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Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions - A Meta-Analysis  

PubMed Central

Background Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. Methods Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO’s or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. Results Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2–3.2%) had preventable adverse drug reactions and 52% (95% CI: 42–62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1–51%) had preventable adverse drug reactions and 45% (95% CI: 33–58%) of adverse drug reactions were preventable. Conclusions This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research.

Petzold, Max; Hagg, Staffan



[Patients reported adverse drug reactions: what's happening in Europe].  


This contribution in based on a report that describes the European situation regarding patient reported Adverse Drug reactions (DPR) and analyzes the literature on the topic. In 7 European countries DPRs are accepted, and used for decision making. Patients reports in general are more vivid that those of health care workers and report information that professional reporters can never be expected to provide. Moreover, DPRs are reliable and comparable to those of professional reporters. PMID:21539077

Herxheimer, Andrew; Crombag, Rose; Alves, Teresa Leonardo


[Adverse reactions to insulin].  


The prevalence of allergic reactions to insuline has decreased during the last few years. Probably this is due to the use of the newly-developed recombinant human insuline. At present, adverse reactions to insuline occur in 5-10% of patients on therapy with insuline. Adverse reactions may be local (more frequent) or systemic (rare). Insuline resistance consists in a different type of immunological reaction. Diagnosis of allergy to insuline is based on clinical history and cutaneous and serological tests. Treatment depends upon the severity of the reaction. When insuline is indispensable despite a previous allergic reaction, a desensitization protocol may be implemented. PMID:9410127

Liñana, J J; Montoro, F J; Hernández, M D; Basomba, A



Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection  

Microsoft Academic Search

HIV-infected patients have a higher risk of developing cutaneous reactions than the general population, which has a significant impact on patients' current and future care options. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. HIV-infected patients just at the beginning of antiretroviral treatment can frequently show a wide variety of adverse drug effects

J. Borras-Blasco; A. Navarro-Ruiz; C. Borras; E. Castera



Contribution of adverse drug reactions to hospital admission of older patients  

Microsoft Academic Search

Objective: to describe the severity of adverse drug reactions as a factor in hospital admission of older patients, and to identify risk indicators for severe adverse drug reactions in these patients. Design: observational cross-sectional study. Setting: Five wards in a university hospital in the Netherlands. Subjects: patients aged 70 and over admitted to general medical wards. Methods: use of statistical



Adverse reaction to tetrazepam.  


Adverse reactions caused by benzodiazepines rarely occur. We present a case of a 70-year-old man who developed a maculopapular exanthema after the ingestion of tetrazepam. For his diagnosis, skin tests were performed, including prick and patch tests, not only with the benzodiazepine implicated in the reaction, but also with benzodiazepines of other groups. Single-blind oral challenge tests were also performed in the patient, in order to assess his tolerance to other benzodiazepines. PMID:11642573

Palacios Benito, R; Domínguez Ortega, J; Alonso Llamazares, A; Rodríguez Morales, A; Plaza Díaz, A; Chamorro Gómez, M; Martínez-Cócera, C



The prevention of adverse reactions to transfusions in patients with haemoglobinopathies: a proposed algorithm  

PubMed Central

Background Transfusion therapy remains the main treatment for patients with severe haemoglobinopathies, but can cause adverse reactions which may be classified as immediate or delayed. The use of targeted prevention with drugs and treatments of blood components in selected patients can contribute to reducing the development of some reactions. The aim of our study was to develop an algorithm capable of guiding behaviours to adopt in order to reduce the incidence of immediate transfusion reactions. Materials and methods Immediate transfusion reactions occurring over a 7-year period in 81 patients with transfusion-dependent haemoglobinopathies were recorded. The patients received transfusions with red cell concentrates that had been filtered prestorage. Various measures were undertaken to prevent transfusion reactions: leucoreduction, washing the red blood cells, prophylactic administration of an antihistamine (loratidine 10 mg tablet) or an antipyretic (paracetamol 500 mg tablet). Results Over the study period 20,668 red cell concentrates were transfused and 64 adverse transfusion reactions were recorded in 36 patients. The mean incidence of reactions in the 7 years of observation was 3.1‰. Over the years the incidence gradually decreased from 6.8‰ in 2004 to 0.9‰ in 2010. Discussion Preventive measures are not required for patients who have an occasional reaction, because the probability that such a type of reaction recurs is very low. In contrast, the targeted use of drugs such as loratidine or paracetamol, sometimes combined with washing and/or double filtration of red blood cells, can reduce the rate of recurrent (allergic) reactions to about 0.9‰. The system for detecting adverse reactions and training staff involved in transfusion therapy are critical points for reliable collection of data and standardisation of the detection system is recommended for those wanting to monitor the incidence of all adverse reactions, including minor ones.

Bennardello, Francesco; Fidone, Carmelo; Spadola, Vincenzo; Cabibbo, Sergio; Travali, Simone; Garozzo, Giovanni; Antolino, Agostino; Tavolino, Giuseppe; Falla, Cadigia; Bonomo, Pietro



Suspected adverse reactions, 2008  

Microsoft Academic Search

Reports to the UK Suspected Adverse Reaction Surveillance Scheme (SARSS) in 2008 increase by around 11 per cent compared with 2007Low incidence of suspected adverse reactions following bluetongue virus vaccinationIncrease in reports of suspected lack of efficacy to canine parvovirus vaccinationRabbit deaths reported after off-label use of dexmedetomidineThese are some of the results from the SARSS in 2008, as discussed

F. Dyer; E. Brown; S. Cooles; A. Tait



Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients  

Microsoft Academic Search

Objective To ascertain the current burden of adverse drug reactions (ADRs) through a prospective analysis of all admissions to hospital. Design Prospective observational study. Setting Two large general hospitals in Merseyside, England. Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission. Main outcome measures Prevalence of admissions due to an ADR,

Munir Pirmohamed; Sally James; Shaun Meakin; Chris Green; Andrew K Scott; Thomas J Walley; Keith Farrar; B Kevin Park; Alasdair M Breckenridge; Alasdair M



Adverse reactions to sulfites  

PubMed Central

Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products.

Yang, William H.; Purchase, Emerson C.R.



Adverse drug reactions in horses  

Microsoft Academic Search

Adverse drug reactions (ADRs) in horses are rare but cause serious anxiety to patients, owners, and veterinarians when they occur and are frequently the reason for legal action against veterinarians. Although not every ADR can be prevented or predicted, equine practitioners should be aware of some of the most common or most serious reactions to frequently used drugs. The most

Patricia M. Dowling



Changes in Risk of Immediate Adverse Reactions to Iodinated Contrast Media by Repeated Administrations in Patients with Hepatocellular Carcinoma  

PubMed Central

Background To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. Materials and Methods We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. Results There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10th, 20th, and 30th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Conclusion Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Fujiwara, Naoto; Tateishi, Ryosuke; Akahane, Masaaki; Taguri, Masataka; Minami, Tatsuya; Mikami, Shintaro; Sato, Masaya; Uchino, Kouji; Enooku, Kenichiro; Kondo, Yuji; Asaoka, Yoshinari; Yamashiki, Noriyo; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Ohtomo, Kuni; Koike, Kazuhiko



Cutaneous adverse drug reaction profile in a tertiary care out patient setting in Eastern India  

PubMed Central

Background: Cutaneous adverse drug reactions (CADR) are the most frequent of all manifestations of drug sensitivity and manifest with varied and diverse morphology. Aims: To study the prevalence and clinical spectrum of CADR among patients attending outpatient department (OPD) in a tertiary care hospital. Materials and Methods: An observational study was undertaken over a 1-year period in dermatology OPD of a tertiary care teaching hospital in Eastern India. Patients presenting with suspected drug-related cutaneous lesions were included if drug identity could be ascertained. Clinical profiling was done. Drug history was recorded in a format specified in Indian National Pharmacovigilance Programme and causality assessment carried out as per World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria. Results: Commonest CADR in our study was morbilliform eruption (30.18%), followed by fixed drug eruption (24.52%), Stevens–Johnson syndrome (SJS)-Toxic epidermal necrolysis (TEN) and overlap of two (24.50%), exfoliative dermatitis (7.54%), urticaria (5.6%), phototoxic drug reaction (3.8%), pityriasis rosea-like eruptions (1.89%), and severe mucositis (1.80%). Drugs implicated were sulfonamides (17%), fixed-dose combinations of fluoroquinolones with nitroimidazoles (11.30%), analgesics (11.30%), antiepileptics (11.30%), beta-lactam antibiotics (9.40%), fluoroquinolones alone (7.50%), allopurinol (7.50%), and azithromycin (5.70%). Reaction latency varied from 1 to 43 days. Causality assessment was certain and probable for 18.9% and 41.5% of the reactions, respectively, and reactions were serious in 33.96% (95% confidence interval 21.21-46.71%). Conclusions: Cutaneous adverse drug reaction profile in this study is similar in many ways to studies conducted earlier in India. Incidence of life-threatening reactions like SJS-TEN was higher compared with studies conducted abroad. Reaction time and lesion patterns are helpful in identifying an offending drug in the setting of multiple drug therapy.

Saha, Abanti; Das, Nilay Kanti; Hazra, Avijit; Gharami, Ramesh Chandra; Chowdhury, Satyendra Nath; Datta, Pijush Kanti



Cutaneous adverse drug reaction in patients with epilepsy after acute encephalitis.  


Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). We focused on the characteristics of cutaneous adverse reaction (CAR). In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9%) (CAR group). High CAR rates were observed with phenytoin, lamotrigine, phenobarbital, and carbamazepine. Severe CARs were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age. CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine. The proportion of patients with serumregulated on activation normal T cell expressed and secreted (RANTES) levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group. Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients. PMID:21996031

Mogami, Yukiko; Takahashi, Yukitoshi; Takayama, Rumiko; Ohtani, Hideyuki; Ikeda, Hiroko; Imai, Katsumi; Shigematu, Hideo; Inoue, Yushi



Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse drug reactions.  


Therapy with the aromatic anticonvulsants phenytoin, phenobarbital and carbamazepine has been associated with the occurrence of rare idiosyncratic hypersensitivity reactions. These drugs are thought to be activated to potentially reactive arene oxide (epoxide) metabolites by cytochrome P450-dependent monooxygenation, while liver microsomal epoxide hydrolase (mEH) plays a detoxifying role by converting such reactive intermediates to non-toxic dihydrodiols. Evidence from in vitro lymphocyte toxicity tests and enzyme inhibitor studies has suggested that an inherited defect in mEH function may be responsible for the enhanced drug toxicity observed in affected individuals. To test this hypothesis we designed methods to directly compare mEH gene structure in patients presenting with anticonvulsant adverse reactions and in control subjects in which no in vivo or in vitro toxicity to anticonvulsants could be demonstrated. Southern analysis of peripheral lymphocyte DNA using a full-length mEH cDNA as hybridization probe revealed no gross differences in mEH gene structure in selected patients when compared with DNA samples from unaffected control subjects. The human mEH gene was then cloned and characterized from a control individual. Nine exons were identified within a 22 kb region and sequences of selected regions, including all exons, were determined. Single strand conformation polymorphism (SSCP) analysis was performed on all exonic regions in genomic DNA from each of 26 subjects, including six unrelated patients with previous toxicity to anticonvulsant therapy and seven siblings (three of whom had displayed toxicity). Several distinct SSCP patterns could be observed among the subjects tested, each corresponding to a specific point mutation within one of the amplified fragments of the mEH gene. However, none of the SSCP patterns reflecting point mutations was correlated with the occurrence of anticonvulsant toxicity. From these observations we conclude that a genetic defect altering the structure and function of the mEH protein is unlikely to be responsible for predisposing patients to anticonvulsant adverse reactions. PMID:7920694

Gaedigk, A; Spielberg, S P; Grant, D M



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.

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



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


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



Adverse drug reaction monitoring in psychiatry out-patient department of an Indian teaching hospital  

PubMed Central

Objectives: Adverse drug reactions (ADRs) to psychotropic agents are common and can lead to noncompliance or even discontinuation of therapy. There is paucity of such data in the Indian context. We deemed it worthwhile to assess the suspected ADR profile of psychotropic drugs in an ambulatory setting in a public teaching hospital in Kolkata. Materials and Methods: A longitudinal observational study was conducted in the outpatient department (OPD) of the concerned psychiatry unit. Twenty consecutive patients per day, irrespective of their psychiatric diagnosis, were screened for suspected ADRs, 2 days in a week, over 15 months. Adverse event history, medication history and other relevant details were captured in a format as adopted in the Indian National Pharmacovigilance Programme. Causality was assessed by criteria of World Health Organization-Uppsala Monitoring Center (WHO-UPC). Results: We screened 2000 patients (68.69% males, median age 34.4 years), of whom 429 were suspected of having at least one ADR; 84 cases had insufficient evidence about causality (WHO-UMC causality status “unlikely”) and were excluded from further analysis. Thus, 17.25% (95% confidence interval: 15.59-18.91%) of our study population reported ADRs with at least “possible” causality. Of 352 events recorded, 327 (92.90%) were “probable” and the rest “possible”. None was labeled “certain” as rechallenge was not performed. Patients received a median of 3.2 psychotropic drugs each. Thirty-three different kinds of ADRs were noted, including tremor (19.60%), weight gain (15.34%) and constipation (14.49%). Among the incriminated drugs, antipsychotics represented the majority (57.10%), with olanzapine topping the list. Conclusions: This study offers a representative profile of ADRs to be expected in psychiatry out-patients in an Indian public hospital. Establishment of a psychotropic drug ADR database can be a worthy long-term goal in the Indian context.

Sengupta, Gairik; Bhowmick, Subhrojyoti; Hazra, Avijit; Datta, Ananya; Rahaman, Musfikur



Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 Breast Cancer patients  

Microsoft Academic Search

Objectves  We analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to\\u000a design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting.\\u000a \\u000a \\u000a \\u000a Methods  From April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from\\u000a 4 collaborating institutions in Japan. We graded skin reactions according

Mayumi Iwakawa; Shuhei Noda; Shigeru Yamada; Naohito Yamamoto; Yukimasa Miyazawa; Hideya Yamazaki; Yoshihiro Kawakami; Yoshifumi Matsui; Hirohiko Tsujii; Junetsu Mizoe; Eisei Oda; Yukihiro Fukunaga; Takashi Imai



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


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



Adverse reactions during treatment with amiodarone hydrochloride  

Microsoft Academic Search

Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in

B McGovern; H Garan; E Kelly; J N Ruskin



The importance of direct patient reporting of suspected adverse drug reactions: a patient perspective  

PubMed Central

AIM To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme. METHODS Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents. RESULTS There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme's independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals. CONCLUSION Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals.

Anderson, Claire; Krska, Janet; Murphy, Elizabeth; Avery, Anthony



Pharmacogenomics of adverse drug reactions.  


ABSTRACT: 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

Daly, Ann K



[Prescription to elderly patients: reducing underuse and adverse drug reactions and improving adherence].  


Many elderly people take multiple medications, usually for multiple health disorders. This "polymedication" increases the risk of iatrogenic disorders, may affect adherence to treatment, and represents an economic burden for society. It is therefore essential to optimize drug prescription to the elderly. The general practitioner is most involved in treating the elderly, who tend not to consult specialists as frequently as younger adults do. Most elderly subjects with comorbidities and polymedication are excluded from clinical trials, and geriatrics is not considered a priority during medical training. Three suboptimal prescription modalities have been described in the elderly population : "overuse", "misuse", and "underuse". Adverse drug reactions are frequent in the elderly and have a major economic cost. They are behind about 10 % of hospital admissions over the age of 65, and 20 % over 80. Yet most advers drug reactions are preventable. The public health consequences of non adherence to drug therapy are poorly documented. Elderly people may have several risk factors for non adherence, and a combination of measures may be necessary to improve the situation. PMID:17969547

Legrain, Sylvie



Chlorhexidine: uses and adverse reactions.  


Chlorhexidine is increasingly being used not only as an antiseptic to prevent hospital infections and an adjuvant in oral hygiene but also as a preservative in personal care products. As exposure to the agent becomes more widespread, reports of adverse reactions to it are increasing. Complications range from mild irritant contact dermatitis to life-threatening anaphylaxis. Allergic contact dermatitis in some cases precedes anaphylaxis. It is imperative that physicians be aware of the many possible sources of contact with this antiseptic and be alert to recognize the potentially debilitating and catastrophic reactions that may occur because of chlorhexidine sensitization. PMID:23665831

Silvestri, Dianne L; McEnery-Stonelake, Melissa


Adverse ocular reactions to drugs.  

PubMed Central

Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration.

Spiteri, M. A.; James, D. G.



Adverse reaction to amoxicillin: a case report.  


Penicillin is the drug that most often leads to allergic reactions and anaphylaxis. The incidence of adverse events triggered by penicillins is believed to be between 1% and 10%. Up to one-tenth of these episodes are life-threatening, with the most serious reactions occurring in patients with no history of allergy. The case of a 5 year, 3 month-old female who had a severe allergic reaction to amoxicillin prior to a dental appointment is described. The literature on penicillin hypersensitivity is reviewed and recommendations for management of an allergic reaction in the pediatric dental office are discussed. PMID:11048309

da Fonseca, M A


Patient-Reported Adverse Drug Reactions and Drug-Drug Interactions: A Cross-Sectional Study on Malaysian HIV\\/AIDS Patients  

Microsoft Academic Search

Objective: This study aimed to explore the adverse drug reactions (ADRs) reported by patients and to identify drug-drug interactions (DDIs) among human immunodeficiency virus\\/acquired immunodeficiency syndrome (HIV\\/AIDS) patients. Subjects and Methods: This cross-sectional study was conducted at the Medication Therapy Adherence Clinic, Hospital Sungai Buloh, an HIV\\/AIDS referral centre. The patients were randomly selected and were encouraged to describe ADRs

Syed S. Hasan; See C. Keong; Christopher L. K. Choong; Syed I. Ahmed; Ting W. Ching; Mudassir Anwar; Keivan Ahmadi; Muneer G. Babar



Pharmacogenetics of cutaneous adverse drug reactions.  


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



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

PubMed Central

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

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



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


Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076-0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292-0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

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



Mechanisms of Adverse Drug Reactions to Biologics  

Microsoft Academic Search

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

Janet B. Clarke


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



Respiratory Paradoxical Adverse Drug Reactions Associated with Acetylcysteine and Carbocysteine Systemic Use in Paediatric Patients: A National Survey  

PubMed Central

Objective To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. Design The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Setting Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. Patients The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. Results The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n?=?27), worsening of respiratory distress during respiratory tract infection (n?=?35), dyspnoea (n?=?18), cough aggravation or prolongation (n?=?11), and bronchospasm (n?=?1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Conclusion Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.

Dubus, Jean-Christophe; Bavoux, Francoise; Boyer-Gervoise, Marie-Jose; Jean-Pastor, Marie-Josephe; Chalumeau, Martin



Epidemiology of cutaneous adverse drug reactions.  


Epidemiologic investigations of cutaneous adverse drug reactions (cADR) are important to evaluate their impact in dermatology and health care in general as well as their burden for affected patients. Few epidemiologic studies have been performed on frequent non-life-threatening cADR including reactions of both delayed and immediate hypersensitivity, such as maculopapular exanthema, fixed drug eruption and urticaria. Concerning rare but life-threatening severe cutaneous adverse reactions, e.g. toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms, several epidemiologic studies have been performed to date, some of which are still ongoing. Such studies enabled the calculation of reliable incidence rates and demographic data, but also allowed to perform risk estimation for drugs. The spectrum of drugs causing cADR differs substantially when separating the various clinical conditions. Whereas antibiotics are by far the most frequent inducers of milder cADR like maculopapular exanthema, they have a much lower risk to induce SJS/TEN, for which high-risk drugs are anti-infective sulfonamides, allopurinol, certain anti-epileptic drugs, nevirapine and nonsteroidal anti-inflammatory drugs (NSAIDS) of the oxicam type. In contrast, acute generalized exanthematous pustulosis is predominantly caused by the antibiotics pristinamycin and aminopenicillins, followed by quinolones, (hydroxy-)chloroquine and sulfonamides. Drug reaction with eosinophilia and systemic symptoms can be induced by a number of drugs known to cause SJS/TEN, such as certain antiepileptics and allopurinol, but also other medications (e.g. minocyclin). PMID:22613850

Mockenhaupt, Maja



[Cutaneous adverse drug reactions: clinical aspects and identification].  


Clinically, mucocutaneous adverse drug reactions are very variable and heterogenic. As they may strongly resemble other clinical pictures they regularly constitute a diagnostic challenge. Moreover, skin manifestations may mirror adverse drug reactions in other organs. Risk factors for cutaneous adverse reactions can be drug- or patient-related and are not always known. Cutaneous adverse drug reactions are usually mild and transient, but they can also be severe or life-threatening. Early recognition and adequate management is the key to preventing progression and restoring health. Supportive therapy may help to reduce the symptoms. Distinguishing between allergic and non-allergic reactions is important in deciding whether to withdraw the suspected medication. Confirming a suspected cutaneous drug reaction necessitates a stepwise approach. The strategy is focused on recognition and characterisation of the reaction pattern, and identification of the suspected medication, followed by adequate management. PMID:23484517

Kardaun, Sylvia H



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.

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



Annual Adverse Biologic Reaction Report: 1988.  

National Technical Information Service (NTIS)

The review provides a descriptive overview of the adverse biologic reaction (ABR) reports received by the US Food and Drug Administration during 1988. As well as general information, the ABR reports are profiled by types of reports, outcomes, body systems...

Z. A. Perry A. L. Britt D. E. Knapp



Validating Adverse Drug Reaction Cases.  

National Technical Information Service (NTIS)

Difficulties in evaluating drug-reaction cases have arisen from failure to study time relationships between drugs and disease makers, failure to rule out other-than-drug causes, failure to use clinical-laboratory data, and lack of communication between cl...

N. S. Irey



Causality Assessment of Cutaneous Adverse Drug Reactions  

PubMed Central

Background Cutaneous adverse drug reactions (ADRs) are the most common adverse reactions attributed to drugs. A systematic and effective approach to a patient with suspected drug eruption allows for prompt recognition, classification and treatment of cutaneous ADRs. A standardized and effective approach for objective causality assessment is necessary to make consistent and accurate identification of ADRs. Objective Although the Naranjo algorithm is the most widely used assessment tool, it contains many components which are not suitable for clinical assessment of ADRs in Korea. The purpose of this study is to compare correlations of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both algorithms in order to make a causal link between drugs and cutaneous ADRs. In addition, this study classifies the clinical types and causative agents of cutaneous ADRs. Methods The authors retrospectively reviewed the clinical types and laboratory findings of patients who were diagnosed with cutaneous ADRs in the dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled in this evaluation. The causal relationship of ADRs was assessed by using the Naranjo algorithm and Korean algorithm (version 2.0). Results A cross-tabulation analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0). Simple correlation analysis and a Bland-Altman plot were used for statistical analysis. Correlation analysis confirmed that the two assessment algorithms were significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues ADRs. The most common causative agents were antibiotics/antimicrobials, antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system depressants. Conclusion The Naranjo algorithm and Korean algorithm (version 2.0) were significantly correlated with each other, and thus reliable assessment methods to determine cutaneous ADRs.

Son, Young-Min; Lee, Jong-Rok



Adverse Reactions to Antihypertensive Therapy  

Microsoft Academic Search

A large number of antihypertensive agents are available today. They belong to different drug classes and permit the treating physician to choose the drug he deems best suited for the treatment of an individual patient. Because hypertension is usually asymptomatic yet requires long-term therapy, consideration of potential undesirable effects of drugs used for its treatment is important for making the

Walter H. Aellig



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.

Naisbitt, Dean J.



Adverse cutaneous reactions to thiacetazone for tuberculosis treatment in Tanzania.  


Because thiacetazone has been linked with serious adverse cutaneous reactions, we undertook 1 year of systematic surveillance for cutaneous thiacetazone-associated adverse reactions within the national tuberculosis programme of Tanzania. For individual cases, we collected information on age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation (toxic epidermal necrolysis, rash without necrolysis, itching without rash), and outcome (dead or alive) within 2 weeks of onset. Univariate and multivariate analyses were done of variables relevant to outcome. 1273 patients with adverse reactions were reported. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients, and 19.1% among patients with toxic epidermal necrolysis. About 60% of all adverse reactions and deaths occurred within 20 days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than reported previously, suggesting that improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent. PMID:7544858

Ipuge, Y A; Rieder, H L; Enarson, D A



Life-threatening acute adverse cutaneous drug reactions  

Microsoft Academic Search

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

Ronni Wolf; Edith Orion; Batsheva Marcos; Hagit Matz



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

PubMed Central

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

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



[Adverse reactions induced by food additives: sulfites].  


Many chemicals are used to preserve, color and flavor foods and drugs. There have been numerous reports of adverse reactions, including urticaria, angioneurotic edema, asthma an anaphylaxis following the ingestion of food additives such as tartrazine, monosodium glutamate and benzoic acid. Recently the food and drug additives reaching medical awareness as a cause of sensitivity are the sulfiting agents. Sulfites are widely used in the food and beverage industry as preservatives and antioxidants. They are also used by the pharmaceutical industry. This work describes the common uses of sulfiting agents, the mechanisms of sulfite sensitivity, the diagnosis, prevention and treatment of adverse reactions to sulfites. PMID:2672278

Montaño García, M L


Mechanisms of adverse drug reactions to biologics.  


Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs. PMID:20020272

Clarke, Janet B



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



[Cutaneous adverse reactions to tattoos and piercings].  


Piercings and tattoos have become very popular in western society in recent decades, particularly among younger generations. Reports of medical complications associated with these decorative techniques have increased in parallel with the rise in their popularity. Due to their high frequency, adverse cutaneous reactions are particularly important among these potential complications. Tattoo-related complications include a number of cutaneous and systemic infections secondary to breach of the epidermal barrier, acute and delayed inflammatory reactions with different histopathological patterns, the appearance of benign and malignant tumors on tattooed areas of skin, and certain dermatoses triggered by isomorphic phenomena. Piercing-related complications are similar, though some, such as pyogenic skin infections, are much more common due to the delayed wound healing after piercing in certain sites. We must differentiate between complications that are independent of the site of piercing, and specific complications, which are closely related to the body area pierced. The rate of complications after performing piercings or tattoos depends on the experience of the artist, the hygiene techniques applied, and the postprocedural care by the customer. However, some of these complications are unpredictable and depend on factors intrinsic to the patient. In this article, we review the most common decorative techniques of body art, with particular focus on the potential cutaneous complications and their management. PMID:19775542

Mataix, J; Silvestre, J F



Cutaneous Adverse Reactions to Tattoos and Piercings  

Microsoft Academic Search

Piercings and tattoos have become very popular in western society in recent decades, particularly among younger generations. Reports of medical complications associated with these decorative techniques have increased in parallel with the rise in their popularity. Due to their high frequency, adverse cutaneous reactions are particularly important among these potential complications. Tattoo-related complications include a number of cutaneous and systemic

J. Mataix; J. F. Silvestre



Adverse Drug Reactions Causing Admission to a Paediatric Hospital  

PubMed Central

Objective(s) To obtain reliable information about the incidence of adverse drug reactions, and identify potential areas where intervention may reduce the burden of ill-health. Design Prospective observational study. Setting A large tertiary children’s hospital providing general and specialty care in the UK. Participants All acute paediatric admissions over a one year period. Main Exposure Any medication taken in the two weeks prior to admission. Outcome Measures Occurrence of adverse drug reaction. Results 240/8345 admissions in 178/6821 patients admitted acutely to a paediatric hospital were thought to be related to an adverse drug reaction, giving an estimated incidence of 2.9% (95% CI 2.5, 3.3), with the reaction directly causing, or contributing to the cause, of admission in 97.1% of cases. No deaths were attributable to an adverse drug reaction. 22.1% (95% CI 17%, 28%) of the reactions were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44/249 (17.7%) of adverse drug reactions, the remainder originating from hospital. 120/249 (48.2%) reactions resulted from treatment for malignancies. The drugs most commonly implicated in causing admissions were cytotoxic agents, corticosteroids, non-steroidal anti-inflammatory drugs, vaccines and immunosuppressants. The most common reactions were neutropenia, immunosuppression and thrombocytopenia. Conclusions Adverse drug reactions in children are an important public health problem. Most of those serious enough to require hospital admission are due to hospital-based prescribing, of which just over a fifth may be avoidable. Strategies to reduce the burden of ill-health from adverse drug reactions causing admission are needed.

Gallagher, Ruairi M.; Mason, Jennifer R.; Bird, Kim A.; Kirkham, Jamie J.; Peak, Matthew; Williamson, Paula R.; Nunn, Anthony J.; Turner, Mark A.; Pirmohamed, Munir; Smyth, Rosalind L.



Disclosing Adverse Events to Patients.  

National Technical Information Service (NTIS)

Institutional and professional policies that require the routine disclosure of adverse events to patients were first seen in the mid-1980s and are now emerging in many health care settings. However, the ethical and legal rationale for such policies is not...



Adverse drug reaction, patent blue V dye and anaesthesia  

PubMed Central

Background and Aim: Patent blue vital (PBV) dye is used for varied perioperative indications, and has a potential for causing life-threatening allergic reactions. In this retrospective case series study, at a tertiary level neurosciences centre, we analysed the nature, management and outcome of adverse drug reaction to the preoperative use of PBV for marking vertebral level prior to back surgeries. Methods: Patients were identified from the theatre and radiology database. Data were collected from the patients’ notes retrieved from the medical records division. Results: Eleven of 1247 (0.88%) patients experienced adverse reactions: 6 (0.48%) patients had minor grade I reactions (urticaria, blue hives, pruritis or generalised rash), 4 (0.32%) had grade II reactions (transient hypotension/bronchospasm/laryngospasm) and grade III reaction (hypotension requiring prolonged vasopressor support) was noted in 1 (0.08%) patient. No mortality was seen. The time of onset (range 10–45 min) frequently coincided with induction of anaesthesia or prone positioning of patient. Seven (63.6%) cases were cancelled or postponed (range 2–63 days). Treatment varied independent of the grade of reaction. Allergy workup (often incomplete) was done for 6 (54%) patients. Conclusion: An awareness of the time of onset and infrequency of life-threatening reactions to patent blue dye may result in better management, less postponement, more complete workup and referral of these events.

Tripathy, Swagata; Nair, Priya V



Adverse drug reactions and cognitive function among hospitalized older adults  

Microsoft Academic Search

Objective. To explore the relationship between cognitive function and the detection of adverse drug reactions (ADRs) and to evaluate whether cognitive function could influence the association between age and ADRs. Methods. A total of 16,926 patients admitted to 81 hospitals throughout Italy between 1991 and 1997 were included in the study. ADRs detected the during hospital stay were recorded by

Graziano Onder; Giovanni Gambassi; Christian J. Scales; Matteo Cesari; Cecilia Della Vedova; Francesco Landi; Roberto Bernabei



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.

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



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.

Pierard-Franchimont, Claudine; Quatresooz, Pascale; Reginster, Marie-Annick; Pierard, Gerald E.



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


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



Pediatric Use Supplement Safety/Adverse Reaction Category  

Center for Drug Evaluation (CDER)

... Pediatric Use Supplement Safety/Adverse Reaction Category. ... Data Element Name. Pediatric Use Supplement Safety/Adverse Reaction Category. ... More results from


21 CFR 606.170 - Adverse reaction file.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Adverse reaction file. 606.170 Section 606.170...Records and Reports § 606.170 Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or...



21 CFR 606.170 - Adverse reaction file.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170...Records and Reports § 606.170 Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or...



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

PubMed Central

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

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



The spontaneous reporting of adverse drug reactions by nurses.  

PubMed Central

In an attempt to improve the low reporting rate of adverse drug reactions (ADR) we examined the potential for hospital nurses to report ADRs through a spontaneous 'yellow card' system. Over 14 months 100 cards were received (compared with 28 cards from doctors). Although reports from doctors for the same period were of a more substantial nature, nurses nevertheless reported many life threatening (17%) or moderately severe (76%) reactions. Nurses identified uncertainty concerning their role and deficient in-service education on drug therapy as major constraints in their participation. Given their unique position in drug administration and recording observations on patients, we believe that nurses could contribute significantly and in a complementary fashion to the spontaneous reporting of adverse reactions.

Hall, M; McCormack, P; Arthurs, N; Feely, J



Adverse drug reactions to antimicrobial agents in a tertiary care hospital in Nagpur.  


Adverse drug reactions are a major cause of hospital admission and in-hospital morbidity. Antimicrobial agents are one of the most commonly prescribed groups of drugs leading to adverse drug reactions. But, limited data is available from hospital settings in our country. Hence, it is important to understand the characteristics of adverse reactions associated with their use. This study was planned to detect the adverse drug reactions through spontaneous reporting system and analyse them using standard assessment scales. It is an observational, prospective study performed in patients attending outpatient department, in-patient department and casualty of tertiary care hospital from 1st June 2005 to 31st May 2009. Patients were examined for adverse drug reactions by spontaneous adverse drug reactions reporting system. Among 2639 total adverse drug reactions reported, 1315 (49.82%) were due to antimicrobial agents. The agents most frequently associated with adverse drug reactions were cotrimoxazole (19.54%), ampicillin (18.25%), rifampicin (6.6%) and azithromycin (5.3%). It is observed that commonly used drugs like antimicrobial agents were causing maximum adverse drug reactions. This study provides a database of adverse drug reactions due to common drugs, which will help clinicians for optimum and safe use of these drugs. PMID:23025221

Uchit, G P; Shrivastava, M P; Badar, V A; Navale, S B; Mayabhate, M M




Microsoft Academic Search

Tuberculosis is a common problem in developing countries including Nepal. Data regarding the safety profile of anti tubercular drugs is lacking in Nepal. The present study analyzed the pattern of ADRs caused by the antitubercular drugs. Inpatient files of all the TB patients who received treatment at the Manipal Teaching Hospital, Pokhara, Nepal during the period from 1st January 2001



Exploring Possible Adverse Drug Reactions by Clustering Event Sequences  

Microsoft Academic Search

\\u000a Historically the identification of adverse drug reactions relies on manual processes whereby doctors and hospitals report\\u000a incidences to a central agency. In this paper we suggest a data mining approach using administrative pharmaceutical usage\\u000a data linked with hospital admissions data. Patients, represented by temporal sequences of drug usage, are clustered using\\u000a unsupervised learning techniques. Such techniques rely on a distance

Hongxing He; Graham J. Williams; Jie Chen; Simon Hawkins; Chris Kelman



Treatment of adverse drug reactions in a dermatology department  

Microsoft Academic Search

The aim of the study was to evaluate the pattern of utilization of systemic drugs used in the management of adverse drug reactions\\u000a (ADRs) leading to hospitalization. A prospective pharmacovigilance study was carried out among patients admitted to the Clinic\\u000a of Dermatology and Venereology in Stara Zagora (July 1999–June 2009). ADRs were classified by type, severity and causality.\\u000a Casecausality was

Maria Ganeva; Tanya Gancheva; Ivan Baldaranov; Jeni Troeva; Evgenya Hristakieva



21 CFR 606.170 - Adverse reaction file.  

Code of Federal Regulations, 2011 CFR

... BIOLOGICS CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports § 606.170 Adverse...complaints of adverse reactions regarding each unit of blood or blood product arising as a result of...



[Adverse drug reaction surveillance system in Korea].  


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



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



[Cutaneous adverse drug reactions in childhood and adolescence].  


Adverse drug reactions (ADR) occur in nearly 10% of hospitalized children and in about 1.5% of ambulatory pediatric patients. The skin is the most frequently affected target organ in drug hypersensitivity (DH) reactions, which account for 20% of all ADR. Due to its pathophysiological heterogeneity and the ensuing morphological diversity, DH often represents a clinical and therapeutic challenge. Urticarial and maculopapular eruptions are usually restricted to the skin and rarely require systemic treatment or hospital admission once the culprit drug has been withdrawn. However, extracutaneous affections should be ruled out promptly in individuals with polymorphous rashes accompanied by fever and lymphadenopathy as well as in patients with bullous skin lesions. Children affected by severe drug reactions usually require in-hospital surveillance and interdisciplinary supportive therapy. PMID:22290276

Ott, H



Children and ADRs (Adverse Drug Reactions).  


Many medicines are prescribed to the paediatric population on an unlicensed or 'off-label' basis because they have not been adequately tested and/or formulated and authorized for use in appropriate paediatric age groups. Regulatory authorities also need to remind health professionals about the importance of their contribution towards the process of paediatric pharmacovigilance thanks to their reporting of adverse drug reactions.The lack of reliable data in the paediatric population is associated with specific problems including: limited availability of safety data due to the lack of clinical trials in the paediatric population; under- or over-dosing in some age groups due to the lack of pharmacokinetics data or dose-finding studies; maturation, growth and development of the paediatric population susceptible to drug-induced growth and development disorders as well as to delayed ADRs not findable in adults.Pre-marketing trials are able to provide information about the benefits of drugs but do not manage to establish a safety profile. Spontaneous reporting of suspected ADRs become an important means to promote reasonable warning signs.Therefore some ADRs may be known in their qualitative aspect and quantitative aspect only after successful marketing and use in the population during a "normal" use. When the drug is used in clinical practice in large unselected populations, epidemiological post-marketing studies are useful as they find their major confirmation in recalling all the events that occur during monitoring, with estimates of incidence of ADRs that can not be obtained by spontaneous reports.In these studies a significant role can be played by the Family Pediatricians with the participation to active pharmacovigilance projects. PMID:20180963

Napoleone, Ettore



Adverse Reactions to Fluoroquinolones. An Overview on Mechanistic Aspects  

Microsoft Academic Search

This review focuses on the most recent research findings on adverse reactions caused by quinolone antibiotics. Reactions of the gastrointestinal tract, the central nervous system (CNS) and the skin are the most often observed adverse effects. Occasionally major events such as phototoxicity, cardiotoxicity, arthropathy and tendinitis occurr, leading to significant tolerability problems. Over the years, several structure-activity and side-effect relationships

Angela De Sarro; Giovambattista De Sarro


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


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



Adverse reactions and interactions of fluoroquinolones.  


Recent research into fluoroquinolone antibacterials has led to the discovery of a number of compounds with greatly improved potency, spectrum, pharmacokinetics and clinical efficacy. In general their safety and tolerance mirrors these attributes. Like previous naphthyridines, cinnolines, and fluoroquinolones, these agents may cause gastrointestinal, central nervous system, and cutaneous reactions, but these are usually mild and self-limiting, affect 5-10% of patients only and rarely require withdrawal from therapy. Extremely rarely, more serious CNS effects including fits and psychosis may accompany high dose therapy. Potentially serious problems, predicted by animal testing and including erosive arthropathy in juvenile rats and dogs, cataract formation and renal damage secondary to crystalluria, have not been encountered in clinical use. All of the new agents give positive results in some tests for mutagenesis but there is no evidence for mutagenicity or carcinogenicity in man. However, the possibility of mutagenesis and joint damage restricts the use of fluoroquinolones in children to life-saving indications only. Interactions may occur with other drugs. Absorption of these agents is interfered with by co-administered antacids, although not by H2 antagonists. Oxo-metabolites of enoxacin and, to a lesser extent, pefloxacin and ciprofloxacin interfere with the hepatic elimination of theophylline and caffeine and may result in toxicity due to these agents if dosage is not modified. With the exception of these avoidable events, the fluoroquinolones have proved a particularly safe group of agents in clinical use. PMID:2646053

Ball, P



Quinolones: review of psychiatric and neurological adverse reactions.  


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

Tomé, Ana M; Filipe, Augusto



Reports of adverse drug reactions in general medical journals  

Microsoft Academic Search

Summary  REPORTS of adverse reactions in 3 medical journals during 1977 were identified. Articles were separated into major and minor\\u000a communications. In the case of major articles only 29% had some form of recognisable research strategy. It is proposed that\\u000a papers which report adverse reactions should have their research structures classified so that the strength of association\\u000a between drug and event

P. C. O'Connor; Janet McCabe; D. H. Lawson



Cutaneous adverse drug reaction to oral acetazolamide and skin tests.  


Background: Few cases of cutaneous adverse drug reactions (CADR) to oral acetazolamide, a non-antimicrobial sulfonamide, have been previously reported, and the interest of acetazolamide skin tests has never been studied. Objectives: We report a series of ten patients with oral acetazolamide CADR and skin tests. Patients and Methods: The files of ten patients with CADR secondary to oral acetazolamide prescribed for cataract surgery in most cases referred between 2001 and 2011 in four French dermatology and allergy departments were retrospectively reviewed. Skin tests with acetazolamide were performed in nine patients and twelve controls. Other sulfonamides were tested in five of ten patients. Results: Seven patients developed maculopapular exanthema and four had acute generalized exanthematous pustulosis. Patch tests were positive for 8/9 patients, prick tests for 2/4 and intradermal tests for 3/3. Patch and prick or intradermal test results were concordant in 2/3 positive subjects. Patch tests for other sulfonamides were negative, as were patch tests in controls. Conclusions: We report the largest series of CADR to oral acetazolamide (maculopapular exanthema or acute generalized exanthematous pustulosis). A drug eruption after cataract surgery should be investigated for accountability of acetazolamide. In view of this retrospective study, skin tests and particularly intradermal tests appear to be an important contribution to demonstrate accountability. © 2013 S. Karger AG, Basel. PMID:23817276

Jachiet, M; Bellon, N; Assier, H; Amsler, E; Gaouar, H; Pecquet, C; Bourrain, J L; Bégon, E; Chosidow, O; Francès, C; Ingen-Housz-Oro, S; Soria, A



Adverse drug reactions to local anesthesia  

Microsoft Academic Search

A dentist's ability to safely administer regional anesthesia is essential for dental practice. Local anesthetic solutions used in the United States for den- tal anesthesia are formulated with several components. The contents of a standard local anesthetic cartridge may include an amide or ester local anes- thetic drug, an adrenergic vasoconstrictor, and an antioxidant. In suscepti- ble patients, any of

Richard L. Finder; Paul A. Moore



Vancomycin-Associated Spontaneous Cutaneous Adverse Drug Reactions  

PubMed Central

Purpose With the increase in vancomycin use, adverse drug reactions (ADRs) associated with vancomycin have been reported increasingly more often. However, the characteristics of cutaneous ADRs with and without systemic reactions (SRs) have not been described. This study investigated the characteristics of spontaneously reported and assessed ADRs associated with vancomycin by a pharmacovigilance center. Methods ADRs (n=121) associated with vancomycin in 96 patients were collected from 2008 to 2009. Records from physician- and nurse-reported suspected cases of vancomycin ADRs, ADR type, latent period, and laboratory results were compared between cutaneous ADRs with and without SRs. Results The main vancomycin-related ADRs were skin rashes (47.9%), hematologic abnormalities (17.36%), fever (12.4%), and elevated serum creatinine (12.4%). Significant differences were observed in latent period (days) and the mean change in eosinophils (%) between cutaneous (9.21±9.71 and 1.4±3.4, respectively) and other ADRs (14.03±11.71 and -0.5±3.5, respectively). Twelve cases of cutaneous ADRs with SRs had been initially reported as cutaneous ADRs only. Mean changes in the eosinophil count were significantly higher for cutaneous ADRs with SRs compared to those without SRs. Conclusions Skin rashes accompanied by peripheral eosinophilia, representing suspected immune-mediated delayed hypersensitivity reactions, are a common vancomycin ADR. For the early and exact detection of ADRs associated with vancomycin administration, close monitoring of laboratory tests, including complete blood counts with differential analysis, is recommended.

An, So-Yeon; Hwang, Eui-Kyung; Kim, Joo-Hee; Kim, Jeong-Eun; Jin, Hyun-Jung; Jin, Sun-Min; Kyun, Jin-Ok; Lee, Young-Hee; Park, Hae-Sim; Choi, Young Wha; Lim, Seung-Kwan



Adverse reactions after tattooing: review of the literature and comparison to results of a survey.  


The number of tattooed people has substantially increased in the past years. Surveys in different countries reveal this to be up to 24% of the population. The number of reported adverse reactions after tattooing has also increased including infections, granulomatous and allergic reactions and tumors. However, the case reports do not reflect the frequency of adverse reactions. This review compares the medically documented adverse reactions published in 1991-2011 with the findings of a nation-wide survey that recently revealed the features and health problems associated with tattoos. To compare the data with the survey, the sex of patients was reported and the location and color of tattoos were evaluated. The results show clearly that colored tattoo inks are mainly responsible for adverse skin reactions and that tattoos on the extremities are involved most. PMID:23689478

Wenzel, Sabrina M; Rittmann, Ines; Landthaler, Michael; Bäumler, Wolfgang



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...



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...



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...



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




[Adverse reactions after vaccination against influenza in chronically ill people].  


The objective was to assess the early and late adverse reactions after vaccination against influenza with the help of SmithKline Beecham's Fluarix vaccine in chronically ill people. 1010 people was selected to undergo vaccination. These included 621 woman aged average 44.2 and 389 men aged average 48.2. The vaccination was conducted simultaneously and the period of monitoring adverse reactions lasted 9 months. The vaccination was done in accordance with recommendations of manufacturer. All the vaccinated people suffered from circulatory system disorders, bone system disorders, mental disorders and endocrinological problems, during the vaccination they were in period of remission. The observed early symptoms fell into two categories: local and general. The late adverse reaction assessed with appearance of aggravation of main chronic disease or with appearance of the new chronic disease. The local symptoms included swelling, reddening and pain in the vaccinated area. 67 people (6.6%) reported swelling, 85 (8.4%) reported reddening, 12 people (1.2%) reported pain in the vaccinated area. The general symptoms included headache, bad mood and temperature over 37.5 degrees C. 19 people (1.9%) reported bad mood, 10 people (1%)--headache and 8 people (0.8%) reported temperature over 37.5 degrees C. Coexistence of two or three types of symptoms was present in 15 cases (1.5%). There were no late adverse reactions in the study group. The low percentage of early adverse reactions and no late adverse reactions encourages a wider use of vaccines against influenza in chronically ill people. PMID:12362669

Ga?aj, Andrzej; Grze?k, Grzegorz; Kuziemski, Arkadiusz; Szadujkis-Szadurski, Leszek; Sinjab, Thabit



Novel CYP2D6 and CYP2C19 variants identified in a patient with adverse reactions towards venlafaxine monotherapy and dual therapy with nortriptyline and fluoxetine.  


We present a case report of novel variants of CYP2D6 and CYP2C19 identified in a patient who experienced adverse effects during antidepressant therapy. CYP2D6 DNA sequencing revealed that the patient was most likely an intermediate metabolizer, owing to the presence of a novel variant (2579C>T), which gives rise to a premature stop codon in exon 5. Because defects in CYP2C19 may also be important, we sequenced the promoter region and all exons of CYP2C19 and identified a cluster of three novel variants (-13G>A, 7C>T and 10T>C) around exon 1, as well as the more common CYP2C19*2 allele. The presence of multiple genetic lesions in CYP2C19 implies that this patient is potentially a CYP2C19 poor metabolizer, and this was confirmed by haplotype analysis. Combined impairment of CYP2D6 and CYP2C19 activities, we believe, may have contributed to the development of the observed drug responses in the present report. PMID:23799451

Chua, Eng Wee; Foulds, James; Miller, Allison L; Kennedy, Martin A



Incidence and cost of adverse drug reactions in a French cancer institute  

Microsoft Academic Search

Objectives: The incidence and the cost of adverse drug reactions (ADR) in patients treated by cancer chemotherapy were assessed using\\u000a hospital database records from 1993 in a French regional cancer institute. \\u000a \\u000a \\u000a \\u000a Methods: Patients with ADRs were identified using a list of ICD-9 codes describing potential adverse events. Direct medical costs\\u000a for treating these ADRs were assessed according to the hospital

M. Lapeyre-Mestre; J. Gary; M. Machelard-Roumagnac; C. Bonhomme; R. Bugat; J. L. Montastruc



"Cutaneous adverse drug reactions" are not always drug-induced.  


Cutaneous adverse drug reactions present as many different clinical symptoms which may be induced by triggers other than drugs. This review focuses on the non-drug causes of fixed "drug" eruptions, acute generalized erythematous pustulosis (AGEP), "drug" reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN), which may be induced by foods, xenobiotics, venoms etc... PMID:24007777

Raison-Peyron, Nadia



Technological Developments with the FDA Adverse Drug Reaction File System  

Microsoft Academic Search

A review of the Food and Drug Administration (FDA) Adverse Drug Reaction (ADR) file system. This paper describes the current operations for maintaining the on-line computerized data entry, storage and retrieval programs, and the microfilm retrieval system. Other technology developments discussed include data diskette exchange and laser disc storage and retrieval.

Alan Gelberg; George D. Armstrong; Michael W. Dreis; Charles Anello



[Undesired cutaneous adverse drug reactions: What is new?].  


New therapeutic agents, i.e., biologicals, may induce a variety of novel cutaneous adverse reactions (CAR), which hardly can be assigned to existing classification systems. Basing on clinical examples, we present a recently established classification system for CAR to novel drugs. In addition, management strategies for CAR to tumor necrosis factor-? antagonists and to epidermal growth factor receptor inhibitors are discussed. PMID:22814563

Treudler, R; Simon, J C



Computerized surveillance of adverse drug reactions in hospital: pilot study  

PubMed Central

Aims To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital. Methods This was a retrospective observational study of 153 sequential medical admissions during a 2-month period to the 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerized laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions. Results Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR-positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR-negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions. Conclusions Application of automatic laboratory signals can increase the rate of recognition of ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.

Azaz-Livshits, Tatyana; Levy, Micha; Sadan, Batami; Shalit, Meir; Geisslinger, Gerd; Brune, Kay



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.

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



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.



Adverse drug reactions/interactions in maintenance therapy.  


This paper begins with a brief review of the early onset, recidivism, and multiple consequences of recurrent major depressions. Increasing attention to these factors underscores the importance of long-term maintenance therapy. Successful maintenance rests on optimizing the risk:benefit profile for the patient. Literature is reviewed that the serotonin selective reuptake inhibitors exhibit a significantly lower discontinuation rate due to adverse events than do other conventional antidepressants. Adverse events clearly detract from patient compliance and, in turn, ultimately contribute to the risk of depressive recurrence. An overview of adverse events, in both short- and long-term anti-depressant trial experience is provided. In addition, extended pharmacotherapy carries an increased probability of concomitant drug therapy. Relevant drug:drug interaction issues are reviewed, including specific attention to those mediated by the hepatic isoenzyme cytochrome P450 IID6. Lastly, long-term clinical trial experience with fluoxetine relative to short- and long-term emergence of adverse events and adverse event experience following drug discontinuation is presented. Overall fluoxetine adverse events do not increase with chronic administration. When side effects occur, they typically emerge early in the course of acute treatment and wane in the face of continued treatment. Upon drug discontinuation, these events usually reverse at a much faster pace than the drug's half-life. In conclusion, the importance of maintenance therapy in recurrent major depression is increasingly recognized as a critical care issue. To optimize a therapeutic outcome, the clinician is challenged to maximize patient compliance through depression awareness education, regular follow-up, minimization of adverse drug events, and sensitivity to other intercurrent psychosocial events. PMID:8253706

Tollefson, G D



Confounding in studies of adverse reactions to vaccines.  


Several social and medical attributes are associated with both avoidance or delay of vaccination and an increased risk of adverse events such as sudden infant death syndrome or childhood encephalopathy. Studies that fail to control adequately for such confounding factors are likely to underestimate the risks of adverse events attributable to vaccination. This paper reviews the literature on studies of severe adverse events after the administration of pertussis antigen-containing vaccines, with particular attention to the measures taken by different investigators to avoid this problem. Most published studies have reported a deficit of sudden infant death syndrome among vaccinees, which may reflect confounding in their study designs. An expression is derived to explore the extent of underestimation that may be introduced in such studies, under different sets of conditions. Confounding of this sort is a general problem for studies of adverse reactions to prophylactic interventions, as they may be withheld from some individuals precisely because they are already at high risk of the adverse event. PMID:1415136

Fine, P E; Chen, R T



Molecular Mechanisms of Adverse Drug Reactions in Cardiac Tissue  

Microsoft Academic Search

The myocardium is the target of toxicity for a number of drugs. Based on pharmacological evidence, cellular targets for drugs\\u000a that produce adverse reactions can be categorized into a number of sites that include the cell membrane-bound receptors, the\\u000a second messenger system, ionic channels, ionic pumps, and intracellular organelles. Additionally, interference with the neuronal\\u000a input to the heart can also

Reza Tabrizchi


Markers of adverse drug reactions in medication histories  

Microsoft Academic Search

Prescription sequence analysis is based on the observation that a subset of adverse drug reactions are themselves indications for the prescription of another drug. We propose an approach to the analysis of clustering of prescriptions in medication histories that contain records of a presumed side-effect-causing drug A and a side-effect-alleviating drug B. This set of histories with records of both

H. Petri; F. Kessels; T. Kamakura



Adverse events and patients' perceptions of antihypertensive drug effectiveness  

Microsoft Academic Search

Adverse events that patients attribute to their drug treatment are generally considered to reduce adherence to medication. However, some patients interpret such symptoms as indicating drug effectiveness. If perceivedly effective drugs are more likely to be taken then adverse events may increase adherence. The extent to which patients interpret adverse events as indicating drug effectiveness is not well known. We

S Svensson; KI Kjellgren



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

Microsoft Academic Search

Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss

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



Determination of Incidence and Characteristics of Preventable Adverse Drug Reactions : A Study in Phrae Hospital  

Microsoft Academic Search

The characteristics of preventable adverse drug reaction (pADR) in hospitalized patients in Phrae Hospital were identified by a retrospective descriptive analysis. All ADR report forms of patient during fiscal year 2003 were explored. From 189 reports, 188 ADR reports were analyzed. Sixty-eight cases (36.17%) were classified with Schumock and Thornton criteria as pADR. Mean age of pADR patient was 42.97

Kannika Thiankhanithikun; Sayam Kaewvichit



How Much Information About Adverse Effects of Medication Do Patients Want From Physicians?  

Microsoft Academic Search

Background: Little information exists concerning the amount of information patients expect from physicians as to the risk for an adverse medication reaction. The present study was designed to determine such opinions in a population sample; to correlate results with sex, age, educational level, and previous experience with adverse effects; and to determine whether patients believe phy- sicians should use discretion

Dewey K. Ziegler; Michael C. Mosier; Maritza Buenaver; Kola Okuyemi



Energy drink use and adverse effects among emergency department patients.  


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



Adverse reaction to mefloquine associated with ethanol ingestion.  

PubMed Central

A 40-year-old man with no history of neuropsychiatric illness was taking one 250-mg tablet of mefloquine (MFQ) weekly for malaria prophylaxis while in Tanzania. He experienced no adverse reaction in association with his first two doses. Concurrently with both his third and his fourth dose he consumed about half a litre of whisky. On both occasions he experienced hallucinations, paranoid delusions and suicidal ideation. Thereafter he continued taking the MFQ, abstained completely from ethanol ingestion and had no recurrence of psychiatric symptoms. It is hypothesized that the combination of MFQ and ethanol caused the two episodes of severe psychiatric disturbance.

Wittes, R C; Saginur, R



Computerized Detection of Adverse Drug Reactions in the Medical Intensive Care Unit  

PubMed Central

Objective Clinical event monitors are a type of active medication monitoring system that can use signals to alert clinicians to possible adverse drug reactions. The primary goal was to evaluate the positive predictive values of select signals used to automate the detection of ADRs in the medical intensive care unit. Method This is a prospective, case series of adult patients in the medical intensive care unit during a six-week period who had one of five signals presents: an elevated blood urea nitrogen, vancomycin, or quinidine concentration, or a low sodium or glucose concentration. Alerts were assessed using 3 objective published adverse drug reaction determination instruments. An event was considered an adverse drug reaction when 2 out of 3 instruments had agreement of possible, probable or definite. Positive predictive values were calculated as the proportion of alerts that occurred, divided by the number of times that alerts occurred and adverse drug reactions were confirmed. Results 145 patients were eligible for evaluation. For the 48 patients (50% male) having an alert, the mean ± SD age was 62 ± 19 years. A total of 253 alerts were generated. Positive predictive values were 1.0, 0.55, 0.38 and 0.33 for vancomycin, glucose, sodium, and blood urea nitrogen, respectively. A quinidine alert was not generated during the evaluation. Conclusions Computerized clinical event monitoring systems should be considered when developing methods to detect adverse drug reactions as part of intensive care unit patient safety surveillance systems, since they can automate the detection of these events using signals that have good performance characteristics by processing commonly available laboratory and medication information.

Kane-Gill, Sandra L.; Visweswaran, Shyam; Saul, Melissa I.; Wong, An-Kwok Ian; Penrod, Louis E.; Handler, Steven M.



Adverse reactions to fluoroquinolones. an overview on mechanistic aspects.  


This review focuses on the most recent research findings on adverse reactions caused by quinolone antibiotics. Reactions of the gastrointestinal tract, the central nervous system (CNS) and the skin are the most often observed adverse effects. Occasionally major events such as phototoxicity, cardiotoxicity, arthropathy and tendinitis occur, leading to significant tolerability problems. Over the years, several structure-activity and side-effect relationships have been developed, in an effort to improve overall antimicrobial efficacy while reducing undesirable side-effects. In this article we review the toxicity of fluoroquinolones, including the newer derivatives such levofloxacin, sparfloxacin, graepafloxacin and the 7-azabicyclo derivatives, trovafloxacin and moxifloxacin. A special attention is given to new data on mechanistic aspects, particularly those regarding CNS effects. In recent years extensive in vivo and in vitro experiments have been performed in an attempt to explain the neurotoxic effects of quinolones sometimes observed under therapeutic conditions. However, the molecular target or receptor for such effects is still not exactly known. Several mechanisms are thought to be responsible. The involvement of gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission and the kinetics of quinolones distribution in brain tissue are discussed. In addition, quinolones may interact with other drugs--theophylline and nonsteroidal antiflammatory drugs (NSAID(s))--in producing CNS effects This article provides information about the different mechanisms responsible of quinolones interaction with NSAID(s), methylxanthines, warfarin and antiacids. PMID:11172695

De Sarro, A; De Sarro, G



Thromboprophylaxis guidelines in cancer with a primary focus on ambulatory patients receiving chemotherapy: a review from the Southern Network on Adverse Reactions (SONAR).  


Patients with cancer are at increased risk for venous thromboembolism (VTE). Factors related to cancer type, site, stage, duration, and extent of disease contribute to the oncology patient's risk of VTE. Patient-specific factors such as history of prior VTE and comorbidity are also contributory. The role of treatment-related factors, including chemotherapy regimen, has been a focus of recent investigation because most cases of VTE in the oncology setting occur in ambulatory patients. Thus, an emerging area of clinical research is primary VTE prophylaxis in the ambulatory cancer setting. Clinical guidelines currently recommend primary thromboprophylaxis in cancer patients who are undergoing surgery, who are hospitalized, and who are in a specific subset of high-risk ambulatory cancer patients. Validated risk stratification tools are essential for identification of patients who are at high risk of thrombosis. Emerging data from recently published clinical trials, as well as ongoing studies, are likely to advance our understanding of the potential utility of antithrombotic agents for primary prophylaxis in ambulatory patients with cancer and may influence future clinical guideline recommendations. PMID:23111863

Maxwell, Whitney D; Bennett, Charles L



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: [RadGenomics Project, National Institute of Radiological Sciences, Chiba (Japan)



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

PubMed Central

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



Monitoring of adverse drug reactions associated with antihypertensive medicines at a university teaching hospital in New Delhi  

PubMed Central

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



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

Microsoft Academic Search

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

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



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

PubMed Central

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

Nikfarjam, Azadeh; Gonzalez, Graciela H.



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.

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



Sedating pediatric dental patients by oral ketamine with alternating bi-lateral stimulation of eye movement desensitization and minimizing adverse reaction of ketamine by acupuncture and Bi-Digital O-Ring Test.  


Ketamine, besides being an anesthetic agent, is also a strong analgesic that can be especially useful for painful procedures. Vivid dreams and nightmare, considered as undesirable side effects of ketamine, are rarely encountered when administrated orally, making it one of the most desirable oral sedative for children because it partially protects the pharyngeal-laryngeal reflex. Besides, if used in recommended dosage, it does not suppress the cardiopulmonary function as most other sedatives do. Ketamine's bronchodilator effect makes it a good sedative for children with asthma, allergies, and hay fever. Alternating bi-lateral stimulation (ABLS) of eye movement desensitization, applying pre-operatively before ketamine was found to reduce the post-operative violent emergence and behavioral problems. Acupressure at P 6 (Neikuan) acupoint helps to decrease nausea and vomiting episodes by ketamine. 36 patients with history of unmanageable behavior were sedated with ketamine 3mg/kg and ABLS. To prevent possible adverse reaction, Bi-Digital O-Ring Test (BDORT) were used to test all patients. ABLS significantly decreased tearful separation from parent. It took 15 to 20 minutes for ketamine to take effect, peak effect took 20 to 25 minutes. Working time ranged from 20 to 40 minutes. Post-operative recovery was more pleasant when ABLS was combined with ketamine, acupuncture/acupressure not only prevented vomiting and BDORT safeguard the patients from unpredictable untoward side effects but also promoting calmness. PMID:23156203

Lu, Dominic P; Wu, Ping-Shi; Lu, Winston I



A prospective survey of delayed adverse reactions to iohexol in urography and computed tomography  

Microsoft Academic Search

.   We investigated 7505 inpatients who underwent intravenous urography or contrast-enhanced computed tomography to assess risk\\u000a factors for delayed adverse drug reactions to iohexol, a non-ionic iodinated contrast medium. Focusing on delayed adverse\\u000a reactions, all adverse events were prospectively investigated for 7 days after injection of iohexol. To explore the relevant\\u000a risk factors, the relationship between occurrence of adverse reactions to

Hirotsugu Munechika; Yoshihiro Hiramatsu; Sho Kudo; Kazuro Sugimura; Chikuma Hamada; Koichi Yamaguchi; Hitoshi Katayama



Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.  


The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction." PMID:23417506

Aronson, Jeffrey K



Rotigotine adverse effects affecting patient's sexual partner.  


Somnolence is one of the most common adverse effects of a dopaminergic agonist, rotigotine. We report putative adverse effects experienced by a spouse of a man treated with this compound because of advanced Parkinson disease. We propose the exposure to rotigotine through the seminal fluid because protected sexual intercourse eliminated her postcoital symptoms. This previously unrecognized mechanism may be more common and associated with other psychoactive compounds penetrating the blood-testis barrier, and it may account for otherwise unexplained postcoital somnolence or fatigue. PMID:20124785

Hedera, Peter


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


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

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



No Correlations Between the Development of Specific IgA and IgM Antibodies Against Anti-TNF Blocking Agents, Disease Activity and Adverse Side Reactions in Patients with Rheumatoid Arthritis.  


The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-? agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity. PMID:24115967

Benucci, Maurizio; Saviola, Gianantonio; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Campi, Paolo; Severino, Maurizio; Iorno, Miriam; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola



No Correlations Between the Development of Specific IgA and IgM Antibodies Against Anti-TNF Blocking Agents, Disease Activity and Adverse Side Reactions in Patients with Rheumatoid Arthritis  

PubMed Central

The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-? agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity.

Benucci, Maurizio; Saviola, Gianantonio; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Campi, Paolo; Severino, Maurizio; Iorno, Miriam; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola



Adverse cutaneous reactions to soft tissue fillers--a review of the histological features.  


The enhanced use of exogenous substances for cosmetic and reconstructive procedures is paralleled by an increase in reports of cutaneous adverse reactions to several of these agents. Recognition of the histological features of these reactions is of importance to both dermatologists and dermatopathologists but is not always easy for several reasons. First, cost-related issues are resulting in an increasing number of these procedures being performed overseas. Thus, patients are often unsure about the exact product used. Compounding this is the fact that practitioners who perform these procedures are not forthright in divulging this information, given that improper substances may be admixed in the filler injected. Furthermore, cutaneous reactions may occur at sites distant from injected sites, secondary to migration of the filler substance and a lapse of months to years may occur prior to the development of a cutaneous reaction. Thus, a causal relationship between the procedure and the reaction is often not made. We present an overview of the histological features of adverse reactions to currently available soft tissue fillers, both in the United States and overseas, in an attempt to enhance awareness of the diversity of these reactions. PMID:18201242

Dadzie, Ophelia Entsir; Mahalingam, Meera; Parada, Meire; El Helou, Therese; Philips, Tania; Bhawan, Jag



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



Medical adverse events in elderly hospitalized patients: A prospective study  

PubMed Central

OBJECTIVES: To determine the frequency of medical adverse events in elderly patients admitted to an acute care geriatric unit, the predictive factors of occurrence, and the correlation between adverse events and hospital mortality rates. METHODS: This prospective study included 171 admissions of patients aged 60 years and older in the acute care geriatric unit in a teaching hospital in Brazil between 2007 and 2008. The following variables were assessed at admission: the patient age, gender, number of prescription drugs, geriatric syndromes (e.g., immobility, postural instability, dementia, depression, delirium, and incontinence), comorbidities, functional status (evaluated with the Katz Index of Independence in Activities of Daily Living), and severity of illness (evaluated with the Simplified Acute Physiology Score II). The incidence of delirium, infection, mortality, and the prescription of potentially inappropriate medications (based on the Beers criteria) were assessed during hospitalization. An observer who was uninvolved in patient care reported the adverse events. RESULTS: The mean age of the sample was 78.12 years. A total of 187 medical adverse events occurred in 94 admissions (55%). The predictors of medical adverse events were undetermined. Compared with the patients with no adverse events, the patients with medical adverse events had a significantly longer hospital stay (21.41±15.08 days versus 10.91±7.21 days) and a higher mortality rate (39 deaths [41.5%] versus 17 deaths [22.1%]). Mortality was significantly predicted by the Simplified Acute Physiology Score II score (odds ratio [OR]?=?1.13, confidence interval [CI] 95%, 1.07 to 1.20), the Katz score (OR?=?1.47, CI 95%, 1.18 to 1.83), and medical adverse events (OR?=?3.59, CI 95%, 1.55 to 8.30). CONCLUSION: Medical adverse events should be monitored in every elderly hospitalized patient because there is no risk profile for susceptible patients, and the consequences of adverse events are serious, sometimes leading to longer hospital stays or even death.

Szlejf, Claudia; Farfel, Jose Marcelo; Curiati, Jose Antonio; de Barros Couto Junior, Euro; Jacob-Filho, Wilson; Azevedo, Raymundo Soares



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



Salicylate intolerance: a masquerader of multiple adverse drug reactions  

PubMed Central

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

Fernando, Suran Loshana; Clarke, Lesley R



[The eye as target of adverse ocular drug reactions. Focus on systemic antiinfective therapy].  


The functions of the eye can be disturbed by pharmaceutical agents via various mechanisms. This review describes the complexity of ocular adverse drug reactions and underlines the need for a close interdisciplinary cooperation especially in this field to optimize drug safety. Antimicrobial agents will be used as examples to describe ocular adverse drug reactions. A recent case control study describes fluoroquinolones to be associated with the occurrence of retinal detachments. The high affinity of these agents to melanin may cause intraocular accumulation. Fluoroquinolones exert toxic effects on collagens which may destabilize the structure of the extracellular matrix. The ketolid telithromycin may cause impaired accommodation and binocular vision potentially due to its anticholinergic effect. Linezolid, an oxazolidinone, used against infections with methicillin resistant staphylococcus aureus (MRSA) may lead to progressive, potentially irreversible neuropathies of the optic nerve especially in long-time application. Treatment with rifabutin or the antiviral drug cidofovir may cause intraocular inflammation. In addition, cidofovir may impair the production of the aqueous fluid due to a toxic effect on ciliary epithelial cells. During therapy with voriconazol about one third of patients suffer from reversible visual disturbances. Liver dysfunction or pharmacogenetic variants in the cytochrome P450 system may contribute to a retarded metabolism with high intraocular drug levels. In summary, this review indicates the complexity of ocular adverse drug reactions and points out that an interdisciplinary approach is necessary to improve pharmacovigilance in this field. PMID:23367659

Huber, Matthias; Stahlmann, Ralf



Adverse Reactions to Chloroquine and Amodiaquine as Used for Malaria Prophylaxis: A Review of the Literature  

PubMed Central

This paper reviews the published material on adverse reactions to chloroquine (CQ) and amodiaquine (ADQ) as used for anti-malarial chemophrophylaxis. Dermatologic reactions, including pruritus and photosensitivity, appear to be rather common. Ophthalmologic reactions include difficulty in visual accommodation, corneal deposits, and retinopathy, the last a serious condition that is reversible in its early stage by drug withdrawal, and that generally will not occur with less than four years of weekly CQ use. Neuromyopathy is a rare and serious reaction that may develop idiosyncratically after a small cumulative dose; it, too, is reversible by drug withdrawal. Seizures, syndromes of involuntary movements, psychosis, and ototoxicity have been reported occasionally. Fatal toxic overdoses may occur, especially following accidental ingestion by children. ADQ should not be used for anti-malarial prophylaxis because of associated agranulocytosis. Rabies vaccine given intradermally is less effective for pre-exposure prophylaxis while the patient is taking CQ. Care should be taken when prescribing prophylactic CQ to patients with heart block. In spite of its adverse effects, however, CQ is generally an extremely safe drug. Cq prophylaxis is recommended for pregnant women in CQ-sensitive malarial areas.

Wittes, Robert



Clinical application of static fluorescence-based cytometry, Cellscan, in cutaneous adverse drug reaction.  


The aim of the present study was to evaluate the effectiveness of Cellscan in identifying culprit drugs causing cutaneous adverse drug reaction. It was a prospective study with 3 months follow up conducted at the Departments of Dermatology, Internal Medicine and Dermatology Outpatient Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel. The study included 36 patients with cutaneous reaction suspected to be secondary to drugs, treated with a total number of 148 drugs. All patients and drugs were classified to three probability groups according to accepted clinical criteria. The effectiveness of the Cellscan test in identifying the culprit drug was addressed according to the clinical probability for cutaneous drug reaction, the drug class and the type of rash. Data analysis according to the clinical probability for cutaneous drug reaction revealed that patients in the moderate and high probability groups had a high test sensitivity of 77.7% and 83.3% with specificity of 71% and 63%, respectively, in identifying the culprit drug. Classifying the data according to drug classes, revealed that for the antibiotic and cardiovascular drug classes the sensitivity of the test was 100% and 92% with specificity of 83.3% and 55.5%, respectively, in identifying the culprit drug. Finally, the classification of patients according to the type of rash revealed a high evaluating accuracy for culprit drugs in maculopapular rashes with sensitivity and specificity of 90% and 60.4%, respectively. The results of this study imply that the Cellscan test is it a good practical tool for identifying the culprit drug in cutaneous adverse drug reaction. PMID:21352273

Salameh, Fares; Kravitz, Martine Szyper; Barzilai, Aviv; Baum, Sharon; Shoenfeld, Yehuda; Schiffenbauer, Yael; Trubniykov, Ela; Trau, Henri



Fatal neuropsychiatric adverse reactions to oseltamivir: Case series and overview of causal relationships  

Microsoft Academic Search

Background: Infection-associated encephalopathies such as Reye's syndrome have been one of the major public health problems in many countries. The not dissimilar neuropsychiatric adverse reactions, including deaths, observed with Tamiflu (oseltamivir phosphate: OP) have been another current problem especially in Japan. Methods: Among the cases with neuropsychiatric adverse reactions to Tamiflu on which I was consulted, those cases in which

Rokuro Hama


Adverse reactions to contrast media: An analysis from spontaneous reporting data  

Microsoft Academic Search

Diagnostic contrast media (CM) are a widely used class of drugs with poor information regarding their safety. Nevertheless, epidemiological studies showed that CM cause adverse reactions commonly considered unpreventable and unavoidable. Because spontaneous reporting is a valuable methodology for better defining the safety profile of drugs after their approval, we analyzed the spontaneous reports of suspected adverse reactions attributed to

Paola Cutroneo; Giovanni Polimeni; Roberto Curcuruto; Gioacchino Calapai; Achille P. Caputi



COSTART - Coding Symbols for Thesaurus of Adverse Reaction Terms. Third Edition.  

National Technical Information Service (NTIS)

The coding symbols for a thesaurus of adverse reaction terms (COSTART) is the terminology developed and used by the Food and Drug Administration (FDA) for coding, filing and retrieving of post-marketing adverse reaction reports. It provides a method to de...



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…

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



Adverse Reactions and Drug–Drug Interactions in the Management of Women with Postmenopausal Osteoporosis  

Microsoft Academic Search

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment\\u000a on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions\\u000a and drug–drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from\\u000a regulatory documents, randomized controlled trials, pharmacovigilance

René Rizzoli; Jean-Yves Reginster; Steven Boonen; Gérard Bréart; Adolfo Diez-Perez; Dieter Felsenberg; Jean-Marc Kaufman; John A. Kanis; Cyrus Cooper


[Pilot study for the surveillance of adverse reactions to herbal preparations and dietary supplements].  


Use of herbal medicine is increasing in Italy. Herbal preparations are generally used as self-medication, often in the wrong belief that "natural" can be equated with "harmless". Whereas use of these products has been associated with serious adverse events, due to the quality of the raw materials used, to interactions with synthetic drugs or to their use in particular conditions, such as pregnancy or lactation. To monitor herbal preparation use in the population is necessary in order to point out possible adverse reactions. This was the objective of this pilot study, together with the urgency to inform health personnel and patients on the correct use of these products. After this experience we strongly believe that a system to assess the safety of herbal preparations is needed. PMID:16037648

Menniti-Ippolito, Francesca; Mazzanti, Gabriela; Firenzuoli, Fabio; Bianchi, Antonio; Raschetti, Roberto



Respiratory depression: An adverse outcome during patient controlled analgesia therapy  

Microsoft Academic Search

Patient-controlled analgesia (PCA) is one of the more popular means of controlling postoperative pain. However, there is very little in the literature concerning the adverse outcome of respiratory depression in PCA. This report is a prospective study of 4,000 patients on PCA postoperatively. Nine of these patients experienced respiratory problems while on PCA. The respiratory depressions were associated with drug

Lian C. Looi-Lyons; Frances F. Chung; Vincent W. Chan; Maurene McQuestion



Severe cutaneous adverse drug reactions: who should treat, where and how?: Facts and controversies.  


Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are uncommon but extremely serious and often life-threatening mucocutaneous reactions characterized by extensive epithelial sloughing and systemic symptoms. There is no effective evidence-based treatment for severe cutaneous adverse reactions (SCAR) to drugs and no consensus on how to treat these patients. This contribution presents some of the controversies concerning the treatment of SCAR patients, including where and by whom, as well as the issue of the value of treatment with corticosteroids and intravenous immunoglobulin. Investigators agree that more studies are needed and that there are insufficient data to draw definite conclusions. The spectrum of disagreement is wide and the debate is ongoing. At the end, the important question is should we wait with our decisions until all these controversies are settled and we have more or full evidence. This question, as well as all others, is open for debate, evidently a "toxic" debate on toxic epidermal necrolysis. PMID:20541690

Wolf, Ronni; Davidovici, Batya


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

SciTech Connect

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

Hirsch, Michael J. [Raytheon, Inc., Network Centric Systems, P.O. Box 12248, St. Petersburg, FL, 33733 (United States); Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle [Department of Industrial and Systems Engineering, University of Florida, 303 Weil Hall, Gainesville, FL, 32611 (United States); Resende, Mauricio G. C. [Algorithms and Optimization Research Department, AT and T Labs Research, 180 Park Avenue, Room C241, Florham Park, NJ 07932 (United States)



Adverse drug reactions and avalanches: life at the edge of chaos.  


Although many reports have described the incidence of adverse drug reactions, none have explained their variable severity or why they happen. Because human physiology shares many of the features of other complex adaptive systems, reactions to drug therapy were examined mathematically for specific patterns to show (1) that the severity of adverse drug reactions follows a distribution seen in other complex adaptive systems, called a power law distribution, and (2) that preventable reactions occurred for reasons fundamentally different from those that underlie the nonpreventable reactions. Two reports detailing adverse drug reaction incidence and severity were evaluated: a meta-analysis of prospective adverse drug reaction studies and a prospective cohort study. Incidence of drug reaction was plotted as a function of severity and fit to an equation. The incidences of overall and nonpreventable drug reaction, plotted as a function of severity, followed a similar power law distribution regardless of sample size or the nature of the population or drugs studied. An exception to this was the preventable reactions, which were described by a different type of equation. Response to pharmacotherapy exhibits many properties of systems with self-organized criticality. An exception to this is the preventable reactions, which seem to be fundamentally different from the nonpreventable ones. These observations suggest that the presence and the distribution of severity of reaction to pharmacotherapy is a consequence of our adaptation as biological systems, and although adverse reactions can be made less frequent, a certain percentage will not be preventable. PMID:16027396

Frattarelli, Daniel A C



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



Adverse drug reaction-related admissions in paediatrics, a prospective single-centre study  

PubMed Central

Objective To investigate the incidence and characteristics of hospital admissions related to adverse drug events in the paediatric setting. Design Prospective single-centre study. Setting A secondary and tertiary paediatric care centre. Participants A total of 683 acutely admitted patients, aged 0–18?year. All acutely admitted patients, using medication before admission, were prospectively screened for possible Adverse Drug Reactions (ADR)-related admission with a trigger list. Included cases were analysed with the Naranjo score for the assessment of causality. Main outcome measures This research explored the incidence of ADR-related admissions and investigated the relation between ADR and the licensing status of the medicines, as well as the severity and potential to prevent the ADRs. Results A total of 683 patients were admitted acutely during the study period, 47 of them were exposed to cancer chemotherapy. Fifteen patients not exposed to chemotherapy (2.4%) were admitted due to an ADR. Five of these 15 ADRs (33%) were caused by unlicensed or off-label used drugs. Thirty-two patients exposed to chemotherapy (68.1%) were admitted due to an ADR; 27 of these (84%) were caused by unlicensed or off-label used drugs. Conclusions In conclusion, this study shows that ADR-related hospital admissions occur more frequently in the paediatric population compared with adults, and more frequently in patients exposed to cancer chemotherapy. No relation was found between the unlicensed and off-label used drugs and the incidence of ADRs.

Posthumus, Anke A G; Alingh, Carien C W; Zwaan, Christian C M; van Grootheest, Kees K; Hanff, Lidwien L M; Witjes, Bregje B C M; 't Jong, Geert W; de Hoog, Matthijs



Histopathological patterns indicative of distinct adverse drug reactions.  


Histologically, drug eruptions may present virtually all patterns of inflammation in the skin, including spongiotic, lichenoid and psoriasiform dermatitis as well as vasculitis or panniculitis. Drug reactions may mimic specific skin diseases such as lupus erythematosus, lichen planus or lymphoma. While a single drug may cause a wide range of reaction patterns, no reaction pattern is specific for a certain drug. Nevertheless, some reactions are quite characteristic for certain drugs as for example psoriasiform dermatitis for anti-TNF agents or folliculitis for epidermal growth factor receptor antagonists. Heightened awareness to the possible mimicry of other skin diseases as well as integration of clinical data is pivotal for the appropriate histological diagnosis of drug reactions in the skin. For practical reasons and in the aim of helping clinicians, the different drug reactions described in this chapter are classified according to the main histological reaction pattern present. Nevertheless, this classification may be somewhat artificial in some cases as drug reactions often reveal a coexistence of different reaction patterns. PMID:22613854

Kerl, Katrin



Red Man Syndrome Adverse Reaction following Intravenous Infusion of Cefepime  

PubMed Central

We report the first case of cefepime-induced “red-man syndrome,” which appeared 30 min following drug infusion and was confirmed with a rechallenge test. This syndrome is classically associated with vancomycin infusion and is the result of non-IgE mediated mast cell degranulation. While this adverse effect can be easily managed with drug withdrawal and antihistamine administration, it is unknown whether it can be prevented with slower cefepime infusion and preinfusion antihistamines, as is the case with vancomycin.

Watson, Dionysios C.; Sargianou, Maria; Kampiotis, Dionysios; Chra, Paraskevi



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



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



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


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



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.

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



Extrapyramidal adverse drug reactions associated with trimetazidine: a series of 21 cases.  


Over the last few years, a number of cases of extrapyramidal disorders associated with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21 cases. All but one of the patients (mean age 74) had been taking TMZ for several years. The indication for prescription of TMZ could not be identified in seven cases. The TMZ-associated adverse drug reactions were typical parkinsonism (akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in three cases (one with orthostatic tremor), and restless leg syndrome in one case. Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases and a significant reduction in the five other patients. TMZ has the same piperazine core as the dopamine antagonists flunarizine and cinnarizine (both of which have been reported to induce extrapyramidal symptoms). Hence, striatal D2 receptor blockade could result in the onset or the worsening of extrapyramidal disorders. Even though this adverse drug reaction is now listed in TMZ's Summary of Product Characteristics (because of the initial reports), the risk remains poorly known by clinicians. There is a need to raise awareness of this phenomenon and to reassess TMZ 's risk-benefit ration, especially in the elderly. PMID:22044594

Masmoudi, Kamel; Masson, Henri; Gras, Valérie; Andréjak, Michel



Comparison of serious adverse reactions between thalidomide and lenalidomide: analysis in the French Pharmacovigilance database.  


Thalidomide and lenalidomide are structural analogs and immunomodulatory drugs. Lenalidomide appears to have a different safety profile than thalidomide and could be less toxic, and as far as we know, we did not found any study comparing their safety profile. The objective of our study was to review and compare serious adverse drug reactions (SADRs) of thalidomide and lenalidomide spontaneously reported to the French Pharmacovigilance database. We extracted all medically confirmed spontaneous reports of SADR for lenalidomide-based regimens and thalidomide-based regimens from the French Pharmacovigilance database. A "serious" adverse drug reaction (ADR) was defined as an ADR that is fatal or life threatening, which causes hospitalization or prolongation of hospitalization, or permanent or significant disability. The study period was between marketing of 2 drugs and January 15, 2012. A total of 392 SADRs related to thalidomide-based regimens were identified in 244 patients and 377 SADRs related to lenalidomide-based regimens in 220 patients. In spite of their structural analogy, this study highlights interesting differences between lenalidomide and thalidomide's safety profile: nervous system and vascular disorders are more frequent with thalidomide-based regimens while hematologic, skin, infectious disorders and secondary primary cancers are more frequent with lenalidomide-based regimens. PMID:24078083

Olivier-Abbal, Pascale; Teisseyre, Anne-Charlotte; Montastruc, Jean-Louis



[Adverse reactions to mosquito bites in scholars from Monterrey, Nuevo Leon, Mexico.  


Background: Allergic reactions to insect bites are a global problem, the true incidence and prevalence of morbidity from adverse reactions to mosquito bites are unknown. Objective: To describe the adverse reactions to mosquito bites in school-age children of Monterrey, Nuevo Leon. Material and methods: A cross-sectional descriptive study was made via a randomized application of questionnaires to children from public elementary schools in the metropolitan area of Monterrey, Nuevo Leon. Results: A total of 11 public schools randomly selected were included in the study. One thousand questionnaires were submitted, of which 506 fulfilled the inclusion criteria; 55% were females. Seventy-six percent referred adverse reactions to mosquito bites, itching (75%) and rash (72%) being the most frequent ones, in the last 12 months. Conclusions: Adverse reactions to mosquito bites occur frequently. Early detection is important to establish a prompt treatment. PMID:21255516

Manrique López, María Amelia; González Díaz, Sandra N; Arias Cruz, Alfredo; Sedó Mejía, Giovanni A; Canseco Villarreal, José Ignacio; Gómez Retamoza, Ernesto Antonio; Padrón López, Olga Magdalena; Cruz Moreno, Miguel Angel; Cisneros Salazar, Guillermo Daniel


Individual differences and setting as determinants of acute adverse reactions to psychoactive drugs.  


The relationship between setting and individual differences in determining acute adverse reactions to psychoactive drugs was examined using retrospective data from 483 drug users. Five dimensions of setting were identified. Although there were some small setting main effects, these effects failed to reach significance when shared variance with individual difference variables was considered. For acute adverse reactions to LSD, however, there were seven independent interaction effects between setting and individual difference variables. There were two interaction effects of smaller magnitude related to acute adverse reactions to marijuana. The significance of these results for the current controversy over the relative importance of situational vs. personality determinants of behavior was discussed. PMID:1185154

Naditch, M P; Alker, P C; Joffe, P



Intravenous immunoglobulin-induced lichenoid dermatitis: a unique adverse reaction.  


Intravenous immunoglobulin (IVIG) therapy has been used to treat various diseases. Generalized allergic reactions (types I, II, and III) to IVIG are uncommon and are usually related to the rate of infusion. Cutaneous reactions have been anecdotally described. Herein we describe a 73-year-old man with Sjögren's syndrome who had development of a lichenoid cutaneous eruption after administration of IVIG therapy. CD3 immunostaining demonstrated the overwhelming presence of T lymphocytes within a lesional skin biopsy specimen, and thus we present an alternative cell-mediated immune mechanism (type IV) by which allergic reactions to IVIG may occur. PMID:9413297

Yockey, S M; Ahmed, I



Adverse reactions in blood and apheresis donors: experience from two Italian transfusion centres  

PubMed Central

Background Blood and apheresis donations are widely considered to be safe with a low incidence of adverse reactions and injuries; however, data reported in the medical literature on the prevalence of adverse events in donors and studies on the predictive risk factors for donor reactions are limited and contradictory. Methods From January 2002 to December 2006 we recorded every adverse reaction verified during 240,596 consecutive blood and apheresis donations (183,855 homologous whole blood donations, 6,669 autologous whole blood donations, 38,647 plasmapheresis, 2,641 plateletpheresis and 8,784 multicomponent donations) at the Italian Transfusion Centres of Verona and Ragusa,. Results Using a special, pre-arranged form within the quality system, a total of 686 adverse reactions (related to 0.28% of all donations) were recorded. Vasovagal reactions, mostly of mild intensity, were the most commonly observed adverse reactions, with a frequency of 0.20% (487/ 240,596). The frequency of the vasovagal reactions varied according to the different types of donation, being 0.19% (346/183,855) for homologous whole blood donations, 0.24% (16/6,669) for autologous whole blood donations, 0.16% (63/38,647) for plasmapheresis, 0.68% (18/2,641) for plateletpheresis and 0.49 (43/8,784) for multicomponent donations. Citrate toxicity was reported in 0.38% (189/50,072) of apheresis donations. Severe adverse reactions were very rare, as they occurred in 0.004% of the donations (10/240,596). Conclusions In conclusion, the results of our 5-year survey document that apheresis and blood donation are safe procedures for the donor with a low incidence of adverse reactions; the adverse reactions that did occur were mostly mild and resolved rapidly.

Crocco, Isabella; Franchini, Massimo; Garozzo, Giovanni; Gandini, Anna Rosa; Gandini, Giorgio; Bonomo, Pietro; Aprili, Giuseppe



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


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 ( ). 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



COSTART: Coding Symbols for Thesaurus of Adverse Reaction Terms. Fourth Edition.  

National Technical Information Service (NTIS)

The Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) is the terminology developed and used by the Food and Drug Administration for the coding, filing and retrieving of post-marketing adverse drug event reports. It provides a method to de...



Analysis of adverse drug reactions using drug and drug target interactions and graph-based methods  

Microsoft Academic Search

ObjectiveThe purpose of this study was to integrate knowledge about drugs, drug targets, and topological methods. The goals were to build a system facilitating the study of adverse drug events, to make it easier to find possible explanations, and to group similar drug–drug interaction cases in the adverse drug reaction reports from the US Food and Drug Administration (FDA).

Shih-Fang Lin; Ke-Ting Xiao; Yu-Ting Huang; Chung-Cheng Chiu; Von-Wun Soo



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.

Susskind, M.; Thurmann, P. A.; Luke, C.; Jeschke, E.; Tabali, M.; Matthes, H.; Ostermann, T.



Evaluation of Adverse Reactions in Hemophiliacs from Long-Term Exposure to Blood and Blood Products.  

National Technical Information Service (NTIS)

This study assesses current therapeutic efficacy and adverse reactions in hemophiliacs. Approximately 50 percent of hemophiliacs showed long term (greater than 6 months) abnormalities of liver function. A significant increase in diastolic blood pressure w...

S. S. Shapiro



The influence of buscopan on adverse reactions to intravascular contrast media.  


We have analysed the ability of prior intravenous Buscopan (hyoscine butylbromide) injection to influence the incidence and severity of adverse reactions to intravascularly administered, iodinated, ionic contrast medium in 258 consecutive digital subtraction angiographic (DSA) examinations. Adverse reactions were seen in 7.9% of the intravenous and 2.4% of the intra-arterial DSA examinations. The incidence of adverse reactions with and without prior Buscopan injection during intravenous DSA examinations was 8.2% and 7.1%, respectively and during intra-arterial DSA examinations was 5.6% and 1.5%, respectively. This difference is not statistically significant (chi 2-test). We conclude that prior intravenous injection of Buscopan has no influence on the incidence or severity of adverse reactions to intravascular contrast media. PMID:2605452

Sharma, S; Rajani, M; Khosla, A; Misra, N; Goulatia, R K



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


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

Mangoni, Arduino A



How many deaths occur annually from adverse drug reactions in the united states?  

Microsoft Academic Search

PURPOSE: The numbers of deaths attributed to adverse drug reactions by death certificates and by the Food and Drug Administration’s (FDA) spontaneous postmarketing surveillance system (MedWatch) were compared in order to characterize national mortality statistics.METHODS: Mortality statistics related to adverse drug reactions were obtained from national public-use databases of death certificates based on appropriate International Classification of Disease (ICD-9) codes

Peter A Chyka



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

Microsoft Academic Search

Nicotine replacement therapies (NRT) are prescribed in smoking cessation programmes to help smokers stop smoking. The ideal\\u000a dosage of NRT should control cravings and withdrawal symptoms but avoid adverse reactions. This report describes a case of\\u000a adverse reaction to nicotine gum in a female Malay smoker. Assays taken 2 h after the gum, showed that her plasma cotinine\\/nicotine\\u000a ratio was 0.4,

Alyson Bond; Kim Wolff



Monitoring adverse reactions to food additives in the U.S. Food and Drug Administration.  


Technological advances in food science have resulted in the development of numerous food additives, most of which require premarket approval by the Food and Drug Administration (FDA). Concomitant with the benefits of these additives, such as extending the shelf life of certain food commodities, is the potential for various risks. These potential risks include the possibility of the consumer experiencing an adverse reaction to the additive. In order to ascertain the character and the gravity of alleged adverse reactions to food products which it regulates, the FDA's Center for Food Safety and Applied Nutrition has developed the Adverse Reaction Monitoring System (ARMS). This postmarketing surveillance system for food additives is designed to analyze consumer reports of adverse reactions in order to alert FDA officials about any potential public health hazard associated with an approved food additive, and to delineate specific syndromes which may lead to focused clinical investigations. To date, among the products routinely monitored in the ARMS, sulfiting agents and the artificial sweetener aspartame have generated the largest volume of consumer reports describing adverse reactions. An overview of the analyses of the sulfite and aspartame adverse reaction reports is presented, along with a description of the mechanics of the postmarketing surveillance system, and a detailed discussion of its limitations. PMID:3222485

Tollefson, L



The radiology of adverse drug reactions and toxic hazards  

SciTech Connect

Dr. Ansell has produced a scholarly review of the radiology of drug reactions and toxic hazards in his latest book, which is based on over 1,200 articles in the world literature. About 800 of these articles are taken from outside the radiology literature, which indicates the need for this subject to be brought to the attention of the radiologist, particularly as concern about drug reactions and toxic hazards is always increasing. The book includes sections covering the chest, gastrointestinal tract, renal tract, skeletal system and soft tissues, and skull and central nervous system. Each section treats specific substances, such as steroids and heavy metals; specific radiologic signs, such as ureteric dilation; specific symptoms, such as dysphagia; industrial toxins; radiographic abnormalities are discussed; and numerous high-quality radiographs.

Ansell, G.



Adverse drug reactions related to the use of non-steroidal anti-inflammatory drugs: results of spontaneous reporting from central India.  


To assess the adverse drug reactions to non-steroidal anti-inflammatory drugs through spontaneous reporting system in IGGMC&H, Nagpur and to analyse them using WHO assessment scales, an observational, prospective study was conducted in patients attending outpatient department, inpatient department and casualty of IGGMC and H Nagpur from 1st June 2005 to 31st May 2009. Data were collected by spontaneous adverse drug reactions reporting system. Among 2639 total adverse drug reactions reported, 336 (12.7%) were due to non-steroidal anti-inflammatory drugs. The non-steroidal anti-inflammatory drugs most frequently implicated with adverse drug reactions were ibuprofen (51.19%) followed by diclofenac (27.08%), paracetamol (6.55%), nimesulide (6.25%), aspirin (5.95%). The most commonly affected organ systems were skin and appendages and gastro-intestinal system. Maculopapular rashes were the most frequent skin Involvement. Non-steroidal anti-inflammatory drugs are the most frequently used drugs. As they are commonly associated with adverse drug reactions, their limited and careful use is needed. Considering their prominent role in therapeutics, close clinical observations are very important in minimising adverse drug reactions and demands need for vigilant surveillance of adverse drug reactions in patients, receiving established as well as newer non-steroidal anti-inflammatory drugs. PMID:24003566

Shrivastava, Meena Pramendra; Chaudhari, Harshal Vikas; Dakhale, Ganesh Nathuji; Hiware, Sachin Keshavrao; Solanke, Bhupendra Prakash; Shinde, Abhijit



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

Microsoft Academic Search

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

Harry M. Marks; Matthew Prior


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


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



Pharmacy-coordinated program that encourages physician reporting of adverse drug reactions.  


A pharmacy-coordinated program for encouraging physician reporting of adverse drug reactions (ADRs) is described. The ADR surveillance program at the Medical Center Hospital of Vermont, a 500-bed tertiary-care hospital, is in its fifth year. Key elements are close interaction between physicians and pharmacists, feedback, program promotion, and financial incentive. The program is promoted chiefly to house staff physicians. A physician may identify a suspected ADR, or he or she may be alerted by a pharmacist. The physician completes the first part of a form, which requests information on the patient, the severity of the reaction, the actions taken, and any predisposing factors. A pharmacist reviews the incident independently and in consultation with the reporter and then completes the second part of the form, which asks the pharmacists to assess the probability that the drug caused the ADR and to classify the reaction. A summary is sent to the physician and may be reported to the FDA and the manufacturer. Each report earns the reporter a $5 stipend. Information from the ADR forms is entered into a dBASEIII PLUS computer program for later retrieval and analysis. During a 12-month period, 175 ADR reports (out of a total of 249 reports) were received from house staff members, compared with about 4 voluntary reports received annually before the program began. The ADR surveillance program has increased physician reporting of ADRs and produced a reliable database that can be used to influence hospital policy and promote education. PMID:2368726

Gilroy, G W; Scollins, M J; Gay, C A; Harry, D J; Giannuzzi, D F



Increased Intrathoracic Impedance May Predict Adverse Events in LVAD Patients.  


We describe a 36-year-old male with a HeartWare LVAD and a Medtronic Virtuoso DR pacemaker in whom increased intrathoracic impedance preceded suction events, low LVAD flows, symptoms of a heart failure exacerbation, and hospitalization. Measurement of intrathoracic impedance may identify fluid shifts prior to symptoms and predict adverse events in patients with an LVAD. doi: 10.1111/jocs.12191 (J Card Surg 2013;28:616-618). PMID:23909444

Bartoli, Carlo R; Vessels, Kimberly M; McCants, Kelly C



When bad things happen to good surgeons: reactions to adverse events.  


Adverse events are, unfortunately, common components of surgical practice. Much has been done to develop safer systems to prevent these adverse events; however, there has been less focus on the surgeon experiencing these events. This article presents a framework to understand surgeons' reactions to adverse events that was derived from a more recent study as well as a review of relevant psychology literatures. This framework is then situated within the broader picture of mindful practice to explore how the psychological and social dimensions of the surgeon can affect judgment and cognition. PMID:22269268

Luu, Shelly; Leung, Shuk On Annie; Moulton, Carol-anne



Reported adverse drug reactions during the use of inhaled steroids in children with asthma in the Netherlands  

Microsoft Academic Search

Objectives  Inhaled corticosteroids (ICS) are widely used in the treatment of asthma. We studied the suspected adverse drug reactions (sADRs) reported during the use of ICS in the Netherlands.Methods  In the Netherlands, health professionals and patients can report suspected ADRs to the Pharmacovigilance Centre Lareb. All reported sADRs on ICS were categorised and assessed as to whether these were likely to be

T. W. de Vries; J. J. de Langen-Wouterse; E. van Puijenbroek; E. J. Duiverman; L. T. W. de Jong-Van den Berg



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

Microsoft Academic Search

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

Diane K. Wysowski; Lynette Swartz



Identifying genomic and developmental causes of adverse drug reactions in children  

PubMed Central

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

Becker, Mara L; Leeder, J Steven



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

PubMed Central

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

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



Adverse drug reaction profile of nanoparticle versus conventional formulation of paclitaxel: An observational study  

PubMed Central

Objectives: Conventional polyethoxylated castor oil (PCO)-based paclitaxel is associated with major adverse drug reactions (ADRs). Nanoxel, a nanoparticle-based formulation, may improve its tolerability by removing the need for PCO vehicle, and also permit its use in a higher dose. We conducted intensive monitoring of the ADR profile of Nanoxel in comparison with conventional paclitaxel in a public tertiary care set-up. Materials and Methods: ADR data were collected from 10 patients receiving Nanoxel and 10 age-matched controls receiving conventional paclitaxel in this longitudinal observational study, conducted in a medical oncology ward over 18 months. Severity was graded as per US National Cancer Institute Common Terminology Criteria for Adverse Events. Results: The groups had comparable demography at baseline. The median disease duration and per cycle median dose of paclitaxel were greater in the Nanoxel arm. Total 119 ADRs were noted with Nanoxel and 123 with conventional paclitaxel. Of these, 25 (21.0%, 95% CI 13.69–28.33%) in the Nanoxel and 20 (16.2%, 95% CI 9.74–22.78%) in paclitaxel group were of grade 3/4 severity. Common events included myalgia, nausea, anemia, paresthesia, alopecia, diarrhea, and vomiting with Nanoxel, and paresthesia, anemia, myalgia, anorexia, alopecia, vomiting, diarrhea, stomatitis, and nausea with paclitaxel. Of the less common events (<5%), grade 2 or 3 arthralgia was seen exclusively with Nanoxel while motor neuropathy with muscular weakness was more frequent and severe with conventional paclitaxel. Hypersensitivity reactions were not encountered in either arm, although no antiallergy premedication was employed for Nanoxel. Conclusions: Despite its ADR profile being statistically comparable to conventional paclitaxel, this observational study suggests that Nanoxel tolerability could be better, considering that a significantly higher dose was employed. This hypothesis needs confirmation through an interventional study.

Brahmachari, Ballari; Hazra, Avijit; Majumdar, Anup



HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone free anti-tuberculosis treatment in Yaounde, Cameroon.  


To determine the HIV seroprevalence in adult patients with pulmonary tuberculosis in Yaounde and to compare the incidence of adverse skin reactions in patients with and without HIV infection receiving thiacetazone-free antituberculosis treatment, we studied 235 consecutive patients aged 15 years or more admitted into the Chest Clinic of Hospital Jamot in Yaounde with a diagnosis of pulmonary tuberculosis from July 1 to December 31, 1994. HIV testing was done using two ELISAs and confirmed by Western blot. Each patient was monitored for adverse skin reactions to antituberculosis treatment during the two month initial phase of therapy in hospital. Of the 235 patients studied, 156 (66%) were males (mean age: 33 years) and 79 were females (mean age: 30.3 years). Overall, 16.6% (39 cases) of the 235 patients were HIV seropositive. The prevalence of HIV infection was significantly higher in women (24%) than in men (12.5%) (p = 0.02). Adverse skin reactions to antituberculosis treatment were observed in eleven (4.7%) of the 235 patients. The incidence of the reactions was significantly higher in HIV seropositive (23.1%) than in HIV seronegative patients (1.0%) (p < 10 - 7). Two HIV seropositive patients who developed Stevens-Johnson syndrome died. The drugs incriminated for adverse skin reactions in the nine patients who survived were pyrazinamide (four cases) and rifampicin (five cases). PMID:9487410

Kuaban, C; Bercion, R; Koulla-Shiro, S



Incidence and costs of adverse drug reactions in a tertiary care pediatric intensive care unit.  


Adverse drug reactions (ADRs) increase morbidity, mortality, and hospital costs in children treated in the Pediatric Intensive Care Unit (PICU). Few studies have reported the incidence and risk factors of ADRs in PICU. Our study aimed to evaluate incidence, risk factors, and economic burden of ADRs in PICU. An intensive ADR surveillance was conducted at the PICU of Children's Hospital of Michigan between November 1, 2010 and May 31, 2011. A trigger list was used to screen for suspected ADR cases. Of the 697 consecutive PICU admissions reviewed, 13.1% experienced at least one episode of ADR. The ADR incidence was 22% in patients with cardiovascular (CV) surgery and 11.5% in other patients. The most frequently detected ADR was electrolyte imbalance associated with diuretic exposure. Mean age at admission was 4 years (interquartile range: 9 months-13 years). Risk factors for ADR included young age (<1 year), Pediatric Risk of Mortality (PRISM) score upon admission ?3, and administration of ?16 medications. ADRs increased total ICU costs by 3.5-fold and length of ICU stay by 3.8-fold. Increased ADR surveillance of high risk patients in conjunction with early intervention may reduce drug related morbidity and costs in the PICU. PMID:23553619

Du, Wei; Tutag Lehr, Victoria; Caverly, Mary; Kelm, Lauren; Reeves, Jaxk; Lieh-Lai, Mary



Preventability analysis of adverse drug reactions detected in two internal medicine departments in Romania.  


In order to improve patient safety, systematic analysis of common and repetitive patterns of preventable adverse drug reactions (pADRs) in the clinical setting should be performed regularly in order to propose adequate prevention strategies. Our aim is to evaluate the preventability of all ADRs collected in a drug information research center database, by spontaneous reporting and clinical surveillance in two internal medicine departments. One reviewer systematically reevaluated all the cases stored in the database. ADRs were deemed preventable if they were due to: a contraindication, an inadequate dose, a drug interaction, an inappropriate prescribing decision for the patient's condition, inadequate monitoring, self-medication, or non-adherence to therapy. Out of 251 ADRs evaluated, 103 (41 %) were considered preventable. Out of the total pADRs, 86.4 % were serious. The most frequent adverse outcomes affected the gastrointestinal system (21.4 %), followed by the renal (11.6 %), metabolic (10.7 %), vascular (10.7 %) and hepatic (6.8 %) systems. Acenocoumarol (28 %), diclofenac (12.6 %), digoxin and furosemide accounted for more than 50 % of all preventable reports. One of up to three factors was involved in the preventability of the analyzed reports. Drug-drug interactions were the cause of 49.5 % of the pADRs. Inappropriate dose accounted for 17.5 % reports out of the total pADRs, inappropriate monitoring for 9.7 % reports, history of allergy to drug or drug class for 5.8 % reports and administration of a contraindicated drug for 4.8 % reports. Identifying prevalent pADRs in this study indicates a clear target for prevention strategies: drug prescription, with a special emphasis on drug interactions. PMID:22907809

Farcas, Andreea; Bucsa, Camelia; Sinpetrean, Aura; Leucuta, Daniel; Mogosan, Cristina; Dumitrascu, Dan; Achimas, Andrei Cadariu; Bojita, Marius



Patients with local adverse effects from dental alloys: frequency, complaints, symptoms, allergy.  


Data on the prevalence of adverse effects from dental cast alloys and on the characteristics of the related patient groups are scarce. Therefore, the aim of the present study was to investigate patients in a defined part of Germany attributing oral complaints or symptoms to dental cast alloys. All dentists in the area of Eastern Bavaria (with 1 million inhabitants) were asked to send corresponding patients to our department during a 3-year period. Out of this collection, patients with complaints or symptoms in the oral cavity were recruited and characterized with regard to number, age and sex distribution, type of subjective complaints and objective intraoral symptoms, and allergy status based on an alloy analysis. Patients reporting to our department with suspected local adverse effects from dental cast alloys represented 0.01% of the population. Thirty-four percent of the patients were 50-59 years old, with females prevailing (76%). A great variety of subjective complaints was reported, which mainly resembles those reported by patients with adverse effects attributed to other dental materials like amalgam or denture base materials. The main objective intraoral symptoms were gingivitis, anomalies of the tongue (lingua plicata, lingua geographica), discoloration of the gingiva, redness of the palate or tongue and lichenoid reactions of the oral mucosa. In not more than 10% of the patients, allergy was diagnosed as contributing to the complaints or symptoms. PMID:11800437

Garhammer, P; Schmalz, G; Hiller, K A; Reitinger, T; Stolz, W



Data Visualization Speeds Review of Potential Adverse Drug Events in Patients on Multiple Medications  

PubMed Central

Patients on multiple medications are at increased risk for adverse drug events. While physicians can reduce this risk by regularly reviewing the side-effect profiles of their patients’ medications, this process can be time-consuming. We created a decision support system designed to expedite reviewing potential adverse reactions through information visualization. The system includes a database containing 16,340 unique drug and side-effect pairs, representing 250 common medications. A numeric score is assigned to each pair reflecting the strength of association between drug and effect. Based on these scores, the system generates graphical adverse reaction maps for any user-selected combination of drugs. A study comparing speed and accuracy of retrieving side-effect data using this tool versus UpToDate® demonstrated a 60% reduction in time to complete a query (61 seconds vs. 155 seconds, p<0.0001) with no decrease in accuracy. These findings suggest that information visualization can significantly expedite review of potential adverse drug events.

Duke, Jon D.; Li, Xiaochun; Grannis, Shaun J.



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


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



Polypharmacy as a risk factor for adverse drug reactions in geriatric nursing home residents  

Microsoft Academic Search

Objective:Polypharmacy is a well-known risk factor for adverse drug reactions (ADRs). The objective of this study was to determine the relationship between the use of ?9 different scheduled medications and the occurrence of ADRs in geriatric nursing home residents.

Julia K. Nguyen; Michelle M. Fouts; Sharon E. Kotabe; Eunice Lo



Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome  

Microsoft Academic Search

Identifying genetic factors responsible for serious adverse drug reaction (SADR) is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might

Lun Yang; Jian Chen; Lin He



Predicting Adverse Drug Reactions Using Publicly Available PubChem BioAssay Data  

Microsoft Academic Search

Adverse drug reactions (ADRs) can have severe consequences, and therefore the ability to predict ADRs prior to market introduction of a drug is desirable. Computational approaches applied to preclinical data could be one way to inform drug labeling and marketing with respect to potential ADRs. Based on the premise that some of the molecular actors of ADRs involve interactions that

Y Pouliot; A P Chiang; A J Butte



Differences in Manufacturer Reporting of Adverse Drug Reactions to the FDA in 1984  

Microsoft Academic Search

Pharmaceutical manufacturers were ranked by the number of adverse drug reaction reports that the FDA received from them in 1984. Twenty companies submitted 79% of all the manufacturer reports. These companies were assessed in terms of their total prescriptions, hospital and drug store sales, and detailing calls. All three variables were correlated with the number of ADR reports, but dollar

Carlene Baum; Gerald A. Faich; Charles Anello; Mary B. Forbes



A Microcomputer-Based Data Entry System for Reporting Adverse Drug Reactions in the United States  

Microsoft Academic Search

A microcomputer-based data entry system has been developed by the Food and Drug Administration as a method of reporting adverse drug reactions that are required by pharmaceutical manufacturers to be periodically submitted to the Agency on an official form. This microcomputer system may also be useful for other interested health professional concerned with the safety of drugs and biologics. The

Michael H. Dong; Charles Anello; John P. Juergens; Wayne M. Turner; Alan Gelberg; George D. Armstrong



A Team Agent Approach to Postmarketing Surveillance of Adverse Drug Reactions  

Microsoft Academic Search

Current postmarketing surveillance methods largely rely on spontaneous reports which suffer from serious underreporting, latency, and inconsistent reporting. Thus they are not ideal for rapidly identifying rare adverse drug reactions (ADRs). We propose an active, multi-agent computer software system, where each agent is empowered with teamwork capabilities such as anticipating information needs, identifying relevant ADR information, and continuously monitoring and

Yanqing Ji; Hao Ying; Daniel C. Barth-Jones; John Yen; Shizhuo Zhu; Richard E. Miller; R. M. Massanari



Application of Quantitative Signal Detection in the Dutch Spontaneous Reporting System for Adverse Drug Reactions  

Microsoft Academic Search

detection of unknown adverse drug reactions (ADRs), or signal detection. Gener- ally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative signal detection, can provide additional information concerning a possible relationship between a drug and an ADR. We describe the role of

Willem L Diemont; Kees van Grootheest



Severe adverse reaction risks during mass treatment with ivermectin in loiasis-endemic areas  

Microsoft Academic Search

The control of onchocerciasis remains a priority in sub-Saharan Africa. Jean-Philippe Chippaux, Michel Boussinesq, Jacques Gardon, Nathalie Gardon-Wendel and Jean-Christophe Ernould here outline studies concerning possible severe adverse reactions to ivermectin used to control onchocerciasis in areas where loiasis is also endemic, and discuss precautions that may be advisable during the implementation of such programmes.

Jean-Philippe Chippaux; Michel Boussinesq; Jacques Gardon; Nathalie Gardon-Wendel; Jean-Christophe Ernould



Gender-Based Differences in Drug Prescription: Relation to Adverse Drug Reactions  

Microsoft Academic Search

Background\\/Aim: The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes with respect to

Y. Zopf; C. Rabe; A. Neubert; C. Janson; K. Brune; E. G. Hahn; H. Dormann



Perception on Adverse Drug Reaction Reporting by Physicians Working in Southern Romania  

PubMed Central

ABSTRACT Aim: The purpose of our study was to investigate and to assess the perceptions of Romanian doctors towards adverse drug reactions (ADRs) reporting. Method: A questionnaire with 20 items accompanied by a letter presenting the study was circulated using Internet and face to face interviews to 532 doctors in Bucharest and two neighboring regions from Romania (Muntenia and Oltenia). Results: 204 (56.2%) of the total number of responders expressed their opinion that the daily number of ADRs observed to be under 5 309 (58%) of responders were never informed about ADRs reporting, 439 (82.52%) did not know that the Romanian College of Physicians is scoring this activity under the "Continuous medical education program". Factors that might encourage voluntary reporting of adverse reactions were identified to be: the easiness of reporting, their periodic information and the training about all adverse reactions reported by doctors and the measures taken. Factors discouraging voluntary reporting of an adverse drug reaction were: the lack of information on where, when and how to report ADRs, the uncertain causality. Conclusion: Currently, the pharmacovigilance activities including reporting of ADRs in Romania are more of an accidental nature, doctors are less or not at all informed about this activity. Doctors have a favorable attitude towards reporting ADRs – as the majority believes that the reporting should be either voluntary or mandatory as opposed to a small number that would expect to be paid for this activity.

PAVELIU, Marian Sorin; BENGEA-LUCULESCU, Simona; TOMA, Mihai; PAVELIU, Silvia Fraga



Spontaneous reporting of adverse drug reactions to non-steroidal anti-inflammatory drugs  

Microsoft Academic Search

Non-steroidal anti-inflammatory drugs (NSAIDs) are the third most commonly prescribed group of drugs in Spain. We present here the profile of adverse drug reactions (ADRs) attributed to them and reported to the Spanish System of Pharmacovigilance (SSPV) between 1983 and 1991, together with a preliminary analysis of topical, slow-release (SR) and enteric-coated (EC) preparations.

A. Figueras; D. Capellà; J. M. Castel; J. R. Laporte



Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria  

Microsoft Academic Search

BACKGROUND: Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR

Kazeem A Oshikoya; Jacob O Awobusuyi



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

Microsoft Academic Search

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

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



How adverse drug reactions can play a role in innovative drug research  

Microsoft Academic Search

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

Floor Rikken; Rein Vos



Information about adverse drug reactions reported in children: a qualitative review of empirical studies  

PubMed Central

AIM To review the literature on adverse drug reactions (ADRs) in children with respect to occurrence, seriousness, type, therapeutic group, age and gender of the child and category of reporter. METHODS Medline and Embase databases were searched from origin and updated until February 2010. We included empirically based articles on ADRs in populations aged 0 to 17 years. Studies monitoring ADRs in patients with particular conditions or drug exposure were excluded. We extracted information about types and seriousness of ADRs, therapeutic groups, age and gender of the child and category of reporter. ADR occurrence was calculated as incidence rate and prevalence. RESULTS We included 33 studies monitoring ADRs in general paediatric populations. The highest numbers of ADRs were reported in national ADR databases where data were collected over a longer period than in studies monitoring inpatients and outpatients. However, prevalence and incidence were much lower in the national databases. Types of reported ADRs, seriousness of ADRs and types of medicines differed substantially between studies due to differences in time periods and patient populations. Information about ADRs was mainly provided by health care professionals, although parents also contributed reports. CONCLUSIONS We found a higher incidence rate of ADRs in hospitalized children and outpatients than in national databases. There seems to be considerable potential for increasing the knowledge of ADRs by advocating the submission of reports to the spontaneous reporting systems. Our study underscores that ADRs in children constitute a significant public health problem.

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



Knowledge, attitudes and practice of nurse regarding adverse drug reaction reporting  

PubMed Central

Background: Adverse drug reactions (ADR) are ranked as some of the major causes of patient morbidity and mortality. Spontaneous reporting of ADRs has remained the cornerstone of pharmacovigilance and is important in maintaining patient safety. This study was conducted to assess the nurses’ knowledge and attitude towards pharmacovigilance, reasons for not reporting ADRs, and their pharmacovigilance practice. Materials and Methods: A questionnaire was prepared to investigate knowledge, attitude and practice (KAP) of nurses regarding ADR reporting. In November 2009, the questionnaires were given to 500 nurses of a teaching hospital in Tehran. Findings: Knowledge and practice of participants were not satisfying; however, their attitude towards pharmacovigilance was at a high level. About 91% of the nurses had never reported an ADR. Most nurses liked to report the ADRs to the physicians (87.1%) and pharmacists in hospital's ADR center (1.8%) rather than the ADR National Center. The main cause of under-reporting of the suspected ADRs was unawareness about the existence of such a national center. Among nurses who had reported ADR for at least once, the majority preferred using phone (10 out of 50) or Yellow Cards (7 out of 50). Only 1 person out of 50 preferred using internet for submitting the reports Conclusions: Since the nurses in this study had little knowledge and poor practice regarding the pharmacovigilance and spontaneous reporting system, interventions such as holding pharmacovigilance workshops in the hospitals focusing on the aims of pharmacovigilance, completing the Yellow Card and clarifying the reporting criteria are strongly recommended.

Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Javadi, Mohammadreza



Barriers and facilitators for preventing adverse drug reactions of long latency: a qualitative study.  


Objective: To understand the practices medical care providers and health care staff utilize in managing and preventing Adverse Drug Reactions of Long Latency (ADRLLs) among their patients on medications such as glucocorticoids. Design: Qualitative study of key informant interviews. Setting: Denver Department of Veterans Affairs (VA) Medical Center. Participants: Fourteen physician providers and health care staff (nurses and pharmacists) in primary care and rheumatology. Methods: A trained interviewer conducted semi-structured interviews in which providers and health care staff were asked about their processes for tracking and averting ADRLLs. Participants were asked about barriers and facilitators to monitoring ADRLLs and solicited for suggestions to improve existing processes. Interviews were analyzed using ATLAS.ti software. Results: Providers overwhelmingly commented on barriers, rather than facilitators. Six core themes emerged regarding ADRLL management barriers: patient noncompliance, provider workload, complications coordinating care, provider unfamiliarity with ADRLLs, lack of a standardized monitoring system, and communication failures. Ideas to improve the monitoring of ADRLLs fell into two domains: improving automated computer generated reminders or assigning a specific person to monitor potential ADRLLs. Conclusions: Interviewees strongly endorsed a more systematic approach to ADRLL management, either through less intrusive computer-generated system reminders or through a dedicated staff person, such as a pharmacist, who could more closely monitor potential ADRLLs. There was disagreement among interviewees about who is responsible for monitoring ADRLLs (specialists versus primary care providers, VA versus non-VA providers, residents versus attending physicians). PMID:22751190

Caplan, Liron; Haverhals, Leah M



Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions.  


Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results. PMID:11846746

Barbaud, A; Gonçalo, M; Bruynzeel, D; Bircher, A



Retrospective evaluation of adverse transfusion reactions following blood product transfusion from a tertiary care hospital: A preliminary step towards hemovigilance  

PubMed Central

Background: The goal of hemovigilance is to increase the safety and quality of blood transfusion. Identification of the adverse reactions will help in taking appropriate steps to reduce their incidence and make blood transfusion process as safe as possible. Aims: To determine the frequency and type of transfusion reactions (TRs) occurring in patients, reported to the blood bank at our institute. Materials and Methods: A retrospective review of all TRs reported to the blood bank at the All India Institute of Medical Sciences, between December 2007 and April 2012 was done. All the TRs were evaluated in the blood bank and classified using standard definitions. Results: During the study period a total of 380,658 bloods and blood components were issued by our blood bank. Out of the total 196 adverse reactions reported under the hemovigilance system, the most common type of reaction observed was allergic 55.1% (n = 108), followed by febrile non-hemolytic transfusion reaction (FNHTR) 35.7% (n = 70). Other less frequently observed reactions were Anaphylactoid reactions 5.1% (n = 10), Acute non-immune HTRs 2.6% (n = 5), Circulatory overload 0.5% (n = 1), Transfusion related acute lung injury 0.5% (n = 1), Delayed HTRs 0.5% (n = 1). Not a single case of bacterial contamination was observed. Conclusion: The frequency of TRs in our patients was found to be 0.05% (196 out of 380,658). This can be an underestimation of the true incidence because of under reporting. It should be the responsibility of the blood transfusion consultant to create awareness amongst their clinical counterpart about safe transfusion practices so that proper hemovigilance system can be achieved to provide better patient care.

Kumar, Praveen; Thapliyal, Rakesh; Coshic, Poonam; Chatterjee, Kabita



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.

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



Community-based treatment of onchocerciasis with ivermectin: acceptability and early adverse reactions.  

PubMed Central

A study of community-based treatment of onchocerciasis with ivermectin was undertaken in a rain forest area of Liberia to investigate the possible occurrence of serious adverse effects. The total population was 13,704, the microfilarial load was 5.35 mf/mg skin, and the prevalence of Onchocerca volvulus infection was 50% at 9 years of age and over 80% among those aged 15 years and older. Certain groups (like pregnant women and young children) were excluded from treatment. Out of the 7956 people eligible for treatment, 7699 (97%) accepted the ivermectin. Data on possible adverse reactions were collected by four different methods, including systematic house-by-house follow-up visits three days after treatment, biweekly population surveillance, and monitoring of both mobile clinic records and hospital records. No severe adverse reactions were noted, and no deaths could be related to ivermectin treatment; only 1.3% of the persons treated had a moderate adverse reaction of the Mazzotti type, presumably related to the killing of microfilariae. The study showed good acceptance by the population, and that mass treatment campaigns with ivermectin are feasible.

Pacque, M. C.; Dukuly, Z.; Greene, B. M.; Munoz, B.; Keyvan-Larijani, E.; Williams, P. N.; Taylor, H. R.



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

PubMed Central

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

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



Adverse transfusion reactions associated with a precipitating anti-C4 antibody of anti-Rodgers specificity.  


A patient suffering from chronic hepatitis exhibited severe transfusion reactions after administration of fresh frozen plasma and a plasma fraction: PPSB (prothrombin complex concentrate). 1 month before these reactions, she received fresh frozen plasma during plasma exchange therapy. The patient's serum obtained 1 week and 6 months after the second reaction gave a precipitation arc against PPSB preparations when examined by double-diffusion technique in agarose gel. An antibody of IgG class present in these sera reacted with a purified preparation of the fourth complement component (C4). This was demonstrated by various experiments (protein A radioimmunoassay and passive hemagglutination) using purified C4 as antigen. The antibody had a limited specificity and reacted only with C4 of Rodgers specificity. Phenotype determination of the patient's C4 group showed that she was Chido positive and Rodgers negative. Her HLA group was A1, Aw30; B8,-; DR3,-. The patient had neither detectable anti-IgA nor other anti-immunoglobulin antibodies. She had not received blood or plasma transfusion before her hepatitis. The coexistence of a precipitating anti-C4 antibody and adverse transfusion reactions to plasma fractions containing large amounts of C4 indicates that in the absence of antibodies of other specificities, this antibody can be considered as the cause of the transfusion reaction. PMID:6464422

Lambin, P; Le Pennec, P Y; Hauptmann, G; Desaint, O; Habibi, B; Salmon, C



Adverse drug events in surgical patients: an observational multicentre study.  


Background Errors occurring during different steps of the medication process can lead to adverse drug events (ADEs). Surgical patients are expected to have an increased risk for ADEs during hospitalization. However, detailed information about ADEs in the surgical patient is lacking. Objective In this study, we aim to measure the incidence and nature of (preventable) ADEs, potential risk factors for and outcome parameters of (preventable) ADEs in surgical patients. Setting Observational multicentre cohort study in which eight surgical wards participated from three Dutch hospitals, all using computerized physician order entry (CPOE) systems with clinical decision support. Methods Electively admitted surgical patients of the participating wards were included from March until June 2009. ADEs were measured using a standardized method with expert judgment. Incidence, severity, preventability and accountable medication were assessed. Poisson regression analysis was applied to determine the associations between possible risk factors and the occurrence of ADEs, expressed as incidence rate ratio (IRR). Also outcomes of ADEs in surgical patients were measured. Main outcome measure The incidence and nature of (preventable) ADEs in surgical patients. Results A total of 567 surgical patients were included. We found an incidence of 27.5 ADEs and 4.2 preventable ADEs (pADEs) per 100 admissions (15.4 %). A quarter of the pADEs were severe or life-threatening. Opioids and anti-coagulation medication play a major role in the occurrence of ADEs and pADEs respectively. Univariate analysis revealed an American Society of Anesthesiologists classification of III or more as a risk factor for ADEs. Patients older than 65 years [IRR 2.77 (1.14-6.72)], with cardiovascular comorbidity [IRR 2.87 (1.13-7.28)], or undergoing vascular surgery [IRR 2.32 (1.01-5.32)] were at risk for pADEs. Patients experiencing an ADE had a significant longer duration of admission than patients without an ADE. Conclusions Surgical patients are at considerable risk of experiencing one or more ADEs during their admission, also in CPOE-hospitals. Risk factors for pADEs are age older than 65 years, cardiovascular comorbidity, and vascular surgery. Intensified monitoring may be needed in patients with a higher than average risk for pADEs. PMID:23722455

de Boer, Monica; Boeker, Eveline B; Ramrattan, Maya A; Kiewiet, Jordy J S; Dijkgraaf, Marcel G W; Boermeester, Marja A; Lie-A-Huen, Loraine



A portable database of adverse reactions and drug interactions with radiopharmaceuticals.  


Our objective was to develop a software application that allows us to easily manage a portable database of information on radiopharmaceutical interactions with drugs or other agents and on radiopharmaceutical adverse effects. Methods: The application was developed and compiled with a commercially available data management system and programming language. All data entered into the database came from the scientific literature and were accompanied by their bibliographic references. Results: We developed the database, which we have called Datinrad. To date, it contains 275 drug interactions and 44 records of adverse reactions to radiopharmaceuticals. Conclusion: Datinrad contains all the information published to date on drug-radiopharmaceutical interactions and adverse effects of radiopharmaceuticals and allows users to introduce new data from future publications. The collection of these data and their easy availability to all nuclear medicine personnel will be useful in the recognition of a possible adverse reaction or drug interaction that may alter the radiopharmaceutical biodistribution and lead to a misdiagnosis. This open-access database application is available free of charge in both English and Spanish at PMID:23857419

Gómez Perales, Jesús Luis; Martínez, Ana Agudo



COSTART: Coding Symbols for Thesaurus of Adverse Reaction Terms, 4th Edition (5 1/4 inch version) (for Microcomputers).  

National Technical Information Service (NTIS)

Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) is the terminology developed and used by the Food and Drug Administration (FDA) for the coding, filing and retrieving of post marketing adverse reaction reports. It provides a method to de...



COSTART: Coding Symbols for Thesaurus of Adverse Reaction Terms, 5th Edition (3 1/2 Inch Version) (for Microcomputers).  

National Technical Information Service (NTIS)

Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) is the terminology developed and used by the Food and Drug Administration (FDA) for the coding, filing and retrieving of post marketing adverse reaction reports. It provides a method to de...



COSTART: Coding Symbols for Thesaurus of Adverse Reaction Terms, 4th Edition, (3 1/2 inch version) (for Microcomputers).  

National Technical Information Service (NTIS)

Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) is the terminology developed and used by the Food and Drug Administration (FDA) for the coding, filing and retrieving of post marketing adverse reaction reports. It provides a method to de...



Genetic polymorphism of cytochrome P 450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions  

Microsoft Academic Search

Background Apart from allergic mechanisms, a lack or mutation of metabolic enzymes may cause adverse drug reactions. Patch testing has rarely been useful in cutaneous adverse drug reactions (CADRs) induced by diphenylhydantoin (DPH). Genetic polymorphisms leading to altered metabolic processes of cytochrome P 450 (CYP) 2C9, a main metabolic enzyme for DPH, may be the pathological mechanism for certain cases

Ai-Young Lee; Min-Jung Kim; Won-Young Chey; Jun Choi; Byung-Gun Kim



Monitoring of adverse reactions and interactions involving veterinary drugs in the U.S.A  

Microsoft Academic Search

Teske, R.H., 1983. Monitoring of adverse reactions and interactions involving veterinary drugs in the U.S.A. Vet. Res. Commun., 7: 215-220. Role of the Bureau of Veterinary Medicine The mission of the Bureau of Veterinary Medicine is, briefly stated, to insure that veterinary drugs and feed additives are safe and efficacious. In order to efficiently carry out this mission, the Bureau

Richard H. Teske



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



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

Microsoft Academic Search

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

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



Detection of adverse drug reactions through the minimum basic data set  

Microsoft Academic Search

Objective To analyze adverse drug reaction (ADR) detection using the Minimum Basic Data Set (MBDS) at hospital discharge and to compare\\u000a the ADR reporting rate to the Pharmacovigilance Referral Centre with other similar hospitals that do not use this reporting\\u000a system. Setting 650-bed University Hospital serving a population of 294,000 inhabitants in Spain. Method: A retrospective descriptive study\\u000a was conducted

Antonio Salmerón-García; José Cabeza Barrera; Maria José Vergara Pavón; Eva Román Márquez; Sol Cortés de Miguel; Inmaculada Vallejo-Rodríguez; Susana Raya García; Emilia Casado Fernández



A Bayesian neural network method for adverse drug reaction signal generation  

Microsoft Academic Search

Objective: The database of adverse drug reactions (ADRs) held by the Uppsala Monitoring Centre on behalf of the 47 countries of the\\u000a World Health Organization (WHO) Collaborating Programme for International Drug Monitoring contains nearly two million reports.\\u000a It is the largest database of this sort in the world, and about 35 000 new reports are added quarterly. The task of

A. Bate; M. Lindquist; I. R. Edwards; S. Olsson; R. Orre; A. Lansner; R. M. De Freitas



[Adverse drug reactions: an update review of the problem in Spain].  


Adverse drug reactions (ADR) are an important clinical problem and their impact on the Spanish population is unknown. The aim of this study was to provide an overview of ADR based on a review of observational studies published in Spain since 1974. Twenty-seven studies of Spanish patients were selected from a total of 90 articles published in national and international journals between 1974 and 2004. Studies eligible for inclusion were identified with an especially designed checklist. The incidence of ADR among 139,799 patients was 3%; 0.6% of the events led to death, and 17% led to severe illness. Two-thirds (67%) of the ADR were classified as type A. The rate of hospitalization for ADR was 6.5%, and mean length stay was 4 +/- 1.3 days. Thirteen percent of the ADR were considered confirmed, and 57% were considered probable. Half (50%) of the ADR were considered preventable. The groups of medications involved most frequently were antibacterial, NSAID, psychoactive medications, bronchodilators, digoxin, non-opiate analgesics, vasodilators, antidiabetics and loop diuretics. The organs and systems involved most frequently were the digestive tract, skin, central nervous system, cardiovascular, endocrine and respiratory systems. The factors associated most strongly with ADR were advanced age and use of multiple medications. The relationships of gender, previous history of ADR and comorbidity with the incidence of ADR have yet to be established. This review of ADR provides useful information on the incidence of ADR in the Spanish population and serves as a baseline for future studies. PMID:16831381

Puche Cañas, E; Luna, J de Dios


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


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

Takahashi, Haruo



Patient safety in hospitals: new insight form the Dutch adverse event study  

Microsoft Academic Search

The adverse event study is the first part of the Dutch national research program on patient safety. The main parts of the program are: (1a) a retrospective epidemiological study in 21 hospitals into the character, severity, extent and costs of adverse events during hospitalization and the resulting harm to patients, (1b) a retrospective epidemiological study of adverse events during day-care

C. Wagner; M. C. Bruyne; M. Zegers; L. Hoonhout; G. van der Wal



[Early adverse reactions after vaccination against influenza in chronically ill people].  


The objective was to assess the early adverse reactions after vaccination against influenza with the use of Fluarix vaccine (SmithKline Beecham) in chronically ill people. 1010 people were selected to undergo vaccination. The group included 621 women aged on average 44.2 years and 389 men aged on average 48.2. The vaccination was conducted simultaneously and the period of adverse reactions monitoring lasted 14 days. The vaccination was performed in accordance with recommendations of manufacturer. All the vaccinated people suffered from circulatory system disorders, bone system disorders, mental disorders and endocrinological problems. They were in the period of remission during the vaccination. The observed symptoms were classified into two categories: local and general. The local symptoms included swelling, reddening and pain in the vaccinated area. 67 people (6.6%) reported swelling, 85 (8.4%) reported reddening, 12 people (1.2%) reported pain in the vaccinated area. The general symptoms included headache, bad mood and temperature over 37.5 degrees C. 19 people (1.9%) reported bad mood, 10 people (1%)--headache and 8 people (0.8%) reported temperature over 37.5 degrees C. Coexistence of two or three types of symptoms was present in 15 cases (1.5%). The low percentage of early adverse reactions encourages a wider use of vaccines against influenza in chronically ill people. PMID:12428564

Ga?aj, Andrzej; Grze?k, Grzegorz; Kuziemski, Arkadiusz; Szadujkis-Szadurski, Leszek; Durmowicz, Anna



Late adverse reactions to intravascular iodine based contrast media: an update  

Microsoft Academic Search

Definition  Late adverse reactions (LAR) to contrast media (CM) are defined as reactions occurring 1 h to 1 week after exposure.\\u000a \\u000a \\u000a \\u000a Need for review  In view of more prospective studies of LAR and new data about their pathophysiology, the Contrast Medium Safety Committee\\u000a (CMSC) of the European Society of Urogenital Radiology (ESUR) reviewed the literature on LAR and updated their guidelines.\\u000a \\u000a \\u000a \\u000a \\u000a Clinical features and

Marie-France Bellin; Fulvio Stacul; Judith A. W. Webb; Henrik S. Thomsen; Sameh K. Morcos; Torsten Almén; Peter Aspelin; Olivier Clement; Gertraud Heinz-Peer; Peter Reimer; Aart van der Molen


Association of cetuximab with adverse pulmonary events in cancer patients: a comprehensive review  

PubMed Central

Compounds derived from biologic sources, or biologicals, are increasingly utilized as therapeutic agents in malignancy. Development of anti-cancer targeted therapies from biologics is increasingly being utilized. Cetuximab, a chimeric monoclonal antibody, is one such anti-cancer targeted therapeutic that has shown efficacy in quelling the rate of patient decline in colorectal, head/neck, and non-small cell lung cancer. However, due to the relatively recent addition of biologic compounds to the therapeutic arsenal, information related to adverse reactions is less well known than those seen in traditional chemotherapeutics. Dermatologic reactions have been demonstrated as the most frequent side effect cited during cetuximab therapy for malignancy; however, other effects may lead to greater morbidity. In general, pulmonary complications of therapeutics can lead to significant morbidity and mortality. The purpose of this review is to compile the various pulmonary side effects seen in patients treated with cetuximab for various malignancies, and to compare the incidence of these adverse reactions to standard therapies.

Hoag, Jeffrey B; Azizi, Aimel; Doherty, Timothy J; Lu, Jason; Willis, Rudolph E; Lund, Mark E



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.

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



Few Adverse Reactions to Metal on Metal Articulation in Total Hip Arthroplasty in a Review Study on 358 Consecutive Cases with 1 to 5 Years Follow-Up  

PubMed Central

The aim of the present study was to determine the frequency of adverse reaction to metal on metal total hip arthroplasty using a M2a-38 articulation and a Magnum articulation, (Biomet Warsaw, Indiana). All patients who had received a Metal on Metal bearing prosthesis, in two centres in Copenhagen, were asked to complete a questionnaire about groin pain. Patients with self-reported groin pain, 68/314, underwent a physical examination and had Co and Cr ion levels measured in full blood samples. Fifty patients also had a CT scan performed. The present study found one patient with bilateral arthroplasty, who had an adverse reaction on one side. In addition the study showed that females had higher values of Co and Cr, and that younger patient reported groin pain more often. The conclusion of this study is that the number of adverse reactions is low, despite the time of observation being relatively short, no high frequency of adverse reactions to this prosthesis is expected.

Sturup, Jens; Dahl, Line B; Jensen, Karl-Erik; Larsen, Anne-Birgitte; Gebuhr, Peter



Cutaneous adverse reactions linked to targeted anticancer therapies bortezomib and lenalidomide for multiple myeloma: new drugs, old side effects.  


Abstract Context: Cutaneous toxicity is a frequent side effect of new anticancer targeted therapies. Skin reactions can severely impact the patient's physical, psychological and social well-being and may sometimes lead to discontinuations either treatment dose reductions. Objective: This study evaluates the impact of cutaneous adverse drug reactions (cADR) of the new therapies bortezomib and lenalidomide and presents a review of their skin side effects. Materials and method: Type, frequency, severity, time of onset and management of cADR were collected and the medical records of all multiple myeloma patients receiving bortezomib or lenalidomide in the Hematology and Medical Oncology Institute of the University of Bologna, were analyzed. Results: A total of 17 cADR occurred in 10 patients of 17 (58.8% of patients) treated with bortezomib: 5 rashes, 3 events of pruriginous rash, 1 purpuric rash, 2 records of mouth swelling, 1 stomatitis-mucositis, 3 cases of edema in the lower limbs, 1 patient referred pruritus and another telogen effluvium. Eight skin manifestations were due to lenalidomide in 7 patients of 25 treated (28%): 2 pruriginous rashes, 3 cases of edema, 2 records of pruritus, 1 case of stomatitis-mucositis. Three adverse events linked to bortezomib and 4 to lenalidomide forced to a complete withdrawal of the drug, while 3 reactions due to bortezomib mandated a dose reduction. Dermatological evaluation was performed only in 2 patients treated with bortezomib and 1 with lenalidomide. Discussion: Evaluations of cADR due to bortezomib and lenalidomide were performed. There are no other reports focused on skin events in patients treated with the triple regimen velcade (bortezomib)-thalidomide-dexamethasone (VTD) up to date. Our study suggests that cutaneous toxicities, when researched by Dermatologists, are a side effect even more frequent than the reported data. Limitations: As it is a single institute and retrospective study, ongoing cADR were rarely evaluated by dermatologists; thus, it is possible that cutaneous reactions (especially mild) may have been under reported by Hematologists and Oncologists in clinical records. Conclusions: Even with the development of new drugs for cancer treatment, "old" cutaneous side effects may still be present, compromising patients' quality of life. Physicians prescribing bortezomib and lenalidomide should monitor their patients for the spectrum of cADR, and they should involve dermatologists in consultations and management of these events. A multidisciplinar approach is necessary to oncologic patient in order to provide a tailored supportive clinical care. PMID:23638756

Patrizi, Annalisa; Venturi, Michela; Dika, Emi; Maibach, Howard; Tacchetti, Paola; Brandi, Giovanni



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.

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



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

Microsoft Academic Search

: Complementary and alternative medicine and dietary supplements are often used by patients. A detailed examination of each preparation used by four patients was carried out. Seven such preparations with the potential to cause bleeding, cardiovascular and central nervous system side effects, and allergic food reactions are described. They were taken by both Asian and Caucasian patients, were purchased locally,

H. C. George Wong



Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs.  

PubMed Central

Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future.

Phillips-Howard, P. A.; Bjorkman, A. B.



A review of safety, efficacy, and utilization of erythropoietin, darbepoetin, and peginesatide for patients with cancer or chronic kidney disease: a report from the Southern Network on Adverse Reactions (SONAR).  


The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin prevent transfusions among chemotherapy-associated anemia patients. Clinical trials, meta-analyses, and guidelines identify mortality, tumor progression, and venous thromboembolism (VTE) risks with ESA administration in this setting. Product labels advise against administering ESAs with potentially curative chemotherapy (United States) or to conduct risk-benefit assessments (Europe/Canada). Since 2007, fewer chemotherapy-associated anemia patients in the United States and Europe receive ESAs. ESAs and the erythropoietin receptor agonist peginesatide prevent transfusions among chronic kidney disease (CKD) patients; clinical trials, guidelines, and meta-analyses demonstrate myocardial infarction, stroke, VTE, or mortality risks with ESAs targeting high hemoglobin levels. U.S. labels recommend administering ESAs or peginesatide at doses sufficient to prevent transfusions among dialysis CKD patients. For dialysis CKD patients, Canadian and European labels recommend targeting hemoglobin levels of 10 to 12 g/dL and 11 to 12 g/dL, respectively, with ESAs. ESA utilization for dialysis CKD patients has decreased in the United States. PMID:23111861

Bennett, Charles L; Spiegel, David M; Macdougall, Iain C; Norris, LeAnn; Qureshi, Zaina P; Sartor, Oliver; Lai, Stephen Y; Tallman, Martin S; Raisch, Dennis W; Smith, Sheila Weiss; Silver, Samuel; Murday, Alanna S; Armitage, James O; Goldsmith, David



The importance of experienced adverse outcomes on patients' future choice of a hospital for surgery  

Microsoft Academic Search

ObjectiveTo assess whether patients who experience adverse outcomes during hospitalisation or after discharge differ in the information they would use for future choices of a hospital for surgery compared with patients without any adverse outcomes.DesignCross-sectional questionnaire study, including questions on (1) adverse outcome occurrence during hospitalisation and after discharge, (2) information patients would use for future hospital choice and (3)

P J Marang-van de Mheen; J Dijs-Elsinga; W Otten; M Versluijs; H J Smeets; W J van der Made; R Vree; J Kievit



Adverse reactions to lipiodol ultra fluid: report of an accidental case.  


A 25-year-old Japanese woman experienced pulmonary edema, shock, encephalopathy and silent pancreatitis after hysterosalpingography using lipiodol ultra fluid, because the contrast media flowed directly into the blood stream from endometrium injured by several curettages for termination of pregnancy. Total iodine concentrations in plasma and urine decreased exponentially and their half-life was 16.12 and 13.04 days, respectively. Clear correlations were observed between the iodine concentration in plasma and the amelioration of both electroencephalogram and neuropsychic abnormalities. Adverse reactions of oil-soluble contrast media are also discussed. PMID:1652663

Ogihara, T; Miyao, H; Katoh, H; Ikenaga, H; Michikawa, N; Ohkubo, N; Kasahara, M; Iyori, S



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

Microsoft Academic Search

Background  Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the\\u000a burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health\\u000a cost.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry\\u000a of Health

Pilar Carrasco-Garrido; López Ana de Andrés; Hernández Valentín Barrera; Gil Ángel de Miguel; Rodrigo Jiménez-García



Adverse tissue reactions in modular exchangeable neck implants: a report of two cases.  


Dual-modular femoral stems with exchangeable necks theoretically allow optimization of hip joint biomechanics via selective restoration of femoral anteversion, offset, and limb length. A potential disadvantage is the possible generation of metal ions and debris by fretting and crevice corrosion at the additional stem-neck interface. We present 2 cases of early-onset adverse inflammatory tissue reactions as a result of accelerated corrosion at the stem-neck interface of a dual-modular implant, requiring subsequent revision of well-fixed components. PMID:23141863

Werner, S Douglas; Bono, James V; Nandi, Sumon; Ward, Daniel M; Talmo, Carl T



Immunologic mechanisms responsible for adverse reactions to routine immunizations in children.  


The principal licensed biologicals for human use in the United States have been listed with special emphasis given to antiviral vaccines. Possible adverse reactions of an immunologic nature which may be encountered in the use of these agents in routine immunization programs are described, while at the same time, their relative rarity is emphasized. The special problems one may encounter in immunizing the atopic child, the immunodeficient child, the child with active tuberculosis and the pregnant woman are considered separately, as are the undesirable consequences of hyperimmunization are mentioned. PMID:133013

Vessal, S; Kravis, L P



Comorbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort study  

PubMed Central

Objectives To identify factors that predict repeat admission to hospital for adverse drug reactions (ADRs) in older adults. Design Population based retrospective cohort study. Setting All public and private hospitals in Western Australia. Participants 28?548 patients aged ?60 years with an admission for an ADR during 1980-2000 followed for three years using the Western Australian data linkage system. Results 5056 (17.7%) patients had a repeat admission for an ADR. Repeat ADRs were associated with sex (hazard ratio 1.08, 95% confidence interval 1.02 to 1.15, for men), first admission in 1995-9 (2.34, 2.00 to 2.73), length of hospital stay (1.11, 1.05 to 1.18, for stays ?14 days), and Charlson comorbidity index (1.71, 1.46 to 1.99, for score ?7); 60% of comorbidities were recorded and taken into account in analysis. In contrast, advancing age had no effect on repeat ADRs. Comorbid congestive cardiac failure (1.56, 1.43 to 1.71), peripheral vascular disease (1.27, 1.09 to 1.48), chronic pulmonary disease (1.61, 1.45 to 1.79), rheumatological disease (1.65, 1.41 to 1.92), mild liver disease (1.48, 1.05 to 2.07), moderate to severe liver disease (1.85, 1.18 to 2.92), moderate diabetes (1.18, 1.07 to 1.30), diabetes with chronic complications (1.91, 1.65 to 2.22), renal disease (1.93, 1.71 to 2.17), any malignancy including lymphoma and leukaemia (1.87, 1.68 to 2.09), and metastatic solid tumours (2.25, 1.92 to 2.64) were strong predictive factors. Comorbidities requiring continuing care predicted a reduced likelihood of repeat hospital admissions for ADRs (cerebrovascular disease 0.85, 0.73 to 0.98; dementia 0.62, 0.49 to 0.78; paraplegia 0.73, 0.59 to 0.89). Conclusions Comorbidity, but not advancing age, predicts repeat admission for ADRs in older adults, especially those with comorbidities often managed in the community. Awareness of these predictors can help clinicians to identify which older adults are at greater risk of admission for ADRs and, therefore, who might benefit from closer monitoring.



Adverse reactions from community directed treatment with ivermectin (CDTI) for onchocerciasis and loiasis in Ondo State, Nigeria.  


Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2331 males and 2469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0-52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol. PMID:19419072

Otubanjo, O A; Adeoye, G O; Ibidapo, C A; Akinsanya, B; Okeke, P; Atalabi, T; Adejai, E T; Braide, E



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



Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS  

PubMed Central

Background Previously, adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. Conclusions The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.



Allergic reactions to iodinated contrast media: premedication considerations for patients at risk.  


The objectives of this article are to review allergy-type reactions to iodinated contrast media and the protocols utilized to prevent or reduce the occurrence of these adverse reactions in high-risk patients. We will begin by discussing the types or classifications of the adverse reactions to iodinated contrast media. We will then discuss reaction mechanisms, identify the patients at highest risk for adverse reactions, and clarify common misperceptions about the risk. Finally, we will discuss the actions of the medications used to help reduce or prevent allergy-type reactions to iodinated contrast media, the protocols used to help reduce or prevent contrast reactions in high-risk patients, and the potential side effects of these medications. We will also discuss the high-risk patient who has received premedication due to a prior index reaction and discuss the risk of having a subsequent reaction, termed "breakthrough reaction." Identifying patient at high risk for an "allergy-type" reaction to contrast media is an essential task of the radiologist. Prevention of or reduction of the risk of an adverse reaction is critical to patient safety. If an examination can be performed without contrast in a patient at high risk for an allergy-type reaction, it may be appropriate to avoid contrast. However, there are situations where contrast media is necessary, and the radiologist plays a vital role in preventing or mitigating an allergy-type reaction. PMID:23430296

Schopp, Jennifer G; Iyer, Ramesh S; Wang, Carolyn L; Petscavage, Jonelle M; Paladin, Angelisa M; Bush, William H; Dighe, Manjiri K



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


Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism. PMID:19997080

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



Determinants of under-reporting of adverse drug reactions: a systematic review.  


A voluntary reporting system of adverse drug reactions (ADRs) is fundamental to drug safety surveillance but under-reporting is its major limitation. This bibliographic review sought to assess the influence of personal and professional characteristics on ADR reporting and to identify knowledge and attitudes associated with ADR reporting. A systematic review was conducted using the MEDLINE and EMBASE databases. We included papers that were published in English, French and Spanish, and covered a study population made up of health professionals. In each case, the following data were extracted: study population; workplace; study type; sample size; type of questionnaire; type of scale for measuring knowledge; response rate; personal and professional factors; and knowledge and attitudes (based on Inman's 'seven deadly sins') associated with reporting. Based on a search of computerized databases, we identified a total of 657 papers in MEDLINE and 973 in EMBASE. In all, the review covered 45 papers that fulfilled the inclusion criteria. Medical specialty was the professional characteristic most closely associated with under-reporting in 76% of studies involving physicians. Other factors associated with under-reporting were ignorance (only severe ADRs need to be reported) in 95%; diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 72%; lethargy (an amalgam of procrastination, lack of interest or time to find a report card, and other excuses) in 77%; indifference (the one case that an individual doctor might see could not contribute to medical knowledge) and insecurity (it is nearly impossible to determine whether or not a drug is responsible for a particular adverse reaction) in 67%; and complacency (only safe drugs are allowed on the market) in 47% of studies. While personal and professional factors display a weak influence, the knowledge and attitudes of health professionals appear to be strongly related with reporting in a high proportion of studies. This result may have important implications in terms of public health, if knowledge and attitudes are viewed as potentially modifiable factors. PMID:19132802

Lopez-Gonzalez, Elena; Herdeiro, Maria T; Figueiras, Adolfo



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.

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.



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

PubMed Central

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

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



What can hospitalized patients tell us about adverse events? Learning from patient-reported incidents  

Microsoft Academic Search

PURPOSE: Little is known about how well hospitalized patients can identify errors or injuries in their care. Accordingly, the purpose\\u000a of this study was to elicit incident reports from hospital inpatients in order to identify and characterize adverse events\\u000a and near-miss errors.\\u000a \\u000a \\u000a SUBJECTS: We conducted a prospective cohort study of 228 adult inpatients on a medicine unit of a Boston

Saul N. Weingart; Odelya Pagovich; Daniel Z. Sands; Joseph M. Li; Mark D. Aronson; Roger B. Davis; David W. Bates; Russell S. Phillips



Allergic Reactions to Local Anesthetics in Dental Patients: Analysis of Intracutaneous and Challenge Tests  

PubMed Central

Some dental patients have histories of adverse reactions to local anesthesia. The aim of the present study was to investigate the frequency of allergy to local anesthetics of dental patients who had histories of adverse reactions to local anesthesia based on the results of allergy tests in our institute over a period of 5 years. We investigated the past medical records of dental patients retrospectively, and twenty patients were studied. Three of the 20 showed a positive or false-positive reaction in the intracutaneous test, and one patient showed a false-positive reaction in the challenge test. Our results suggest that the frequency of allergy to local anesthetics is low even if patients have histories of adverse reactions to local anesthesia. However, allergy tests of local anesthetics should be performed in patients in whom it is uncertain whether they are allergic.

Tomoyasu, Yumiko; Mukae, Kazuo; Suda, Michiyo; Hayashi, Tomoko; Ishii, Minako; Sakaguchi, Mai; Watanabe, Yoshihisa; Jinzenji, Ayako; Arai, Yukiko; Higuchi, Hitoshi; Maeda, Shigeru; Miyawaki, Takuya



Adverse events during intrahospital transport of critically ill patients: incidence and risk factors  

PubMed Central

Background Transport of critically ill patients for diagnostic or therapeutic procedures is at risk of complications. Adverse events during transport are common and may have significant consequences for the patient. The objective of the study was to collect prospectively adverse events that occurred during intrahospital transports of critically ill patients and to determine their risk factors. Methods This prospective, observational study of intrahospital transport of consecutively admitted patients with mechanical ventilation was conducted in a 38-bed intensive care unit in a university hospital from May 2009 to March 2010. Results Of 262 transports observed (184 patients), 120 (45.8%) were associated with adverse events. Risk factors were ventilation with positive end-expiratory pressure >6 cmH2O, sedation before transport, and fluid loading for intrahospital transports. Within these intrahospital transports with adverse events, 68 (26% of all intrahospital transports) were associated with an adverse event affecting the patient. Identified risk factors were: positive end-expiratory pressure >6 cmH2O, and treatment modification before transport. In 44 cases (16.8% of all intrahospital transports), adverse event was considered serious for the patient. In our study, adverse events did not statistically increase ventilator-associated pneumonia, time spent on mechanical ventilation, or length of stay in the intensive care unit. Conclusions This study confirms that the intrahospital transports of critically ill patients leads to a significant number of adverse events. Although in our study adverse events have not had major consequences on the patient stay, efforts should be made to decrease their incidence.



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

Microsoft Academic Search

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

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



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



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: [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)



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



Possible pathogenic pathways in the adverse clinical events seen following ivermectin administration to onchocerciasis patients.  

PubMed Central

Background Reactions are commonly associated with the chemotherapy of onchocerciasis. However unmanageable reactions are uncommon when ivermectin (Mectizan®) is used for the treatment of this infection, and this drug has proved to be a great improvement over previously used agents. Serious adverse events (SAE) nevertheless have occurred, and there is considerable concern about the negative effect such events may have on mass drug administration programs. This paper reviews the basic pathogenic mechanisms that can be involved in the destruction of microfilaria by chemotherapeutic agents. A central challenge to filarial chemotherapy is the need to remove parasites from biologically sensitive tissues, a more difficult medical challenge than eliminating nematodes from the gastrointestinal tract. Explanations for the etiology of the serious adverse reactions occurring with ivermectin treatment in specific geographic areas where there is coincident heavy Loa loa infections are hampered by a lack of specific pathological case material. Ways to investigate these possibilities are reviewed. Possible pathogenic mechanisms include embolic vascular pathology accompanied by local inflammation, blood brain barrier mdr1 abnormalities, and genetic predisposition to excessive inflammatory responses. Conclusion It is important to keep ivermectin, and all its associated adverse clinical events, in perspective with the many other chemotherapeutic agents in general use – many of which produce serious adverse events even more frequently than does ivermectin. Currently available evidence indicates that the pathogenesis of the Loa-associated adverse reactions are probably related to inflammatory responses to microfilariae in specific tissues. However, the possibility of genetic predispositions to pathology should also be considered.

Mackenzie, Charles D; Geary, Timothy G; Gerlach, John A



Attitudes and knowledge of hospital pharmacists to adverse drug reaction reporting  

PubMed Central

Aims To investigate the attitudes of UK hospital pharmacists towards, and their understanding, of adverse drug reaction (ADR) reporting. Methods A postal questionnaire survey of 600 randomly selected hospital pharmacists was conducted. Results The response rate was 53.7% (n = 322). A total of 217 Yellow Cards had been submitted to the CSM/MCA by 78 (25.6%) of those responding. Half of those responding felt that ADR reporting should be compulsory and over three-quarters felt it was a professional obligation. However, almost half were unclear as to what should be reported, while the time available in clinical practice and time taken to complete forms were deemed to be major deterrents to reporting. Pharmacists were not dissuaded from reporting by the need to consult a medical colleague or by the absence of a fee. Education and training had a significant influence on pharmacists' participation in the Yellow Card Scheme. Conclusions Pharmacists have a reasonable knowledge and are supportive of the Yellow Card spontaneous ADR reporting scheme. However, education and training will be important in maintaining and increasing ADR reports from pharmacists.

Green, Christopher F; Mottram, David R; Rowe, Philip H; Pirmohamed, Munir



Adverse Reactions Associated With Studying Persons Recently Exposed to Mass Urban Disaster  

PubMed Central

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

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



Application of quantitative signal detection in the Dutch spontaneous reporting system for adverse drug reactions.  


The primary aim of spontaneous reporting systems (SRSs) is the timely detection of unknown adverse drug reactions (ADRs), or signal detection. Generally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative signal detection, can provide additional information concerning a possible relationship between a drug and an ADR. We describe the role of quantitative signal detection and the way it is applied at the Netherlands Pharmacovigilance Centre Lareb. Results of the statistical analysis are implemented in the traditional case-by-case analysis. In addition, for data-mining purposes, a list of associations of ADRs and suspected drugs that are disproportionally present in the database is periodically generated. Finally, quantitative signal generation can be used to study more complex relationships, such as drug-drug interactions and syndromes. The results of quantitative signal detection should be considered as an additional source of information, complementary to the traditional analysis. Techniques for the detection of drug interactions and syndromes offer a new challenge for pharmacovigilance in the near future. PMID:12650632

van Puijenbroek, Eugène; Diemont, Willem; van Grootheest, Kees



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

PubMed Central

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

Tognetti, Linda; Giorgini, Simonetta; Lotti, Torello



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


We report a case of a 34-year-old woman presenting with an erythema multiforme (EM)-like eruption. Lesions developed after a 12-day treatment with a slimming drug preparation (food integrator with thermogenic activity) and a herbal remedy (pilosella tincture). Serological investigations excluded viral or bacterial infections. Patch testing with galenic preparations of both drugs demonstrated sensitization to the slimming drug preparation. According to literature reports and immune-chemical properties, those components that are likely to have triggered the skin eruption are clorazepate dipotassium and theobromine. Their interaction with other two constituents such as pseudoephedrine hydrochloride and dehydrocholic acid may have caused the adverse reaction by means of a summation effect. There are no reports specifically about EM caused by a slimming drug preparation and no studies have identified thermogenic pills as cause of EM/EM-like eruption. Weight-loss compounds in slimming preparations should be kept in mind as a possible cause of drug-induced EM-like eruption. PMID:23130230

Tognetti, Linda; Giorgini, Simonetta; Lotti, Torello



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.

Zeng, Zhi-Ping; Jiang, Jian-Guo



Innovations in monitoring of adverse drug reactions: the role of a technical advisor.  


Adverse drug reactions (ADRs) have ethical implications. These include assessment of the risk-benefit ratio and re-administering informed consent based on the new ADRs identified. The Indian Council of Medical Research ethical guidelines mandate the scrutiny of ADR; and the standard operating procedures of the ethics committee of the authors' medical school endorse this line. However, institutional review board members are often hardpressed for time and are unable to analyse all the reported ADRs as thoroughly as required. This calls for a dedicated system for the scrutiny of ADRs. This paper seeks to share the experience of development and implementation of a review mechanism for ADR monitoring. The authors report an innovation in ADR monitoring by appointing a technical advisor on ADR (TA-ADR). During routine assessment, an unusual occurrence of ADRs was noticed from internal and external sites which were related to the study drug, which in turn resulted in the trial being put on hold. This system is being reported here for possible adoption by others. PMID:23912733

Ramalingam, S; Ponnuswamy, Tk; Sivan, Ys


Adverse effects of smoking on patients with ocular inflammation  

PubMed Central

Background To evaluate how smoking affects the time to disease quiescence and time to disease recurrence in patients with ocular inflammation. Methods A 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. Results Among 2676 patients with active ocular inflammation, smokers were more likely to have bilateral ocular disease and poorer visual acuity on presentation compared with non-smokers and previous smokers. In a multivariate analysis, there was no statistically significant difference in the time to disease quiescence between groups. However, the median time to recurrence of ocular inflammation was statistically significantly longer for non-smokers (9.4 months) and for previous smokers (10.7 months) than for current smokers (7.8 months) (p=0.02). The RR of ocular inflammation recurrence was higher for smokers than for non-smokers (adjusted HR=1.19, 95% CI 1.03 to 1.37) and tended towards significance in previous smokers (adjusted HR=1.11, 95% CI 0.93 to 1.35). Conclusions Smoking was associated with an increased likelihood of bilateral ocular inflammation and reduced vision upon presentation, and an increased risk of recurrence compared with not smoking. These results suggest that patients with ocular inflammation should be counselled to stop smoking as part of routine management.

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



Predictors of Adverse Outcome in Patients Hospitalised for Exacerbation of Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Background: It is crucial to identify risk factors for poor evolution of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) in order to provide adequate intensive therapy and closer follow-up. Objectives: To identify predictors of adverse outcomes in patients hospitalised for exacerbation of COPD. Methods: A prospective, observational study was conducted in patients admitted for exacerbation of COPD.

Zinka Matkovic; Arturo Huerta; Nestor Soler; Rebeca Domingo; Albert Gabarrús; Antoni Torres; Marc Miravitlles



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

Microsoft Academic Search

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

Izhar Wallach; Navdeep Jaitly; Ryan Lilien; Ulrich Zanger



The frequency of adverse drug reaction related admissions according to method of detection, admission urgency and medical department specialty  

Microsoft Academic Search

BACKGROUND: Adverse Drug Reactions (ADRs) have been regarded as a major public health problem since they represent a sizable percentage of admissions. Unfortunately, there is a wide variation of ADR related admissions among different studies. The aim of this study was to evaluate the frequency of ADR related admissions and its dependency on reporting and method of detection, urgency of

Miran Brvar; Nina Fokter; Matjaz Bunc; Martin Mozina



Brine chemistry and control of adverse chemical reactions with natural gas production. Annual report, January-December 1984  

Microsoft Academic Search

Monitoring brine chemistry to determine the extent of potential adverse reactions was simplified by the development of a field brine test kit and a series of nomographs. Results of the kit analyses serve as input to the nomographs, which provide a graphic means of determining the scaling tendency (Saturation Index value) of a brine. Brines that do not tend to

J. M. Matty; G. G. Waggett; K. Varughese; J. Greenberg; M. B. Tomson



Brine Chemistry and Control of Adverse Chemical Reactions with Natural Gas Production. Annual Report January-December 1986,  

National Technical Information Service (NTIS)

Monitoring brine chemistry to determine the extent of potential adverse reactions has been simplified by the development of a field brine test kit and a series of nomographs. Results of the kit analyses serve as input to the nomographs, which provide a gr...

P. O'Day M. H. Salimi J. Greenberg G. Sethuraman M. B. Tomson



A distributed adverse drug reaction detection system using intelligent agents with a fuzzy recognition-primed decision model  

Microsoft Academic Search

Abstract Discovering unknown ,adverse drug reactions (ADRs) in postmarketing surveillance as early ,as possible is highly desirable. Nevertheless, current postmarketing surveillance methods largely rely on spontaneous reports which suffer from serious underreporting, latency, and inconsistent reporting. Thus these methods are not ideal for rapidly identifying rare ADRs. The multi-agent systems paradigm is an emerging and effective approach to tackling distributed

Yanqing Ji; Hao Ying; John Yen; Shizhuo Zhu; Daniel C. Barth-jones; Richard E. Miller; R. Michael Massanari



[Evidence of indications of influenza vaccine and its efficacy--including Guillain-Barré syndrome as an adverse reaction(?)].  


With respect to the indications of influenza vaccine, the US CDC guidelines are the most rational. All people aged not less than 50 years old, patients with pulmonary diseases, cardiac diseases and metabolic diseases such as diabetes mellitus, residents in old-age homes, high-risk subjects such as pregnant women, medical professionals at the position liable to infect the populations with influenza, employees of institutions, persons in charge of home care, and lodgers with high-risk patients are the subjects recommended for vaccination. There are many evidences of the efficacy of influenza vaccine in the world, and recently, it has been reported that vaccination has significantly reduced hospitalization and death due to not only influenza and pneumonia but also other diseases such as cerebrovascular diseases and cardiac diseases. Since Guillain-Barré syndrome which has been considered an adverse reaction of influenza vaccine was attributable to the swine influenza vaccine (swine type virus vaccine) used in the USA in the season from 1976 to 1977 and no incidence in the syndrome has been reported with subsequent vaccines, this syndrome does not become a reason for avoidance from vaccination in the subjects other than those with a history of the syndrome. PMID:14619443

Watanabe, Akira



Adverse reaction to metal debris following hip resurfacing: the influence of component type, orientation and volumetric wear.  


We sought to establish the incidence of joint failure secondary to adverse reaction to metal debris (ARMD) following metal-on-metal hip resurfacing in a large, three surgeon, multicentre study involving 4226 hips with a follow-up of 10 to 142 months. Three implants were studied: the Articular Surface Replacement; the Birmingham Hip Resurfacing; and the Conserve Plus. Retrieved implants underwent analysis using a co-ordinate measuring machine to determine volumetric wear. There were 58 failures associated with ARMD. The median chromium and cobalt concentrations in the failed group were significantly higher than in the control group (p < 0.001). Survival analysis showed a failure rate in the patients with Articular Surface Replacement of 12.8% [corrected] at five years, compared with < 1% at five years for the Conserve Plus and 1.5% at ten years for the Birmingham Hip Resurfacing. Two ARMD patients had relatively low wear of the retrieved components. Increased wear from the metal-on-metal bearing surface was associated with an increased rate of failure secondary to ARMD. However, the extent of tissue destruction at revision surgery did not appear to be dose-related to the volumetric wear. PMID:21282753

Langton, D J; Joyce, T J; Jameson, S S; Lord, J; Van Orsouw, M; Holland, J P; Nargol, A V F; De Smet, K A



Interstitial lung disease caused by TS-1: a case of long-term drug retention as a fatal adverse reaction  

PubMed Central

TS-1 is an oral anti-cancer agent for gastric cancer with a high response rate and low toxicity. We report a case of long-term drug retention of TS-1 causing interstitial lung disease (ILD) as a fatal adverse reaction. A 65-year-old woman underwent a total gastrectomy with pathologic confirmation of gastric adenocarcinoma. She received 6 cycles of TS-1 and low-dose cisplatin for post-operative adjuvant chemotherapy followed by single-agent maintenance therapy with TS-1. After 8 months, the patient complained of a productive cough with sputum and mild dyspnea. A pulmonary evaluation revealed diffuse ILD in the lung fields, bilaterally. In spite of discontinuing chemotherapy and the administration of corticosteroids, the pulmonary symptoms did not improve, and the patient died of pulmonary failure. TS-1-induced ILD can be caused by long-term drug retention that alters the lung parenchyma irreversibly, the outcome of which can be life-threatening. Pulmonary evaluation for early detection of disease is recommended.

Park, Joong-Min; Hwang, In Gyu; Suh, Suk-Won



Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study  

PubMed Central

Objectives: Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. Materials and Methods: One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Results: Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P < 0.05). No cases of hypotension were observed with the use of d-ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P < 0.05). Three patients (10%; 0 to 20.7) on d-ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P < 0.05). Conclusions: The phosphonate group in p-ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.

Sangole, Nishant V.; Dadkar, Vaishali N.



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.

Dang, Amit; Bhandare, P. N.



Harmonising adverse drug reaction terminology: the role of the Council for International Organizations of Medical Sciences.  


Health professionals from different countries are known to differ considerably in their use of medical terminology, including the terminology used for adverse drug reactions (ADRs) and in the exact meanings attributed to terms. To remedy this situation, the Council for International Organizations of Medical Sciences (CIOMS) has attempted to provide definitions and basic requirements for proper use of ADR terms. The work has concentrated on terms liable to be misinterpreted and those used for serious and frequently reported ADRs. For every selected term a short monograph has been prepared. It consists of a preamble, definition, basic requirements for use of the term and additional comments, if any. In cooperation with medical experts, drug regulators and the pharmaceutical industry, 13 papers have been published so far. Approximately 160 terms have been defined and work on another 50 terms continues. The full collection of monographs will eventually appear in the form of a book and CD-ROM intended to help doctors fill in case reports, and regulatory agencies and the pharmaceutical industry assess reports. Pharmaceutical companies receive numerous reports of suspected ADRs from medical practitioners and other prescribing professionals. Each company is required to transmit these reports to the drug regulatory agency of the country, or countries, in which the drug is used. Therefore, in addition to receiving the correct name of the ADR, collecting and evaluating centres, regardless of whether they are part of a regulatory agency or a pharmaceutical company, need to be provided with sufficient supporting data to be convinced that what is reported was what was actually observed, and that the ADR term used represents the observed event. PMID:9747664

Venulet, J; Bankowski, Z



Immunological principles of T-cell-mediated adverse drug reactions in skin.  


Drug hypersensitivity reactions in skin are an immune-mediated phenomenon associated with significant patient mortality and morbidity. Antigen-specific T cells, which have been isolated from the peripheral circulation and target organs of hypersensitive patients, are thought to propagate and regulate the development of clinical symptoms. The investigation of clinical cases with respect to the basic cellular and chemical mechanisms that underpin drug hypersensitivity has resulted in: i) the need to redress some aspects of present immunological dogma; and ii) additional fundamental immunological questions. Thus, the aim of this review article is to summarise present opinion on how and why drugs initiate a pathogenic T-cell response in a small section of the population and subsequently reflect on gaps in basic immunology and where future research might lead. PMID:17367257

Naisbitt, Dean J; Pirmohamed, Munir; Park, B Kevin



Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria  

PubMed Central

Background Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR reporting and to suggest possible ways of improving this method of reporting. Methods A total of 120 doctors working at the Lagos State University Teaching Hospital (LASUTH), in Nigeria were evaluated with a questionnaire for their knowledge and attitudes to ADR reporting. The questionnaire sought the demographics of the doctors, their knowledge and attitudes to ADR reporting, the factors that they perceived may influence ADR reporting, and their levels of education and training on ADR reporting. Provision was also made for suggestions on the possible ways to improve ADR reporting. Results The response rate was 82.5%. A majority of the respondents (89, 89.9%) considered doctors as the most qualified health professionals to report ADRs. Forty (40.4%) of the respondents knew about the existence of National Pharmacovigilance Centre (NPC) in Nigeria. Thirty-two (32.3%) respondents were aware of the Yellow Card reporting scheme but only two had ever reported ADRs to the NPC. About half (48.5%) of the respondents felt that all serious ADRs could be identified after drug marketing. There was a significant difference between the proportion of respondents who felt that ADR reporting should be either compulsory or voluntary (?2 = 38.9, P < 0.001). ADR reporting was encouraged if the reaction was serious (77, 77.8%) and unusual (70, 70.7%). Education and training was the most recognised means of improving ADR reporting. Conclusion The knowledge of ADRs and how to report them are inadequate among doctors working in a teaching hospital in Lagos, Nigeria. More awareness should be created on the Yellow Card reporting scheme. Continuous medical education, training and integration of ADR reporting into the clinical activities of the doctors would likely improve reporting.

Oshikoya, Kazeem A; Awobusuyi, Jacob O



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.



Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients  

Microsoft Academic Search

Background  Although anastrozole (ANA), an aromatase inhibitor (AI), has been widely used for breast cancer patients; adverse events during\\u000a ANA therapy in Japanese patients have not been reported.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The study included 656 postmenopausal breast cancer patients receiving ANA as postoperative adjuvant therapy in our hospital.\\u000a Adverse events during ANA therapy, such as musculoskeletal effects and cerebro- and cardiovascular accidents, were investigated

Yasuaki Sagara; Shoichiro Kosha; Shinichi Baba; Fumiko Dokiya; Shugo Tamada; Yoshiaki Sagara; Yoshito Matsuyama; Yasuyo Ohi; Mitsutake Ando; Yoshiaki Rai; Yoshiatsu Sagara; Tsutomu Douchi



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.



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

Microsoft Academic Search

BACKGROUND: The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity. METHODS: Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more

Yuichi Michikawa; Tomo Suga; Atsuko Ishikawa; Hideki Hayashi; Akira Oka; Hidetoshi Inoko; Mayumi Iwakawa; Takashi Imai



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,…

Bisgaier, Joanna; Rhodes, Karin V.



Cognitive and Other Adverse Effects of Diphenhydramine Use in Hospitalized Older Patients  

Microsoft Academic Search

Background: Diphenhydramine hydrochloride is a com- monly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. Methods: We enrolled 426 hospitalized medical pa- tients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included base- line and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method rat- ings,

Joseph V. Agostini; Linda S. Leo-Summers; Sharon K. Inouye



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



[Cutaneous adverse reactions of EGFR (epidermal growth factor receptor)-inhibitors: therapeutic algorithm of the French PROCUR group].  


The epidermal growth factor receptors (EGFR)-inhibitors are frequently responsible for cutaneous adverse drug reactions that may alter the patients' quality of life and hamper the continuation of treatment. We present here the experience of a group of French multidisciplinary experts - the PROCUR group (PRise en charge de la tOxicité CUtanée des anti-EGFR) - created in order to establish a therapeutic algorithm. It was built in three steps under the responsibility of a steering committee: (1) a systematic literature review was performed by a group of three dermatologists and one oncologist; (2) regional meetings evaluated practical aspect of the treatments in France; (3) a final meeting confrontating the practices in France and the evidence-based medicine including the steering committee, the bibliographic group, and oncologists, radiotherapists, dermatologists and hepato-gastroenterologists involved in regional scientific committees, resulted in a therapeutic algorithm, resulting in the collegial writing of this algorithm. This multidisciplinary study should facilitate the standardised, optimised management of skin toxicity associated with EGFR-inhibitors. PMID:23694934

Bachmeyer, Claude; Reguiaï, Ziad; Peuvrel, Lucie; Bachet, Jean-Baptiste; Bensadoun, René-Jean; Ychou, Marc; André, Thierry; Bouché, Olivier; Dréno, Brigitte



Adverse drug reaction monitoring of antidepressants in the psychiatry outpatients department of a tertiary care teaching hospital.  


Background and Introduction: Depression is a prevalent mental disorder and the 4(th) leading cause of disability in the world as per the World Health Organization (WHO). The adverse Drug Reactions (ADRs) to antidepressants are common and they can lead to a non compliance or even a discontinuation of the therapy. This study entitled us to monitor the ADR profile of the antidepressants in a tertiary care teaching hospital. Patients and Methods: A longitudinal, observational study was conducted in the Outpatients Department of Psychiatry in S.C.B. Medical College and Hospital l in collaboration with the I.M.S and SUM Hospital. A total of 160 cases were studied for ADRs by using a predesigned CDSCO form. The patients who were on TCAs, SSRIs and newer antidepressants (SNRIs/NDRIs) were assessed by doing physical examinations, neurological examinations and relevant lab tests. The causalities were assessed by the criteria of the WHO-UMC. The analysis of ADRs was done by using the Chi square test. Results: Among the 160 patients who took antidepressants, 26.87% reported ADRs, with at least one possible causality.None were labeled as certain, as a rechallenge was not performed.ADRs were mostly observed in polytherapy (14.37%) and with antidepressants like TCAs (58.84%). Conclusions: Agitation, anxiety and insomnia were the common ADRs which were associated with the use of antidepressants. This study offers a representative profile of the ADRs which can be expected in the Psychiatry Outpatients Department and due care must be taken to avoid these ADRs. PMID:23905119

Mishra, Swati; Swain, Trupti Rekha; Mohanty, Manjushree



Adverse Drug Reaction Monitoring of Antidepressants in the Psychiatry Outpatients Department of a Tertiary Care Teaching Hospital  

PubMed Central

Background and Introduction: Depression is a prevalent mental disorder and the 4th leading cause of disability in the world as per the World Health Organization (WHO). The adverse Drug Reactions (ADRs) to antidepressants are common and they can lead to a non compliance or even a discontinuation of the therapy. This study entitled us to monitor the ADR profile of the antidepressants in a tertiary care teaching hospital. Patients and Methods: A longitudinal, observational study was conducted in the Outpatients Department of Psychiatry in S.C.B. Medical College and Hospital l in collaboration with the I.M.S and SUM Hospital. A total of 160 cases were studied for ADRs by using a predesigned CDSCO form. The patients who were on TCAs, SSRIs and newer antidepressants (SNRIs/NDRIs) were assessed by doing physical examinations, neurological examinations and relevant lab tests. The causalities were assessed by the criteria of the WHO-UMC. The analysis of ADRs was done by using the Chi square test. Results: Among the 160 patients who took antidepressants, 26.87% reported ADRs, with at least one possible causality.None were labeled as certain, as a rechallenge was not performed.ADRs were mostly observed in polytherapy (14.37%) and with antidepressants like TCAs (58.84%). Conclusions: Agitation, anxiety and insomnia were the common ADRs which were associated with the use of antidepressants. This study offers a representative profile of the ADRs which can be expected in the Psychiatry Outpatients Department and due care must be taken to avoid these ADRs.

Mishra, Swati; Swain, Trupti Rekha; Mohanty, Manjushree



Multidisciplinary Treatments, Patient Characteristics, Context of Care, and Adverse Incidents in Older, Hospitalized Adults  

PubMed Central

The purpose of this study was to examine factors that contribute to adverse incidents by creating a model that included patient characteristics, clinical conditions, nursing unit context of care variables, medical treatments, pharmaceutical treatments, and nursing treatments. Data were abstracted from electronic, administrative, and clinical data repositories. The sample included older adults hospitalized during a four-year period at one, academic medical facility in the Midwestern United States who were at risk for falling. Relational databases were built and a multistep, statistical model building analytic process was used. Total registered nurse (RN) hours per patient day (HPPD) and HPPDs dropping below the nursing unit average were significant explanatory variables for experiencing an adverse incident. The number of medical and pharmaceutical treatments that a patient received during hospitalization as well as many specific nursing treatments (e.g., restraint use, neurological monitoring) were also contributors to experiencing an adverse incident.

Shever, Leah L.; Titler, Marita G.



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


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



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.

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



Platinum Agent-Induced Hypersensitivity Reactions: Data Mining of the Public Version of the FDA Adverse Event Reporting System, AERS  

PubMed Central

Objective: Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to confirm the platinum agent-associated mild, severe, and lethal hypersensitivity reactions. Methods: Authorized pharmacovigilance tools were used for quantitative signal detection, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Excess2, given by the multi-item gamma Poisson Shrinker algorithm, was used to evaluate the effects of dexamethasone and diphenhydramine on oxaliplatin-induced hypersensitivity reactions. Results: Based on 1,644,220 AERs from 2004 to 2009, carboplatin and oxaliplatin proved to cause mild, severe, and lethal hypersensitivity reactions, whereas cisplatin did not. Dexamethasone affected oxaliplatin-induced mild hypersensitivity reactions, but had lesser effects on severe and lethal reactions. The effects of diphenhydramine were not confirmed. Conclusion: The FDA's adverse event reporting system, AERS, with optimized data mining tools is useful to authorize potential associations between platinum agents and hypersensitivity reactions.

Sakaeda, Toshiyuki; Kadoyama, Kaori; Yabuuchi, Hiroaki; Niijima, Satoshi; Seki, Kyoko; Shiraishi, Yukinari; Okuno, Yasushi



Adverse Events for Hospitalized Medicare Patients: Is There a Difference between HMO and FFS Enrollees?  


The study examines the likelihood of adverse outcomes associated with selected hospital safety events for two groups of Medicare patients: those enrolled in health maintenance organizations (HMOs) versus those enrolled in fee-for-service (FFS) insurance plans. The authors hypothesize that HMO patients may receive different qualities of hospital services and/or physician services relative to FFS patients. Based on the Healthcare Cost and Utilization Project State Inpatient Database, the authors include discharge data on all hospitalized elderly Medicare patients in Florida in 2002 and use multivariate logistic regression models with adjustments for hospital-level clusters. The findings demonstrate that, after adjusting for hospital quality, Medicare HMO patients were at higher risk of adverse outcomes than Medicare FFS patients for iatrogenic pneumothorax, accidental puncture or laceration, and postoperative respiratory failure. PMID:24074128

Basu, Jayasree; Friedman, Bernard



Retrospective Analysis of Early Steroid-Induced Adverse Reactions in Kidney and Kidney-Pancreas Transplant Recipients  

Microsoft Academic Search

Corticosteroids (steroids) are associated with numerous adverse drug reactions (ADRs). Long-term ADRs are well characterized, but there are limited data on the incidence and likelihood of short-term ADRs. We sought to determine the incidence of ADRs potentially related to early administration of steroids in kidney and kidney-pancreas transplant recipients and to determine the probability that the ADR was due to

A. S. Mathis; M. T. Liu; R. T. Adamson; S. S. Nambi; A. M. Patel



Adverse drug reactions in a department of systemic diseases-oriented internal medicine: prevalence, incidence, direct costs and avoidability  

Microsoft Academic Search

Objective: Adverse drug reactions (ADRs) are a major cause of hospital admission and in-hospital morbidity. Departments of internal\\u000a medicine are at the forefront of this problem. To increase the knowledge base, we did a study of the frequency, hazard function,\\u000a avoidability, and cost of ADRs as a cause for admission in internal medicine, or when occurring after admission.\\u000a \\u000a \\u000a \\u000a Methods: This

R. Lagnaoui; N. Moore; J. Fach; M. Longy-Boursier; B. Bégaud



Mycoplasma pneumoniae vaccine protective efficacy and adverse reactions—Systematic review and meta-analysis  

Microsoft Academic Search

Mycoplasma pneumoniae is a leading cause of both upper and lower respiratory infections that can lead to devastating sequela. Currently no primary prevention measures are available. During the 1960s and 1970s several inactivated M. pneumoniae vaccines were tested, some with encouraging results. Here we present a systematic review and meta-analysis on the efficacy and adverse effects of M. pneumoniae inactivated

Inbal Linchevski; Eyal Klmenet; Ran Nir-Paz



Evaluation of Adverse Reactions in Hemophiliacs from Long-Term Exposure to Blood and Blood Products.  

National Technical Information Service (NTIS)

The study was done to assess the current clinical states of hemophiliacs and to see if there was any adverse effect from chronic infusion with blood products. Clinical and laboratory evaluation of 108 hemophiliacs (including hemophilia A and Von Wille bra...

H. R. Roberts W. P. Webster



Performance of different data sources in identifying adverse drug events in hospitalized patients  

Microsoft Academic Search

Purpose  The incidence of adverse drug events (ADE) is an important parameter in determining the quality of medical care. We identified\\u000a the probability that a specific data source would identify ADEs in patients on the oncology ward, that could be assigned to\\u000a one substance.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We captured all medical adverse events (AE) from five different data sources. Each AE was determined to

Marco Egbring; Elmira Far; Alexander Knuth; Malgorzata Roos; Wilhelm Kirch; Gerd A. Kullak-Ublick


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.

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



In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs.  


Idiosyncratic adverse drug reactions (IADRs) in humans can result in a broad range of clinically significant toxicities leading to attrition during drug development as well as postlicensing withdrawal or labeling. IADRs arise from both drug and patient related mechanisms and risk factors. Drug related risk factors, resulting from parent compound or metabolites, may involve multiple contributory mechanisms including organelle toxicity, effects related to compound disposition, and/or immune activation. In the current study, we evaluate an in vitro approach, which explored both cellular effects and covalent binding (CVB) to assess IADR risks for drug candidates using 36 drugs which caused different patterns and severities of IADRs in humans. The cellular effects were tested in an in vitro Panel of five assays which quantified (1) toxicity to THLE cells (SV40 T-antigen-immortalized human liver epithelial cells), which do not express P450s, (2) toxicity to a THLE cell line which selectively expresses P450 3A4, (3) cytotoxicity in HepG2 cells in glucose and galactose media, which is indicative of mitochondrial injury, (4) inhibition of the human bile salt export pump, BSEP, and (5) inhibition of the rat multidrug resistance associated protein 2, Mrp2. In addition, the CVB Burden was estimated by determining the CVB of radiolabeled compound to human hepatocytes and factoring in both the maximum prescribed daily dose and the fraction of metabolism leading to CVB. Combining the aggregated results from the in vitro Panel assays with the CVB Burden data discriminated, with high specificity (78%) and sensitivity (100%), between 27 drugs, which had severe or marked IADR concern, and 9 drugs, which had low IADR concern, we propose that this integrated approach has the potential to enable selection of drug candidates with reduced propensity to cause IADRs in humans. PMID:22646477

Thompson, Richard A; Isin, Emre M; Li, Yan; Weidolf, Lars; Page, Ken; Wilson, Ian; Swallow, Steve; Middleton, Brian; Stahl, Simone; Foster, Alison J; Dolgos, Hugues; Weaver, Richard; Kenna, J Gerry



Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study  

Microsoft Academic Search

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations.Design Prospective cohort study.Setting 28 hospitals in the Netherlands and Belgium.Participants 1920 consecutive women treated with tocolytics for threatened preterm labour.Main outcome measures Maternal adverse events (those suspected of being causally related to treatment were

Roel de Heus; Ben Willem Mol; Jan-Jaap H M Erwich; Herman P van Geijn; Wilfried J Gyselaers; Myriam Hanssens; Linda Härmark; Caroline D van Holsbeke; Johannes J Duvekot; Fred F A M Schobben; Hans Wolf; Gerard H A Visser



Adverse Drug Reaction Mining in Pharmacovigilance Data Using Formal Concept Analysis  

Microsoft Academic Search

\\u000a In this paper we discuss the problem of extracting and evaluating associations between drugs and adverse effects in pharmacovigilance\\u000a data. Approaches proposed by the medical informatics community for mining one drug - one effect pairs perform an exhaustive\\u000a search strategy that precludes from mining high-order associations. Some specificities of pharmacovigilance data prevent from\\u000a applying pattern mining approaches proposed by the

Jean Villerd; Yannick Toussaint; Agnès Lillo-Le Louët



Adverse reactions following injection with a permanent facial filler polyacrylamide hydrogel (Aquamid): causes and treatment  

Microsoft Academic Search

Background  Polyacrylamide hydrogel (Aquamid), an atoxic non-immunogenic gel of the non-resorbable type, has gained widespread popularity as an injectable filler for facial augmentation. However, adverse events (AEs) have occurred, the nature of which seems obscure because of negative findings on culture and a pattern of foreign-body response on microscopy.Design  This is a prospective study of case reports provided by physicians injecting Aquamid

Lise Christensen; Vibeke Breiting; Jens Vuust; Estrid Hogdall



Adverse Drug Reactions in Hospitalised Children in Germany Are Decreasing: Results of a Nine Year Cohort-Based Comparison  

PubMed Central

Background In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period. Methodology Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis. Results A total of 520 patients (574 admissions) were included [1999: n?=?144 (167); 2008: n?=?376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001). Conclusions Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed.

Oehme, Ann-Kathrin; Rashed, Asia N.; Hefele, Barbara; Wong, Ian C. K.; Rascher, Wolfgang; Neubert, Antje



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


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



A prediction model for adverse outcome in hospitalized patients with diabetes.  


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

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



Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue.  


We asked if the factors that predict overall mortality following two common surgical procedures are different from those that predict adverse occurrences (complications) during the hospitalization or death after an adverse occurrence, which we refer to as "failure to rescue." We examined 5,972 Medicare patients undergoing elective cholecystectomy or transurethral prostatectomy using three outcome measures: 1) the death rate (number of deaths/number of patients); 2) the adverse occurrence rate (number of patients who developed an adverse occurrence/number of patients); and 3) the failure rate (number of deaths in patients who developed an adverse occurrence/number of patients with an adverse occurrence). The death rate was associated with both hospital and patient characteristics. The adverse occurrence rate was associated primarily with patient characteristics. In contrast, failure to rescue was associated more with hospital characteristics, and was less influenced by patient admission severity of illness as measured by the MedisGroups score. We concluded that factors associated with hospital failure to rescue are different from factors associated with adverse occurrences or death. Understanding the reasons behind variation in mortality rates across hospitals should improve our ability to use mortality statistics to help hospitals upgrade the quality of care. PMID:1614231

Silber, J H; Williams, S V; Krakauer, H; Schwartz, J S



A perspective from clinical and business ethics on adverse events in hospitalized patients.  


Adverse events occur in a significant, but undetermined, number of hospitalized patients. These types of patient injuries are more often the result of faulty systems than human maleficence. A culture exists among health care providers that discourages the reporting of such events and resists the implementation of formal efforts to eliminate them. This resistance serves to perpetuate the problem. Both business and clinical ethics argue that sound reasons exist for hospitals to reduce, if not eliminate, adverse events. To do so is cost effective, particularly in a managed care environment. It is also at the heart of responsible professional behavior. Physicians are afforded an opportunity to be at the forefront in this quality improvement effort. PMID:9401346

Wagner, J T; Meier, C; Higdon, T



Longitudinal Incidence and Prevalence of Adverse Outcomes of Diabetes Mellitus in Elderly Patients  

Microsoft Academic Search

Results: The DM group had excess mortality of 9.2% by year 11 compared with the control group. By 2004, 91.8% of the DM group experienced an adverse compli- cation compared with 72.0% of the control group. The DM group had a higher prevalence and incidence of mi- crovascular and macrovascular complications at all time points compared with controls. Patients with

M. Angelyn Bethel; Frank A. Sloan; Daniel Belsky; Mark N. Feinglos




Microsoft Academic Search

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




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

NASA Astrophysics Data System (ADS)

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

Robson, C.; Mueller, E. J.



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


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

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



Cystatin C Identifies Patients with Stable Chronic Heart Failure at Increased Risk for Adverse Cardiovascular Events  

PubMed Central

Background Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect and Cystatin C (CysC) is promoted as a better marker of glomerular filtration rate (GFR). This study compares the prognostic utility of CysC and derived GFR estimates with other measures of renal function in patients with chronic heart failure. Methods and Results We measured serum CysC levels in 823 heart failure patients undergoing coronary angiography with follow-up of major adverse cardiovascular events (MACE = death, myocardial infarction, stroke). Cystatin C levels strongly correlated with creatinine (r = 0.73), blood urea nitrogen (r = 0.70), and eGFRMDRD (r = ?0.62) (all p < 0.001). However, the correlation was lower in eGFR ? 60ml/min/1.73m2. CysC-based measures significantly improved areas under the ROC curve for the prediction of MACE, especially in eGFR ? 60ml/min/1.73m2 (p < 0.01). Net reclassification improvement was 22.2% (p < 0.001) in this group. CysC remained an independent predictor of MACE (p < 0.001) after adjustment for traditional risk factors and BNP. Conclusions Cystatin C is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with “preserved” renal function.

Dupont, Matthias; Wu, Yuping; Hazen, Stanley L.; Wilson Tang, W. H.



Pertussis Vaccine Project: Rates, Nature and Etiology of Adverse Reactions Associated with DTP Vaccine.  

National Technical Information Service (NTIS)

Sixteen thousand five hundred and thirty-six children ages 0-6 years received either DTP (15,752) or DT (784) vaccine and were prospectively evaluated by mail, in questionnaire, telephone call, or home visit for reactions occurring within 48 hours of immu...

C. L. Cody J. D. Cherry L. J. Baraff



What puts the adverse in 'adverse events'? Patients' perceptions of post-treatment experiences in osteopathy--a qualitative study using focus groups.  


Patients commonly report mild to moderate effects following all forms of manual therapy. These are often regarded as adverse events by practitioners but there is limited evidence on how patients view their post-treatment experiences, and what meaning they ascribe to them. This qualitative study used three focus group discussions (19 participants) to explore osteopathic patients' perspectives; a framework approach was used to analyse the data. There were four emergent themes (and 23 sub-themes). Interpretative (level two) analysis of the data led to a conceptual model of meaning with four inter-related components: Expectations; Personal investment; Osteopathic encounter; Clinical change, under an overarching construct, the 'global osteopathic experience'. These four components, designated EPOC, can have a profound impact on a patient's post-treatment experiences and their perception of what is adverse. This model suggests there is disparity between patient perceptions and clinical definitions of adverse events; awareness by practitioners of this disparity is essential for effective clinical management. PMID:22425134

Rajendran, Dévan; Bright, Philip; Bettles, Steven; Carnes, Dawn; Mullinger, Brenda



Association between concomitant use of several systemic NSAIDs and an excess risk of adverse drug reaction. A case\\/non-case study from the French Pharmacovigilance system database  

Microsoft Academic Search

Aims To examine whether the risk of some selected adverse effects increases with the number of systemic non-steroidal anti-inflammatory (NSAID) drugs. Methods The French Pharmacovigilance database was examined for an association between drug reaction reports and the exposure to one and two or more NSAIDs using a case\\/non-case study design. In the analysis, 54,583 spontaneous reports of adverse drug reactions

François Clinard; Catherine Sgro; Marc Bardou; Patrick Hillon; Monique Dumas; Carmen Kreft-Jais; André Escousse; Claire Bonithon-Kopp



Adverse skin reactions to personal protective equipment against severe acute respiratory syndrome--a descriptive study in Singapore.  


Severe acute respiratory syndrome (SARS) was first recognized in February 2003. It is the first severe and readily transmissible new disease to emerge in the 21st century. Healthcare workers in affected countries were exposed to the regular use of personal protective equipment (PPE) such as the N95 mask, gloves, and gowns. Our aim was to study the prevalence of adverse skin reactions to PPE among healthcare workers in Singapore during the SARS outbreak. Healthcare staff in the National Skin Centre and Tan Tock Seng Hospital were surveyed using questionnaires. Of those asked to participate, 322 (94.7%) agreed. 14.3% of the respondents were doctors, 73.0% nurses, and 12.7% other ancillary staff. Mean age of respondents was 32.4 years, with the majority being women (85.7%) and Chinese (53.7%). 109 (35.5%) of the 307 staff who used masks regularly reported acne (59.6%), facial itch (51.4%), and rash (35.8%) from N95 mask use. 64 (21.4%) of the 299 who used gloves regularly reported dry skin (73.4%), itch (56.3%), and rash (37.5%). The use of PPE is associated with high rates of adverse skin reactions. There is a need to find suitable alternatives for affected staff and to encourage awareness among staff of the role of dermatologists in their care. PMID:17026695

Foo, Chris C I; Goon, Anthony T J; Leow, Yung-Hian; Goh, Chee-Leok



Cutaneous adverse drug reactions in children: an analysis of reports from the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).  


Cutaneous adverse drug reactions (CADRs) are the most prevalent adverse drug reactions (ADRs) in hospitalized children, with an estimated rate of 2-3%. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) is a pan-Canadian active surveillance network identifying genomic biomarkers of risk for serious ADRs. The purpose of this paper is to describe the characteristics of paediatric CADR cases reported to the CPNDS from February 2005 to December 2008. The CPNDS database was mined and details of CADRs and key clinical data from cases were extracted. Reports were individually analyzed and classified in two main groups: severe and non-severe CADRs, with subcategories. In total, 326 CADR cases were included in the study; 214 (65.6%) severe and 112 (34.4%) non-severe CADRs. Overall L-asparaginase (n=56, 16%), amoxicillin (n=29, 8.3%), cotrimoxazole (n=25, 7.2%), carbamazepine (n=17, 4.9%) and lamotrigine (n=13, 3.7%) accounted for 40% of all suspected medications. We have demonstrated the ability to comprehensively collect clinical data on a wide range of severe and non-severe CADRs to drugs commonly used in the care of children. Our study provides additional real world evidence to promote the proactive detection, collection, reporting and assessment of CADRs in children. PMID:21467602

Castro-Pastrana, Lucila I; Ghannadan, Reza; Rieder, Michael J; Dahlke, Erin; Hayden, Michael; Carleton, Bruce



Adverse events in patients initiated on dabigatran etexilate therapy in a pharmacist-managed anticoagulation clinic  

PubMed Central

Background Vitamin K antagonists have been the treatment of choice in preventing thromboembolic events, but problems such as frequent dose adjustment and monitoring of coagulation status, including multiple drug and food interactions, make their use difficult. Dabigatran etexilate is a new oral direct thrombin inhibitor not requiring routine monitoring and since its approval in the United States, many clinicians have been interested in utilizing this new therapy. Objective This study documented adverse drug events (ADEs) recorded in patients started on dabigatran therapy, including those who were previously controlled on warfarin and those who were anticoagulant naïve. Methods In an outpatient pharmacist-managed anticoagulation clinic, a total of 221 patients were initiated on dabigatran therapy over an 18-month period. 43.0% of these patients were previously controlled on warfarin. Results 54 of the 221 patients (24.4%) developed an ADE while on dabigatran. The average time to event was 48.4 days. Nine of the fifty-four patients experienced a major bleeding ADE; six patients developed a serious non-bleeding ADE. Five of these fifteen patients died; one death was directly related to dabigatran therapy. The remaining thirty-nine of the fifty-four patients experienced a clinically relevant non-major ADE. Of the fifty-four patients who experienced an ADE, thirty were male. The average age was 73.8 years and the average weight was 92.8kg. Fifty-four percent of those who experienced an ADE were previously anticoagulant naïve. Conclusions While many clinicians have been interested in utilizing the new direct thrombin inhibitor dabigatran etexilate, this new therapy is not without risks. This study documented adverse drug events in 24.4% of patients who were initiated on dabigatran etexilate therapy over an eighteen month period. ADEs were more common in patients who were anticoagulant naïve prior to dabigatran etexilate therapy and not those who were previously controlled on warfarin therapy.

Donaldson, Mark; Norbeck, Amber Olivia


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


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



Effectiveness of relaxation training in reducing adverse reactions to cancer chemotherapy  

Microsoft Academic Search

Cancer patients who had developed negative conditioned responses to their chemotherapy either did (relaxation training) or did not (no relaxation training) receive progressive muscle relaxation training and guided relaxation imagery instructions immediately before and during their chemotherapy treatments. Physiological (blood pressure and pulse rate) measures of arousal, frequency of vomiting, and patient-reported and nurse-reported indices of negative affect and nausea

Thomas G. Burish; Jeanne Naramore Lyles



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.



Risk Factors for Severe Adverse Effects and Treatment-related Deaths in Japanese Patients Treated with Irinotecan-based Chemotherapy: A Postmarketing Survey†  

PubMed Central

Objectives This analysis was conducted to clarify risk factors for severe adverse effects and treatment-related deaths reported during a postmarketing survey of irinotecan. Methods The survey covered all patients treated with irinotecan in Japan between April 1995 and January 2000. The patient background data and adverse drug reactions were collected through case report forms. Univariate and multivariate logistic regression analyses including 14 explanatory variables were performed to determine the risk factors for grade 3–4 leukopenia, thrombocytopenia and diarrhea for all patients and subgroups with five major cancers. Treatment-related deaths were also analyzed. Results Case report forms of 13 935 patients (94.1% of 14 802 patients registered) treated with irinotecan-based chemotherapy were collected. Major grade 3–4 adverse drug reactions were leukopenia (34.8%), thrombocytopenia (12.4%) and diarrhea (10.1%). Multivariate analysis revealed that the risk factors (odds ratio ?1.5) common for all these three adverse drug reactions were performance status (?3), infection and renal dysfunction before starting irinotecan therapy. Additionally, the risk factors for leukopenia were being female and prior radiotherapy, those for thrombocytopenia were age (?65 years), while those for diarrhea were pleural effusion and watery stool. The risk factors in each cancer were also identified. The incidence of treatment-related death was 1.3% (176). Myelosuppression-related deaths accounted for 70% and interstitial lung disease for 11% of all treatment-related deaths. Being male, age, performance status ?3, massive ascites and infection and renal dysfunction were identified as risk factors for treatment-related death. Conclusions To ensure the safety of irinotecan therapy, it is important to select appropriate patients by considering the risk factors.

Shiozawa, Tomoo; Tadokoro, Jun-ichi; Fujiki, Toshitaka; Fujino, Koji; Kakihata, Koji; Masatani, Shuji; Morita, Satoshi; Gemma, Akihiko; Boku, Narikazu



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.

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



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

PubMed Central

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

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



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

PubMed Central

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

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



Depression and risk for adverse falls in older home health care patients.  


Because falls are highly prevalent, harmful events for older adults, identification of patients at risk is a high priority for home health care agencies. Using routine administrative data, we demonstrated that patients with depressive symptoms on the Outcome and Assessment Information Set are at risk for falls. A prospective case-control study that matched 54 patients who experienced an adverse fall with 854 controls showed that patients who fell had twice the odds of being depressed (odds ratio = 1.90, 95% confidence interval = 1.01 to 3.59). Bowel incontinence, high medical comorbidity, stair use, injury and poisoning, memory deficit, and antipsychotic medication use were also predictors, but no association was found for antidepressant medications. These data suggest the potential benefit of including depression screening for multifactorial fall prevention interventions. PMID:20077999

Byers, Amy L; Sheeran, Thomas; Mlodzianowski, Amy E; Meyers, Barnett S; Nassisi, Pamella; Bruce, Martha L



Depression and Risk for Adverse Falls in Older Home Health Care Patients  

PubMed Central

Because falls are highly prevalent, harmful events for older adults, identification of patients at risk is a high priority for home health care agencies. Using routine administrative data, we demonstrated that patients with depressive symptoms on the Outcome and Assessment Information Set are at risk for falls. A prospective case-control study that matched 54 patients who experienced an adverse fall with 854 controls showed that patients who fell had twice the odds of being depressed (odds ratio = 1.90, 95% confidence interval = 1.01 to 3.59). Bowel incontinence, high medical comorbidity, stair use, injury and poisoning, memory deficit, and antipsychotic medication use were also predictors, but no association was found for antidepressant medications. These data suggest the potential benefit of including depression screening for multifactorial fall prevention interventions.

Byers, Amy L.; Sheeran, Thomas; Mlodzianowski, Amy E.; Meyers, Barnett S.; Nassisi, Pamella; Bruce, Martha L.



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.

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



Do no harm--but first we need to know more: the case of adverse drug reactions with antiepileptic drugs.  


An adverse drug reaction (ADR) is defined by the World Health Organization as a noxious, unintended, and undesired drug effect, when used for therapeutic purposes in humans. ADRs to anti-epileptic drugs (AEDs) significantly impact the quality of life of people with epilepsy and account for a little less than half of all recorded treatment failures with AEDs. Hence prevention and early recognition of ADRs constitute an important aspect of management of epilepsy. Recent developments have improved our ability to predict and hence potentially prevent the occurrence of some of the serious ADRs to AEDs. One example is the potential prediction of the risk of severe cutaneous hypersensitivity reactions including Stevens Johnson syndrome and toxic epidermal necrolysis by testing for expression of HLA BFNx011502 allele in people of Asian origin who are prescribed carbamazepine. The association between HLA BFNx011502 expression and carbamazepine skin reactions has been documented in India but the role of HLA testing in Indian populations needs to be clarified in larger studies across different ethnic groups within the country. PMID:21339660

Singh, Gagandeep


Kava for the Treatment of Generalized Anxiety Disorder RCT: Analysis of Adverse Reactions, Liver Function, Addiction, and Sexual Effects.  


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. Copyright © 2013 John Wiley & Sons, Ltd. 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



Contact dermatitis and adverse oral mucous membrane reactions related to the use of dental prostheses.  


The latest trends in the use and composition of dental prostheses have been reviewed, and 66 patients referred by dermatologists and odontologists patch tested. The allergen series used were: TRUE Test standard series; Chemotechnique dental screening series; specially prepared metals series. The allergens found to be positive, in order of frequency, were: nickel, cobalt, potassium dichromate, rhodium, palladium, mercury, beryllium, methyl methacrylate, copper and zinc. PMID:8187507

Vilaplana, J; Romaguera, C; Cornellana, F



Pharmacogenetics and Pharmacogenomics II: Genetic Determinants of Drug Responses and Adverse Drug Reactions  

Microsoft Academic Search

\\u000a The ability to predict efficacy and safety is crucial for drug discovery and development. To date, there are only a few genetic\\u000a biomarkers whose clinical validity in predicting drug response has been clearly established; for example, HER-2\\/neu-positivity\\u000a in breast cancer as a predictor of response to trastuzumab (Herceptin) [1]. Patient variability in response to medications\\u000a can range from failure to

Stephane Dalle; Sandra Knowles; Neil H. Shear


Cutaneous adverse drug reactions to anti-tuberculosis drugs: state of the art and into the future.  


First- and second-line anti-tuberculosis drugs are associated with a diverse presentation of cutaneous adverse drug reactions (CADR), ranging from mild to life threatening. An individual drug can cause multiple types of CADR, and a specific type of CADR can be due to any anti-tuberculosis drug, which can make the management of tuberculosis (TB) following CADR challenging. The higher incidence of TB and CADR in HIV-infected persons makes TB-associated CADR a burgeoning problem for clinicians, particularly in high HIV-prevalence settings. This review discusses the pathogenesis, epidemiology, clinical presentation, diagnosis and management of TB-associated CADR. Clinical controversies including its impact on treatment outcomes, challenges in restarting optimal anti-tuberculosis therapy and the timing of highly active antiretroviral therapy initiation in those with HIV coinfection are also discussed. Finally, gaps in the current knowledge of TB-associated CADR have been identified and a research agenda has been proposed. PMID:22512756

Lehloenya, Rannakoe J; Dheda, Keertan



Ambulance Personnel Perceptions of Near Misses and Adverse Events in Pediatric Patients  

PubMed Central

Objective To identify Emergency Medical Services (EMS) provider perceptions of factors that may affect the occurrence, identification, reporting, and reduction of near misses and adverse events in the pediatric EMS patient. Methods This was a subgroup analysis of a qualitative study examining the nature of near misses and adverse events in EMS as it relates to pediatric prehospital care. Complimentary qualitative methods of focus groups, interviews, and anonymous event reporting were used to collect results and emerging themes were identified and assigned to specific analytic domains. Results Eleven anonymous event reports, 17 semi-structured interviews, and 2 focus groups identified 61 total events, of which 12 (20%) were child-related. Eight (66%) of those were characterized by participants as having resulted in no injury, 2 (16%) resulted in potential injury, and 2 (16%) involved an ultimate fatality. Three analytic domains were identified which included the following five themes: reporting is uncommon, blaming errors on others, provider stress/discomfort, errors of omission, and limited training. Among perceived causes of events, participants noted factors relating to management problems specific to pediatrics, problems with procedural skill performance, medication problems/calculation errors, improper equipment size, parental interference, and omission of treatment related to providers’ discomfort with the patient’s age. Few participants spoke about errors they had themselves committed; most discussions centered on errors participants observed being made by others. Conclusions It appears that adverse events and near misses in the pediatric EMS environment may go unreported in a large proportion of cases. Participants attributed the occurrence of errors to the stress and anxiety produced by a lack of familiarity with pediatric patients and to a reluctance to cause pain or potential harm, as well as to inadequate practical training and experience in caring for the pediatric population. Errors of omission, rather than those of commission, were perceived to predominate. This study provides a foundation on which to base additional studies of both qualitative and quantitative nature that will shed further light on the factors contributing to the occurrence, reporting, and mitigation of adverse events and near misses in the pediatric EMS setting.

Cushman, Jeremy T; Fairbanks, Rollin J; O'Gara, Kevin G; Crittenden, Crista N; Pennington, Elliot C; Wilson, Matthew A; Chin, Nancy P; Shah, Manish N



Placental Growth Factor for the Prediction of Adverse Outcomes in Patients with Suspected Preeclampsia or Intrauterine Growth Restriction  

PubMed Central

Background The circulating concentration of PlGF is reported to be lower in patients experiencing preeclampsia and patients delivering a small for gestational age (SGA) neonate. To evaluate the predictive value of circulating PlGF for preeclampsia and adverse outcome in patients with suspected preeclampsia or intrauterine growth restriction (IUGR). Methodology/Principal Findings A double blind prospective study. We enrolled 96 women for suspected preeclampsia or IUGR, and measured plasma levels of PlGF (Triage®) at enrolment. We defined adverse outcome as severe preeclampsia, SGA neonate (<10th centile) or elective delivery for maternal or fetal complication. Severe adverse outcome was studied among patients included <34 weeks gestation (WG) and defined as eclampsia, HELLP syndrome, very SGA (<3rd centile) or elective delivery <34 WG. The mean logtransformed PlGF level was lower for women who experienced preeclampsia (2.9 vs 3.7, p?=?0.02), and was markedly lower for patients who experienced adverse outcome (2.9 vs 4.3, p<0.001). The odds of presenting an adverse outcome were higher for the lowest tertile of PlGF compared to the higher (OR?=?13 , 95% CI [3–50]). For severe adverse outcome, odds were respectively for the lowest and intermediate tertile as compared with the higher tertile : OR?=?216, 95% CI [18–2571]; and OR?=?17, 95% CI [3–94]. When included <34 WG, patients with a PlGF level <12 pg/ml experienced a severe adverse outcome in 96% of cases (24/25), and only 1 of 20 patients with a PlGF level >5th centile experienced a severe adverse outcome within 15 days (5%). Conclusions/Significance Among women with suspected preeclampsia or IUGR, PlGF helps identify women who will experience an adverse outcome and those who will not within a time period of 15 days.

Sibiude, Jeanne; Guibourdenche, Jean; Dionne, Marie-Danielle; Le Ray, Camille; Anselem, Olivia; Serreau, Raphael; Goffinet, Francois; Tsatsaris, Vassilis



Relative Importance of Preoperative Health Status Versus Intraoperative Factors in Predicting Postoperative Adverse Outcomes in Geriatric Surgical Patients  

Microsoft Academic Search

OBJECTIVES: To determine the prevalence and predic- tors of adverse postoperative outcomes in older surgical patients undergoing noncardiac surgery. DESIGN: Prospective cohort study of consecutive patients undergoing noncardiac surgery in 1997. SETTING: A medical school-affiliated teaching commu- nity hospital. PARTICIPANTS: Patients age 70 and older undergoing noncardiac surgery. Patients presenting for surgery requir- ing only local anesthesia or monitored anesthesia

Jacqueline M. Leung; Samir Dzankic



Economic burden of selected adverse events in patients aged ?65 years with metastatic renal cell carcinoma.  


Abstract Objective: To estimate the costs of adverse events (AEs) in patients aged ?65 years with metastatic renal cell carcinoma (mRCC). Methods: Retrospective study using the linked Surveillance, Epidemiology and End Results (SEER) Medicare database. Study subjects consisted of persons in SEER-Medicare, aged ?65 years, with evidence of newly diagnosed mRCC between January 1, 2007 and December 31, 2007. Adverse events of interest consisted of Grade 3 or 4 toxicities that have been reported with frequency ?5% in randomized controlled trials of sunitinib, sorafenib, bevacizumab, and pazopanib (i.e., targeted therapies for mRCC), and included abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Patients in SEER-Medicare with these events were identified based on ICD-9-CM diagnosis codes on Medicare claims. For each AE of interest, costs were tallied among evented patients over 30 days, beginning with the date of each patient's first mention of the AE, and were compared with those of non-evented patients over a similar 30-day period beginning with an identical 'shadow' index date. Total costs were compared on an unadjusted basis and with adjustment for differences in baseline characteristics using a generalized linear model. Results: A total of 881 patients with mRCC met study entry criteria; 60% of these patients had Medicare claims with mention of one or more AEs of interest. Events occurring with frequency >20% included abdominal pain, dyspnea, and fatigue/asthenia; 10-20% of study subjects had encounters for back pain, extremity pain, and nausea/vomiting. Mean (standard deviation) total cost of care over 30 days was substantially higher among patients with AEs ($13,944 [$14,529]) compared with those without mention of these events ($1878 [$5264]). Adjusting for differences in baseline characteristics, the mean (95% confidence interval) difference in costs between evented and non-evented patients was $12,410 ($9217-$16,522). Study limitations include problems in event ascertainment due to inaccuracies in ICD-9-CM coding on Medicare claims data, and restriction of the study population to patients with metastatic involvement at initial diagnosis of RCC. Conclusions: Costs of care are substantially higher in patients aged ?65 years with mRCC who experience AEs commonly associated with sunitinib, sorafenib, bevacizumab, and pazopanib. Efforts to prevent and/or better manage these events potentially can reduce healthcare costs. PMID:24004437

Hagiwara, May; Hackshaw, Michelle D; Oster, Gerry



Reduced Expression of Plakoglobin Correlates with Adverse Outcome in Patients with Neuroblastoma  

PubMed Central

Plakoglobin and its homologue ?-catenin are cytoplasmic proteins that mediate adhesive functions by interacting with cadherin receptors and signaling activities by interacting with transcription factors. It has been suggested that plakoglobin can suppress tumorigenicity whereas ?-catenin can act as an oncogene. We investigated the correlation between the expression pattern of N-cadherin, ?-catenin, and plakoglobin and tumor behavior in primary tumors of 20 neuroblastoma patients of all stages and in 11 human neuroblastoma cell lines. N-cadherin and ?-catenin were detected in 9 of 11 and 11 of 11 cell lines, respectively, whereas plakoglobin was undetectable or severely reduced in 6 of 11 cell lines. Tumor cells from 16 of 20 patients expressed N-cadherin and 20 of 20 patients expressed ?-catenin at levels similar to those of normal ganglion cells. Plakoglobin was undetectable in 9 of 20 tumors. Plakoglobin deficiency in the primary tumors was significantly associated with adverse clinical outcome. Five of the patients with plakoglobin-negative tumors died whereas four patients are alive without evident disease. In contrast, all patients with plakoglobin-positive tumors are alive; 2 of 11 are alive with the disease and 9 of 11 are alive without evident disease. These results suggest that down-regulation of plakoglobin may be of prognostic value for neuroblastoma patients aspredictor of poor outcome.

Amitay, Raya; Nass, Dvora; Meitar, Dafna; Goldberg, Iris; Davidson, Ben; Trakhtenbrot, Luba; Brok-Simoni, Frida; Ben-Ze'ev, Avri; Rechavi, Gideon; Kaufmann, Yael



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


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

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



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.

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



Perioperative risk factors for adverse airway events in patients undergoing cleft palate repair.  


Objective :? To establish the incidence of perioperative airway complications in a large series of pediatric patients undergoing palatoplasty and to identify which specific patient, procedural, and provider factors are associated with increased risk for perioperative adverse airway events (AAEs). Design :? Retrospective chart review. Setting :? Tertiary pediatric hospital. Patients :? Included were 300 patients who underwent primary cleft palate repair using the modified Furlow technique between 2008 and 2011. Patients were 2 years or younger at the time of the operation. Main Outcome Measure(s) :? Charts were reviewed for perioperative AAEs, which were defined as postoperative airway obstruction, oxyhemoglobin saturation ?85% for ?45 seconds, bronchospasm, laryngospasm, reintubation, and unplanned admission to the intensive care unit. Patient-specific factors (diagnosis of a craniofacial syndrome, Veau cleft type, preoperative pulmonary and airway history), procedural factors (operative time, anesthesia time, opioid dose, administration and reversal of neuromuscular blockers), and provider factors (experience, number of providers), were documented, and associations with AAEs were investigated. Results :? AAEs occurred in 23% of patients overall and were significantly more common in syndromic patients (P = .003), patients with jaw or tracheal anomalies (P = .001), and patients with a history of difficult airway (P = .001). Other significant factors included prior history of difficult intubation (P = .05), surgeon (P = .02) and anesthesiologist experience (P = .05), and operative time (P = .02). Conclusions :? Diagnosis of a craniofacial syndrome, a history of preoperative airway problems, and provider inexperience correlated with increased risk for airway complications after palatoplasty. Recognizing patients at risk for AAEs may permit improved preoperative planning to optimize surgical outcomes and minimize complications. PMID:23083121

Jackson, Oksana; Basta, Marten; Sonnad, Seema; Stricker, Paul; Larossa, Don; Fiadjoe, John



Prevalence of Unplanned Hospitalizations Caused by Adverse Drug Reactions Among Older Veterans  

PubMed Central

Objectives To describe the prevalence of unplanned hospitalizations caused by ADRs among older Veterans and examine the association between this outcome and polypharmacy after controlling for comorbidities and other patient characteristics. Design Retrospective cohort. Setting Veterans Affairs Medical Centers (VAMC). Participants 678 randomly selected unplanned hospitalizations of older (age ? 65 years) Veterans between 10/01/03 and 09/30/06. Measurements Naranjo ADR algorithm, ADR preventability, and polypharmacy (0–4, 5–8, and ? 9 scheduled medications). Results Seventy ADRs involving 113 drugs were determined in 68 (10%) older Veterans’ hospitalizations, of which 36.8% (25/68) were preventable. Extrapolating to the population of over 2.4 million older Veterans receiving care during the study period, 8,000 hospitalizations may have been unnecessary. The most common ADRs that occurred were bradycardia (n=6; beta blockers, digoxin), hypoglycemia (n=6; sulfonylureas, insulin), falls (n=6; antidepressants, ACE-inhibitors), and mental status changes (n=6; anticonvulsants, benzodiazepines). Overall, 44.8% of Veterans took ? 9 outpatient medications and 35.4% took 5–8. Using multivariable logistic regression and controlling for demographic, health status, and access to care variables, polypharmacy (? 9 and 5–8) was associated with an increased risk of ADR-related hospitalization (AOR 3.90, 95% CI 1.43–10.61 and AOR 2.85, 95% CI 1.03–7.85, respectively). Conclusion ADRs determined by a validated causality algorithm are a common cause of unplanned hospitalization among older Veterans, are frequently preventable, and are associated with polypharmacy.

Marcum, Zachary A.; Amuan, Megan E.; Hanlon, Joseph T.; Aspinall, Sherrie L.; Handler, Steven M.; Ruby, Christine M.; Pugh, Mary Jo V.



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

PubMed Central

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

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



ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions  

PubMed Central

The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at, and it is constantly growing.



Epidemiology of medication-related adverse events in nursing homes  

Microsoft Academic Search

Background:Nursing home residents are prescribed more medications than patients in any other clinical setting. Although pharmacotherapy for older nursing home residents is usually safe and effective, it can lead to medication-related adverse events such as adverse drug reactions (ADRs), adverse drug withdrawal events (ADWEs), and therapeutic failures (TFs).

Steven M. Handler; Rollin M. Wright; Christine M. Ruby; Joseph T. Hanlon



Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy  

PubMed Central

Aims To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM). Methods We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years) who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. Results MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm2, p = 0.0009), while there were no differences in the other echocardiographic parameters. LAV/BSA of ? 40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. Conclusion LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.



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

PubMed Central

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



Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.  


The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-? in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-? production as well as a suppression of TGF-? production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. PMID:23147110

Bottasso, Oscar; Bay, María Luisa; Besedovsky, Hugo; Del Rey, Adriana



Prescribing Discrepancies Likely to Cause Adverse Drug Events after Patient Transfer  

PubMed Central

Background Medication prescribing discrepancies are used as a quality measure for patients transferred between sites of care. The objective of this study was to quantify the rate of adverse drug events (ADEs) caused by prescribing discrepancies and the discrimination of an index of high-risk transition drug prescribing. Methods We examined medical records of patients transferred between 7 nursing homes and 3 hospitals between 1999–2005 in New York and Connecticut for transfer-associated prescribing discrepancies. ADEs caused by discrepancies were determined by 2 clinician raters. We calculated the fraction of medication discrepancies that caused ADEs in each of 22 drug classes by calculating positive predictive values (PPVs). We calculated the discrimination of a count of high-risk drug discrepancies, selected from published lists of high-risk medications and using observed PPVs. Results 208 patients were hospitalized 304 times. Overall, 65 of 1350 prescribing discrepancies caused ADEs, for a PPV of .048 (95%CI .037–.061). PPVs by drug class ranged from 0 – .28. Drug classes with the highest PPVs were opioid analgesics, metronidazole, and non-opioid analgesics. Patients with 0, 1–2, and ? 3 high-risk discrepancies had a 13%, 23%, and 47% chance of experiencing a discrepancy-related ADE, respectively. Conclusions Discrepancies in certain drug classes more often caused ADEs than other types of discrepancies in hospitalized nursing home patients. Information about ADEs caused by medication discrepancies can be used to enhance measurement of care quality, identify high-risk patients, and inform development of decision-support tools at the time of patient transfer.

Boockvar, Kenneth S.; Liu, Sophia; Goldstein, Nathan; Nebeker, Jonathan; Siu, Albert; Fried, Terri



Improving patient safety via automated laboratory-based adverse event grading  

PubMed Central

The identification and grading of adverse events (AEs) during the conduct of clinical trials is a labor-intensive and error-prone process. This paper describes and evaluates a software tool developed by City of Hope to automate complex algorithms to assess laboratory results and identify and grade AEs. We compared AEs identified by the automated system with those previously assessed manually, to evaluate missed/misgraded AEs. We also conducted a prospective paired time assessment of automated versus manual AE assessment. We found a substantial improvement in accuracy/completeness with the automated grading tool, which identified an additional 17% of severe grade 3–4 AEs that had been missed/misgraded manually. The automated system also provided an average time saving of 5.5?min per treatment course. With 400 ongoing treatment trials at City of Hope and an average of 1800 laboratory results requiring assessment per study, the implications of these findings for patient safety are enormous.

Stiller, Tracey; Neat, Jennifer; Londrc, Adina; Johnson, Dina; Pannoni, Susan



Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review  

PubMed Central

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients. METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 ?g/wk) or PegIFN alpha 2b (1 or 1.5 ?g/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk. RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001). CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.

Bota, Simona; Sporea, Ioan; Sirli, Roxana; Popescu, Alina; Neghina, Adriana Maria; Danila, Mirela; Strain, Mihnea



Risk factors for serious adverse effects of thiopurines in patients with Crohn's disease.  


Purpose: Thiopurines are effective in attaining and maintaining remission in patients with inflammatory bowel diseases (IBD). The major drawback of these drugs are their serious adverse effects (SAE), highlighting the importance of preemptive identification of patients at risk. We aimed to examine whether gene polymorphisms in GSTM1, GSTT1 and TPMT, combined with various clinical parameters, can predict thiopurine induced SAE. Methods: A retrospective cohort of 176 Crohn's Disease (CD) patients treated with thiopurines (131 with 6MP and 45 with azathioprine) was genotyped for common polymorphisms in GSTM1, GSTT1 and TPMT. Clinical data including SAE, age, ethnicity, gender and smoking status were extracted from patient charts. SAEs evaluated were myelosuppression, hepatotoxicity and pancreatitis. Associations between demographic, clinical, and genetic variables and thiopurine induced SAE were assessed. Results: Twenty-four patients (14%) developed SAE, revealing a significant association between thiopurine induced SAE and GSTM1-null genotype (P=0.05), older age (P=0.016) and active smoking status (P=0.043) and SAE. On multi-variant analysis, past or current smokers were at increased risk for developing thiopurine related SAE (OR 2.915, CI 95%: 1.199- 7.084), specifically pancreatitis (p<0.001). No association was found between TPMT or GSTT1 polymorphisms and the development of SAE. Conclusions: Active smoking and GSTM1-null genotype appear to be risk factors for thiopurine induced SAEs (i.e. myelosuppression, hepatotoxicity and pancreatitis) in patients with CD. Corroboration of these associations in larger cohorts is warranted. PMID:23845145

Mazor, Yoav; Koifman, Eduard; Elkin, Hela; Chowers, Yehuda; Krivoy, Norberto; Karban, Amir; Efrati, Edna



Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service  

PubMed Central

BACKGROUND—In Australia an adverse event following immunisation (AEFI), with the exception of anaphylaxis and encephalopathy, is no longer considered an absolute contraindication to continuing vaccination with the suspect vaccine. Despite these recommendations there is a paucity of information on the re-vaccination of such children.?AIMS—To describe the re-vaccination of a large number of children with a past history of an AEFI.?METHODS—A review of children attending special immunisation services in three Australian tertiary care paediatric centres.?RESULTS—During the review 970 children attended of whom 469 had experienced a past AEFI. Of these, 293 had experienced minor while 176 children had experienced significant neurological or allergic reactions. The majority (421/469) were re-vaccinated, with only one child having a significant neurological event; this was transient and resolved spontaneously.?CONCLUSIONS—Re-vaccination of children who have a past history of an AEFI appears safe. A special immunisation service should be part of a comprehensive immunisation programme.??

Gold, M.; Goodwin, H.; Botham, S.; Burgess, M.; Nash, M.; Kempe, A.



Founding an adverse drug reaction (ADR) network: A method for improving doctors spontaneous ADR reporting in a general hospital.  


Adverse drug reactions (ADR) are underreported by doctors despite numerous efforts. We aimed to determine if establishing an "ADR reporting doctor's network" within a hospital would increase the quantity of ADRs reported by hospital doctors. One hundred hospital doctors joined the network. Email reminders were sent to network members during the 1 year study period, conveying information about ADRs reported, amusingly and pleasantly reminding them to report ADRs in minimal detail, by phone, email, text message or mail to the Clinical Pharmacology Unit, who would further complete the report. A total of 114 ADRs were reported during the study period in comparison to 48, 26, and 17 in the previous 3 years (2008, 2009, 2010, respectively). In the 3 years prior, doctors reported 41.7% of the reported ADRs whereas in the study period, doctors reported 74.3% of ADRs (P?

Goldstein, Lee Hilary; Berlin, Maya; Saliba, Walid; Elias, Mazen; Berkovitch, Matitiyahu



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.

Clarke, John D; Cherrington, Nathan J



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

PubMed Central

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

Aagaard, Lise; Hansen, Ebba Holme



A patch testing and cross-sensitivity study of carbamazepine-induced severe cutaneous adverse drug reactions.  


Background? The usefulness of the drug patch testing for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA-B*1502 is strongly associated with CBZ-SJS/TEN in Chinese and Southeast Asian populations. Objective? To evaluate the usefulness of patch tests for patients with carbamazepine (CBZ)-induced SJS, TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) and the cross-reactivity in patch tests among the aromatic antiepileptic drugs. Methods? We measure the frequency of positive patch test reactions and cross-sensitivity to structure-related aromatic anti-epileptic drugs (AEDs) for patients after SJS/TEN or DRESS episodes caused by CBZ. CBZ and other structure-related AEDs used for patch testing were prepared in 10% and 30% petrolatum. Secondary measures included the association of HLA-B*1502 genotype and frequency of possible side effects from the patch tests. Results? Positive patch test reactions to 30% CBZ in the CBZ-SJS/TEN were 62.5% (10/16), and 70% (7/10) in the CBZ-DRESS. None of the 10 healthy controls displayed a positive reaction to tested agents. Cross-sensitivity to other aromatic AEDs was observed in both the CBZ-SJS/TEN and the CBZ-DRESS. Only the HLA-B*1502 genotype was present and strongly associated with the CBZ-SJS/TEN, but not with the CBZ-DRESS. Conclusion? Drug patch testing is a safe and useful method for the identification of CBZ as the culprit drug of SJS/TEN as well as DRESS. Testing of chemically or pharmacologically related AEDs may provide information on cross-reactivity for these patients. PMID:22211830

Lin, Y-T; Chang, Y-C; Hui, R C-Y; Yang, C-H; Ho, H-C; Hung, S-I; Chung, W-H



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


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



Drug burden index, physical function, and adverse outcomes in older hospitalized patients.  


The Drug Burden Index (DBI) is associated with poorer physical function in stable, community-dwelling, older people. The authors speculated that a higher DBI is associated with reduced physical function (Barthel Index, primary outcome) and predicts adverse outcomes (length of stay, in-hospital mortality, secondary outcomes) in frail, acutely ill, older hospitalized patients. Clinical and demographic characteristics, Barthel Index, DBI, and full medication exposure were recorded on admission in 362 consecutive patients (84 ± 7 years old) admitted to 2 acute geriatric units between February 1, 2010, and June 30, 2010. A unit increase in DBI was associated with a 29% reduction in the odds of being in a higher Barthel Index quartile than a lower quartile (odds ratio, 0.71; 95% confidence interval, 0.55-0.91; P = .007). The Barthel Index components mostly affected were bathing (P < .001), grooming (P < .001), dressing (P = .001), bladder function (P < .001), transfers (P = .001), mobility (P < .001), and stairs (P < .001). A higher DBI independently predicted length of stay (hazard ratio, 1.23; 95% confidence interval, 1.06-1.42; P = .005) but not in-hospital mortality (hazard ratio, 1.17; 95% confidence interval, 0.72-1.90; P = .52). Higher DBI scores on admission are independently associated with lower scores of the Barthel Index and predict length of stay among older hospitalized patients. The DBI may be useful in the acute setting to improve risk stratification. PMID:22167569

Lowry, Estelle; Woodman, Richard J; Soiza, Roy L; Hilmer, Sarah N; Mangoni, Arduino A



Effect of childhood adversity on health related quality of life in patients with upper abdominal or chest pain  

PubMed Central

Background and aims: This study assessed whether childhood and current adversities: (a) were more prevalent in patients with functional dyspepsia (FD) or non-cardiac chest pain (NCCP) than in patients with gastro-oesophageal reflux disease (GORD) or ischaemic heart disease (IHD); and (b) predicted health related quality of life in these disorders. Patients: Cohort study of consecutive attenders to gastroenterology and cardiology clinics in a secondary/tertiary referral centre. Methods: Patients were interviewed using the childhood experience of care and abuse and life events and difficulties schedules. Distress was assessed by questionnaire. Outcome was assessed using SF36 at the index clinic visit and six months later. Results: A total of 133 patients were included (40 NCCP, 43 FD, 29 GORD, and 21 IHD) (67% response rate). The diagnostic groups did not differ significantly in the proportion reporting childhood adversity (30%), ongoing social stress (40%), lack of a close confidant (14%), or level of psychological distress. Reported childhood adversity was associated with poor outcome at the index visit (SF36 physical component score: 36.6 (SEM 1.8) v 42.3 (SEM 1.2) for the remainder; p?=?0.014). In multiple regression analysis, childhood adversity was a significant independent predictor for patients with functional disorders (NCCP and FD) but not organic disorders (GORD or IHD). Change in SF36 score at six months was determined by age and distress score at the index visit in both groups. Conclusion: Childhood adversity was common among this consecutive sample but was associated directly with poor outcome only in patients with functional gastrointestinal syndromes. Distress is an important predictor of outcome in all patients. Greatest impairment occurs when lack of social support accompanies reported childhood adversity.

Biggs, A-M; Aziz, Q; Tomenson, B; Creed, F



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

Microsoft Academic Search

The effects of video games on the adverse corollaries of chemotherapy were assessed in 3 pediatric oncology patients using a combined multiple-baseline and ABAB design. Patients were three males, 11, 16, and 17 years old, who reported and exhibited distress both prior to and following chemotherapy. Self-report measures of the presence of several anticipatory distress and anxiety symptoms and the

David J. Kolko; Jorge L. Rickard-Figueroa



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



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

Microsoft Academic Search

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




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



Preoperative HO-1 Levels as Prognostic Factor for Adverse Cardiac Events in Elder Patients Undergoing Non-Cardiac Surgery  

PubMed Central

Background Hypoxia-inducible factor-1? (HIF-1?) and heme oxygenase-1(HO-1) are involved in the tissue hypoxic response. Hypothesis HIF-1? and HO-1 levels may predict cardiac ischemia and adverse cardiac events during non-cardiac surgery. Methods HIF-1? and HO-1 levels were determined in elderly patients undergoing non-cardiac surgery preoperatively and at 30 minutes, 48 and 72 hours postoperatively. Results were analyzed with respect to the occurrence of adverse cardiac events. Results A total of 380 patients with a mean age of 65.3 years were included, and 54 (14.2%) who had adverse cardiac events during or after the surgery. HIF-1? and HO-1 levels in the adverse cardiac event group were significantly higher than in the group without adverse cardiac events at each time point (all, P<0.05). In multivariates regression analysis, the odds of an adverse cardiac event was increased by every 1-year increase in age (odd ratio [OR] 1.39, P<0.001), abnormal ECG at baseline (OR 2.27, P?=?0.048), myocardial infarction history (OR 3.18, P?=?0.015), and positive baseline cTnI level were associated with an increased likelihood of an adverse cardiac event (OR 8.78, P?=?0.019), and for every 1 unit increase of HO-1, the odds of an adverse cardiac event increased by 1.30 (P?=?0.002). Conclusion Determination of preoperative HO-1 levels may aid in identifying patients at risk of developing ischemic cardiac events.

Zheng, Hong; Ma, Hai-Ping; Wang, Jiang; Ma, Ming



Perception of the risk of gastrointestinal adverse drug reactions with non-steroidal anti-inflammatory drugs (including coxibs): differences among general practitioners, gastroenterologists and rheumatologists  

Microsoft Academic Search

Objective To compare the perception of risk of gastrointestinal adverse drug reactions (ADRs) with non-steroidal anti-inflammatory drugs (NSAIDs) (including coxibs) in general practitioners, gastroenterologists and rheumatologists. Methods Physicians (69 general practitioners, 45 gastroenterologists and 58 rheumatologists; 172 total) were interviewed using visual analogue scales in order to define a score of perceived risk (ranking from 0 to 10) of gastrointestinal

J. L. Montastuc; V. Bongard; M. Lapeyre-Mestre



Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain  

Microsoft Academic Search

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a

Julio Bobes; Fernando Cañas; Javier Rejas; Joan Mackell



HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese.  


Aim: Allopurinol is widely used as an effective urate-lowering drug and is one of the most frequent causes of cutaneous adverse drug reactions (cADRs). Recently, a strong association of HLA-B*58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B*5801 in a Han population from mainland China. Patients & methods:HLA-B genotyping was performed on 38 Chinese patients with different types of allopurinol-cADRs from 2008 to 2011. Results: All the allopurinol-cADR patients carried HLA-B*58:01, in contrast with only 11.11% (7/63) in the allopurinol-tolerant patients (odds ratio [OR] = 580.07; p < 0.0001) and 13.99% (80/572) in a Han Chinese population from the human MHC database (dbMHC; OR: 471.09; p < 0.0001) carried the genotype. Each type of allopurinol cADRs revealed a statistically significant association with HLA-B*58:01. In particular, the risk of allopurinol-induced maculopapular eruption was significantly higher in patients with HLA-B*58:01 (OR: 339.00; p < 0.0001). Conclusion: The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012. PMID:22909208

Cao, Zhi-hao; Wei, Zhi-yun; Zhu, Qin-yuan; Zhang, Jun-yu; Yang, Lun; Qin, Sheng-ying; Shao, Li-yan; Zhang, Yi-ting; Xuan, Jie-kun; Li, Qiao-li; Xu, Jin-Hua; Xu, Feng; Ma, Li; Huang, Hui-yuan; Xing, Qing-he; Luo, Xiao-qun



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


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



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


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



Linking drugs to obscure illnesses: lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and Reye's syndrome. a report from the Southern Network on Adverse Reactions (SONAR).  


Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States' NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common. PMID:22692632

Bennett, Charles L; Starko, Karen M; Thomsen, Henrik S; Cowper, Shawn; Sartor, Oliver; Macdougall, Iain C; Qureshi, Zaina P; Bookstaver, P Brandon; Miller, April D; Norris, LeAnn B; Xirasagar, Sudha; Trenery, Alyssa; Lopez, Isaac; Kahn, Adam; Murday, Alanna; Luminari, Stefano; Cournoyer, Denis; Locatelli, Francesco; Ray, Paul; Mattison, Donald R



Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls.  


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: P(adjust) =?2.54×10(-5); HTR1B_cg06031989: P(adjust) ?=?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



CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia.  


Patients with acute myeloid leukemia (AML) harboring an NPM1 mutation exhibit a heterogeneous clinical outcome. Recent studies have shown that the absence of FLT3 internal tandem duplication (FLT3-ITD) mutation confers a favorable prognosis in NPM1-positive AML. However, the prognostic impact of immunophenotypes in this subgroup remains unclear. In this study, FLT3 mutation status and immunophenotypic profile of 85 NPM1-positive patients with de novo AML were retrospectively analyzed and correlated with their clinical features and survival outcomes. Univariate analysis detected 5 markers with prognostic relevance: older age (?60 years), high white blood cell (WBC) count (>30 × 10(9)/L), FLT3-ITD, CD7, and CD34 expression. Multivariate analysis showed that high WBC count was the only independent predictor of a lower complete remission rate (P = .019). Older age (P = .035), high WBC count (P = .008), FLT3-ITD (P = .012), and CD34 expression (P = .006) were independent predictors of a shorter event-free survival (EFS). High WBC count (P = .014), FLT3-ITD (P = .005), and CD34 expression (P = .047) were independent predictors of a shorter overall survival (OS). Furthermore, based on FLT3-ITD status in NPM1 mutation-positive patients, we showed that both high WBC and CD34 expression conferred a poor EFS (P = .010 and P = .016, respectively) and OS (P = .032 and P = .001, respectively) in the FLT3-ITD-negative group, whereas high WBC predicted a poor EFS (P = .016) and OS (P = .027) in the FLT3-ITD-positive group. Our results confirm the prognostic value of assessing FLT3-ITD mutations in NPM1-positive AML and identify the adverse prognostic impact of high WBC and CD34 expression in this subgroup of AML. PMID:23701943

Dang, Harry; Chen, Yan; Kamel-Reid, Suzanne; Brandwein, Joseph; Chang, Hong



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

PubMed Central

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

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



The Reaction of Delayed Hypersensitivity in Patients with Malignant Melanoma.  

National Technical Information Service (NTIS)

A study was made to evaluate allergic skin reactions of a delayed type in patients with malignant melanoma, mammary cancer and nonmelanoma skin tumors. Melanoma antigen was injected into these patients with the following results: allergic reactions to mel...

V. V. Gorodilova Z. M. Saraeva R. I. Slesareva G. D. Monzul



The Effect of Race/Ethnicity on Adverse Perinatal Outcomes among Patients with Gestational Diabetes  

PubMed Central

OBJECTIVE To determine racial/ethnic differences in perinatal outcomes among women with gestational diabetes mellitus (GDM). STUDY DESIGN Retrospective cohort study of 32,193 singleton births among GDMs in California from 2006, using Vital Statistics Birth and Death Certificate and Patient Discharge Data. Women were divided by race/ethnicity: White, Black, Hispanic, or Asian. Multivariable logistic regression analyzed associations between race/ethnicity and adverse outcomes, controlling for potential confounders. Outcomes included: primary cesarean, preeclampisa, neonatal hypoglycemia, preterm delivery, macrosomia, fetal anomaly, respiratory distress syndrome (RDS). RESULTS Compared to other races, Black women had higher odds of preeclampsia [aOR=1.57, 95%CI(1.47-1.95)], neonatal hypoglycemia [aOR=1.79, 95%CI(1.07-3.00)], and preterm delivery <37 weeks [aOR=1.56, 95%CI(1.33-1.83)]. Asians had the lowest odds of primary cesarean [aOR=0.75, 95%CI(0.69-0.82)], large for gestational age infants [aOR=0.40, 95%CI(0.33-0.48)], and neonatal RDS [aOR=0.54, 95%CI(0.40-0.73)]. CONCLUSION Perinatal outcomes among women with GDM differ by race/ethnicity and may be attributed to inherent sociocultural differences that may impact glycemic control, the development of chronic co-morbidities, genetic variability, and variation in access to as well as quantity and quality of prenatal care.

NGUYEN, Brian T.; CHENG, Yvonne W.; SNOWDEN, Jonathan M.; ESAKOFF, Tania F.; FRIAS, Antonio E.; CAUGHEY, Aaron B.



Adverse Drug Reactions Related Hospital Admissions in Persons Aged 60 Years and over, The Netherlands, 1981-2007: Less Rapid Increase, Different Drugs  

PubMed Central

Background Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population. Methodology and Principal Findings Secular trend analysis of ADR-related hospital admissions in patients ?60 years between 1981 and 2007, using the National Hospital Discharge Registry of the Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ?60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981–1996 (percentage annual change 2.56%). Conclusion/Significance ADR-related hospital admissions in older persons have shown a rapidly increasing trend in the Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem.

Hartholt, Klaas A.; van der Velde, Nathalie; Looman, Caspar W. N.; Panneman, Martien J. M.; van Beeck, Ed F.; Patka, Peter; van der Cammen, Tischa J. M.



Patient-Reported Discontinuation of Endocrine Therapy and Related Adverse Effects Among Women With Early-Stage Breast Cancer  

PubMed Central

Background: Approximately 20% to 50% of women diagnosed with hormone receptor–positive breast cancer discontinue endocrine therapy early; most reports come from automated pharmacy data or small self-report evaluations. We conducted a larger self-report evaluation of endocrine therapy discontinuation associated with patient characteristics and therapy-related adverse effects. Methods: We surveyed 538 women from a single health plan who were diagnosed with early-stage breast cancer from 2002 to 2008 and received endocrine therapy. Women reported adverse effects and reasons for discontinuation via mailed survey; tumor characteristics were obtained via registry linkage. We classified women as discontinuers if they self-reported stopping therapy and their self-reported duration of tamoxifen plus aromatase inhibitor (AI) use was < 5 years, and nondiscontinuers if they self-reported ? 5 years use or current use. We estimated odds ratios (ORs) with 95% CIs for discontinuation versus continuation by using logistic regression adjusted for age and year of diagnosis. Results: Among 538 women, 98 (18.2%) discontinued endocrine therapy early. Women with positive lymph nodes (v negative) were significantly less likely to discontinue therapy (odds ratio [OR] = 0.54; 95% CI, 0.31 to 0.93). Almost all women (94%) experienced adverse effects. Experiencing headaches was associated with discontinuation of AIs (OR = 4.16; 95% CI, 2.16 to 8.01) and tamoxifen (OR = 2.34; 95% CI, 1.24 to 4.41); few other individual adverse effects were related to discontinuation despite most discontinuers reporting they “did not like adverse effects” (AIs: 66.7%, tamoxifen: 59.1%). Conclusion: Few individual adverse effects or patient characteristics were significantly associated with endocrine therapy discontinuation, yet adverse effects were prevalent and were the most common reason women reported for discontinuing therapy.

Aiello Bowles, Erin J.; Boudreau, Denise M.; Chubak, Jessica; Yu, Onchee; Fujii, Monica; Chestnut, Janet; Buist, Diana S.M.



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.



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.



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.



Multiple Biomarker Use for Detection of Adverse Events in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome  

Microsoft Academic Search

Background: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients pre- senting with symptoms of acute coronary syndrome. Methods: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI),

Fred S. Apple; Lesly A. Pearce; Adrine Chung; Ranka Ler; MaryAnn M. Murakami


Potential Utility of Data-Mining Algorithms for Early Detection of Potentially Fatal\\/Disabling Adverse Drug Reactions: A Retrospective Evaluation  

Microsoft Academic Search

The objective of this study was to apply 2 data-mining algorithms to a drug safety database to determine if these methods would have flagged potentially fatal\\/disabling adverse drug reactions that triggered black box warnings\\/drug withdrawals in advance of initial identification via “traditional” methods. Relevant drug-event combinations were identified from a journal publication. Data-mining algorithms using commonly cited disproportionality thresholds were

Manfred Hauben; Lester Reich



A comparative study on efficacy and adverse reaction of MVP and MVP combined with Kanglaite Injection in the treatment of non-small cell lung cancer (NSCLC)  

Microsoft Academic Search

MMC 8mg, d1; VDS 4mg, d1, 8; DDP 40mg, d1-3. During the 56th-60th days after the completion of chemotherapy, evaluation was undertaken on efficacy as well as adverse reactions. Results Control group: effective rate 27.0%, degree III GI toxicity (WHO criteria) appeared in 4 cases and degree III hematological toxicity in 3 cases. Karnofsky score elevated rate 23.3%. Treatment group:

REN Hongxuan; ZHANG Canzhen; LI Yang; SHEN Lida


Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population.  


An anticonvulsant, carbamazepine (CBZ), is known to show incidences of cutaneous adverse drug reactions (cADRs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS). To identify a gene(s) susceptible to CBZ-induced cADRs, we conducted a genome-wide association study (GWAS) in 53 subjects with the CBZ-induced cADRs, including SJS, TEN and DIHS, and 882 subjects of a general population in Japan. Among the single nucleotide polymorphisms (SNPs) analyzed in the GWAS, 12 SNPs showed significant association with CBZ-induced cADRs, and rs1633021 showed the smallest P-value for association with CBZ-induced cADRs (P = 1.18 × 10?¹³). These SNPs were located within a 430 kb linkage disequilibrium block on chromosome 6p21.33, including the HLA-A locus. Thus, we genotyped the individual HLA-A alleles in 61 cases and 376 patients who showed no cADRs by administration of CBZ (CBZ-tolerant controls) and found that HLA-A*3101 was present in 60.7% (37/61) of the patients with CBZ-induced cADRs, but in only 12.5% (47/376) of the CBZ-tolerant controls (odds ratio = 10.8, 95% confidence interval 5.9-19.6, P = 3.64 × 10?¹?), implying that this allele has the 60.7% sensitivity and 87.5% specificity when we apply HLA-A*3101 as a risk predictor for CBZ-induced cADRs. Although DIHS is clinically distinguished from SJS and TEN, our data presented here have indicated that they share a common genetic factor as well as a common pathophysiological mechanism. Our findings should provide useful information for making a decision of individualized medication of anticonvulsants. PMID:21149285

Ozeki, Takeshi; Mushiroda, Taisei; Yowang, Amara; Takahashi, Atsushi; Kubo, Michiaki; Shirakata, Yuji; Ikezawa, Zenro; Iijima, Masafumi; Shiohara, Tetsuo; Hashimoto, Koji; Kamatani, Naoyuki; Nakamura, Yusuke



Impact of adiponectin and leptin on long-term adverse events in Japanese patients with acute myocardial infarction.  


Background:?Low adiponectin levels and high leptin levels are associated with a high incidence of developing cardiovascular disease. However, the relationship between the levels of these adipokines and the development of adverse events after acute myocardial infarction (AMI) remains unclear. Methods and Results:?This study enrolled 724 Japanese subjects with AMI who underwent successful emergency percutaneous coronary intervention (PCI). Their serum adiponectin and leptin levels were measured 7 days after AMI onset. There were 63 adverse events during the 3-year follow-up. The levels of adiponectin and leptin and the leptin to adiponectin ratio, were significantly associated with adverse events [hazard ratio 2.08 (95% confidence interval (CI) 1.33-3.24), P=0.001; hazard ratio 0.62 (95% CI 0.43-0.90), P=0.012; hazard ratio 0.59 (95% CI 0.45-0.76), P<0.001, respectively]. The leptin to adiponectin ratio remained a significant independent predictor of adverse events during long-term follow-up in a multivariable analysis [adjusted hazard ratio 0.60 (95% CI 0.43-0.83), P=0.002]. Conclusions:?Higher adiponectin and lower leptin levels are associated with a high incidence of adverse events in Japanese patients after AMI, and the leptin to adiponectin ratio independently predicts prognosis after AMI.??(Circ J?2013; 77: 2778-2785). PMID:23924849

Morita, Yasuhiro; Maeda, Kengo; Kondo, Takahisa; Ishii, Hideki; Matsudaira, Kyoko; Okumura, Naoki; Mitsuhashi, Hirotsugu; Shibata, Rei; Murohara, Toyoaki



Drugs causing adverse events in patients aged 45 or older: a randomised survey of Australian general practice patients  

PubMed Central

Objective To determine prevalence of adverse drug events (ADEs) in patients aged 45?years or older presenting to Australian general practitioners (GPs) and identify drug groups related to ADEs, their severity and manifestation. Design Substudy of the Bettering the Evaluation and Care of Health continuous survey of Australian GP clinical activity in which randomly selected GPs collected survey data from patients. Data are reported with 95% CIs. Setting General practice in Australia. Main outcome measures Prevalence in the preceding 6?months, type, implicated drugs, severity (including hospitalisation) and manifestation of ADEs. Participants From three survey samples, January–October 2007, and two samples, January–March 2010, responses were received from 482 GPs about 7561 patients aged 45?years or older. Results Of a final sample of 7518 patients (after duplicate patients removed), 871 (11.6%) reported ADEs in the previous 6?months. The type of ADE was recognised side effect (75.8%, 95% CI 72.0 to 79.7), drug sensitivity (9.9%, 95% CI 7.2 to 12.7) and drug allergy (7.4%, 95% CI 4.7 to 10.1). Drug interaction (1.0%, 95% CI 0.1 to 1.8), overdose (0.8%, 95% CI 0.0 to 1.5) and contraindications (0.2%, 95% CI 0.0 to 0.6) were very infrequent. A severity rating was provided for 846 patients. Almost half (45.9%, 95% CI 42.0 to 49.7) were rated as ‘mild’ events, 42.2% (95% CI 38.8 to 45.6) ‘moderate’, 11.8% (95% CI 9.5 to 14.1) severe and 5.4% (95% CI 3.8 to 7.0) had been hospitalised as a result of the most recent ADE. Thirteen commonly prescribed drug groups accounted for 58% of all ADEs, opioids being the group most often implicated. Conclusion ADEs in patients aged 45 or older are frequent and are associated with significant morbidity. Most of ADEs result from commonly prescribed drugs at therapeutic dosage. The list of causative agents bears little relationship to published lists of ‘inappropriate medications’.

Miller, Graeme C; Valenti, Lisa; Britt, Helena; Bayram, Clare



Performance Characteristics of a Methodology to Quantify Adverse Events over Time in Hospitalized Patients  

PubMed Central

Objective To assess the performance characteristics of the Institute for Healthcare Improvement Global Trigger Tool (GTT) to determine its reliability for tracking local and national adverse event rates. Data Sources Primary data from 2008 chart reviews. Study Design A retrospective study in a stratified random sample of 10 North Carolina hospitals. Hospital-based (internal) and contract research organization–hired (external) reviewers used the GTT to identify adverse events in the same 10 randomly selected medical records per hospital in each quarter from January 2002 through December 2007. Data Collection/Extraction Interrater and intrarater reliability was assessed using ? statistics on 10 percent and 5 percent, respectively, of selected medical records. Additionally, experienced GTT users reviewed 10 percent of records to calculate internal and external teams' sensitivity and specificity. Principal Findings Eighty-eight to 98 percent of the targeted 2,400 medical records were reviewed. The reliability of the GTT to detect the presence, number, and severity of adverse events varied from ?=0.40 to 0.60. When compared with a team of experienced reviewers, the internal teams' sensitivity (49 percent) and specificity (94 percent) exceeded the external teams' (34 and 93 percent), as did their performance on all other metrics. Conclusions The high specificity, moderate sensitivity, and favorable interrater and intrarater reliability of the GTT make it appropriate for tracking local and national adverse event rates. The strong performance of hospital-based reviewers supports their use in future studies.

Sharek, Paul J; Parry, Gareth; Goldmann, Donald; Bones, Kate; Hackbarth, Andrew; Resar, Roger; Griffin, Frances A; Rhoda, Dale; Murphy, Cathy; Landrigan, Christopher P



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

Microsoft Academic Search

BACKGROUND: Prescription drugs account for approximately 11% of national health expenditures. Prior research on adverse childhood experiences (ACEs), which include common forms of child maltreatment and related traumatic stressors, has linked them to numerous health problems. However, data about the relationship of these experiences to prescription drug use are scarce. METHOD: We used the ACE Score (an integer count of

Robert F Anda; David W Brown; Vincent J Felitti; Shanta R Dube; Wayne H Giles



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.

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


QTc dispersion is prolonged in patients with early postoperative adverse cardiovascular events and those with silent myocardial ischemia  

Microsoft Academic Search

Objective: To determine if increased QT interval dispersion (corrected and not corrected for heart rate) is associated with perioperative silent myocardial ischemia or postoperative adverse cardiovascular events.Design: Blinded retrospective observational study.Setting: University hospital.Participants: One hundred eighty-one perioperative patients receiving general anesthesia for elective major vascular or orthopedic surgery.Interventions: None.Measurements and main results: QT dispersion, corrected and uncorrected for heart rate,

Keith J Anderson; John W Sear



Hypersensitivity reaction to all drugs of category-1 anti-tuberculosis regime in an adult tuberculosis patient.  


Adverse drug reaction to tuberculous chemotherapy is not an uncommon problem. Usually it occurs to single drug and can be treated easily with minimal intervention. We follow WHO recommended guideline for National Tuberculosis Control Programs to treat these adverse reactions. Here we found an adult who has been suffering left sided pleural tuberculosis developed anaphylactic reaction to first dose of category-1 anti-TB regime. Later on it was found that he could not even tolerate smaller challenging doses of isoniazide, Ethambutol, Rifampicin and Pyrazinamide separately. It became very difficult to choose an alternate regime for this patient. Lastly a regime with levofloxacin, streptomycin and clarithromycin was give to treat him and patient was recovered with this regime successfully. This experience will help in management of unusual drug reactions to anti-tuberculosis drugs. PMID:23982557

Rashid, M M; Hoque, M N; Hossain, D A; Hassan, M R



High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis  

PubMed Central

Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ? 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin.

Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.



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

Microsoft Academic Search

Background  Patient record review is believed to be the most useful method for estimating the rate of adverse events among hospitalised\\u000a patients. However, the method has some practical and financial disadvantages. Some of these disadvantages might be overcome\\u000a by using existing reporting systems in which patient safety issues are already reported, such as incidents reported by healthcare\\u000a professionals and complaints and

Ingrid Christiaans-Dingelhoff; Marleen Smits; Laura Zwaan; Sanne Lubberding; Gerrit van der Wal; Cordula Wagner



Adverse events associated with botulinum toxin injection: A multidepartment, retrospective study of 5310 treatments administered to 1819 patients.  


Background: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported. Objective: To retrospectively evaluate and analyze the safety of botulinum toxin injections in terms of purpose and the type of toxin administered. Materials and methods: Data were collected on 1819 patients who underwent a total of 5310 treatments between 2005 and 2011 at a single tertiary medical center. Information on the dosage, treatment purpose, type of botulinum toxin, and any adverse events associated with these treatments were collected and analyzed. The generalized estimating equation (GEE) with the logistic link function was used to estimate the overall frequencies of adverse events. A multivariable GEE with the logistic link function was used to identify the factors associated with adverse events. Results: Among the 5310 botulinum toxin treatments in our study cohort, 2258 of which (42.5%) were used to treat hemifacial spasm, 184 adverse events (3.73%) were recorded, 114 (2.26%) muscle-related, and 71 (1.47%) muscle-unrelated. The highest number of adverse events (8.29%) was associated with the treatment of blepharospasm and the lowest (1.07%) with masseter hyperplasia. By multivariate analysis, the odds ratio for females was 1.577 (95% confidence interval [CI] = 1.052-2.364; p = 0.027) and for the dose was 1.006 (95% CI = 1.002-1.010; p = 0.005). When compared with upper face wrinkles, the odds ratio was 2.510 (95% CI = 1.400-4.499; p = 0.002) for blepharospasm, 0.375 (95% CI = 0.202-0.695; p = 0.002) for cervical dystonia, and 0.114 (95% CI: 0.015-0.862; p = 0.035) for masseter hyperplasia. Conclusion: When injecting botulinum toxin for cosmetic purposes, practitioners should be cautious, especially when targeting the areas around the eyes, as these treatments are prone to cause adverse events. PMID:23537074

Kim, Byung Wook; Park, Gyeong-Hun; Yun, Woo Jin; Rho, Nark Kyoung; Jang, Kyoung Ae; Won, Chong Hyun; Chang, Sung Eun; Chung, Sun Ju; Lee, Mi Woo



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

PubMed Central

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

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



A distance-learning programme in pharmacovigilance linked to educational credits is associated with improved reporting of suspected adverse drug reactions via the UK yellow card scheme  

PubMed Central

Aims The effect of a distance-learning package linked to educational credits on the rate and quality of spontaneous adverse drug reaction (ADR) reporting by general practitioners (GPs) and pharmacists in Wales was investigated. Methods In April 2000, 477 GPs and 261 pharmacists enrolled in the 12 month programme. Results The number and quality of yellow card reports improved compared with those of a control region in England (Northern Region). Conclusions We conclude that an educational initiative in drug safety linked to incentives may be associated with a significant but perhaps short-lived improvement in the rate and quality of ADR reporting.

Bracchi, Robert C G; Houghton, Jane; Woods, Fiona J; Thomas, Simon; Smail, Simon A; Routledge, Philip A



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