand. Methods Generic symptom checklist questionnaires for self-reporting AEs were distributed to patients prescribed simvastatin, atorvastatin, or rosuvastatin at outpatient clinics. Clinical information was obtained from medical records. Reported symptoms were assessed for causality considering previously known statin AEs, concomitant diseases and drugs. Main outcome measure Potential statin AEs reported by patients and monitoring of laboratory parameters related to musculoskeletal and liver disorders. Results Of the total 718 valid responses, 76.0 % of patients reported at least one symptom, most of which (69.0 %) were probable/possible statin AEs. Musculoskeletal and liver-related symptoms were reported by 283 (39.4 %) and 134 patients (18.7 %), respectively. Probable/possible AEs were categorized in 56.7 % of their musculoskeletal and gastrointestinal symptoms. Majority of patients had at least one laboratory test on initiation of (64.8 %) and during statin treatment (61.8 %). Patients taking atorvastatin or rosuvastatin, and patients with history of chronic renal diseases were more likely to have creatine kinase (CK) monitored on initiation of and during statin treatment. Additionally, taking drugs which could potentially increase muscle injury (OR 1.929, P < 0.01) and self-reporting of musculoskeletal symptoms (OR 1.805, P < 0.01) were associated with CK monitoring during statin treatment. Reporters of musculoskeletal symptoms also had significantly higher mean CK level than those not reporting any musculoskeletal symptoms (207.35 ± 155.40 vs. 143.95 ± 83.07 U/L, respectively; P = 0.037). Patient reporting of liver AEs was not related to alanine aminotransferase (ALT) level and monitoring, however, prior history of liver disorders was significantly associated with monitoring of ALT on initiation of and during statin treatment (OR 5.745 and OR 23.063, respectively; P < 0.01). Conclusion Many patients experienced at least one possible adverse effects on a statin. The findings suggest that laboratory monitoring is relatively selective in relation to risks and patient-reported adverse symptoms. PMID:25630895

Chaipichit, Nataporn; Krska, Janet; Pratipanawatr, Thongchai; Jarernsiripornkul, Narumol

2015-04-01

232

Under-reporting of adverse drug reactions: A challenge for pharmacovigilance in India  

PubMed Central

Aim: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. Materials and Methods: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. Results: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. Conclusion: UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.

Tandon, Vishal R.; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2015-01-01

233

Adverse Drug Reactions to Off-label Drugs on a Paediatric Ward: an Italian Prospective Pilot Study  

Microsoft Academic Search

Recently published studies examining the extent of off-label drug prescribing in various European paediatric wards have reported that off-label use is widespread and particularly high in Italy. So far, however, no studies have investigated the extent to which adverse drug reactions (ADRs) due to off-label drug use occur in Italy. To evaluate the risk associated with off-label drug use in

Piero Impicciatore; Angelika Mohn; F Chiarelli; Chiara Pandolfini; Maurizio Bonati

2002-01-01

234

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

235

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

236

Physicians' Reactions to Overweight Patients  

NSDL National Science Digital Library

This case study, by David M. Lane of Rice University, assesses the question, "Do physicians discriminate against overweight patients?" This study indicates that, at least in one respect, they do. Basic concepts are t-test, means, and boxplots. The experimental design, materials, descriptive statistics, inferential statistics, and raw data are given.

Lane, David M.

237

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

238

Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.  

PubMed

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5 ± 12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level ?5.00 ?U/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p = 0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p = 0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p <0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p = 0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. PMID:25743211

Sharma, Ajay K; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D; Singh, Jagmeet P; Parks, Kimberly A; Heist, E Kevin

2015-05-01

239

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

240

PLASMA FIBRINOGEN AS A MARKER OF MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS OF TYPE 2 DIABETES WITH UNSTABLE ANGINA  

Microsoft Academic Search

Unstable angina patients with type 2 diabetes have higher mortality and morbidity. The present study aimed at determining the differences i n the inflammatory status between non-diabetic and diabetic patients with unstable angina, and evaluating fibrinogen concentration as predictor of in hospital major adverse cardiac events in diabetic patients. 142 cases of unstable angina were analyzed. 37 patients were found

V. S. Sahashrabhojney; R. G. Salkar

241

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

242

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

243

Clinical benefit, survival and adverse events in patients with implantable cardioverter defibrillators: the initial Rotterdam experience  

PubMed Central

Background The implantable cardioverter defibrillator (ICD) has become a widely accepted therapy for patients with severe life-threatening ventricular tachyarrhythmias. The aim of this study was to illustrate the possible advantages of ICDs with respect to survival and clinical events. Methods and results Between 1998 and 2000, 92 patients (aged 58±15 years; ejection fraction 36±15%; coronary artery disease 71%) were treated with an ICD in combination with an endocardial lead system. Benefit of the ICD was estimated as the difference between total cardiac death and the projected death rate of fast ventricular tachyarrhythmias (>200 bpm), assuming that most fast ventricular tachyarrhythmias would have been fatal without termination by the ICD. Adverse events were classified according to European standards. The cardiac mortality rate was 5.5% and 9.8%, at one and two years respectively. The recurrence rate of fast VT (>200 bpm) was 22.4% and 30.2%, at one and two years respectively. The observed difference between cardiac death and projected death was very significant (p=0.002) and suggests a clear benefit from ICD implantation. Low ejection fraction (<35%) and NYHA class ?II correlated with a higher projected death. The most common adverse event was inappropriate therapy (18%). Conclusion The results from our small series support the existing data that especially patients with poor ejection fraction (<35%) benefit from ICD implantation. The adverse event rate was low. However, inappropriate therapy remains a matter of concern. Given the high workload of correct screening and follow-up, we expect that the actual number of centres in the Netherlands permitted to implant ICDs will be unable to cope with the widening spectrum of ICD indications. PMID:25696731

Theuns, D.A.M.J.; Klootwijk, A.P.J.; Kimman, G.P.; Simoons, M.L.; Roelandt, J.R.T.C.; Jordaens, L.J.L.M.

2001-01-01

244

Gender Differences in Health Status and Adverse Outcomes Among Patients With Peripheral Arterial Disease  

PubMed Central

Background Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self?reported health status at PAD diagnosis and 12?months later, and explored (2) whether outcomes in women with PAD differ with regard to long?term major adverse events. Methods and Results A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form?12 (SF?12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12?months later. Women had similar ages and clinical characteristics, but poorer socio?economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental (MCS: 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12?months, women still reported a poorer overall PCS score (41±12 versus 46±11, P=0.006) and MCS score (42±14 versus 49±12, P=0.002). Female gender was an independent determinant of a poorer baseline and 12?month PCS and MCS scores. However, there were no significant differences by gender on either mortality (unadjusted hazard ratio [HR]=0.93, 95% CI 0.60;1.44, P=0.74) or major adverse events (unadjusted HR=0.90, 95% CI 0.63;1.29, P=0.57), after a median follow?up of 3.2 years. Conclusions Women's physical and mental health status is compromised both at initial PAD diagnosis and at 12?month follow?up, despite experiencing a similar magnitude of change in their health scores throughout the first 12?months after diagnosis. PMID:25537275

Dreyer, Rachel P.; van Zitteren, Moniek; Beltrame, John F.; Fitridge, Robert; Denollet, Johan; Vriens, Patrick W.; Spertus, John A.; Smolderen, Kim G.

2015-01-01

245

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

246

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

247

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

248

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

PubMed Central

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

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

2014-01-01

249

Adverse reactions to Patent Blue V dye used in sentinel lymph node biopsy for Melanoma  

Microsoft Academic Search

Sentinel lymph node biopsy (SLNB) is an established investigation used in the management of melanoma, and contributes to disease\\u000a staging. In the UK, Patent Blue V is injected intra-operatively to help identify the sentinel node. However little is known\\u000a about the adverse effects associated with Patent Blue V in this technique. We performed a targeted survey of UK surgeons conducting

Milap G. Rughani; Marc C. Swan; Titus S. Adams; Mark R. Middleton; Oliver C. Cassell

2011-01-01

250

Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population.  

PubMed

Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded. PMID:21071176

An, Dong-Mei; Wu, Xin-Tong; Hu, Fa-Yun; Yan, Bo; Stefan, Hermann; Zhou, Dong

2010-12-01

251

Fiduciary disclosure of medical mistakes: the duty to promptly notify patients of adverse health care events.  

PubMed

Fiduciary obligations are imposed by the common law to ensure that a person occupying a societal role with a high potential for the manipulation of vulnerable persons exercises utmost good faith. Australian law has recognised that the doctor-patient relationship, while not wholly fiduciary, has fiduciary aspects. Amongst such duties are those prohibiting sexual or financial abuse of patients or disclosure without express authority of confidential information. One important consequence of attaching such fiduciary duties to the doctor-patient relationship is that the onus of proof falls not upon the vulnerable party (the patient), but upon the doctor (to disprove the allegation). Another is that consent cannot be pleaded as an absolute defence. In this article the authors advocate that the law should now accept that the fiduciary obligations of the doctor-patient relationship extend to creating a legal duty that any adverse health care event be promptly reported to the patient involved. The reasons for creating such a presumption, as well as its elements and exceptions, are explained. PMID:15957590

Faunce, T A; Bolsin, S N

2005-05-01

252

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

253

Oral Adverse Reactions Caused by Over-the-Counter Oral Agents  

PubMed Central

Over-the-counter products rarely cause unwanted reactions in the oral cavity. Oral reactions to these agents are not specific and might present with various clinical oral findings. Detailed medical history is a key to the proper diagnosis of these lesions and fortunately other diagnostic procedures are rarely needed. Lesions are usually managed with elimination of the offending agent and with topical steroids. In more severe cases systemic steroids should be applied.

Andabak Rogulj, Ana; Vidovic Juras, Danica; Gabric, Dragana; Vrdoljak, Danko Velimir

2015-01-01

254

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

255

CHADS2 Scores in the Prediction of Major Adverse Cardiovascular Events in Patients with Cushing's Syndrome  

PubMed Central

Vascular events are one of the major causes of death in case of Cushing's syndrome (CS). However, due to the relative low frequency of CS, it is hard to perform a risk assessment for these events. As represented congestive heart failure (C), hypertension (H), age (A), diabetes (D), and stroke (S), the CHADS2 score is now accepted to classify the risk of major adverse cardiovascular events (MACEs) in patients with atrial fibrillation. In this study, participants were enrolled from the National Health Research Institute Database (NHIRD) of Taiwan, and we reviewed 551 patients with their sequential clinically diagnosed CS data between 2002 and 2009 in relation to MACEs risk using CHADS2 score. Good correlation could be identified between the CS and CHADS2 score (AUC = 0.795). Our results show that patients with CS show significantly higher risk of vascular events and the CHADS2 score could be applied for MACEs evaluation. Adequate lifestyle modifications and aggressive cardiovascular risks treatment are suggested for CS patients with higher CHADS2 score. PMID:25101124

Chuang, Mei-Hua; Chuang, Tzyy-Ling; Huang, Kung-Yung; Lyu, Shaw-Ruey; Huang, Chih-Yuan; Lee, Ching-Chih

2014-01-01

256

Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population.  

PubMed

Lamotrigine (LTG) is a commonly used antiepileptic drug. However, the use of LTG is limited because of its cutaneous adverse drug reactions (cADRs) ranging from mild maculopapular eruption (MPE) to severe Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between HLA-B*1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai. Although three of seven cases with HLA-B*1502 have been reported in LTG-induced SJS/TEN so far, the relationship between HLA-B*1502 and LTG-induced SJS/TEN needs further investigation. It is also unclear whether there is a specific genetic marker associated with LTG-induced MPE in Chinese. In this study, we genotyped 43 Han Chinese patients treated with LTG (14 cases with LTG-induced cADRs and 29 LTG-tolerant controls), using PCR-SSP for HLA-B*1502 testing and low-resolution genotyping, as well as sequencing for four-digit genotyping. The two cases with SJS were negative for HLA-B*1502, with B1301/1301 and 4601/5610, respectively. Combining the data with previous studies, there was no significant difference in the frequency of subjects with HLA-B*1502 between the LTG-induced SJS/TEN group and the LTG-tolerant group (p?=?0.08, OR 4.23, 95% CI 0.94-18.97). In the MPE group, only one was positive for HLA-B*1502. There was no significant difference in the frequency of a specific HLA-B allele between the MPE group and the LTG-tolerant group either. In this study, no significant association between HLA-B*1502 and LTG-induced SJS or MPE was found. Given the small sample size and only HLA-B locus genotyping, further large-scale studies are required to explore genetic associations with LTG-induced cADRs. PMID:21306565

Shi, Yi-Wu; Min, Fu-Li; Liu, Xiao-Rong; Zan, Li-Xuan; Gao, Mei-Mei; Yu, Mei-Juan; Liao, Wei-Ping

2011-07-01

257

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

PubMed Central

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

2015-01-01

258

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

2015-01-01

259

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients.  

PubMed

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3-5, days 7-9 and days 12-14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3-5 (p=0.002) after SAH, peaked on days 7-9 (p<0.001) and remained elevated until days 12-14 (p<0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7-9 (correlation coefficient=-0.55, p=0.012; 95% confidence interval -0.80 to -0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7-9 predicted a poor clinical outcome at 2year follow-up after SAH (odds ratio=1.722, p=0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH. PMID:24814854

Li, Hua; Wu, Wei; Liu, Ming; Zhang, Xin; Zhang, Qing-Rong; Ni, Li; Hang, Chun-Hua

2014-08-01

260

Onset of palmoplantar pustular psoriasis while on adalimumab for psoriatic arthritis: a 'class effect' of TNF-alpha antagonists or simply an anti-psoriatic treatment adverse reaction?  

PubMed

Adalimumab is a human, recombinant IgG1 monoclonal antibody that specifically blocks the interaction of tumour necrosis factor (TNF)-alpha with the p55 and the p75 TNF-alpha cell surface receptors. We report the appearance of palmoplantar pustular psoriasis in a patient after 6 months of successful adalimumab administration for psoriatic arthritis. The development or worsening of psoriatic skin lesions is a known side effect of adalimumab and other TNF-alpha antagonists increasingly reported in the literature. Although it has been reported as a 'class-effect' of TNF-alpha antagonists, we believe that the deterioration or new onset of psoriasis is an adverse reaction seen mainly with drugs used for the treatment of psoriasis and not solely with anti-TNF agents. The latter is probably implying an existing gap in the understanding of the pathophysiology of psoriasis or of the anti-psoriatic drugs' mechanisms of action. PMID:19701844

Rallis, Efstathios; Korfitis, Chrysovalantis; Stavropoulou, Evgenia; Papaconstantis, Markos

2010-01-01

261

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

2015-02-01

262

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

263

Incidence of adverse wear reactions in hip resurfacing arthroplasty: a single surgeon series of 2,600 cases.  

PubMed

A single surgeon performed 2,559 metal-on-metal hip resurfacing arthroplasties in ?2,109 patients. The Corin Cormet 2000 (393 cases) and Biomet Recap implants (2,166 cases) were used in our series. In this study, the adverse wear failure (AWF) rate was 0.27%. At 10 years postoperatively, our Kaplan-Meier cumulative revision rate for AWF was 1% for all patients, 0.2% for men, 2.6% for women, and 9% for patients with a diagnosis of dysplasia. All AWF failures had component sizes ?48 mm. All had metal ion levels above 15 ug/ml. All had acetabular inclination angles (AIA) ?50° on standing pelvis radiographs. All had severe metallosis found at the time of revision. Six of the seven AWF cases were in women. There were no failures from pseudotumours without AWF (metallosis) in this series. PMID:23760745

Gross, Thomas P; Liu, Fei

2013-01-01

264

Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction.  

PubMed

Administration of anti-tumor necrosis factor (anti-TNF) agents is beneficial in a variety of chronic inflammatory conditions, including psoriasis. We describe 5 patients in whom psoriasiform skin lesions developed 6-9 months after the initiation of anti-TNF therapy for longstanding, seropositive rheumatoid arthritis (etanercept or adalimumab), typical ankylosing spondylitis (infliximab), and Adamantiades-Behçet's disease (infliximab). In all 5 patients, the underlying disease had responded well to anti-TNF therapy. Four patients developed a striking pustular eruption on the palms and/or soles accompanied by plaque-type psoriasis at other skin sites, while 1 patient developed thick erythematous scaly plaques localized to the scalp. In 3 patients there was nail involvement with onycholysis, yellow discoloration, and subungual keratosis. Histologic findings from skin biopsies were consistent with psoriasis. None of these patients had a personal or family history of psoriasis. In all patients, skin lesions subsided either with topical treatment alone, or after discontinuation of the responsible anti-TNF agent. The interpretation of this paradoxical side effect of anti-TNF therapy remains unclear but may relate to altered immunity induced by the inhibition of TNF activity in predisposed individuals. PMID:16052599

Sfikakis, P P; Iliopoulos, A; Elezoglou, A; Kittas, C; Stratigos, A

2005-08-01

265

Adverse Event Management of Oral Mucositis in Patients with Breast Cancer  

PubMed Central

Summary Oral mucositis (OM) is a clinically important and frequent adverse event (AE) associated with cancer treatment with conventional chemotherapy as well as new targeted agents. Incidence and severity of OM vary from treatment to treatment and from patient to patient. The pathogenesis of chemotherapy-induced OM can be divided into 5 phases. OM induced by targeted therapies differs among other things in appearance, course, concomitant AEs and toxicity, and thus could be perceived as an entity distinct from chemotherapy-induced OM with an innate pathogenic mechanism. OM has a severe impact on a patient's quality of life (QoL) by causing complications such as pain and discomfort. Even more important are associated restrictions in nutrition and hydration. Thus, the efficacy of cancer therapy might be impaired due to the necessity of dose delays and dose reductions. Numerous preventive and therapeutic approaches have been evaluated, but currently no single agent has changed the standard of care in preventing and treating OM. Thus, the current management has evolved from clinical experience rather than clinical evidence. This article will review the AE ‘OM’ induced by breast cancer treatment with chemotherapy and targeted agents in order to provide practical guidance for management and prevention. PMID:25404881

Seiler, Sabine; Kosse, Jens; Loibl, Sibylle; Jackisch, Christian

2014-01-01

266

Clinical Pharmacology, Uses, and Adverse Reactions of Iodinated Contrast Agents: A Primer for the Non-radiologist  

PubMed Central

Iodinated contrast agents have been in use since the 1950s to facilitate radiographic imaging modalities. Physicians in almost all specialties will either administer these agents or care for patients who have received these drugs. Different iodinated contrast agents vary greatly in their properties, uses, and toxic effects. Therefore, clinicians should be at least superficially familiar with the clinical pharmacology, administration, risks, and adverse effects associated with iodinated contrast agents. This primer offers the non-radiologist physician the opportunity to gain insight into the use of this class of drugs. PMID:22469351

Pasternak, Jeffrey J.; Williamson, Eric E.

2012-01-01

267

Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational study  

PubMed Central

Aims To describe the frequency, nature and preventability of community-acquired and hospital-acquired adverse drug reactions (ADRs) in a South African hospital serving a community with a high prevalence of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome. Methods A 3-month prospective observational study of 665 adults admitted to two medical wards. Results Forty-one (6.3%) patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in hospital. Many of the ADRs (46.2%) were considered preventable, although less likely to be preventable in HIV-infected patients than in those with negative or unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital-acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but 60% of community-acquired ADRs at hospital admission were in patients <60 years old. Among patients <60 years old, those HIV infected were more likely to be admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17, 4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral therapy (ART) were more likely to be admitted with an ADR than those not receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs were fatal. Antibiotics and drugs used for opportunistic infections were implicated in two-thirds of hospital-acquired ADRs. Conclusions ADRs are an important, often preventable cause of hospitalizations and inpatient morbidity in South Africa, particularly among the elderly and HIV-infected. Although ART-related injury contributed to hospital admissions, many HIV-related admissions were among patients not receiving ART, and many ADRs were associated with medicines used for managing opportunistic infections. What is already known about this subject Studies conducted primarily in developed countries have shown that adverse drug reactions (ADRs) are a significant cause of hospital admission, prolong hospital stay and consequently increase the cost of disease management in patients.Cardiovascular medicines, hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are the most frequently implicated medicines in these studies.A large proportion of these ADRs have been shown to be preventable through improved drug prescribing, administration and monitoring for adverse effects. What this paper adds This is the first Sub-Saharan African study in the HIV/AIDS era that describes the contribution of ADRs to patient morbidity, hospitalisation and mortality.Cardiovascular medicines and antiretroviral therapy contributed the most to community-acquired ADRs at the time of hospital admission while medicines used for opportunistic infections (such as antifungals, antibiotics and antituberculosis medicines were most frequently implicated in hospital acquired ADRs.ADRs in HIV-infected patients were less likely to be preventable. PMID:18070223

Mehta, Ushma; Durrheim, David N; Blockman, Marc; Kredo, Tamara; Gounden, Ronald; Barnes, Karen I

2008-01-01

268

Blood rheology at term in normal pregnancy and in patients with adverse outcome events.  

PubMed

Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05patients with different adverse outcome of pregnancy compared to normal pregnancy. Interestingly, in pre-eclampsia hemo concentration and increased fibrinogen turnover due to enhanced coagulation activation are weighty co factors of pv but were associated with lower pv in patients with pre-eclampsia. However, coincidental increased RBC aggregation and hemo concentration may potentially derogate blood flow in the materno-fetal unit that is commonly traceable using vessel duplex ultra sound in pre-eclampsia. PMID:19433886

von Tempelhoff, Georg-Friedrich; Velten, Eva; Yilmaz, Asli; Hommel, Gerhard; Heilmann, Lothar; Koscielny, Jürgen

2009-01-01

269

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study  

PubMed Central

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs. PMID:21483481

Chen, Jian; Jegga, Anil G.; Luo, Heng; Shi, Leming; Wan, Chunling; Guo, Xizhi; Qin, Shengying; He, Guang; Feng, Guoyin; He, Lin

2011-01-01

270

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

271

Effectiveness of and adverse events after percutaneous coronary intervention in patients with mild versus severe renal failure  

Microsoft Academic Search

Patients with renal failure undergoing percutaneous coronary intervention (PCI) experience reduced procedural success rates and increased in-hospital and long-term follow-up major adverse cardiac events. This study was designed to determine whether the severity of preprocedural renal failure influences the outcomes of patients with renal failure undergoing PCI. We compared the immediate and long-term outcomes of 192 patients with mild renal

Mark H Rubenstein; Boris V Sheynberg; Lari C Harrell; Heribert Schunkert; Hasan Bazari; Igor F Palacios

2001-01-01

272

Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.  

PubMed

In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

2014-10-01

273

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

274

Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.  

PubMed

Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n?=?75) involving chronic administration of kava (one tablet of kava twice per day; 120?mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240?mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p?=?0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample. PMID:23348842

Sarris, J; Stough, C; Teschke, R; Wahid, Z T; Bousman, C A; Murray, G; Savage, K M; Mouatt, P; Ng, C; Schweitzer, I

2013-11-01

275

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma*  

PubMed Central

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ? 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here. PMID:24068261

Pinto, Charleston Ribeiro; Almeida, Natalie Rios; Marques, Thamy Santana; Yamamura, Laira Lorena Lima; Costa, Lindemberg Assunção; Souza-Machado, Adelmir

2013-01-01

276

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

277

Adverse drug reactions reporting : Knowledge and opinion of general public in Penang, Malaysia  

PubMed Central

Objective: The objective of this study was to explore the knowledge of the general population towards ADR and their reporting system. Methods: An anonymous, self-administered questionnaire (15 items) was designed. The questionnaire was subjected to face validity and content validity. The reliability coefficient was found to be 0.71. This study recruited proportionately large convenience sample of the general public in Penang. Interviews using a structured questionnaire were conducted over a week period in August 2009. The recommended sample size was calculated to be 368. Results: Three hundred thirty-four responses were received. Slightly more than half of the respondents were in the age group of 18-25 years (53.6%; n = 179). When asked about the sources of their medication majority of them reported medical doctor (85.6%), whereas small number (34.7%) reported community pharmacists as sources of medications. Three-quarter of the respondents (77.2%) get their information about the side-effects of drugs from physicians, followed by pharmacist (44.6%). More than half of the respondents (65.6%, n = 219) reported unawareness about the existence of ADR center set up by the Ministry of Health. Conclusion: Respondents reflected inadequate knowledge on ADR reporting. This needs to be corrected as the trend of future pharmacovigilance is toward the patient. Moreover, the new trend seems to be more appropriate as the patient is the group of the people who are directly affected from the ADR of a particular drug and not the health-care providers. Furthermore, the patient will be informed about the economic implications of not reporting ADR. It is recommended that government agencies, like MADRAC needs to find ways to increase patient- reported ADR cases. PMID:24082699

Elkalmi, Ramadan; Hassali, Mohamed Azmi; Al-lela, Omar Qutaiba; Jawad Awadh, Ammar Ihsan; Al-Shami, Abdul Kareem; Jamshed, Shazia Qasim

2013-01-01

278

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

279

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

SciTech Connect

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

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

2014-01-01

280

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

281

Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom  

PubMed Central

The objective was to compare the incidence of adverse reactions reported with three nonsteroidal anti-inflammatory drugs with different cyclo-oxygenase (COX)-2 selectivity. All spontaneous adverse reaction notifications in the pharmacovigilance database of the World Health Organisation Collaborating Centre for International Drug Monitoring with aceclofenac, meloxicam, and rofecoxib that were recorded during the first year of marketing were included. The incidence rate (adverse reactions/106 defined daily dose) and 95% confidence interval for total adverse reactions was 8.7 (6.1–12.0) for aceclofenac, 24.8 (23.1–26.6) for meloxicam, and 52.6 (49.9–55.4) for rofecoxib. Aceclofenac had a lower incidence of gastrointestinal bleeding, abdominal pain, and arterial hypertension than meloxicam and a lower incidence of gastrointestinal bleeding, abdominal pain, liver toxicity, thromboembolic cardiovascular events, arterial hypertension, and edema than rofecoxib. The incidence of total and gastrointestinal adverse reactions was significantly lower with aceclofenac than with meloxicam or rofecoxib, thus raising doubts about the hypothetical advantage of COX-2 selective inhibitors. PMID:18360631

Raber, Anna; Heras, Joan; Costa, Joan; Fortea, Josep; Cobos, Albert

2007-01-01

282

Social Dominance Orientation Predicts Heterosexual Men's Adverse Reactions to Romantic Rejection.  

PubMed

We examined the role of social dominance orientation (SDO) as a predictor of men's reactions to romantic rejection and attitudes toward female sexuality. In Study 1 (n = 158), we found that men who scored higher in SDO were more likely to blame women for romantic rejection, and report having responded to women's past rejection with persistence and manipulation (e.g., convincing her to "give him another chance"), as well as with aggression and threats of violence. In Study 2 (n = 398), we replicated these findings, and further found that men higher in SDO were more likely to endorse rape myths (e.g., believing that sometimes a woman's barriers need to be "broken down" in order to attain sex), and to want to lower the legal age of sexual consent in women. Two mediators explained this relationship, hostile sexism and the belief that insubordinate women need to be disciplined. Practical and theoretical implications are discussed. PMID:25224507

Kelly, Ashleigh J; Dubbs, Shelli L; Barlow, Fiona Kate

2015-05-01

283

Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review.  

PubMed

After reports from Japan of neuropsychiatric adverse events (NPAEs) in children taking oseltamivir phosphate (hereafter referred to as oseltamivir [Tamiflu; F. Hoffmann-La Roche Ltd, Basel, Switzerland]) during and after the 2004--5 influenza season, Roche explored possible reasons for the increase in reporting rate and presented regular updates to the US FDA and other regulatory authorities. This review summarizes the results of a comprehensive assessment of the company's own preclinical and clinical studies, post-marketing spontaneous adverse event reporting, epidemiological investigations utilizing health claims and medical records databases and an extensive review of the literature, with the aim of answering the following questions: (i) what the types and rates of neuropsychiatric abnormalities reported in patients with influenza are, and whether these differ in patients who have received oseltamivir compared with those who have not; (ii) what levels of oseltamivir and its active metabolite, oseltamivir carboxylate are achieved in the CNS; (iii) whether oseltamivir and oseltamivir carboxylate have pharmacological activity in the CNS; and (iv) whether there are genetic differences between Japanese and Caucasian patients that result in different levels of oseltamivir and/or oseltamivir carboxylate in the CNS, differences in their metabolism or differences in their pharmacological activity in the CNS. In total, 3051 spontaneous reports of NPAEs were received by Roche, involving 2466 patients who received oseltamivir between 1999 and 15 September 2007; 2772 (90.9%) events originated from Japan, 190 (6.2%) from the US and 89 (2.9%) from other countries. During this period, oseltamivir was prescribed to around 48 million people worldwide. Crude NPAE reporting rates (per 1,000,000 prescriptions) in children (aged < or =16 years) and adults, respectively, were 99 and 28 events in Japan and 19 and 8 in the US. NPAEs were more commonly reported in children (2218 events in 1808 children aged < or =16 years vs 833 in 658 adults) and generally occurred within 48 hours of the onset of influenza illness and initiation of treatment. After categorizing the reported events according to International Classification of Diseases (9th edition) codes, abnormal behaviour (1160 events, 38.0%) and delusions/perceptual disturbances (661 events, 21.7%) were the largest categories of events, and delirium or delirium-like events (as defined by the American Psychiatric Association) were very common in most categories. No difference in NPAE reporting rates between oseltamivir and placebo was found in phase III treatment studies (0.5% vs 0.6%). Analyses of US healthcare claims databases showed the risk of NPAEs in oseltamivir-treated patients (n = 159,386) was no higher than those not receiving antivirals (n = 159,386). Analysis of medical records in the UK General Practice Research Database showed that the adjusted relative risk of NPAEs in influenza patients was significantly higher (1.75-fold) than in the general population. Based on literature reports, NPAEs in Japanese and Taiwanese children with influenza have occurred before the initiation of oseltamivir treatment; events were also similar to those occurring after the initiation of oseltamivir therapy. No clinically relevant differences in plasma pharmacokinetics of oseltamivir and its active metabolite oseltamivir carboxylate were noted between Japanese and Caucasian adults or children. Penetration into the CNS of both oseltamivir and oseltamivir carboxylate was low in Japanese and Caucasian adults (cerebrospinal fluid/plasma maximum concentration and area under the plasma concentration-time curve ratios of approximately 0.03), and the capacity for converting oseltamivir to oseltamivir carboxylate in rat and human brains was low. In animal autoradiography and pharmacokinetic studies, brain : plasma radioactivity ratios were generally 20% or lower. Animal studies showed no specific CNS/behavioural effects after administration of doses corresponding to > or =100 times the clinical dos

Toovey, Stephen; Rayner, Craig; Prinssen, Eric; Chu, Tom; Donner, Barbara; Thakrar, Bharat; Dutkowski, Regina; Hoffmann, Gerhard; Breidenbach, Alexander; Lindemann, Lothar; Carey, Ellen; Boak, Lauren; Gieschke, Ronald; Sacks, Susan; Solsky, Jonathan; Small, Ian; Reddy, David

2008-01-01

284

Profiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls  

PubMed Central

The increased vulnerability to alcohol dependence (AD) seen in individuals with childhood adversity (CA) may result in part from CA-induced epigenetic changes. To examine CA-associated DNA methylation changes in AD patients, we examined peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 candidate genes in 279 African Americans [AAs; 88 with CA (70.5% with AD) and 191 without CA (38.2% with AD)] and 239 European Americans [EAs; 61 with CA (86.9% with AD) and 178 without CA (46.6% with AD)] using Illumina GoldenGate Methylation Array assays. The effect of CA on methylation of individual CpGs and overall methylation in promoter regions of genes was evaluated using a linear regression analysis (with consideration of sex, age, and ancestry proportion of subjects) and a principal components-based analysis, respectively. In EAs, hypermethylation of 10 CpGs in seven genes (ALDH1A1, CART, CHRNA5, HTR1B, OPRL1, PENK, and RGS19) were cross validated in AD patients and healthy controls who were exposed to CA. P values of two CpGs survived Bonferroni correction when all EA samples were analyzed together to increase statistical power [CHRNA5_cg17108064: Padjust?=?2.54×10?5; HTR1B_cg06031989: Padjust?=?8.98×10?5]. Moreover, overall methylation levels in the promoter regions of three genes (ALDH1A1, OPRL1 and RGS19) were elevated in both EA case and control subjects who were exposed to CA. However, in AAs, CA-associated DNA methylation changes in AD patients were not validated in healthy controls. Our findings suggest that CA could induce population-specific methylation alterations in the promoter regions of specific genes, thus leading to changes in gene transcription and an increased risk for AD and other disorders. PMID:23799031

Zhang, Huiping; Wang, Fan; Kranzler, Henry R.; Zhao, Hongyu; Gelernter, Joel

2013-01-01

285

Development of a combined system for identification and classification of adverse drug reactions: Alerts Based on ADR Causality and Severity (ABACUS)  

PubMed Central

Currently, adverse drug reaction (ADR) causality and severity are assessed using different systems but there is no standard method to combine the results. In this work, a combined ADR causality and severity assessment system, including an online version, was developed. Logical rules were defined to translate the score obtained from the system into three alert zones: green, amber, and red. The alert zones are useful for triaging ADR cases as they help define the seriousness of the ADR and the urgency of the responses required. This new scoring system may be useful for clinicians, investigators, and regulators seeking information on the likelihood of a drug causing an adverse reaction, and whether an adverse reaction is sufficiently dangerous for the drug to be withheld or undergo further investigation. PMID:20962137

Koh, Yvonne; Yap, Chun Wei

2010-01-01

286

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

287

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

288

Gut microbes and adverse food reactions: Focus on gluten related disorders.  

PubMed

Immediately following birth, the gastrointestinal tract is colonized with a complex community of bacteria, which helps shape the immune system. Under conditions of health, the immune system is able to differentiate between innocuous antigens, including food protein and commensals, and harmful antigens such as pathogens. However, patients with celiac disease (CD) develop an intolerance to gluten proteins which results in a pro-inflammatory T-cell mediated immune response with production of anti-gluten and anti-tissue transglutaminase antibodies. This adaptive immune response, in conjunction with activation of innate inflammatory cells, lead to destruction of the small intestinal mucosa. Overall 30% of the global population has genetic risk to develop CD. However, only a small proportion develop CD, suggesting that additional environmental factors must play a role in disease pathogenesis. Alterations in small intestinal microbial composition have recently been associated with active CD, indicating a possible role for the microbiota in CD. However, studies demonstrating causality are lacking. This review will highlight the recent data on the potential role of the microbiota in CD pathogenesis, the potential mechanisms, and discuss future research directions. PMID:25483329

Galipeau, Heather J; Verdu, Elena F

2014-01-01

289

Use of an Interactive, Telephone-based Self-management Support Program to Identify Adverse Events Among Ambulatory Diabetes Patients  

PubMed Central

BACKGROUND There is growing interest in the use of interactive telephone technology to support chronic disease management. We used the implementation of an automated telephone self-management support program for diabetes patients as an opportunity to monitor patient safety. METHODS We identified adverse and potential adverse events among a diverse group of diabetes patients who participated in an automated telephone health-IT self-management program via weekly interactions augmented by targeted nurse follow-up. We defined an adverse event (AE) as an injury that results from either medical management or patient self-management, and a potential adverse event (PotAE) as an unsafe state likely to lead to an event if it persists without intervention. We distinguished between incident, or new, and prevalent, or ongoing, events. We conducted a medical record review and present summary results for event characteristics including detection trigger, preventability, potential for amelioration, and primary care provider awareness. RESULTS Among the 111 patients, we identified 111 AEs and 153 PotAEs. Eleven percent of completed calls detected an event. Events were most frequently detected through health IT–facilitated triggers (158, 59%), followed by nurse elicitation (80, 30%), and patient callback requests (28, 11%). We detected more prevalent (68%) than incident (32%) events. The majority of events (93%) were categorized as preventable or ameliorable. Primary care providers were aware of only 13% of incident and 60% of prevalent events. CONCLUSIONS Surveillance via a telephone-based, health IT–facilitated self-management support program can detect AEs and PotAEs. Events detected were frequently unknown to primary providers, and the majority were preventable or ameliorable, suggesting that this between-visit surveillance, with appropriate system-level intervention, can improve patient safety for chronic disease patients. PMID:18373145

Handley, Margaret A.; Gupta, Reena; Tang, Audrey; Murphy, Elizabeth; Seligman, Hilary K.; Shojania, Kaveh G.; Schillinger, Dean

2008-01-01

290

Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients  

PubMed Central

Background Recently, several reports issued clevudine induced myopathy in the long term use. Objectives The aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB). Patients and Methods The subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period. Results In HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy. Conclusions Long-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine. PMID:23805155

Kim, Byung Kook; Ko, Soon Young; Kwon, So Young; Park, Eugene; Kim, Jeong Han; Choe, Won Hyeok; Lee, Chang Hong

2013-01-01

291

Real-World Efficiency of Pharmacogenetic Screening for Carbamazepine-Induced Severe Cutaneous Adverse Reactions  

PubMed Central

Objectives We evaluated the cost and efficiency of routine HLA-B*15?02 screening to prevent carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in Hong Kong. Methods Data were extracted from patients who commenced CBZ as the first-ever AED treatment or tested for HLA-B*15?02 allele in three years before policy implementation (pre-policy: 16 September 2005 to 15 September 2008) and three years after (post-policy: 16 September 2008 to 15 September 2011). Using published unit costs, we estimated the cost of screening by comparing the costs to prevent and treat CBZ-SJS/TEN. We compared the number of person-tests needed and the cost to prevent resultant death with cancer screening programs. Results The number of screening tests needed to prevent one case of CBZ-SJS/TEN was 442, and to prevent one resultant death was 1,474 to 8,840. The screening cost was $332 per person, of which 42% was attributed to an additional consultation to review result and prescribe appropriate medication. HLA-B*15?02 screening expended $146,749 to prevent a case of CBZ-SJS/TEN, and $489,386– $2,934,986 to prevent a resultant death. The corresponding numbers of tests and costs for mammography and Pap smear to prevent death due to breast and cervical cancers were 7,150 and 7,000, and $614,900 and $273,000, respectively. Comparing to the SJS/TEN treatment cost, HLA-B*15?02 screening would become cost saving if a point-of-care test of less than $37 was available. Conclusions HLA-B*15?02 screening is as efficient as mammography and Pap smear in preventing death. Development of point-of-care testing will vastly improve efficiency. PMID:24806465

Chen, Zhibin; Liew, Danny; Kwan, Patrick

2014-01-01

292

The Scars of Childhood Adversity: Minor Stress Sensitivity and Depressive Symptoms in Remitted Recurrently Depressed Adult Patients  

PubMed Central

Background Childhood adversity may lead to depressive relapse through its long-lasting influence on stress sensitivity. In line with the stress sensitization hypothesis, minor (daily) stress is associated with depressive relapse. Therefore, we examine the impact of childhood adversity on daily stress and its predictive value on prospectively assessed depressive symptoms in recurrently depressed patients. Method Daily stress was assessed in recurrently depressed adult patients, enrolled into two randomized trials while remitted. The reported intensity and frequency of dependent and independent daily stress was assessed at baseline. Independent stress is externally generated, for example an accident happening to a friend, while dependent stress is internally generated, for example getting into a fight with a neighbor. Hierarchical regression analyses were performed with childhood adversity, independent and dependent daily stress as predictor variables of prospectively measured depressive symptoms after three months of follow-up (n?=?138). Results We found that childhood adversity was not significantly associated with a higher frequency and intensity of daily stress. The intensity of both independent and dependent daily stress was predictive of depressive symptom levels at follow-up (unadjusted models respectively: B?=?0.47, t?=?2.05, p?=?0.041, 95% CI?=?0.02–0.92; B?=?0.29, t?=?2.20, p?=?0.028, 95% CI?=?0.03–0.55). No associations were found between childhood adversity and depressive symptoms at follow-up. Conclusion No evidence was found supporting stress sensitization due to the experience of childhood adversity in this recurrently depressed but remitted patient group. Nevertheless, our research indicates that daily stress might be a target for preventive treatment. Trial Registration Trial A: Nederlands Trial Register NTR1907 Trial B: Nederlands Trial Register NTR2503 PMID:25393812

Burger, Huibert; Elgersma, Hermien; Riper, Heleen; Cuijpers, Pim; Dekker, Jack; Smit, Filip; Bockting, Claudi

2014-01-01

293

Adverse Effects of Plasma Transfusion  

PubMed Central

Plasma utilization has increased over the last two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions following infusion of fresh frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: (1) transfusion related acute lung injury; (2) transfusion associated circulatory overload, and (3) allergic/anaphylactic reactions. Other less common risks include (1) transmission of infections, (2) febrile non-hemolytic transfusion reactions, (3) RBC allo-immunization, and (4) hemolytic transfusion reactions. The affect of pathogen inactivation/reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

294

HLA-A31 strongly associates with carbamazepine-induced adverse drug reactions but not with carbamazepine-induced lymphocyte proliferation in a Japanese population.  

PubMed

Carbamazepine (CBZ) is the most frequent culprit drug for severe cutaneous adverse drug reactions (ADR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS). A strong association between human leukocyte antigen (HLA)-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese, Thai, Malaysian and Indian populations, but not in Caucasian or Japanese populations. Recent studies showed an association between HLA-A*3101 and CBZ-induced ADR in Caucasian and Japanese populations. We conducted a case-control study to determine HLA genotyping of patients with CBZ-induced ADR in a Japanese population. Fifteen patients with CBZ-induced ADR and 33 subjects who had taken CBZ for more than 3 months without evidence of any ADR as a control were enrolled. In addition, the results of a CBZ-induced lymphocyte stimulation test were compared between the groups. A strong association was found between HLA-A31 and CBZ-induced ADR (P < 0.001), and a weak association was found between HLA-A11 and HLA-B51 with CBZ-induced ADR. No HLA-B*1502 was found in either patients or control subjects. The mean CBZ-induced lymphocyte stimulation index was significantly high in patients with CBZ-induced ADR compared with CBZ-tolerant patients (P < 0.001); however, no significant difference was seen between HLA-A31-positive subjects and HLA-A31-negative subjects in either group. These findings suggest that HLA-A31 is strongly associated with CBZ-induced ADR in the Japanese, but does not determine CBZ-induced lymphocyte proliferation. PMID:22211527

Niihara, Hiroyuki; Kakamu, Takeyasu; Fujita, Yasuyuki; Kaneko, Sakae; Morita, Eishin

2012-07-01

295

Comprehensive medical examination of a group of patients with alleged adverse effects from dental amalgams.  

PubMed

Mercury from dental amalgams does not seem to cause dose-related intoxications. However, animal studies have shown that high-dose exposure to mercury may support various types of immunologic reactions. Ten patients claiming that their symptoms were caused and aggravated by amalgam therapy were selected for a study of the effects of removal of one amalgam restoration followed by placing of a composite filling. Clinical symptoms and the result of laboratory tests were recorded. Six patients had contact allergies to metals, three of them to mercury ammonium chloride. The comparison of pre- and post-experimental test results showed significant reductions in p-IgE and dU-albumin and significant increases in p-C3d and dU-beta 2-microglobulin. There was no laboratory evidence of a direct toxic effect by mercury on the patients. The observed response by some of the studied factors to the low acute exposure to amalgam may imply that an activation of the immune system occurred. PMID:1604964

Anneroth, G; Ericson, T; Johansson, I; Mörnstad, H; Ryberg, M; Skoglund, A; Stegmayr, B

1992-04-01

296

Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: Data from the FDA Adverse Event Reporting System.  

PubMed

Rare but serious cardiovascular and pulmonary adverse events (AEs) have been reported in patients with chronic myeloid leukemia treated with BCR-ABL inhibitors. Clinical trial data may not reflect the full AE profile of BCR-ABL inhibitors because of stringent study entry criteria, relatively small sample size, and limited duration of follow-up. To determine the utility of the FDA AE Reporting System (FAERS) surveillance database for identifying AEs possibly associated with the BCR-ABL inhibitors imatinib, dasatinib, and nilotinib in the postmarketing patient population, we conducted Multi-Item Gamma Poisson Shrinker disproportionality analyses of FAERS reports on AEs in relevant system organ classes. Signals consistent with the known safety profiles of these agents as well as signals for less well-described AEs were detected. Bone marrow necrosis, conjunctival hemorrhage, and peritoneal fluid retention events were uniquely associated with imatinib. AEs that most commonly reached the threshold for dasatinib consisted of terms relating to hemorrhage and fluid retention, including pleural effusion and pericardial effusion. Most terms that reached the threshold solely with nilotinib were related to peripheral and cardiac vascular events. Although this type of analysis cannot determine AE incidence or establish causality, these findings elucidate the AEs reported in patients treated with BCR-ABL inhibitors across multiple clinical trials and in the community setting for all approved and nonapproved indications, suggesting drug-AE associations warrant further investigation. These findings emphasize the need to consider patient comorbidities when selecting amongst BCR-ABL inhibitors. Am. J. Hematol. 90:E66-E72, 2015. © 2015 Wiley Periodicals, Inc. PMID:25580915

Cortes, Jorge; Mauro, Michael; Steegmann, Juan Luis; Saglio, Giuseppe; Malhotra, Rachpal; Ukropec, Jon A; Wallis, Nicola T

2015-04-01

297

68?Immediate and No Immediate Reactions Induced by Iodinated Contrast Medium Nonionic Among Hospitalized Patients: Incidence and Severity  

PubMed Central

Background Contrast media (CM) are among the most widely used medications in the world. Our objective was to estimate the severity and incidence of adverse reactions to MC, first administered in hospitalized patients. Methods We prospectively studied 99 patients requiring computed tomography (CT) enhanced with MC. Immediate adverse reactions were identified by direct questioning and/or physical examination after administration of iodinated CM nonionic low osmolarity. Additionally, blood pressure, heart rate, oxygen saturation, serum creatinine and total count of eosinophils were measured before and after the procedure. Results Mean age of patients was 50.4 ± 20.2 years, women were 52. The occurrence of immediate adverse reactions and no immediate observed were 26.3 and 10.1% respectively. Eighteen (69.2%) of the immediate reactions were mild, 6 (23.1%) moderate and 2 (7.7%) severe (both developed symptomatic arrhythmias). The most common manifestations were warmth, nausea and itching, nephrotoxicity was observed in 5.1% of patients and eosinophilia in 3.1%. No skin reactions documented. Median serum creatinine before and after the procedure not observed significant difference (P = 0.130), instead the total number of eosinophils did show difference (P < 0.001). Conclusions Our results demonstrate a high incidence of adverse reactions compared with previously published reports worldwide. Although most adverse reactions are mild, those of severe intensity, with increased mortality and morbidity, increased costs and hospital length of stay continue to occur despite the increased use of contrast media of low osmolarity. More prospective studies that share the same methodology are needed to determine the actual frequency.

Bedolla-Barajas, Martín

2012-01-01

298

Adverse Reactions to Foods  

Microsoft Academic Search

Over the past 20 years, food allergy has emerged as an important clinical problem in Westernized countries. Not only has food allergy prevalence al- most doubled but its severity and scope have increased. Consequently, research focusing on characterization, mapping, and cloning of food allergens, as well as on deciphering the nature of immune responses to food allergens and the mechanisms

Anna Nowak-Wegrzyn; Hugh A. Sampson

2006-01-01

299

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

300

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

PubMed Central

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

2015-01-01

301

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; da Silva, Andrea Luciana Soares; Teles e Silva, André Luiz; Ghattaoraya, Gurpreet S; Alfirevic, Ana; Jones, Andrew R; Middleton, Derek

2015-01-01

302

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

303

[Study of analysis 1 390 adverse drug reactions cases of parenterally administered dengzhan xixin based on China's spontaneous response system].  

PubMed

Adverse drug reaction (ADR) monitoring of spontaneous reporting system (SRS) data to detect signals, is the main method of pharmacovigilance by China food and drug administration (CFDA). This study conducted a data analysis of 1 390 ADR cases of parenterally administered Dengzhan Xixin based on China SRS data collected between Jan, 2009 and Dec, 2012. The proportional reporting ratio method (PRR) and Bayesian confidence propagation neural network method (BCPNN) were used for data mining analysis. The results showed that 71 cases of serious ADRs accounted for 1 390, 5.11% of cases reported. There were more men than women (613/593), and people over the age of 60 accounted for 64.03%. The most common ADRs were itching, rash, dizziness, chills, and palpitations. With damage to skin and its accessories 55 forming the highest percentage of ADRs. When propensity score method to control for confounding factors, PRR method and BCPNN methods were applied, headache, dizziness, palpitation, and chills were ADRs warning signals. Due to the limitation of the SRS data, the results still need to be combined with other research to form a comprehensive body of safety evidence, and to guide the rational clinical use and reduce risks. PMID:24471319

Li, Yuan-Yuan; Xiang, Yong-Yang; Xie, Yan-Ming; Shen, Hao

2013-09-01

304

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  

Microsoft Academic Search

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

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

2007-01-01

305

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

306

Delayed Adverse Reaction to Contrast-enhanced CT: A Prospective Single-Center Study Comparison to Control Group without Enhancement 1  

PubMed Central

Purpose: To prospectively assess the incidence of delayed adverse reactions (DARs) in patients undergoing contrast material–enhanced computed tomography (CT) with the low osmolar nonionic contrast agent iohexol and compare with the incidence of DARs in patients undergoing unenhanced CT as control subjects. Materials and Methods: Institutional review board approval and informed written consent for this prospective study were obtained. The study was HIPAA compliant. Patients undergoing CT for routine indications were enrolled from a random next-available scheduling template by an on-site clinical trials monitor. All subjects received a questionnaire asking them to indicate any DAR occurring later than 1 hour after their examination. Sixteen manifestations were listed and included rash, skin redness, skin swelling, nausea, vomiting, and dizziness, among others. To ensure maximal surveillance, a clinical trials coordinator initiated direct telephone contact for further assessment. Patients suspected of having moderately severe cutaneous reactions were invited to return for a complete dermatologic clinical assessment including skin biopsy, if indicated. Statistical analysis was performed by using a two-sided Wilcoxon-Mann-Whitney test, a logistic regression utilizing a ?2 test to adjust for sex and age, and a two-sided Fisher exact test. Results: A total of 539 patients (258 receiving iohexol and 281 not receiving contrast material) were enrolled. DARs were observed in 37 (14.3%) of 258 subjects receiving iohexol and in seven (2.5%) of 281 subjects in the control group (P < .0001, ?2 test) after adjusting for sex and age. Specific manifestations of DARs that were significantly more frequent at contrast-enhanced CT were skin rash (P = .0311), skin redness (P = .0055), skin swelling (P = .0117), and headache (P = .0246). DARs involving the skin included generalized rashes of the face, neck, chest, back, and extremities and were often associated with swelling, erythema, and pruritus. Conclusion: This study substantiates a frequent occurrence of DARs at contrast-enhanced CT compared with that in control subjects. Continued growth in the use of contrast-enhanced CT suggests a need for greater awareness and attention to prevention and management. © RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10091848/-/DC1 PMID:20406882

Bagheri, Sepideh; Katzberg, Richard W.; Fung, Maxwell A.; Li, Chin-Shang

2010-01-01

307

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

Microsoft Academic Search

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 pro- vide a stigma-reduction strategy. This article reports an investi- gation of this hypothetical association between simulation dis- comfort and mental illness stigma. Methods: ASPs were randomly assigned to one of two simu- lation

Mark D. Hanson; Samantha Johnson; Anne Niec; Anna Marie Pietrantonio; B. High; H. MacMillan; K. W. Eva

2008-01-01

308

Renal Function Interferes with Copeptin in Prediction of Major Adverse Cardiac Events in Patients Undergoing Vascular Surgery  

PubMed Central

Objective Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient’s perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease. Methods 477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE). Results 41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages. Conclusion Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery. PMID:25875814

Sahlmann, Bianca; Meinders, Antje; Larmann, Jan; Wilhelmi, Mathias; Aper, Thomas; Rustum, Saad; Lichtinghagen, Ralf; Theilmeier, Gregor; Teebken, Omke E.

2015-01-01

309

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

2015-04-01

310

Are the adverse effects of body position in patients with obstructive sleep apnea dependent on sleep stage?  

Microsoft Academic Search

Purpose  The purpose of the study was to determine if the adverse effect of body position on obstructive sleep apnea (OSA) is worsened\\u000a during rapid eye movement (REM) sleep and if patients with OSA decrease the time spent supine during REM sleep.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Overnight polysomnography from 80 sequential patients referred to Buffalo VA Sleep Lab for suspected OSA were analyzed with\\u000a 20

M. Jeffery Mador; Youngmi Choi; Abid Bhat; Jacek Dmochowski; Mark Braun; V. A. Gottumukkala; Brydon J. Grant

2010-01-01

311

Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy.  

PubMed

Patients with Stage 5 chronic kidney disease who have hyperphosphatemia require treatment with phosphate binders to lower serum phosphorus levels. Existing binders are effective but may be associated with important safety disadvantages. Lanthanum carbonate is a phosphate binder with demonstrated efficacy, safety, and tolerability in clinical trials. Changes in cognitive function were evaluated over time using the Cognitive Drug Research computerized cognitive assessment system (Simple Reaction Time, Digit Vigilance Task, Choice Reaction Time, Numeric Working Memory, and Delayed Picture Recognition) in 360 hemodialysis patients who were enrolled in a 2-year, multicenter, comparative study of lanthanum carbonate versus standard therapy. A decline in cognitive function from baseline was observed in both groups. The deterioration in cognitive function was similar in both the lanthanum carbonate and standard therapy groups. One parameter - Numeric Working Memory - showed a statistically significant between-group difference in favor of lanthanum carbonate (P=0.02). Given the magnitude of the changes, however, and the differences that were observed at baseline between treatment groups, the clinical significance of this difference is doubtful. This study demonstrates that cognitive function deteriorates in hemodialysis patients over a 2-year time period. Use of lanthanum carbonate as a phosphate binder does not adversely affect cognitive function compared with standard therapy. PMID:17035945

Altmann, P; Barnett, M E; Finn, W F

2007-02-01

312

Stakeholder perspectives on implementing the National Cancer Institute’s patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)  

Microsoft Academic Search

The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse\\u000a Events, called the “PRO-CTCAE.” The PRO-CTCAE consists of a library of patient-reported items which can be administered in\\u000a clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software\\u000a platform for administering these items via

Deborah Watkins Bruner; Laura J Hanisch; Bryce B Reeve; Andy M Trotti; Deborah Schrag; Laura Sit; Tito R Mendoza; Lori Minasian; Ann O’Mara; Andrea M Denicoff; Julia H Rowland; Michael Montello; Cindy Geoghegan; Amy P Abernethy; Steven B Clauser; Kathleen Castro; Sandra A Mitchell; Laurie Burke; Ann Marie Trentacosti; Ethan M Basch

2011-01-01

313

Notes from the field: adverse events associated with administration of simulation intravenous fluids to patients - United States, 2014.  

PubMed

On December 23, 2014, the New York State Department of Health (NYSDOH) was notified of adverse health events in two patients who had been inadvertently administered nonsterile, simulation 0.9% sodium chloride intravenous (IV) fluids at an urgent care facility. Simulation saline is a nonsterile product not meant for human or animal use; it is intended for use by medical trainees practicing IV administration of saline on mannequins or other training devices. Both patients experienced a febrile illness during product administration and were hospitalized; one patient developed sepsis and disseminated intravascular coagulation. Neither patient died. Staff members at the clinic reported having ordered the product through their normal medical supply distributor and not recognizing during administration that it was not intended for human use. PMID:25742384

Robyn, Misha P; Hunter, Jennifer C; Burns, Amy; Newman, Alexandra P; White, Jennifer; Clement, Ernest J; Lutterloh, Emily; Quinn, Monica; Edens, Chris; Epstein, Lauren; Seiber, Kathy; Nguyen, Duc; Kallen, Alexander; Blog, Debra

2015-03-01

314

[Adverse events following influenza vaccination: reaction to specific reports and the necessity of a central registration system].  

PubMed

The influenza vaccine is considered safe, but information on vaccine-related adverse events is limited and a nationwide overview of adverse events is lacking. In 2006, after deaths occurred in Israel and the Netherlands following influenza vaccination, the Dutch Ministry of Health, Welfare and Sport (VWS) asked the National Institute for Public Health and the Environment (RIVM) twice for a recommendation regarding the continuation of the national vaccination campaign. After 4 deaths were reported in Israel in October 2006 following administration of Vaxigrip, the Dutch vaccination campaign was suspended for one week. One month later, 4 additional deaths were reported after influenza vaccination in the Netherlands. The newly appointed outbreak management team concluded that a causal relationship between vaccination and the deaths was highly unlikely, based on data regarding the individual cases, background mortality rates and prior reports of adverse events. Further suspension of the vaccination campaign was deemed unnecessary this time. A centralised nationwide registry of adverse events has since been established to provide further insight into the incidence of adverse events following influenza vaccination. Physicians are advised to report potential adverse events following influenza vaccination to the Netherlands Pharmacovigilance Centre Lareb (www.lareb.nl). PMID:17957995

Swaan, C M; van der Sande, M A B; Speelman, P; Conyn-van Spaendonck, M A E; Straus, S M J M; Coutinho, R A

2007-09-29

315

Adverse Events in Patients with Blood Loss: A Pooled Analysis of 51 Clinical Studies from the Celecoxib Clinical Trial Database  

PubMed Central

Background: Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of gastrointestinal (GI) toxicity, including occult blood loss and the development of clinically significant anemia. The aim of this study was to investigate the clinical importance of clinically significant anemia/blood loss. Methods: Pooled analysis of 51 blinded, controlled clinical studies ?4 weeks duration from the celecoxib clinical trial database, comparing celecoxib with NSAIDs or placebo. The adverse event (AE) profile in patients with clinically significant anemia/blood loss (defined as decreases in hemoglobin ?2 g/dL and/or hematocrit by ?10% from baseline) was compared with the AE profile in patients without blood loss. Events that occurred in <0.5% of patients were excluded from any comparisons. A threefold difference between groups was defined arbitrarily as being markedly higher. Results: Overall 932/51,048 patients experienced clinically significant anemia/blood loss. Baseline demographics were similar in both groups. The incidence of AEs was markedly higher in patients who experienced clinically significant anemia/blood loss than those who did not; the majority of these differences were for GI AEs or their likely sequelae. The incidence of the following non-GI related AEs was also markedly higher in patients with blood loss: coronary artery disease (1.2% vs 0.3%), myocardial infarction (0.6% vs 0.2%), and pneumonia (1.7% vs 0.4%). Withdrawals due to AEs were more common among patients who experienced blood loss (16.7% vs 10.4%). Conclusions: Clinically significant anemia/blood loss may have clinically important adverse consequences beyond the sequelae previously known to be associated with NSAID-related GI effects. PMID:22629288

Sands, GH; Shell, B; Zhang, R

2012-01-01

316

Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations.  

PubMed

Protamine insulin use may immunologically sensitize patients to protamine, leading to anaphylactoid reactions upon subsequent exposure to protamine sulfate during cardiac catheterization or cardiovascular surgery. The risk of such reactions in protamine insulin-dependent patients is uncertain. One catheterization study reported a 50-fold greater risk while a second showed no increased risk! To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions. Protamine was administered in 3,341/7,750 procedures (43%), including 171 in diabetics receiving NPH insulin. Adverse reactions to protamine occurred in 2/3, 170 noninsulin patients, 0.06%, and adverse reactions due to probable NPH insulin sensitization occurred in 1/171, 0.6%, of NPH diabetics, p = .034. Meta-analysis of risk showed an odds ratio of 7.96 for the NPH diabetic patients, and combining these results with the other large series in the literature (269 NPH diabetics total) showed an odds ratio of 4.19 compared to a non-NPH insulin group. Meta-analysis of the surgical literature showed the risk in surgical patients to be 2.1% in NPH patients versus 0.12% with no NPH, with an odds ratio of 15.52. The greater incidence in surgical patients may be due to protamine sensitization at prior catheterization and to the larger dose of protamine administered to surgical patients. PMID:1831070

Vincent, G M; Janowski, M; Menlove, R

1991-07-01

317

Upper gastrointestinal adverse drug reactions and cyclo-oxygenase-2 inhibitors (celecoxib and rofecoxib): a case\\/non-case study from the French Pharmacovigilance Database  

Microsoft Academic Search

Objective To evaluate the gastrointestinal safety of cyclo-oxygenase-2 inhibitors under their real conditions of use. Design Case\\/non-case study. Setting Adverse drug reactions (ADRs) in adults recorded in the French Pharmacovigilance Database between 25 May 2000 and 31 December 2002. Materials Cases were all reports of “serious” oeso-gastro-duodenal ADRs (oeso-gastro-duodenal ulcers, oesophagitis, gastritis, duodenitis). Five non-cases were randomly selected for one

S. Lugardon; M. Lapeyre-Mestre; J. L. Montastruc

2004-01-01

318

Factors associated with adverse reactions to cocaine among a sample of long-term, high-dose users in São Paulo, Brazil  

Microsoft Academic Search

This cross-sectional survey investigates the frequency of adverse cocaine reactions and associated factors among regular cocaine misusers. A sample of 332 cocaine misusers from a range of treatment and nontreatment settings in São Paulo, Brazil, were interviewed using a questionnaire that includes the Severity of Dependence Scale (SDS), the General Health Questionnaire (GHQ-28), the CAGE, and an eight-item questionnaire investigating

Cleusa P. Ferri; John Dunn; Michael Gossop; Ronaldo Laranjeira

2004-01-01

319

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control.  

PubMed

Background and aimsElevated plasma asymmetric dimethylarginine (ADMA) levels have been observed in patients with insulin resistance and diabetes, and have been reported to predict adverse cardiovascular events in type 2 diabetic patients. However, the relationship between ADMA and glycemic control in patients with type 2 diabetes remained controversial.Methods and resultsWe evaluated 270 patients with type 2 diabetes and measured their plasma ADMA and hemoglobin A1c (HbA1c) levels by high performance liquid chromatography. The mean age was 67¿±¿12 years. The mean plasma ADMA and HbA1c level were 0.46¿±¿0.09 ¿mol/l and 7.8¿±¿1.6%, respectively. There was no significant correlation between plasma ADMA level and HbA1c level (r¿=¿¿0.09, p¿=¿0.13). During the median follow-up period of 5.7 years (inter-quartile range: 5.0¿¿¿7.3 years), major adverse cardiovascular event (MACE, including cardiovascular death, myocardial infarction and stroke) was observed in 55 patients (20.4%). Multivariate Cox regression analysis revealed that the ADMA tertile was an independent risk factor for MACE (ADMA tertile III versus ADMA tertile I: p¿=¿0.026, HR: 2.31, 95% CI: 1.10¿¿¿4.81). The prognosis predictive power of ADMA disappeared in patients with well glycemic control (HbA1c ¿6.5%), and the ADMA-HbA1c interaction p value was 0.01.ConclusionsIn patients with type 2 diabetes, ADMA might be an independent risk factor for long-term adverse cardiovascular events. However, ADMA was not correlated with serum HbA1c level, and in diabetic patients with HbA1c ¿6.5%, elevated ADMA level was no longer associated with increased risk of long-term prognosis. Our findings suggested that the prognosis predictive value of ADMA in type 2 diabetes might be modified by the glycemic control. PMID:25467091

Hsu, Chiao-Po; Hsu, Pai-Feng; Chung, Ming-Yi; Lin, Shing-Jong; Lu, Tse-Min

2014-12-01

320

Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions.  

PubMed

Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in ?1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity. PMID:25562554

Saff, Rebecca R; Banerji, Aleena

2015-01-01

321

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.

322

Comparison of Newcastle disease vaccine administered as powder or liquid in relation to the serum antibody response and adverse vaccinal reactions in broilers.  

PubMed

Liquid spray and aerosol mass vaccination of poultry have several drawbacks, such as uncontrolled deposition of vaccine particles in the respiratory tract and vaccine virus inactivation by formation and evaporation of droplets. These may be addressed by using dry powder vaccines with defined particle size distribution targeting the upper (primary vaccination) or the entire respiratory tract (booster vaccination). Therefore, a coarse Newcastle disease (LZ58 strain) powder vaccine was administered to specified pathogen free (SPF) broiler hens to compare the antibody response and adverse vaccinal reactions with those induced by a coarse liquid spray and a fine liquid aerosol. Groups of 40 broilers each housed in isolators were vaccinated at 4 days of age and intratracheally inoculated with Escherichia coli (strain 506) at 11 days of age. Adverse vaccinal reactions were evaluated by measuring body weight gain and mortality between 4 and 11 days of age and between 11 and 18 days of age, and by recording colibacillosis lesions at 18 days of age. The antibody serum response was measured at 18 days of age by the haemagglutination inhibition test. Despite the relative low initial vaccine virus loss and narrow particle size distribution of the powder vaccines in comparison with their liquid counter parts, no significant differences (P > 0.05) regarding adverse vaccinal reactions and antibody response were observed between broilers vaccinated with the powder vaccines or with their liquid counterparts. PMID:25588317

Landman, W J M; Huyge, K; Remon, J P; Vervaet, C; van Eck, J H H

2015-04-01

323

Hormonal regulation of energy-protein homeostasis in hemodialysis patients: an anorexigenic profile that may predispose to adverse cardiovascular outcomes  

PubMed Central

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, ?-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients. PMID:20959536

Suneja, Manish; Murry, Daryl J.; Stokes, John B.

2011-01-01

324

Comparison of reversal and adverse effects of sugammadex and combination of — Anticholinergic-Anticholinesterase agents in pediatric patients  

PubMed Central

Background: We aimed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients. Materials and Methods: A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this randomized double-blinded clinical trial. Fentanyl 1 ?g/kg, propofol 2 mg/kg, rocuronium 0.6 mg/kg were used in induction and sevofluran, 50% O2-50% N2O in maintenance of anesthesia. Neuromuscular conductions were assessed by train of four (TOF)-Watch SX (Organon, Schering-Plough, Ireland) acceleromyograph. Patients were intubated at the moment of TOF 0. At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine +0.02 mg/kg atropine in group 2. At the moment of T0.9 inhalation, gases were ceased, and patients were extubated. Hemodynamic alterations, access to T0.9, extubation time, recovery parameters, drug consumptions and adverse effects were recorded. Results: Train of four scores showed a lesser increase in group 2 than group 1 from 15th s to 30th min during post reverse period (from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1) (p < 0.0004). Group 1 patients exhibited much more complete muscle strength rates than group 2 (P < 0.001). T0.9 and extubation times were significantly longer in group 2 than group 1 (P < 0.001). Comparison of adverse effects yielded no difference. Conclusion: Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients. PMID:25422663

Özgün, Çi?dem; Çakan, Türkay; Baltac?, Bülent; Ba?ar, Hülya

2014-01-01

325

Incidence of early postoperative cognitive dysfunction and other adverse events in elderly patients undergoing elective total hip replacement (THR).  

PubMed

In elderly patients cognitive dysfunction and other adverse events (AEs) can impair the outcome of surgical procedures. As THR is performed with increasing frequency in aging populations, it is important to know the impact of these problems on the postoperative result. In this prospective cohort study 60 patients older than 65 years (66.7% female, 33.3% male) who received THR were included. The cognitive function was measured preoperatively, one week and six months postoperatively by the mini-mental state test (MMSE). Shortly after surgery 4 patients (6.7%) developed postoperative cognitive dysfunction, which has recovered at six-months-follow-up. In 41 patients (68.3%) AEs were recorded. Postoperative anemia occurred as the most common AE (n=32; 53.3%). During hospital stay older patients are at an increased risk for AEs. The incidence of postoperative cognitive dysfunction was observed less often than expected. Further research is necessary to assess the effect of early interventions in case of cognitive dysfunction. With use of a simple and quickly performed test like the MMSE patients can be effectively screened for impaired cognitive function. Secure identification of those patients is mandatory to avoid complications with harmful long-term effects. PMID:21288579

Postler, A; Neidel, J; Günther, K-P; Kirschner, S

2011-01-01

326

Abacavir-induced reaction with fever and severe skin rash in a patient tested human leukocyte antigen-B*5701 negative.  

PubMed

The most serious adverse event caused by abacavir is the hypersensitivity reaction, which is usually associated with the presence of the human leukocyte antigen (HLA) subtype B*5701, as shown in recent studies. We describe the case of a 41-year-old Caucasian female patient, who tested HLA-B*5701 negative and developed fever and severe skin rash 10 weeks after the start of abacavir therapy. Similar reports suggest that not all severe abacavir-induced adverse events occur as a result of classic hypersensitivity reactions, and can present also in HLA-B*5701-negative patients. PMID:19304978

Calza, L; Rosseti, N; Biagetti, C; Pocaterra, D; Colangeli, V; Manfredi, R

2009-04-01

327

Do family practitioners in Lithuania inform their patients about adverse effects of common medications?  

Microsoft Academic Search

Objectives:(1) To investigate the extent to which family physicians (GPs) in Lithuania inform their patients about possible side-effects when a common treatment is proposed. (2) To examine the relation between physicians’ estimation of the severity and frequency of these side-effects and their willingness to inform patients. (3) To identify the reasons for informing or not informing the patients.Methods:A questionnaire, presenting

I Liseckiene; Z Liubarskiene; R Jacobsen; L Valius; M Norup

2008-01-01

328

The effect of obesity on adverse outcomes and metabolism in pediatric burn patients  

Microsoft Academic Search

HYPOTHESIS:Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients.DESIGN:Retrospective, single-center study.SUBJECTS:In all, 592 severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ?85th percentile (n=277) and normal

R Kraft; D N Herndon; F N Williams; A M Al-Mousawi; C C Finnerty; M G Jeschke

2012-01-01

329

Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital  

PubMed Central

Aims To examine the impact of off-label and unlicensed (OLUL) prescribing on adverse drug reactions (ADRs) causing unplanned admissions to a paediatric hospital. Methods Prescription data from a 12 month prospective cohort study of ADRs detected in children admitted to a paediatric hospital were scrutinized. The relative risk for off-label and unlicensed medicines being implicated in an ADR was calculated. Logistic regression analyses were carried out with exposure to off-label and unlicensed medicines and number of off-label and unlicensed medicines administered as predictor variables. Results Off-label and unlicensed medicines were more likely to be implicated in an ADR than authorized medicines (relative risk 1.67, 95% CI 1.38, 2.02, P?patients demonstrated that the number of authorized medicines (odds ratio 1.33, 95% CI 1.23, 1.44, P?

Bellis, Jennifer R; Kirkham, Jamie J; Nunn, Anthony J; Pirmohamed, Munir

2014-01-01

330

No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain.  

PubMed

A large number of studies have suggested that being a woman represents a potential risk factor for the development of adverse drug reactions (ADRs). The aim of this study is to further explore the differences between men and women with regard to reported ADRs, particularly those associated with psychotropic drugs. We used spontaneous reports of suspected ADRs collected by Midi-Pyrénées (France), Veneto (Italy) and Castilla y León (Spain) Regional Pharmacovigilance Centres (January 2007-December 2009). All the reports including a psychotropic medication were selected in a first step; age distribution, seriousness and type of ADRs were compared between men and women. Reports of nonpsychotropic drugs were similarly identified and treated. The absolute number of reports and the proportion, considering population, were higher in women than in men. This was observed for all reports, but was particularly higher for psychotropic drugs (592 vs. 375; P < 0.001) than for nonpsychotropics drugs (5193 vs. 4035; P < 0.001). Antidepressants were the most reported (women, 303; men, 141; P < 0.001); the reporting rates (number of reports divided by exposed patients in the same period, estimated through sales data) for these drugs, however, were not significantly different between women (0.87 cases per 10 000 treated persons per year) and men (0.81 cases per 10 000 treated persons per year). Although there was a higher number of reports of ADRs in women, ADR reporting rates might be similar as highlighted by the case of antidepressants. Antidepressant ADRs in fact were similarly reported in men and in women. Gender differences are sometimes subtle and difficult to explore. International networks, as the one established for this study, do contribute to better analyse problems associated with medications. PMID:23617454

D'Incau, Paola; Lapeyre-Mestre, Maryse; Carvajal, Alfonso; Donati, Monia; Salado, Inés; Rodriguez, Lauriane; Sáinz, María; Escudero, Antonio; Conforti, Anita

2014-06-01

331

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

332

The use of targeted therapies in pancreatic neuroendocrine tumours: patient assessment, treatment administration, and management of adverse events  

PubMed Central

Together with the use of novel oral targeted therapies, a multidisciplinary approach can be used to effectively treat patients with advanced pancreatic neuroendocrine tumours (pNETs). Here we review the integration of the oncology nurse to the newly developed oral treatment setting for patients with pNETs. From the outset, the nurse must be involved in various processes, including performance of baseline assessments (e.g. blood pathology, cardiac and lung function testing, patient history) and general medical observations, treatment administration, dietary guidance, evaluation of comorbidities, and review of concomitant medications. Patient education and establishment of a strong partnership in care before the start of pNET therapy ultimately increase treatment adherence and reduce potential toxicities. Regular review of general patient status and disease progression and continuous monitoring of adverse events also help enhance treatment outcomes and subsequently improve quality of life. Nurses’ knowledge of agent-specific toxicities and prompt, proactive management is a critical aspect of care. In essence, as the pNET treatment landscape evolves, the role of the healthcare professional in overall patient care must shift accordingly. PMID:23997829

Pavlakis, Nick

2013-01-01

333

A risk score system for predicting adverse outcomes and magnitude of benefit with glycoprotein IIb\\/IIIa inhibitor therapy in patients with unstable angina pectoris  

Microsoft Academic Search

Clinical outcomes of patients with unstable angina are variable. We sought to identify predictors of adverse clinical outcomes in patients with unstable angina and to investigate whether these factors would predict the magnitude of benefit achieved with platelet glycoprotein IIb\\/IIIa inhibition. We analyzed 20 variables in the 1,915 patients enrolled in the Platelet Receptor Inhibition for Ischemic Syndrome Management in

Marc S Sabatine; James L Januzzi; Stephen Snapinn; Pierre Théroux; Ik-Kyung Jang

2001-01-01

334

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

335

Adverse Hospital Events for Mentally Ill Patients Undergoing Coronary Artery Bypass Surgery  

PubMed Central

Context Patients with mental disorders show higher burden of coronary heart disease, and may face special safety issues during in-hospital cardiac care. Objectives To compare the postoperative complication rate between patients with and without mental disorders undergoing isolated coronary artery bypass graft (CABG) surgery. Design, Setting, and Patients Retrospective analyses of New York state hospital claims between 1997 and 2004 (N=135,701). Complications were defined using the Agency for Healthcare Research and Quality Patient Safety Indicators (AHRQ PSI). Principal Findings Mental disorders were significantly associated with higher anesthesia complications (adjusted odds ratio [AOR]=6.44, p<.001), decubitus ulcer (AOR=1.42, p=.006), postoperative hip fracture (AOR=3.29, p<.001), and overall complication rate representing nine PSIs (AOR=1.27, p<.001). Conclusions Mentally ill patients undergoing CABG surgery are more likely to experience potentially preventable complications and injuries. The mechanism underlying this observation warrants further study. PMID:18665856

Li, Yue; Glance, Laurent G; Cai, Xueya; Mukamel, Dana B

2008-01-01

336

Overweight and obesity adversely affect outcomes of assisted reproductive technologies in polycystic ovary syndrome patients.  

PubMed

Overweight and obesity may have negative impact on IVF/ICSI treatment outcomes. However, it is not clear whether overweight and obesity have impact on IVF/ICSI outcomes in PCOS patients. The aim of this study was to examine the effect of overweight and obesity on IVF/ICSI treatment outcomes in PCOS patients treated with GnRH agonist long protocol. This retrospective study was conducted in a reproductive medicine center from January 2009 to June 2013. IVF/ICSI characteristics and outcomes were analyzed in 688 PCOS patients according to their BMI. A total of 409 normal weight patients (group A, 18.5 kg/m(2) ? BMI <24 kg/m(2)) and 279 overweight and obese patients (group B, BMI ?24 kg/m(2)) were included into this study. Patient age, basal FSH, basal LH and peak E2 concentration were comparable in the two groups. Compared with patients in group A, patients in group B had similar number of retrieved oocytes, 2PN, and high quality embryos. However, overweight and obese women needed more ampoules of gonadotrophin and longer days of stimulation. In addition, the implantation rate (38.3% vs. 35.6%; P=0.000) was also higher in normal weight patients. Overweight and obese women seemed to have lower clinical pregnancy rate (56.9% vs. 53.4%; P>0.05), but the difference was not statistically significant. In conclusion, overweight and obesity is associated with unfavorable IVF/ICSI outcomes in PCOS patients treated with GnRH agonist long protocol. PMID:24260609

Bu, Zhiqin; Dai, Wei; Guo, Yihong; Su, Yingchun; Zhai, Jun; Sun, Yingpu

2013-01-01

337

Reoperations and late adverse outcome in Marfan patients following cardiovascular surgery  

Microsoft Academic Search

Objectives: Anulo-aortic ectasia represents the most common cardiovascular manifestation requiring surgery in Marfan patients. Aim of this report was to analyze the type of presentation and the incidence of cardiovascular lesions and the clinical follow-up after initial surgery, mainly aortic root repair or replacement. Methods: Between 1\\/1990 and 6\\/2003 a total of 71 patients (mean age 29±17 years, 8–65 years)

Thierry Carrel; Lukas Beyeler; Aurelia Schnyder; Pia Zurmühle; Pascal Berdat; Jürg Schmidli; Friedrich S. Eckstein

2004-01-01

338

Factors contributing to adverse soft tissue reactions due to the use of tartar control toothpastes: report of a case and literature review.  

PubMed

Tetrasodium and/or tetrapotassium pyrophosphate (Ppi) is the anticalculus component of most tartar control dentifrices on the market today. While pyrophosphates alone are not responsible for hypersensitivity reactions, several modifications which may lead to adverse oral manifestations may occur when pyrophosphates are added to a dentifrice. First, tetrasodium pyrophosphate in a dentifrice forms a slightly alkaline solution upon oral use which could irritate oral membranes. Second, increased concentrations of flavoring agents, known to be sensitizers, are needed to mask the strong bitter taste of pyrophosphates. Third, increased concentrations of detergents, capable of producing hypersensitivity reactions, are necessary to allow the pyrophosphates to become soluble in the dentifrice. Fourth, a pre-existing condition of reduced salivary flow may augment hypersensitivity to tartar control toothpastes. While pyrophosphates have been approved as additives in dentifrices, these compounds along with the increased concentrations of flavorings and detergents and their higher intraoral alkalinity are strongly implicated as the causative factor in certain hypersensitivity reactions. PMID:10440643

DeLattre, V F

1999-07-01

339

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

340

Psychosis in Patients with Narcolepsy as an Adverse Effect of Sodium Oxybate  

PubMed Central

Aim: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep–wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy. Method: We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia. Results: Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone) alleviated psychotic symptoms in two cases. Conclusion: Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia; however, the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried. PMID:25191304

Sarkanen, Tomi; Niemelä, Valter; Landtblom, Anne-Marie; Partinen, Markku

2014-01-01

341

Measuring severe adverse events and medication selection using a “PEER Report” for nonpsychotic patients: a retrospective chart review  

PubMed Central

We previously reported on an objective new tool that uses quantitative electroencephalography (QEEG) normative- and referenced-electroencephalography sampling databases (currently called Psychiatric EEG Evaluation Registry [PEER]), which may assist physicians in determining medication selection for optimal efficacy to overcome trial-and-error prescribing. The PEER test compares drug-free QEEG features for individual patients to a database of patients with similar EEG patterns and known outcomes after pharmacological interventions. Based on specific EEG data elements and historical outcomes, the PEER Report may also serve as a marker of future severe adverse events (eg, agitation, hostility, aggressiveness, suicidality, homicidality, mania, hypomania) with specific medications. We used a retrospective chart review to investigate the clinical utility of such a registry in a naturalistic environment. Results This chart review demonstrated significant improvement on the global assessment scales Clinical Global Impression – Improvement and Quality of Life Enjoyment and Satisfaction – Short Form as well as time to maximum medical improvement and decreased suicidality occurrences. The review also showed that 54.5% of previous medications causing a severe adverse event would have been raised as a caution had the PEER Report been available at the time the drug was prescribed. Finally, due to the significant amount of off-label prescribing of psychotropic medications, additional, objective, evidence-based data aided the prescriber toward better choices. Conclusion The PEER Report may be useful, particularly in treatment-resistant patients, in helping to guide medication selection. Based on the preliminary data obtained from this chart review, additional studies are warranted to establish the safety and efficacy of adding PEER data when making medication decisions. PMID:22802691

Hoffman, Daniel A; DeBattista, Charles; Valuck, Robert J; Iosifescu, Dan V

2012-01-01

342

Exercise capacity as an independent risk factor for adverse cardiovascular outcomes among nondiabetic and diabetic patients  

PubMed Central

Introduction To investigate if decreased exercise capacity is an independent risk factor for major adverse cardiovascular events (MACE) in diabetics and nondiabetics. Material and methods The association of decreased exercise capacity (EC) during a treadmill exercise sestamibi stress test with MACE was investigated in 490 nondiabetics and 404 diabetics. Mean follow-up was 53 months. Results Nondiabetics with a predicted EC < 85% had a higher prevalence of myocardial ischemia (34% vs. 19%, p = 0.0002), 2- or 3-vessel obstructive coronary artery disease (CAD) (31% vs. 13%, p = 0.016), myocardial infarction (MI) (17% vs. 7%, p = 0.0005), stroke (8% vs. 2%, p = 0.002), death (11% vs. 3%, p = 0.0002), and MI or stroke or death at follow-up (32% vs. 11%, p < 0.001) compared to nondiabetics with a predicted EC ? 85%. Diabetics with a predicted EC < 85% had a higher prevalence of myocardial ischemia (48% vs. 32%, p = 0.0009), 2- or 3-vessel obstructive CAD (54% vs. 28%, p = 0.001), MI (32% vs. 14%, p < 0.001), stroke (22% vs. 6%, p < 0.001), death (17% vs. 9%, p = 0.031), and MI or stroke or death at follow-up (65% vs. 27%, p < 0.001). Stepwise Cox regression analysis showed decreased EC was an independent and significant risk factor for MACE among nondiabetics (hazard ratio 3.3, p < 0.0001) and diabetics (hazard ratio 2.7, p < 0.0001). Conclusions Diabetics and nondiabetics with decreased EC were at increased risk for MACE with nondiabetics and decreased EC at similar risk as diabetics with normal EC. PMID:24701210

Pierre-Louis, Bredy; Guddati, Achuta K.; Khyzar Hayat Syed, Muhammed; Gorospe, Vanessa E.; Manguerra, Mark; Bagchi, Chaitali; Ahn, Chul

2014-01-01

343

Serum Apelin Level Predicts the Major Adverse Cardiac Events in Patients With ST Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention.  

PubMed

The cardiovascular profile of the apelin makes it a promising therapeutic target for heart failure and ischemic heart disease. However, it remains unknown whether apelin affect the clinical outcome of patients with ST elevation myocardial infarction (STEMI) and received percutaneous coronary intervention (PCI).We enrolled a total of 120 patients with acute STEMI who underwent primary PCI. Serum apelin was detected. After PCI procedure, all patients were followed for 12 months. The follow-up end-point was occurrence of major adverse cardiovascular event (MACE).Lower serum apelin levels (<0.54?ng/mL) was significantly associated with higher serum low density lipoprotein-cholesterol level, higher peak creatine kinase MB fraction (CK-MB) and peak troponin-I (TNI) levels, the number of obstructed vessels, and need for inotropic support. The incidence of MACE was significantly higher in the low apelin group (23 patients out of 67) than in the high apelin group (10 patients out of 75, P?patients with low apelin than those with high apelin (P?patients with STEMI. PMID:25634182

Liu, Hai-Tao; Chen, Mai; Yu, Jin; Li, Wei-Jie; Tao, Ling; Li, Yan; Guo, Wen-Yi; Wang, Hai-Chang

2015-01-01

344

The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome  

PubMed Central

Multiple myeloma (MM) is a plasma cell neoplasm that proceeds through a premalignant state of monoclonal gammopathy of unknown significance; however, the molecular events responsible for myelomagenesis remain uncharacterized. To identify cellular pathways deregulated in MM, we addressed that sumoylation is homologous to ubiquitination and results in the attachment of the ubiquitin-like protein Sumo onto target proteins. Sumoylation was markedly enhanced in MM patient lysates compared with normal plasma cells and expression profiling indicated a relative induction of sumoylation pathway genes. The Sumo-conjugating enzyme Ube2I, the Sumo-ligase PIAS1, and the Sumo-inducer ARF were elevated in MM patient samples and cell lines. Survival correlated with expression because 80% of patients with low UBE2I and PIAS1 were living 6 years after transplantation, whereas only 45% of patients with high expression survived 6 years. UBE2I encodes the sole Sumo-conjugating enzyme in mammalian cells and cells transfected with a dominant-negative sumoylation-deficient UBE2I mutant exhibited decreased survival after radiation exposure, impaired adhesion to bone marrow stroma cell and decreased bone marrow stroma cell–induced proliferation. UBE2I confers cells with multiple advantages to promote tumorigenesis and predicts decreased survival when combined with PIAS1. The sumoylation pathway is a novel therapeutic target with implications for existing proteasomal-based treatment strategies. PMID:19965618

Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Fulciniti, Mariateresa; Prabhala, Rao H.; Greipp, Philip R.; Barlogie, Bart; Tai, Yu-Tzu; Anderson, Kenneth C.; Shaughnessy, John D.; Annunziata, Christina M.

2010-01-01

345

Periodontal disease adversely affects the survival of patients with end-stage renal disease  

Microsoft Academic Search

Periodontal disease is associated with cardiovascular disease and is thought to accelerate systemic atherosclerosis. Here we examined the relationship between periodontitis and cardiovascular disease mortality in outpatients on hemodialysis using a retrospective analysis of 168 adult patients in New York City and North Carolina. During 18 months of follow-up, cardiovascular disease and all-cause mortality were determined from a centralized dialysis

Abhijit V Kshirsagar; Ronald G Craig; Kevin L Moss; James D Beck; Steven Offenbacher; Peter Kotanko; Philip J Klemmer; Maki Yoshino; Nathan W Levin; Julie K Yip; Khalid Almas; Eva M Lupovici; Len A Usvyat; Ronald J Falk

2009-01-01

346

Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality  

PubMed Central

Objectives To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Design Cross-sectional study of screened patients. Setting 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011. Participants The participating pharmacy staff screened consecutive patients, or agents of patients, who were dropping or picking up prescription medications. Primary outcome measures Patients were screened to determine the proportions of them using prescription drugs and/or NHPs, as well as their respective AE rates. All AEs reported by the screened patients who took a NHP, consented to, and were available for, a detailed telephone interview (14%) were adjudicated fully to assess for causality. Results Over a total of 105 pharmacy weeks and 1118 patients screened, 410 patients reported taking prescription drugs only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI 2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE, representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3% (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients who reported using prescription drugs, the patients who reported using prescription drugs and NHPs concurrently were 6.4 times more likely to experience an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario, Canada, a national proportion was calculated, which found that 45.4% (95% CI 43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report an AE. Conclusions A substantial proportion of community pharmacy patients use prescription drugs and NHPs concurrently; these patients are at a greater risk of experiencing an AE. Active surveillance provides a means of detecting such AEs and collecting high-quality data on which causality assessment can be based. PMID:24682573

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

2014-01-01

347

A pilot study to evaluate a community pharmacy–based monitoring system to identify adverse drug reactions associated with paediatric medicines use  

Microsoft Academic Search

Introduction  Current pharmacovigilance systems are limited by spontaneous reporting of adverse drug reactions (ADRs), lack of a denominator,\\u000a and lower than expected reporting rates. The aim of our study was to undertake a formal pilot evaluation of a community pharmacy–led\\u000a ADR monitoring system.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The setting was community pharmacies in five Health Boards areas of Scotland. Subjects were parents, guardians, or children

Mansour Tobaiqy; Derek Stewart; Peter J. Helms; Christine Bond; Amanda Jane Lee; Nick Bateman; Dorothy McCaig; James McLay

2010-01-01

348

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

349

TGFB1 Single Nucleotide Polymorphisms Are Associated With Adverse Quality of Life in Prostate Cancer Patients Treated With Radiotherapy  

SciTech Connect

Purpose: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. Methods and Materials: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). Results: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). Conclusions: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

Peters, Christopher A. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)], E-mail: christopher.peters@mountsinai.org; Stock, Richard G.; Cesaretti, Jamie A.; Atencio, David P.; Peters, Sheila B.A.; Burri, Ryan J. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Stone, Nelson N. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Department of Urology, Mount Sinai School of Medicine, New York, NY (United States); Ostrer, Harry [Human Genetics Program, Department of Pediatrics, New York University School of Medicine, New York, NY (United States); Rosenstein, Barry S. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States); Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY (United States); Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)

2008-03-01

350

Doing No Harm? Adverse Events in a Nation-Wide Cohort of Patients with Multidrug-Resistant Tuberculosis in Nigeria  

PubMed Central

Background Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria. Method This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed. Results Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28–42] and median weight was 51 kg (IQR: 45–59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1–2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs. Conclusion Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated. PMID:25781958

Avong, Yohanna Kamabi; Isaakidis, Petros; Hinderaker, Sven Gudmund; Van den Bergh, Rafael; Ali, Engy; Obembe, Bolajoko Oladunni; Ekong, Ernest; Adebamowo, Clement; Ndembi, Nicaise; Okuma, James; Osakwe, Adeline; Oladimeji, Olanrewaju; Akang, Gabriel; Obasanya, Joshua Olusegun; Eltayeb, Osman; Agbaje, Aderonke Vivian; Abimiku, Alash’le; Mensah, Charles Olalekan; Dakum, Patrick Sunday

2015-01-01

351

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

352

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

353

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

354

Incidence of and Risk Factors for Adverse Cardiovascular Events Among Patients With Systemic Lupus Erythematosus  

PubMed Central

Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987–June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk. PMID:23024137

Magder, Laurence S.; Petri, Michelle

2012-01-01

355

The adverse effects of smoking on postoperative outcomes in cancer patients  

PubMed Central

Background The possible negative effects of smoking on postoperative outcomes have not been well-studied in cancer patients. Methods We used the VA Surgical Quality Improvement Program (VASQIP) database for the years 2002–2008, which assesses pre-operative risk factors and post-operative outcomes for patients undergoing major surgery within the VA healthcare system. Results Compared to never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI)( Odds ratio, OR:1.25, 95%CI:1.09–1.44)(OR:1.20, 95%CI:1.05–1.38), combined pulmonary complications (CPO: pneumonia, failure to wean from ventilator, reintubation) (OR:1.60, 95%CI:1.38–1.87)(OR:1.96, 95%CI:1.68–2.29) and return to the operating room (OR:1.20, 95%CI:1.03–1.39)(OR:1.31 95%CI:1.13–1.53), respectively. Both prior and current smokers had a significantly higher mortality at 30 days (OR:1.50, 95%CI:1.19–1.89)(OR: 1.41, 95%CI:1.08–1.82) and one year (OR:1.22, 95%CI:1.08–1.38)(OR:1.62, 95%C I:1.43–1.85). Thoracic surgery patients who were current smokers were more likely to develop CPO (OR:1.62, 95%CI:1.25–2.11), and mortality within one year (OR:1.50, 95%CI:1.17–1.92) compared to non-smokers, but SSI rates were not affected by smoking status. Current smokers had a significant increase in postsurgical length of stay (overall 4.3% [p<0.001], GI 4.7% [p=0.003], thoracic 9.0% [p<0.001]) compared to prior smokers. Conclusions Prior and current smoking status is a significant risk factor for major postoperative complications and mortality following GI cancer and thoracic operations in veterans. Smoking cessation should be encouraged prior to all major cancer surgery in the VA population to decrease postoperative complications and length of stay. PMID:22065194

Gajdos, Csaba; Hawn, Mary T; Campagna, Elizabeth J; Henderson, William G.; Singh, Jasvinder A.; Houston, Thomas

2014-01-01

356

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

357

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.  

PubMed

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range?=?2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac tests. PMID:25213120

Nicolau-Raducu, Ramona; Gitman, Marina; Ganier, Donald; Loss, George E; Cohen, Ari J; Patel, Hamang; Girgrah, Nigel; Sekar, Krish; Nossaman, Bobby

2015-01-01

358

Using patients’ experiences of adverse events to improve health service delivery and practice: protocol of a data linkage study of Australian adults age 45 and above  

PubMed Central

Introduction Evidence of patients’ experiences is fundamental to creating effective health policy and service responses, yet is missing from our knowledge of adverse events. This protocol describes explorative research redressing this significant deficit; investigating the experiences of a large cohort of recently hospitalised patients aged 45 years and above in hospitals in New South Wales (NSW), Australia. Methods and analysis The 45 and Up Study is a cohort of 265?000 adults aged 45?years and above in NSW. Patients who were hospitalised between 1 January and 30 June 2014 will be identified from this cohort using data linkage and a random sample of 20?000 invited to participate. A cross-sectional survey (including qualitative and quantitative components) will capture patients’ experiences in hospital and specifically of adverse events. Approximately 25% of respondents are likely to report experiencing an adverse event. Quantitative components will capture the nature and type of events as well as common features of patients’ experiences. Qualitative data provide contextual knowledge of their condition and care and the impact of the event on individuals. Respondents who do not report an adverse event will report their experience in hospital and be the control group. Statistical and thematic analysis will be used to present a patient perspective of their experiences in hospital; the characteristics of patients experiencing an adverse event; experiences of information sharing after an event (open disclosure) and the other avenues of redress pursued. Interviews with key policymakers and a document analysis will be used to create a map of the current practice. Ethics and dissemination Dissemination via a one-day workshop, peer-reviewed publications and conference presentations will enable effective clinical responses and service provision and policy responses to adverse events to be developed. PMID:25311039

Walton, Merrilyn; Smith-Merry, Jennifer; Harrison, Reema; Manias, Elizabeth; Iedema, Rick; Kelly, Patrick

2014-01-01

359

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

360

Flare up reaction during provocation test to glatiramer acetate in a patient with allergy to interferon beta1a.  

PubMed

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

Minciullo, Paola L; Calapai, Gioacchino; Gangemi, Sebastiano

2014-09-01

361

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

362

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

363

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

364

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

365

Glucose at admission or time-averaged glucose during hospital stay: predict major adverse cardiac events in patients with acute myocardial infarction?  

Microsoft Academic Search

Abstract Background Elevated,blood ,glucose ,values ,are ,a prognostic ,factor ,in myocardial ,infarction ,(MI) patients. The unfavorable ,relation between ,hyperglycemia ,and ,outcome ,is known ,for admission,glucose ,and ,fasting ,glucose ,after admission. ,These ,predictors ,are single measurements,and,thus not indicative of overall hyperglycemia.,Increased time-averaged glucose,may,better predict adverse,events in MI patients. Methods Ina,prospective ,study ,of MI ,patients ,treated ,with ,primary ,percutaneous ,coronary intervention (PCI)

Felix Zijlstra

366

2010 Mid-America Orthopaedic Association Physician in Training Award: Predictors of Early Adverse Outcomes after Knee and Hip Arthroplasty in Geriatric Patients  

Microsoft Academic Search

Background  Geriatric patients experience more adverse events owing to early complications after TKA or THA related to preexisting comorbidities.\\u000a However, associations between patient and surgery variables, including age, BMI, and comorbidities with complications are\\u000a unclear. Knowing these relationships is necessary for developing risk stratification, defining contraindications, and predicting\\u000a complications and adverse outcomes.\\u000a \\u000a \\u000a \\u000a \\u000a Questions\\/purposes  We wished to establish and quantify the associations among

Carlos A. Higuera; Karim Elsharkawy; Alison K. Klika; Matthew Brocone; Wael K. Barsoum

2011-01-01

367

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

368

Left ventricular global longitudinal systolic strain predicts adverse remodeling and subsequent cardiac events in patients with acute myocardial infarction treated with primary percutaneous coronary intervention.  

PubMed

To determine whether left ventricular (LV) global longitudinal strain (GLS) predicts adverse LV remodeling and cardiac events. In a prospective cohort study of patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), we recorded clinical data and GLS, global circumferential strain and radial strain using two-dimensional speckle-tracking echocardiography of the left ventricle. At 6-month and 3-year follow-ups, patients were grouped by presence or absence of adverse LV remodeling. We used logistic regression to identify factors associated with adverse LV remodeling and a Cox model to determine the relationships between these factors and cardiac events. Of 97 patients (mean age 56 ± 12 years; 76 men), 38 showed LV remodeling. Diabetes mellitus [odds ratio (OR) 1.95 % confidence interval (CI) 1.2-4.8, p = 0.05], peak troponin I (OR 1.2, 95 % CI 1.1-1.3, p = 0.004), and GLS (OR 1.6, 95 % CI 1.3-2.3, p = 0.009) independently predicted LV remodeling. During follow-up (22.8 ± 12.3 months), 20 patients suffered adverse events, which were independently predicted by GLS alone (OR 4.9, 95 % CI 1.7-13.9, p = 0.002). Optimal GLS cutoffs for predicting <