Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

Acute physical exercise under hypoxia improves sleep, mood and reaction time.

PubMed

de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

2016-02-01

This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time.

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products.

PubMed

Patterson, J; Rousseau, A; Kessler, R J; Giger, U

2011-01-01

Transfusion of red blood cell (RBC) products carries considerable risk for adverse reactions, including life-threatening hemolytic reactions. To report the occurrence and investigation of life-threatening acute transfusion reactions with hemolysis in dogs likely related to inappropriate blood product storage. Four dogs with acute transfusion reactions and other recipients of blood products. Medical records were reviewed from 4 dogs with suspected acute hemolytic transfusion reactions after receiving RBC products at a veterinary clinic over a 1-month period. Medical records of other animals receiving blood products in the same time period also were reviewed. Blood compatibility and product quality were assessed, subsequent transfusions were closely monitored, and products were diligently audited. During or immediately after RBC product transfusion, 4 dogs developed hemolysis, hemoglobinuria, or both. Two dogs died and 1 was euthanized because of progressive clinical signs compatible with an acute hemolytic transfusion reaction. Blood type and blood compatibility were confirmed. RBC units from 2 blood banks were found to be hemolyzed after storage in the clinic's refrigerator; no bacterial contamination was identified. After obtaining a new refrigerator dedicated to blood product storage, the problem of hemolyzed units and acute transfusion reactions with hemolysis completely resolved. Acute life-threatening transfusion reactions can be caused by inappropriate storage of RBC products. In addition to infectious disease screening and ensuring blood-type compatibility, quality assessment of blood products, appropriate collection, processing, and storage techniques as well as recipient monitoring are critical to provide safe, effective transfusions. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Adverse Effects of Plasma Transfusion

PubMed Central

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

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

Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy.

PubMed

Sukumaran, Lakshmi; McCarthy, Natalie L; Kharbanda, Elyse O; Weintraub, Eric S; Vazquez-Benitez, Gabriela; McNeil, Michael M; Li, Rongxia; Klein, Nicola P; Hambidge, Simon J; Naleway, Allison L; Lugg, Marlene M; Jackson, Michael L; King, Jennifer P; DeStefano, Frank; Omer, Saad B; Orenstein, Walter A

2015-11-01

To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. We conducted a retrospective cohort study of pregnant women aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared with sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low-birth-weight, or small-for-gestational-age neonates between women vaccinated concomitantly compared with sequentially in pregnancy. Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared with sequential vaccination. II.

Acute Cervical Dystonia Induced by Clebopride.

PubMed

Choi, Jin Kyo; Hong, Jin Yong

2017-01-01

Antidopaminergic drugs are known to induce extrapyramidal symptoms. Clebopride, a dopamine antagonist, also can produce parkinsonism, tardive dyskinesia, tardive dystonia, hemifacial dystonia, or oculogyric crisis; however, acute dystonic reaction caused by clebopride has not been reported in adults. We report two young men who experienced acute cervical dystonia within a few days of taking clebopride. The patients recovered after discontinuation of the drug. Physicians prescribing clebopride should be aware of the adverse effects of this drug.

[Research progress of Chinese herbal medicine and traditional Chinese medicine resulting in liver injury].

PubMed

Wang, Jingli; Zhou, Chaofan

2011-12-01

The adverse reactions caused by Chinese herbal medicine and traditional Chinese medicine are reported increased in recent years, among which the acute liver injury caused by Chinese herbal medicine accounts for 21.5% of total liver injuries. Despite the misuse of traditional Chinese medicine not in accordance with differentiation of symptoms and signs, the adverse reaction of Chinese herbal medicine itself can't be little to these adverse events. The paper summarizes the most common categories of traditional Chinese medicine resulting in liver injury, the mechanism, pathological characteristics, clinical symptom of liver injury, the reasons of the reaction and how to prevent. The research aims to enhance the clinical physician recognition of liver injury caused by Chinese herbal medicine, in order to ensure the safe and rational usage of traditional Chinese medicine.

Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

PubMed

Xue, Xiaobin; Song, Yun; Yu, Xiaojie; Fan, Qiang; Tang, Jiyou; Chen, Xu

2018-02-01

This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs). The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded. Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference. Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

Acute Cervical Dystonia Induced by Clebopride

PubMed Central

2017-01-01

Antidopaminergic drugs are known to induce extrapyramidal symptoms. Clebopride, a dopamine antagonist, also can produce parkinsonism, tardive dyskinesia, tardive dystonia, hemifacial dystonia, or oculogyric crisis; however, acute dystonic reaction caused by clebopride has not been reported in adults. We report two young men who experienced acute cervical dystonia within a few days of taking clebopride. The patients recovered after discontinuation of the drug. Physicians prescribing clebopride should be aware of the adverse effects of this drug. PMID:29333306

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients. PMID:16168114

Cimetidine: II. Adverse reactions and patterns of use.

PubMed

Freston, J W

1982-11-01

Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).

[Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia].

PubMed

Zheng, Miao-Miao; Yue, Li-Jie; Chen, Xiao-Wen; Wen, Fei-Qiu; Li, Chang-Gang; Yang, Chun-Lan; Xie, Cai; Ding, Hui

2013-03-01

To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

PubMed Central

Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

2010-01-01

Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events. PMID:20725567

[Vaccinovigilance: Reports of adverse reactions in the year 2016].

PubMed

Albrecht, N; Ottiger, H

2017-08-01

In the year 2016, 107 reports of adverse reactions following the application of various authorized vaccines were received and evaluated by the IVI (Institute of Virology and Immunology). The notifications were submitted primarily by marketing authorization holders (81) or veterinarians and private persons (26). The aim of the Vigilance System is the identification of rare events to assess the individual risks of the vaccine application. During the last year, the correlation between reaction and vaccination was considered probable in 34% of the cases. As in previous years, companion animals were involved in most of the adverse effects (48% dogs, 21% cats), followed by cattle (13%). In dogs, approximately half of the reports concern the combination vaccines against distemper, hepatitis, parvovirus, parainfluenza and leptospirosis. The reported symptoms, such as itching, facial edema, acute vomiting and diarrhea, usually indicated forms of hypersensitivity. In cats, apathy was most frequently observed regardless of the vaccination.

Adverse reactions associated with acetylcysteine.

PubMed

Sandilands, E A; Bateman, D N

2009-02-01

Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and treatment of adverse reactions to acetylcysteine and identifies particular "at-risk" patient groups. Given the commonality of adverse reactions associated with acetylcysteine, it is important to ensure that any adverse event does not preclude patients from receiving maximal hepatic protection, particularly in the context of significant paracetamol ingestion. Further work on mechanisms should allow specific therapies to be developed.

[Cutaneous adverse drug reaction: prospective study of 118 cases].

PubMed

Chaabane, Hend; Masmoudi, Abderrahmen; Amouri, Meriem; Ghorbel, Sonda; Boudaya, Sonia; Hammami, Serriya; Zghal, Khaled; Turki, Hamida

2013-01-01

Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions. To describe the adverse cutaneous reactions, their epidemiologic characteristics as well as the different causative drugs through a prospective hospital study. A 12-month prospective study was managed in our department of dermatology of the teaching hospital Hedi Chaker of Sfax. Requested information included patient characteristics (associated disorders), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). The diagnosis was based on a beam of clinical and anamnestic arguments. The drug imputability was evaluated according to the Begaud's French method. One hundred eighteen cases were collected. A prevalence of 1.08/100 among patients consulting in dermatology department was estimated. The macular and papular exanthema represented the most frequent clinical aspects (42 cases) followed by acute urticaria (23 cases), photosensitivity (19 cases) and fixed drug eruption (15 cases). Principal imputable drugs were antibiotics, mainly penicillins followed by analgesics and non-steroidal anti-inflammatory. Although it was monocentric, this study revealed a high frequency of drug-induced dermatitis with different clinical presentation. The high incidence of drug-induced dermatitis induced by antibiotics, analgesics and anti-inflammatory is due to their widespread use, often in self-medication.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol.

PubMed

Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito

2014-10-06

Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR).The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15-87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

PubMed Central

2014-01-01

Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

Acute adverse reactions of rapid Rituximab infusion among adult patients with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia.

PubMed

Lang, Dora; George, Cobie

Rapid Rituximab infusion has become increasingly popular globally. Although pharmaceutical manufacturers recommend second and subsequent infusions to run over 2-3 hours, many cancer centres have changed their clinical practice based on their own research and the results from other primary studies. Such research studies claim that it is safe to administer Rituximab rapidly among cancer patients especially in Non Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). In addition, the studies suggest that the rapid infusion of Rituximab also results in benefits of cost saving and better resource utilisation. However, these studies have not been critically appraised for their validity and application to the global population. No previous systematic reviews on this topic have been identified.Objective The objective of this review was to critically appraise, synthesise and present the best available evidence related to the safety of rapid Rituximab infusion among adult patients with NHL and CLL. The participants of interest were adults aged 18 years old and above who had a diagnosis of NHL or CLL at any stage, have had prior exposure to Rituximab and received Rituximab with or without combination of any chemotherapy.The intervention of interest was rapid Rituximab infusion to be completed in 120 minutes or less.The studies of interest were both experimental and non-experimental studies.The primary outcomes of interest were the presence of acute adverse reactions and their severity. The secondary outcomes of interest were the management of the acute adverse reactions and patient mortality rate resulting from adverse reactions.Search strategy The search sought to identify published and unpublished studies from 1997 till 2010. A three-step search strategy was used for electronic databases, grey literature and reference lists.Methodological quality Two independent reviewers used the standard critical appraisal tool from JBI-MAStARI to assess the methodological qualities of the studies that matched with inclusion criteria.Data collection A standard data form from JBI-MAStARI was used to extract the data across all included studies.Data synthesis Proportional Meta-analysis based on DerSimonian-Laird weights for the random effects model was used for statistical pooling through Stats Direct. Heterogeneity was assessed using Cochran Q. When statistical pooling is not possible, the findings are presented in narrative summary. A total of 753 patients were included in this review. All except one patient completed a total of 2298 cycles of rapid Rituximab infusions. Seventeen and one acute adverse reactions were reported among NHL and CLL patients respectively. There were five reactions which were not clearly stated if they were occurring in NHL or CLL patients. All were mild to moderate reactions except one patient developed severe reaction and withdrew from the study. Rapid Rituximab infusion is safe for NHL patients especially in a 90-minute regimen. However, rapid rituximab infusion is not recommended for CLL patients due to lack of evidence. 90-minute rapid Rituximab infusion with or without steroid premedication is recommended for NHL patient at second and subsequently infusions. No recommendations can be made in relation to stage of disease or the presence of bulky disease or leucocytosis. It is not recommended, based on the current evidence, to use rapid Rituximab for CLL patients. Further research is needed on the role of monoclonal antibodies development in rapid infusion, especially in the second and subsequent cycles. Currently, this review broadly establishes that rapid Rituximab infusion over 90 minutes is safe for NHL patients. However, more research and detailed analysis is needed to develop more specific guidelines.

Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy.

PubMed

Miceli Sopo, Stefano; Monaco, Serena; Badina, Laura; Barni, Simona; Longo, Giorgio; Novembre, Elio; Viola, Serena; Monti, Giovanna

2015-12-01

The study describes the demographic features, culprit foods, clinical features and outcomes for children presenting with acute fish and/or shellfish food protein-induced enterocolitis syndrome (FPIES) in four Italian paediatric allergy centres. A retrospective/prospective study was undertaken. All children diagnosed with fish or shellfish FPIES were enrolled. The diagnosis of FPIES was based on Sicherer's or Miceli Sopo clinical criteria. Skin prick tests (SPT) were performed in all patients, at the time of diagnosis and prior to OFC. Seventy children were enrolled. Mean age at first episode was 14 months (range 6-46 months); mean age at diagnosis was 34 months (range 6-164 months). Sole and cod were the fish most commonly implicated. Fifty-seven of 70 (81%) children had FPIES exclusively to fish, 37 of 57 (65%) children had single-fish FPIES, 20 of 57 (35%) multiple-fish FPIES, nine of 70 (13%) presented adverse reactions exclusively to shellfish, and four of 70 (6%) presented adverse reactions to both fish and shellfish. Only four (5.7%) children presented episodes of acute FPIES with different foods (2 to cow's milk, 1 to egg, 1 to beef); in all cases, onset was prior to that of fish or shellfish FPIES. Fifteen of 70 (21%) children tolerated fish other than the offending fish. Twenty-four of 70 (34%) children achieved tolerance (age range 24-102 months). The chief peculiarities of acute fish and shellfish FPIES, compared to more frequent cow's milk or soy FPIES, are (i) later age of onset, (ii) longer persistence and (iii) possibility of tolerating fish other than the offending fish. Adverse reactions with shellfish are possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute Generalized Exanthematous Pustulosis Due to Insect Bites?

PubMed

Bhat, Yasmeen J; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Wani, Rohi

2015-01-01

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs and rarely associated with viral infections, food allergens or toxins. Here we present the report of three patients who got admitted in our hospital for generalized pustulosis and fever after insect bites. The diagnosis of acute generalized exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was excluded and spider bite was implicated as the etiological agent in these cases of AGEP which are the first such reported cases in India.

Time to significant pain reduction following DETP application vs placebo for acute soft tissue injuries.

PubMed

Yanchick, J; Magelli, M; Bodie, J; Sjogren, J; Rovati, S

2010-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide fast and effective acute pain relief, but systemic administration has increased risk for some adverse reactions. The diclofenac epolamine 1.3% topical patch (DETP) is a topical NSAID with demonstrated safety and efficacy in treatment of acute pain from minor soft tissue injuries. Significant pain reduction has been observed in clinical trials within several hours following DETP application, suggesting rapid pain relief; however, this has not been extensively studied for topical NSAIDs in general. This retrospective post-hoc analysis examined time to onset of significant pain reduction after DETP application compared to a placebo patch for patients with mild-to-moderate acute ankle sprain, evaluating the primary efficacy endpoint from two nearly identical studies. Data from two double-blind, randomized, parallel-group, placebo-controlled studies (N = 274) of safety and efficacy of the DETP applied once daily for 7 days for acute ankle sprain were evaluated post-hoc using statistical modeling to estimate time to onset of significant pain reduction following DETP application. Pain on active movement on a 100 mm Visual Analog Scale (VAS) recorded in patient diaries; physician- and patient-assessed tolerability; and adverse events. DETP treatment resulted in significant pain reduction within approximately 3 hours compared to placebo. Within-treatment post-hoc analysis based on a statistical model suggested significant pain reduction occurred as early as 1.27 hours for the DETP group. The study may have been limited by the retrospective nature of the analyses. In both studies, the DETP was well tolerated with few adverse events, limited primarily to application site skin reactions. The DETP is an effective treatment for acute minor soft tissue injury, providing pain relief as rapidly as 1.27 hours post-treatment. Statistical modeling may be useful in estimating time to onset of pain relief for comparison of topical and oral NSAIDs.

Acute hepatic failure in children.

PubMed Central

Riely, C. A.

1984-01-01

Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4 PMID:6433587

Acute hypersensitivity to mannitol: a case report

NASA Astrophysics Data System (ADS)

Siahaan, A. M.; Fithrie, A.

2018-03-01

Mannitol is an osmotic diuretic agent that has been considered a main therapeutic option in cerebral edema for the past several decades. The most common adverse effect reported is acute kidney injury and electrolyte imbalance. Hypersensitivity associated with mannitol is not a usual finding. Here we describe a case of a traumatic brain injury patient who had a hypersensitivity reaction to mannitol. It is the first reported case report about hypersensitivity to Mannitol in Indonesia.

Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review

PubMed Central

Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

2017-01-01

Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated. PMID:28293455

Inhaled budesonide and oral dexamethasone prevent acute mountain sickness.

PubMed

Zheng, Cheng-Rong; Chen, Guo-Zhu; Yu, Jie; Qin, Jun; Song, Pan; Bian, Shi-Zhu; Xu, Bai-Da; Tang, Xu-Gang; Huang, Yong-Tao; Liang, Xiao; Yang, Jie; Huang, Lan

2014-10-01

This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure. There were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide (200 μg, twice a day [bid]), oral dexamethasone (4 mg, bid), or placebo (46 in each group). They traveled to 3900 m altitude from 400 m by car. Medication started 1 day before high-altitude exposure and continued until the third day of exposure. Primary outcome measure was the incidence of acute mountain sickness after exposure. One hundred twenty-four subjects completed the study (42, 39, and 43 in the budesonide, dexamethasone, and placebo groups, respectively). Demographic characteristics were comparable among the 3 groups. After high-altitude exposure, significantly fewer participants in the budesonide (23.81%) and dexamethasone (30.77%) groups developed acute mountain sickness compared with participants receiving placebo (60.46%) (P = .0006 and P = .0071, respectively). Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation (SpO2) than the placebo group at altitude. Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group. Four subjects in the dexamethasone group reported adverse reactions. Both inhaled budesonide (200 μg, bid) and oral dexamethasone (4 mg, bid) were effective for the prevention of acute mountain sickness, especially its severe form, compared with placebo. Budesonide caused fewer adverse reactions than dexamethasone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

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

Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao; Kabekkodu, Shama Prasada

Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluatemore » the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by gene–gene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles.« less

Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study

PubMed Central

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

2015-01-01

Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR. PMID:25657416

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

PubMed

Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

2011-11-01

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Lack of cross-reactivity between 5-aminosalicylic acid-based drugs: a case report and review of the literature.

PubMed

Kung, Shiang-Ju; Choudhary, Cuckoo; McGeady, Stephen J; Cohn, John R

2006-09-01

5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease, but adverse reactions to these medications are relatively common. Because there may be a lack of cross-reactivity among the various 5-ASA formulations, treatment with alternative preparations is sometimes possible even after an apparent allergic reaction to a 5-ASA product. To describe a patient with a possible allergy to 2 different 5-ASA drugs who tolerated a third. A 27-year-old man with Crohn disease developed a rash while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was discontinued, and 6-mercaptopurine and prednisone were prescribed. He then experienced multiorgan failure secondary to herpes simplex infection, which required discontinuation of the immunosuppressive therapy. After recovery from the acute infection, he underwent successful graded challenge with balsalazide. The patient continued treatment with balsalazide for 9 months, with good control of his inflammatory bowel disease and no adverse effects. Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the use of others in the same class. A treatment algorithm for patients with adverse reactions to 5-ASA is outlined based on the case report and review of the literature.

Acute Generalized Exanthematous Pustulosis Due to Insect Bites?

PubMed Central

Bhat, Yasmeen J; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Wani, Rohi

2015-01-01

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs and rarely associated with viral infections, food allergens or toxins. Here we present the report of three patients who got admitted in our hospital for generalized pustulosis and fever after insect bites. The diagnosis of acute generalized exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was excluded and spider bite was implicated as the etiological agent in these cases of AGEP which are the first such reported cases in India. PMID:26288442

Treatments for Severe Cutaneous Adverse Reactions

PubMed Central

Cho, Yung-Tsu

2017-01-01

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations. PMID:29445753

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning.

PubMed

Isbister, Geoffrey K; Downes, Michael A; Mcnamara, Kylie; Berling, Ingrid; Whyte, Ian M; Page, Colin B

2016-01-01

The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions. We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Acute bilateral parotitis occurring during venlafaxine titration in an adolescent female with major depression.

PubMed

Bonnet, U; Khalil-Boutros, Y

2014-01-01

Parotitis is a fairly uncommon adverse drug reaction of psychopharmacological treatment. Here, we report on an acute bilateral parotitis, which was associated with titration of venlafaxine in a 20-year-old female suffering from a severe depressive episode. The parotitis recovered quickly with oral penicillin and was most likely caused by bacteria assumed to spread from oral flora into Stensen's duct as a complication of pronounced venlafaxine-induced xerostomia. © Georg Thieme Verlag KG Stuttgart · New York.

Hoigne Syndrome Caused by Intralesional Meglumine Antimoniate

PubMed Central

Guarneri, Claudio; Tchernev, Georgi; Wollina, Uwe; Lotti, Torello

2017-01-01

Hoigne syndrome (HS) is the term coined to describe an acute, non-allergic, psychiatrically based reaction occurring with a wide list of medications, mainly antibiotics. Since its first description by Hoigne and Schoch in 1959, few cases have been reported in medical literature and, although antimicrobials are commonly used, very rarely in dermatology. The authors describe the first case occurred after intralesional administration of meglumine antimoniate and briefly discuss the pathogenetic hypotheses on this atypical adverse drug reaction. PMID:28785339

Does the time between CT scan and chemotherapy increase the risk of acute adverse reactions to iodinated contrast media in cancer patients?

PubMed

Farolfi, Alberto; Carretta, Elisa; Luna, Corradina Della; Ragazzini, Angela; Gentili, Nicola; Casadei, Carla; Barone, Domenico; Minguzzi, Martina; Amadori, Dino; Nanni, Oriana; Gavelli, Giampaolo

2014-10-31

Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients.

[Fenspiride in patients with acute bronchitis].

PubMed

Płusa, Tadeusz; Ochwat, Agnieszka

2005-07-01

Fenspiride is an anti-inflammatory drug that may have a role in inhibition of histamine receptor H1 and influence a production of archidonic acid metabolites. The efficacy and tolerance of fenspiride therapy have been performed in patients with acute bronchitis. 597 patients, 51% females and 49% males, aged 39+/-18 years, were observed because of acute bronchitis. Fenspiride (Eurespal, Servier) was given in a dose of 240 mg per day (80 mg three times daily) for 14 consecutive days. During two following medical examinations - after 7 and 14 days of treatment, clinical symptoms of disease, therapy efficacy and tolerance were determined. Mean duration of acute bronchitis before fenspiride therapy was 2.3+/-1.3 days. In most of the patients (72%) a moderate, and in 27% mild degree of disease was diagnosed. Only 1% of patients were diagnosed as severe. Total evaluation of fenspiride efficacy in examined patients with acute bronchitis showed complete relief of symptoms after 7 days of therapy in 24% and after 14 days in 87% of patients. In 6% of patients after 7 days and in 1% after 14 days of fenspiride therapy no improvement was obtained. 28 adverse reactions were determined in 26 patients (4.3%): vertigo in 7, nausea in 6, somnolence in 5, palpitations in 4, fatigue in 2, abdominal pain in 2 and other symptoms in 2 patients. In 8 patients the therapy was discontinued after 7 days because of adverse reactions. In performed observations in patients with acute bronchitis the high clinical efficacy of fenspiride therapy. In 12% of patients an antibiotic support was necessary to obtain relief of the symptoms. Very good tolerance of the 14 days therapy was determined and it is recommended for safe clinical application.

Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

PubMed

Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

2014-03-01

In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

Pharmacodynamic effects of pilocarpine eye drop enhanced by decreasing its volume of instillation.

PubMed

Lal, A; Kataria, V; Rajpal, A; Khanna, N

1995-07-01

Previous studies have proved that as the volume of the drug solution instilled into the eye is decreased, the fraction of the dose absorbed into the ocular tissue is increased and the adverse drug reactions lowered. The present study investigated the acute effects of different drop volumes (10 microliters, 20 microliters, 40 microliters, and 80 microliters) of pilocarpine nitrate (2%) on pupil diameter, heart rate, and adverse reaction profile, in 12 healthy human volunteers. The drop volumes of 10 microliters and 20 microliters produced more miosis and less side effects than 40 microliters and 80 microliters drop volumes. This may be due to more penetration of the drug into the ocular tissue and less drainage into the nasolacrimal system.

Transfusion risks and transfusion-related pro-inflammatory responses.

PubMed

Despotis, George John; Zhang, Lini; Lublin, Douglas M

2007-02-01

Despite improvements in blood screening and administration techniques, serious adverse events related to transfusion continue to occur, albeit at a much lower incidence. In addition to the development and implementation of new screening and blood purification/modification techniques and implementation of an optimal blood management program, the incidence and consequences of transfusion reactions can be reduced by a basic understanding of transfusion-related complications. Although acute hemolytic transfusion reactions, transfusion-associated anaphylaxis and sepsis, and transfusion-associated acute lung injury occur infrequently, diligence in administration of blood and monitoring for development of respective signs/symptoms can minimize the severity of these potentially life-threatening complications. In addition, emerging blood-banking techniques such as psoralen-UV inactivation of pathogens and use of patient identification systems may attenuate the incidence of adverse events related to transfusion. With respect to optimizing blood management by means of an effective blood management program involving pharmacologic and nonpharmacologic strategies, the ability to reduce use of blood products and to decrease operative time or re-exploration rates has important implications for disease prevention, blood inventory and costs, and overall health care costs.

Immediate reaction to lidocaine with periorbital edema during upper blepharoplasty.

PubMed

Presman, Benjamin; Vindigni, Vincenzo; Tocco-Tussardi, Ilaria

2016-01-01

Blepharoplasty is the fourth most commonly performed cosmetic surgery in the US, with 207,000 operations in 2014. Lidocaine is the preferred anesthetic agent for blepharoplasty. We describe the unusual case of acute periorbital edema following local anesthesia with lidocaine for upper blepharoplasty. At present, only two other reports of periorbital reactions to lidocaine are present in the literature. The reactions observed are significant palpebral swelling and erythema with scaling of the cheek. Fortunately the swelling, although marked, is transient in nature and resolves almost spontaneously without affecting the visual acuity. Patients reporting adverse reactions should be screened for allergy according to the standard protocols, but skin testing has only been reported to be positive in less than 10% of all cases and allergy confirmation with IgE is even more rare. In clinical practice, we recommend that patient should be informed about the possibility of recurrence of an adverse reaction in case of re-exposure to lidocaine, even in the vast majority of cases where true allergy could not be proven. In case of further need for local anesthesia with history of an adverse event, a different agent may be chosen even from the same class (another amide) as cross-reactions in the amide group are rare. Otherwise, an anesthetic from the ester group can also be safely used. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immediate reaction to lidocaine with periorbital edema during upper blepharoplasty

PubMed Central

Presman, Benjamin; Vindigni, Vincenzo; Tocco-Tussardi, Ilaria

2016-01-01

Introduction Blepharoplasty is the fourth most commonly performed cosmetic surgery in the US, with 207,000 operations in 2014. Lidocaine is the preferred anesthetic agent for blepharoplasty. Presentation of case We describe the unusual case of acute periorbital edema following local anesthesia with lidocaine for upper blepharoplasty. At present, only two other reports of periorbital reactions to lidocaine are present in the literature. The reactions observed are significant palpebral swelling and erythema with scaling of the cheek. Fortunately the swelling, although marked, is transient in nature and resolves almost spontaneously without affecting the visual acuity. Discussion Patients reporting adverse reactions should be screened for allergy according to the standard protocols, but skin testing has only been reported to be positive in less than 10% of all cases and allergy confirmation with IgE is even more rare. Conclusion In clinical practice, we recommend that patient should be informed about the possibility of recurrence of an adverse reaction in case of re-exposure to lidocaine, even in the vast majority of cases where true allergy could not be proven. In case of further need for local anesthesia with history of an adverse event, a different agent may be chosen even from the same class (another amide) as cross-reactions in the amide group are rare. Otherwise, an anesthetic from the ester group can also be safely used. PMID:26785079

Cutaneous Manifestation of Food Allergy.

PubMed

Tam, Jonathan S

2017-02-01

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

Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

PubMed

Harada, Yukinori; Hara, Yuuta

2017-01-01

Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

Live bee acupuncture (Bong-Chim) dermatitis: dermatitis due to live bee acupuncture therapy in Korea.

PubMed

Park, Joon Soo; Lee, Min Jung; Chung, Ki Hun; Ko, Dong Kyun; Chung, Hyun

2013-12-01

Live bee acupuncture (Bong-Chim) dermatitis is an iatrogenic disease induced by so-called live bee acupuncture therapy, which applies the honeybee (Apis cerana) stinger directly into the lesion to treat various diseases in Korea. We present two cases of live bee acupuncture dermatitis and review previously published articles about this disease. We classify this entity into three stages: acute, subacute, and chronic. The acute stage is an inflammatory reaction, such as anaphylaxis or urticaria. In the chronic stage, a foreign body granuloma may develop from the remaining stingers, similar to that of a bee sting reaction. However, in the subacute stage, unlike bee stings, we see the characteristic histological "flame" figures resulting from eosinophilic stimulation induced by excessive bee venom exposure. We consider this stage to be different from the adverse skin reaction of accidental bee sting. © 2013 The International Society of Dermatology.

National Athletic Trainers' Association Position Statement: Management of Acute Skin Trauma

PubMed Central

Beam, Joel W.; Buckley, Bernadette; Holcomb, William R.; Ciocca, Mario

2016-01-01

Objective: To present recommendations for the cleansing, debridement, dressing, and monitoring of acute skin trauma in patients. Background: Acute skin trauma is common during participation in athletic and recreational activities. Clinical decisions and intervention protocols after injury vary among athletic trainers and are often based on ritualistic practices. An understanding of cleansing, debridement, and dressing techniques; clinical features of infection and adverse reactions; and monitoring of acute skin trauma is critical for certified athletic trainers and other allied health and medical professionals to create a local wound environment that promotes healing and lessens the risk of complications. Recommendations: These guidelines are intended to provide the certified athletic trainer and others participating in athletic health care with specific knowledge about and recommendations for the management of acute skin trauma. PMID:28092169

National Athletic Trainers' Association Position Statement: Management of Acute Skin Trauma.

PubMed

Beam, Joel W; Buckley, Bernadette; Holcomb, William R; Ciocca, Mario

2016-12-01

  To present recommendations for the cleansing, debridement, dressing, and monitoring of acute skin trauma in patients.   Acute skin trauma is common during participation in athletic and recreational activities. Clinical decisions and intervention protocols after injury vary among athletic trainers and are often based on ritualistic practices. An understanding of cleansing, debridement, and dressing techniques; clinical features of infection and adverse reactions; and monitoring of acute skin trauma is critical for certified athletic trainers and other allied health and medical professionals to create a local wound environment that promotes healing and lessens the risk of complications.   These guidelines are intended to provide the certified athletic trainer and others participating in athletic health care with specific knowledge about and recommendations for the management of acute skin trauma.

The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results.

PubMed

Politis, C; Wiersum, J C; Richardson, C; Robillard, P; Jorgensen, J; Renaudier, P; Faber, J-C; Wood, E M

2016-11-01

The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety. © 2016 International Society of Blood Transfusion.

The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction

PubMed Central

Gibon, Emmanuel; Córdova, Luis A.; Lu, Laura; Lin, Tzu-Hua; Yao, Zhenyu; Hamadouche, Moussa; Goodman, Stuart B.

2017-01-01

Novel evidence-based prosthetic designs and biomaterials facilitate the performance of highly successful joint replacement (JR) procedures. To achieve this goal, constructs must be durable, biomechanically sound, and avoid adverse local tissue reactions. Different biomaterials such as metals and their alloys, polymers, ceramics, and composites are currently used for JR implants. This review focuses on (1) the biological response to the different biomaterials used for TJR and (2) the chronic inflammatory and foreign-body response induced by byproducts of these biomaterials. A homeostatic state of bone and surrounding soft tissue with current biomaterials for JR can be achieved with mechanically stable, infection free and intact (as opposed to the release of particulate or ionic byproducts) implants. Adverse local tissue reactions (an acute/chronic inflammatory reaction, periprosthetic osteolysis, loosening and subsequent mechanical failure) may evolve when the latter conditions are not met. This article (Part 2 of 2) summarizes the biological response to the non-metallic materials commonly used for joint replacement including polyethylene, ceramics, and polymethylmethacrylate (PMMA), as well as the foreign body reaction to byproducts of these materials. PMID:27080740

Immunological aspects of nonimmediate reactions to beta-lactam antibiotics.

PubMed

Rodilla, Esther Morena; González, Ignacio Dávila; Yges, Elena Laffond; Bellido, Francisco Javier Múñoz; Bara, María Teresa Gracia; Toledano, Félix Lorente

2010-09-01

beta-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include a broad number of clinical entities like mild maculopapular exanthemas, the most common, and other less frequent but more severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute exanthematic pustulosis or cytopenias. These nonimmediate reactions are mainly mediated by T cells but the precise underlying mechanisms are not well elucidated. This fact complicates the allergological evaluation of patients with this type of reaction and available tests have demonstrated poor sensitivity and specificity.

Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

PubMed Central

Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

2012-01-01

Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

Muscle Reaction Time During a Simulated Lateral Ankle Sprain After Wet-Ice Application or Cold-Water Immersion.

PubMed

Thain, Peter K; Bleakley, Christopher M; Mitchell, Andrew C S

2015-07-01

Cryotherapy is used widely in sport and exercise medicine to manage acute injuries and facilitate rehabilitation. The analgesic effects of cryotherapy are well established; however, a potential caveat is that cooling tissue negatively affects neuromuscular control through delayed muscle reaction time. This topic is important to investigate because athletes often return to exercise, rehabilitation, or competitive activity immediately or shortly after cryotherapy. To compare the effects of wet-ice application, cold-water immersion, and an untreated control condition on peroneus longus and tibialis anterior muscle reaction time during a simulated lateral ankle sprain. Randomized controlled clinical trial. University of Hertfordshire human performance laboratory. A total of 54 physically active individuals (age = 20.1 ± 1.5 years, height = 1.7 ± 0.07 m, mass = 66.7 ± 5.4 kg) who had no injury or history of ankle sprain. Wet-ice application, cold-water immersion, or an untreated control condition applied to the ankle for 10 minutes. Muscle reaction time and muscle amplitude of the peroneus longus and tibialis anterior in response to a simulated lateral ankle sprain were calculated. The ankle-sprain simulation incorporated a combined inversion and plantar-flexion movement. We observed no change in muscle reaction time or muscle amplitude after cryotherapy for either the peroneus longus or tibialis anterior (P > .05). Ten minutes of joint cooling did not adversely affect muscle reaction time or muscle amplitude in response to a simulated lateral ankle sprain. These findings suggested that athletes can safely return to sporting activity immediately after icing. Further evidence showed that ice can be applied before ankle rehabilitation without adversely affecting dynamic neuromuscular control. Investigation in patients with acute ankle sprains is warranted to assess the clinical applicability of these interventions.

Poisoning by hallucinogenic mushroom hikageshibiretake (Psilocybe argentipes K. Yokoyama) indigenous to Japan.

PubMed

Musha, M; Ishii, A; Tanaka, F; Kusano, G

1986-01-01

Five cases of poisoning by indigenous mushroom Hikageshibiretake (Psilocybe argentipes) are reported. As this mushroom contains psilocybin, in general, clinical features were similar to those seen by pure psilocybin. Acute toxic stuporous state with complete amnesia in the culminating period occurred in one case, psychedelic state with dreamy consciousness in one case and psychotic adverse reactions with vivid visual hallucinations with consciousness in three cases. There were accompanied with anxiety and panic reactions to subjective experiences. Though these toxic effects were usually short-lived, for management of such patients it is important to recognize that horrible emotional reactions and other harmful behavioral problems can also occur.

Endothelial safety of radiological contrast media: why being concerned.

PubMed

Scoditti, Egeria; Massaro, Marika; Montinari, Maria Rosa

2013-01-01

Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of adverse drug reaction induced by dispensing error.

PubMed

Gallelli, L; Staltari, O; Palleria, C; Di Mizio, G; De Sarro, G; Caroleo, B

2012-11-01

To report about a case of acute renal failure due to absence of communication between physician and patient. A 78 year old man with human immunodeficiency virus (HIV) accessed our hospital and was brought to our attention in August 2011 for severe renal failure. Clinical history revealed that he had been taking highly active antiretroviral therapy with lamivudine/abacavir and fosamprenavir since 2006. In April 2011 due to an augmentation in creatinine plasma levels, a reduction in lamivudine dosage to 100 mg/day and the prescription of abacavir 300 mg/day became necessary. Unfortunately, the patient took both lamivudine and abacavir therefore the association of the two medications (lamivudine/abacavir) lead to asthenia and acute renal failure within a few days. This case emphasizes the importance about how physicians must pay very careful attention during drug prescription, most particularly, as far as elderly patients are concerned. In fact, communication improvement between physicians and patients can prevent increase of adverse drug reactions related to drug dispensing, with consequential reduction of costs in the healthcare system. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Practical Management of Antibiotic Hypersensitivity in 2017.

PubMed

Macy, Eric; Romano, Antonino; Khan, David

Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Energy drink-induced acute kidney injury.

PubMed

Greene, Elisa; Oman, Kristy; Lefler, Mary

2014-10-01

To report a case of acute renal failure possibly induced by Red Bull. A 40-year-old man presented with various complaints, including a recent hypoglycemic episode. Assessment revealed that serum creatinine was elevated at 5.5 mg/dL, from a baseline of 0.9 mg/dL. An interview revealed a 2- to 3-week history of daily ingestion of 100 to 120 oz of Red Bull energy drink. Resolution of renal dysfunction occurred within 2 days of discontinuation of Red Bull and persisted through 10 months of follow-up. Rechallenge was not attempted. Energy-drink-induced renal failure has been reported infrequently. We identified 2 case reports via a search of MEDLINE, one of which occurred in combination with alcohol and the other of which was not available in English. According to the Food and Drug Administration's (FDA's) Center for Food Safety and Applied Nutrition Adverse Event Reporting System, between 2004 and 2012, the FDA has received 166 reports of adverse events associated with energy drink consumption. Only 3 of the 166 (0.18%) described renal failure, and none were reported with Red Bull specifically. A defined mechanism for injury is unknown. Assessment of the Naranjo adverse drug reaction probability scale indicates a probable relationship between the development of acute renal failure and Red Bull ingestion in our patient. Acute kidney injury has rarely been reported with energy drink consumption. Our report describes the first English language report of acute renal failure occurring in the context of ingestion of large quantities of energy drink without concomitant alcohol. © The Author(s) 2014.

Acute pancreatitis with saw palmetto use: a case report.

PubMed

Bruminhent, Jackrapong; Carrera, Perliveh; Li, Zhongzhen; Amankona, Raymond; Roberts, Ingram M

2011-08-25

Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto. A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto. It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

PubMed Central

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

2018-01-01

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management. PMID:29844705

Relative Incidence of Acute Adverse Events with Ferumoxytol Compared to Other Intravenous Iron Compounds: A Matched Cohort Study.

PubMed

Wetmore, James B; Weinhandl, Eric D; Zhou, Jincheng; Gilbertson, David T

2017-01-01

Concerns persist about adverse reactions to intravenous (IV) iron. We aimed to determine the relative safety of ferumoxytol compared to other IV iron compounds. This retrospective cohort study with propensity-score matching for patients and drug doses used the Medicare 20% random sample to identify patients (1) without chronic kidney disease (non-CKD) and (2) with non-dialysis-dependent chronic kidney disease (NDD-CKD) who received a first dose of IV iron in 2010-2012. Exposures were ferumoxytol, iron sucrose, sodium ferric gluconate, or iron dextran. Outcomes were hypersensitivity symptoms, anaphylaxis, emergency department (ED) encounters, hospitalizations, and death after acute IV iron exposure. In the primary analysis for reactions on the day of or following exposure, there was no difference in hypersensitivity symptoms (hazard ratio 1.04, 95% confidence interval 0.94-1.16) or hypotension (0.83, 0.52-1.34) between 4289 non-CKD ferumoxytol users and an equal number of users of other compounds; results were similar for 7358 NDD-CKD patients and an equal number of controls. All-cause ED encounters or hospitalizations were less common in both the non-CKD (0.56, 0.45-0.70) and NDD-CKD ferumoxytol-treated patients (0.83, 0.71-0.95). Fewer than 10 deaths occurred in both the non-CKD and NDD-CKD ferumoxytol users and in matched controls; the hazard for death did not differ significantly between ferumoxytol users and controls in the non-CKD patients (2.00, 0.33-11.97) or in the NDD-CKD patients (0.25, 0.04-1.52). Multiple sensitivity analyses showed similar results. Ferumoxytol did not appear to be associated with more adverse reactions than other compounds for the treatment of iron-deficiency anemia in both non-CKD and NDD-CKD patients.

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

PubMed

Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Not all pustules are infective in nature: acute generalised exanthematous pustulosis causing pustular eruptions in an elderly woman.

PubMed

Kwah, Y C; Leow, Y H

2005-07-01

Acute generalised exanthematous pustulosis (AGEP) is an adverse drug reaction that can occur in any age group. It is commonly mistaken as pustular psoriasis or cutaneous infection, resulting in unnecessary commencement of medications such as methotrexate and antibiotics that can cause harm to the patient or interact and adversely affect the efficacy of other medications. Early diagnosis of AGEP avoids unnecessary investigations and treatment, which not only can harm the patient but also escalate health care, as the condition is self-limiting. This case report illustrates AGEP secondary to Cefaclor occurring in a 72-year-old Chinese woman. Although the literature has documented the occurrence of AGEP with Cefaclor, the unique feature of this case is the occurrence of AGEP following repeated uneventful courses of Cefaclor. This case highlights that AGEP must never be forgotten in the work-up for pustular eruptions in an elderly patient.

Clinical application analysis of andrographolide total ester sulfonate injection, a traditional Chinese medicine licensed in China.

PubMed

Zhao, Ying; Huang, Pu; Chen, Zhe; Zheng, Si-Wei; Yu, Jin-Yang; Shi, Chen

2017-04-01

Andrographolide total ester sulfonate (ATES) injection is one of the products of traditional Chinese medicine (TCM) currently used against viral infection in China. ATES injection was approved for manufacturing and marketing in January 2002. It is indicated for acute respiratory infections, tonsillitis, chronic obstructive pulmonary disease, influenza, foot and mouth disease, bronchiolitis, herpangina, mumps, infectious mononucleosis and psychosis. However, its usage also carries risk. We investigated the use of ATES at the Wuhan Union Hospital from January 2014 to December 2014 and evaluated its real-world clinical application using the hospital centralized monitoring method. A total of 848 cases were enrolled in this study. In these cases, it was mainly used for postoperative anti-inflammation and treating upper respiratory infection, pneumonia and bronchitis. Among them, 39.86% were contraindicated. Irregular medication of adults and children accounted for 1.91% and 23.38%, respectively. Improper choice of solvent accounted for 3.18%. The choice of intravenous drip versus aerosol inhalation was reasonable. A case of adverse events (AEs) was observed in the monitoring period, and the incidence of adverse drug reaction (ADR) of ATES injection was 0.12%. ATES injection in our hospital is relatively safe with a low incidence of adverse reactions. The study assesses the clinical usage and adverse reactions of ATES injection, and provides suggestions for rational use in clinical practice.

Taxanes as a risk factor for acute adverse reactions to iodinated contrast media in cancer patients.

PubMed

Farolfi, Alberto; Della Luna, Corradina; Ragazzini, Angela; Carretta, Elisa; Gentili, Nicola; Casadei, Carla; Aquilina, Michele; Barone, Domenico; Minguzzi, Martina; Amadori, Dino; Nanni, Oriana; Gavelli, Giampaolo

2014-08-01

The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74-1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14-2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02-4.16). Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs. ©AlphaMed Press.

Taxanes as a Risk Factor for Acute Adverse Reactions to Iodinated Contrast Media in Cancer Patients

PubMed Central

Farolfi, Alberto; Della Luna, Corradina; Ragazzini, Angela; Carretta, Elisa; Gentili, Nicola; Casadei, Carla; Aquilina, Michele; Barone, Domenico; Minguzzi, Martina; Amadori, Dino; Nanni, Oriana

2014-01-01

Background. The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. Methods. We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. Results. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74–1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14–2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02–4.16). Conclusion. Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs. PMID:25063226

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their upredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity.

PubMed

Elinav, Eran; Pinsker, Galia; Safadi, Rifaat; Pappo, Orit; Bromberg, Michal; Anis, Emilia; Keinan-Boker, Lital; Broide, Efrat; Ackerman, Zvi; Kaluski, Dorit Nitzan; Lev, Boaz; Shouval, Daniel

2007-10-01

Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. In 2004, identification of four index cases of acute hepatitis associated with Herbalife intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife products were investigated. Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. Three patients resumed consumption of Herbalife products following normalization of liver enzymes, resulting in a second bout of hepatitis. An association between intake of Herbalife products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease.

Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.

PubMed

Gershwin, Laurel J

2018-03-01

Vaccines are important for providing protection from infectious diseases. Vaccination initiates a process that stimulates development of a robust and long-lived immune response to the disease agents in the vaccine. Side effects are sometimes associated with vaccination. These vary from development of acute hypersensitivity responses to vaccine components to local tissue reactions that are annoying but not significantly detrimental to the patient. The pathogenesis of these responses and the consequent clinical outcomes are discussed. Overstimulation of the immune response and the potential relationship to autoimmunity is evaluated in relation to genetic predisposition. Copyright © 2017 Elsevier Inc. All rights reserved.

Combing signals from spontaneous reports and electronic health records for detection of adverse drug reactions

PubMed Central

Harpaz, Rave; Vilar, Santiago; DuMouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol

2013-01-01

Objective Data-mining algorithms that can produce accurate signals of potentially novel adverse drug reactions (ADRs) are a central component of pharmacovigilance. We propose a signal-detection strategy that combines the adverse event reporting system (AERS) of the Food and Drug Administration and electronic health records (EHRs) by requiring signaling in both sources. We claim that this approach leads to improved accuracy of signal detection when the goal is to produce a highly selective ranked set of candidate ADRs. Materials and methods Our investigation was based on over 4 million AERS reports and information extracted from 1.2 million EHR narratives. Well-established methodologies were used to generate signals from each source. The study focused on ADRs related to three high-profile serious adverse reactions. A reference standard of over 600 established and plausible ADRs was created and used to evaluate the proposed approach against a comparator. Results The combined signaling system achieved a statistically significant large improvement over AERS (baseline) in the precision of top ranked signals. The average improvement ranged from 31% to almost threefold for different evaluation categories. Using this system, we identified a new association between the agent, rasburicase, and the adverse event, acute pancreatitis, which was supported by clinical review. Conclusions The results provide promising initial evidence that combining AERS with EHRs via the framework of replicated signaling can improve the accuracy of signal detection for certain operating scenarios. The use of additional EHR data is required to further evaluate the capacity and limits of this system and to extend the generalizability of these results. PMID:23118093

Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame?

PubMed

Petrou, Emmanouil; Iakovou, Ioannis; Boutsikou, Maria; Girasis, Chrysafios; Mavrogeni, Sophie; Pavlides, Gregory

2014-01-01

Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia. Copyright © 2014 Elsevier Inc. All rights reserved.

Review of liver injury associated with dietary supplements.

PubMed

Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

2011-05-01

Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. © 2011 John Wiley & Sons A/S.

Acute pancreatitis with saw palmetto use: a case report

PubMed Central

2011-01-01

Introduction Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto. Case presentation A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto. Conclusion It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions. PMID:21867545

Muscle Reaction Time During a Simulated Lateral Ankle Sprain After Wet-Ice Application or Cold-Water Immersion

PubMed Central

Thain, Peter K.; Bleakley, Christopher M.; Mitchell, Andrew C. S.

2015-01-01

Context Cryotherapy is used widely in sport and exercise medicine to manage acute injuries and facilitate rehabilitation. The analgesic effects of cryotherapy are well established; however, a potential caveat is that cooling tissue negatively affects neuromuscular control through delayed muscle reaction time. This topic is important to investigate because athletes often return to exercise, rehabilitation, or competitive activity immediately or shortly after cryotherapy. Objective To compare the effects of wet-ice application, cold-water immersion, and an untreated control condition on peroneus longus and tibialis anterior muscle reaction time during a simulated lateral ankle sprain. Design Randomized controlled clinical trial. Setting University of Hertfordshire human performance laboratory. Patients or Other Participants A total of 54 physically active individuals (age = 20.1 ± 1.5 years, height = 1.7 ± 0.07 m, mass = 66.7 ± 5.4 kg) who had no injury or history of ankle sprain. Intervention(s) Wet-ice application, cold-water immersion, or an untreated control condition applied to the ankle for 10 minutes. Main Outcome Measure(s) Muscle reaction time and muscle amplitude of the peroneus longus and tibialis anterior in response to a simulated lateral ankle sprain were calculated. The ankle-sprain simulation incorporated a combined inversion and plantar-flexion movement. Results We observed no change in muscle reaction time or muscle amplitude after cryotherapy for either the peroneus longus or tibialis anterior (P > .05). Conclusions Ten minutes of joint cooling did not adversely affect muscle reaction time or muscle amplitude in response to a simulated lateral ankle sprain. These findings suggested that athletes can safely return to sporting activity immediately after icing. Further evidence showed that ice can be applied before ankle rehabilitation without adversely affecting dynamic neuromuscular control. Investigation in patients with acute ankle sprains is warranted to assess the clinical applicability of these interventions. PMID:26067429

[Approach and Registry of Anaphylaxis in Portugal].

PubMed

Mota, Inês; Pereira, Ana Margarida; Pereira, Celso; Tomaz, Elza; Ferreira, Manuel Branco; Sabino, Filipa; Coelho, Anabela; Santos, Anabela; Martins, Henrique; Morais-Almeida, Mário

2015-01-01

Anaphylaxis has a growing incidence, especially in children. It represents a medical emergency and its successful therapy depends on early and proper intervention. Intramuscular epinephrine, with dose adjustment according to weight and age, is the drug of choice for anaphylaxis treatment. After resolution of the acute reaction, the patient should be kept under clinical surveillance for 6 to 24 hours, due to possible biphasic reactions. Prescription of an epinephrine auto injectable device should be considered in all patients with diagnosed or suspected anaphylaxis; additionally these patients should always be referred to an Immunoallergy consultation, to perform adequate investigation and management in order to reduce future risk. All anaphylaxis episodes must be recorded in The Portuguese Catalogue of Allergies and other Adverse Reactions (Catálogo Português de Alergias e outras Reações Adversas, CPARA), which represents a fundamental tool to share clinical information within the Health System. The present manuscript intends to disclose the most recent Portuguese guidelines for the diagnosis and treatment of anaphylaxis, making its clinical approach more effective and homogeneous, and to promote the use of The Portuguese Catalogue of Allergies and other Adverse Reactions as an essential tool to register and share information on anaphylaxis in Portugal.

[A case of acute pancreatitis caused by 5-aminosalicylic acid suppositories in a patient with ulcerative colitis].

PubMed

Kim, Kook Hyun; Kim, Tae Nyeun; Jang, Byung Ik

2007-12-01

Oral 5-aminosalicylic acid (5-ASA) has been known as a first-choice drug for ulcerative colitis. However, hypersensitivity reactions, including pancreatitis, hepatitis, and skin rash, have been reported with 5-ASA. Topical formulations of 5-ASA like suppositories have been rarely reported to induce adverse reactions because of their limited absorption rate. We recently experienced a case of acute pancreatitis caused by 5-ASA suppositories in a patient with ulcerative colitis. A 26-year-old male was admitted with abdominal pain and diagnosed as ulcerative colitis. Acute pancreatitis occurred soon after 24 hours of treatment with oral mesalazine. Drug-induced pancreatitis was suspected and administration of mesalazine was discontinued. Then 5-ASA suppositories were started instead of oral mesalazine. Twenty-four hours after taking 5-ASA suppositories, he experienced severe abdominal pain, fever, and elevation of amylase levels. The suppositories were immediately stopped and symptoms resolved over next 48 hours. Herein, we suggest that, in patients treated with 5-ASA suppositories who complain of severe abdominal pain, drug-induced pancreatitis should be suspected.

Severe Cutaneous Adverse Drug Reactions in Pediatric Patients: A Multicenter Study.

PubMed

Dibek Misirlioglu, Emine; Guvenir, Hakan; Bahceci, Semiha; Haktanir Abul, Mehtap; Can, Demet; Usta Guc, Belgin Emine; Erkocoğlu, Mustafa; Toyran, Muge; Nacaroglu, Hikmet Tekin; Civelek, Ersoy; Buyuktiryaki, Betul; Ginis, Tayfur; Orhan, Fazil; Kocabas, Can Naci

The severe cutaneous adverse drug reactions (SCARs) are rare but could be life-threatening. These include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis. The purpose of this study was the evaluation of the clinical characteristics of patients with the diagnosis of SCARs. Patients who were diagnosed with SCARs between January 2011 and May 2016 by pediatric allergy clinics in the provinces of Ankara, Trabzon, Izmir, Adana, and Bolu were included in this multicenter study. Clinical and laboratory findings, the time between suspected drug intake and development of clinical findings, treatments they have received, and length of recovery time were recorded. Fifty-eight patients with SCARs were included in this study. The median age of the patients was 8.2 years (interquartile range, 5.25-13 years) and 50% (n = 29) were males. Diagnosis was Stevens-Johnson syndrome/TEN in 60.4% (n = 35), DRESS in 27.6% (n = 16), and acute generalized exanthematous pustulosis in 12% (n = 7) of the patients. In 93.1% of the patients, drugs were the cause of the reactions. Antibiotics ranked first among the drugs (51.7%) and antiepileptic drugs were the second (31%) most common. A patient who was diagnosed with TEN developed lagophthalmos and a patient who was diagnosed with DRESS developed secondary diabetes mellitus. Only 1 patient with the diagnosis of TEN died. SCARs in children are not common but potentially serious. Early diagnosis and appropriate treatment of SCARs will reduce the incidence of morbidity and mortality. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction.

PubMed

Gibon, Emmanuel; Córdova, Luis A; Lu, Laura; Lin, Tzu-Hua; Yao, Zhenyu; Hamadouche, Moussa; Goodman, Stuart B

2017-08-01

Novel evidence-based prosthetic designs and biomaterials facilitate the performance of highly successful joint replacement (JR) procedures. To achieve this goal, constructs must be durable, biomechanically sound, and avoid adverse local tissue reactions. Different biomaterials such as metals and their alloys, polymers, ceramics, and composites are currently used for JR implants. This review focuses on (1) the biological response to the different biomaterials used for TJR and (2) the chronic inflammatory and foreign-body response induced by byproducts of these biomaterials. A homeostatic state of bone and surrounding soft tissue with current biomaterials for JR can be achieved with mechanically stable, infection free and intact (as opposed to the release of particulate or ionic byproducts) implants. Adverse local tissue reactions (an acute/chronic inflammatory reaction, periprosthetic osteolysis, loosening and subsequent mechanical failure) may evolve when the latter conditions are not met. This article (Part 2 of 2) summarizes the biological response to the non-metallic materials commonly used for joint replacement including polyethylene, ceramics, and polymethylmethacrylate (PMMA), as well as the foreign body reaction to byproducts of these materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1685-1691, 2017. © 2016 Wiley Periodicals, Inc.

[Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

PubMed

Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

2013-01-01

To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

Objective We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Methods Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Results Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). Conclusions We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization–Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results. PMID:26544039

Intentional overdose of azathioprine in a patient with systemic lupus erythematosus.

PubMed

Mahmood, K; Khan, A M; Ramanan, A V; Martin, K

2013-11-01

A 14-year-old girl with systemic lupus erythematosus presented with a mixed overdose of paracetamol, ibuprofen and azathioprine (1500 mg) following a deliberate self-harm attempt. The patient was admitted and monitored. No adverse effects were observed. A review of the literature showed very few reported azathioprine overdoses. Lupus patients are at risk of developing low mood and depression (and related self-harm including overdose of medication). This can be as a consequence of the disease process itself or in reaction to the stresses of living with a chronic disease, which are perhaps particularly acute in some adolescents with the disease. An intentional overdose in a patient with lupus is clearly a cry for help and should be appropriately managed. Counselling of young people and their parents about possible mood disorders is an important part of the management of this chronic disease. Despite the theoretical risk of significant myelosuppression as well as other potential adverse effects, azathioprine in acute overdose seems to be generally well tolerated.

Crotalidae polyvalent immune Fab: a guide to its use in North American crotaline envenomation.

PubMed

Keating, Gillian M; Lyseng-Williamson, Katherine A

2012-08-01

Intravenous crotalidae polyvalent immune Fab (CroFab(®)) is effective in patients with minimal, moderate or severe crotaline envenomation, halting the progression of local venom effects and ameliorating haematological and other systemic abnormalities of envenomation. Despite treatment, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab is generally well tolerated, with acute hypersensitivity reactions being the most commonly occurring adverse event.

Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

PubMed Central

Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

2012-01-01

BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

Topical NSAIDs for acute pain in adults

PubMed Central

Massey, Thomas; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

2014-01-01

Background Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. Objectives To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. Selection criteria We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Data collection and analysis Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from placebo. There were very few systemic adverse events or withdrawals due to adverse events. There were insufficient data to reliably compare individual topical NSAIDs with each other or the same oral NSAID. Authors’ conclusions Topical NSAIDs can provide good levels of pain relief, without the systemic adverse events associated with oral NSAIDs, when used to treat acute musculoskeletal conditions. PMID:20556778

Safety of intravenous equine F(ab')2: insights following clinical trials involving 1534 recipients of scorpion antivenom.

PubMed

Boyer, Leslie; Degan, Janice; Ruha, Anne-Michelle; Mallie, Joanne; Mangin, Emmanuelle; Alagón, Alejandro

2013-12-15

The technology of antivenom production has gradually changed since the earliest production of antisera around the turn of the 20th century. Use of early antisera was associated with frequent acute adverse reactions and serum sickness. New F(ab')2 products, manufactured using pepsin degradation of immunoglobulin together with precipitation of unwanted protein and albumin serum fractions, should in concept cause fewer immune reactions in clinical use. A linked set of five prospective clinical trials of an equine F(ab')2 antivenom, together with one historical control study, were completed during development of the product for a Biological License Application through the US FDA. Adverse events were recorded and categorized, with particular attention to the frequency of immune reactions. A total of 1534 patients ages 0.1-90.5 years received antivenom, in Arizona and in Mexico, for treatment of scorpion envenomation. Total dosing ranged from 1 to 5 vials except for one outlier who received 10 vials. Estimated protein exposure was 12-275 mg per patient (outlier, up to 550 mg). Three patients (0.2%) had acute reactions to antivenom infusion (one urticaria, one urticaria and dyspnea, and one panic attack). Eight (0.5%) had rashes suggestive of Type 3 immune reactions, although none had the full syndrome of serum sickness. Two women were treated for envenomation during the first trimester of pregnancy, one of whom subsequently experienced a spontaneous abortion. Rates of immune reaction to this product were two orders of magnitude lower than the range (up to 75% for early and 81% for late reactions) historically reported with use of minimally refined whole immunoglobulin products against a variety of infections and envenomations. Lower protein dose, greater purity of the active component, lack of the immunogenic Fc portion of the immunoglobulin molecule, and slow intravenous infusion are likely to be the reason for this. Clinical implications of a safer product include that it can be employed in settings where antivenom was once considered too dangerous to use, such as primary care clinics and remote rural areas. Copyright © 2013 Elsevier Ltd. All rights reserved.

A case of all-trans retinoic acid-induced myositis in the treatment of acute promyelocytic leukaemia.

PubMed

Chan, K H; Yuen, S L S; Joshua, D

2005-12-01

The use of all-trans retinoic acid (ATRA) is now standard therapy for the treatment of acute promyelocytic leukaemia (APML). There have been increasing reports of ATRA-induced myositis, with its frequent association with retinoic acid syndrome and Sweet's syndrome. We report a case of a young man with APML who developed ATRA-induced myositis characterized by unexplained fevers, bilateral leg swelling and a non-painful purpuric, petechial rash, with prompt resolution of symptoms and signs with high-dose steroids and cessation of ATRA. Rapid recognition of this adverse reaction and prompt institution of steroids is of prime importance given its potentially fatal course.

Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

PubMed Central

Lu-Qun, Wang; Hao, Li; Xiao-Peng, He; Fang-Lin, Li; Ling-Ling, Wang; Xue-Liang, Chen; Ming, Hou

2014-01-01

Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL). Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlow regimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity. PMID:24963332

Clinical study on prospective efficacy of all-trans Acid, realgar-indigo naturalis formula combined with chemotherapy as maintenance treatment of acute promyelocytic leukemia.

PubMed

Xiang-Xin, Li; Lu-Qun, Wang; Hao, Li; Xiao-Peng, He; Fang-Lin, Li; Ling-Ling, Wang; Xue-Liang, Chen; Ming, Hou

2014-01-01

Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL). Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlow regimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

21 CFR 606.170 - Adverse reaction file.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of the...

[Adverse reaction caused by rabies vaccine in China: a Meta-analysis].

PubMed

Zhang, X R; Wu, Z G; Zhang, W S

2017-06-10

Objective: To conduct a Meta-analysis on the rate of adverse reaction related to rabies vaccine, so as to provide reference for rabies vaccine immunization in China. Methods: We electronically searched databases including CNKI, VIP information resource integration service platform, WanFang Data, CBM, PubMed and The Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using the R software. Results: A total of 29 related papers had met the inclusion criteria, with no publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94 222 respondents, with an incidence of adverse reactions as 1.04 % -47.78 % . The overall incidence rate of adverse reaction was 9.82 % (95 %CI : 7.58 % -12.72 % ). A combined local adverse reaction rate appeared as 12.05 % (95 % CI : 9.26 % -15.69 % ). The systemic adverse reaction rate was 9.06 % (95 %CI : 7.07 % -11.61 % ). The overall adverse reaction rate on aqueous vaccine was 32.39 % (95 %CI : 21.88 % -47.94 % ). Combined adverse reaction rate of freeze dried vaccine appeared as 8.65 % (95 %CI : 4.54 % -16.51 % ). Significant differences were seen between both groups ( P <0.05). Conclusions: The local adverse reaction rate caused by rabies vaccination was higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the aqueous vaccine should gradually be eliminated.

Study of the prevalence of chronic, non-specific lung disease and related health problems in the grain-handling industry. Technical report

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

Rankin, J.; Bates, J.; Claremont, A.

1986-10-01

A total of 310 grain handlers was studied, with attention to prevalence and characteristics of clinical, psychological, immunological, radiological, serological blood and urine parameters to determine any apparent effects from grain-dust exposure. Grain handlers had a higher prevalence of respiratory symptoms and signs than did the city workers who comprised the comparison group. Evidence of accumulative respiratory effect due to recurring exposures to grain dust was found. Acute and chronic airway reactions were induced by exposure to grain dust. Wheezing and dyspnea on exposure were related to length of employment. Grain fever syndrome was prevalent. Cases of acute recurrent conjunctivitismore » and rhinitis were found along with skin pruritus, mainly on exposure to barley dust. Pesticide exposure caused temporary disabling symptoms. Lung function was adversely affected by grain-dust exposure. Exposure to grain mites and insects in contaminated cereal grain caused a reaction among grain workers.« less

21 CFR 606.170 - Adverse reaction file.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of adverse...

Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

PubMed Central

2017-01-01

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis. PMID:29226159

Diltiazem-induced acute generalised exanthematous pustulosis.

PubMed

Wakelin, S H; James, M P

1995-07-01

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several clinical and histological features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel blocker diltiazem hydrochloride. The eruption followed a biphasic course, and improved following treatment with systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.

Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

PubMed

Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

2014-10-15

Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

Acute Generalised Exanthematous Pustulosis: An Update.

PubMed

De, Abhishek; Das, Sudip; Sarda, Aarti; Pal, Dayamay; Biswas, Projna

2018-01-01

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is attributed to drugs in more than 90% of cases. It is a rare disease, with an estimated incidence of 1-5 patients per million per year. The clinical manifestations characterised by the rapid development of sterile pustular lesions, fever and leucocytosis. Number of drugs has been reported to be associated with AGEP, most common being the antibiotics. Histopathologically there is intraepidermal pustules and papillary dermal oedema with neutrophilic and eosinophilic infiltrations. Systemic involvement can be present in more severe cases. Early diagnosis with withdrawal of the causative drug is the most important step in the management. Treatment includes supportive care, prevention of antibiotics and use of a potent topical steroid.

Acute Generalised Exanthematous Pustulosis: An Update

PubMed Central

De, Abhishek; Das, Sudip; Sarda, Aarti; Pal, Dayamay; Biswas, Projna

2018-01-01

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is attributed to drugs in more than 90% of cases. It is a rare disease, with an estimated incidence of 1–5 patients per million per year. The clinical manifestations characterised by the rapid development of sterile pustular lesions, fever and leucocytosis. Number of drugs has been reported to be associated with AGEP, most common being the antibiotics. Histopathologically there is intraepidermal pustules and papillary dermal oedema with neutrophilic and eosinophilic infiltrations. Systemic involvement can be present in more severe cases. Early diagnosis with withdrawal of the causative drug is the most important step in the management. Treatment includes supportive care, prevention of antibiotics and use of a potent topical steroid. PMID:29527022

Bicalutamide-induced hepatotoxicity: A rare adverse effect.

PubMed

Hussain, Salwa; Haidar, Abdallah; Bloom, Robert E; Zayouna, Nafea; Piper, Michael H; Jafri, Syed-Mohammed R

2014-01-01

Male, 81 FINAL DIAGNOSIS: Prostate cancer Symptoms: Anorexia • dark urine • joundice • letargy Casodex Clinical Procedure: - Specialty: Oncology. Adverse events of drug therapy. Bicalutamide is a nonsteroidal anti-androgen used extensively during the initiation of androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist to reduce the symptoms of tumor flare in patients with metastatic prostate neoplasm. It can cause gynecomastia, hot flashes, fatigue, and decreased libido through competitive androgen receptor blockade. Although not as common, acute drug-induced liver injury is also possible with bicalutamide therapy. Typically, this results in transient derangement of liver function and patients remain asymptomatic. We share our experience with a case of symptomatic acute hepatotoxicity secondary to the use of bicalutamide and use this opportunity to present a brief review of existing literature. An 81-year-old African American male with metastatic prostate neoplasm presented with nonspecific symptoms along with jaundice of 1-day duration. He was started on a trial of bicalutamide 3 weeks prior to presentation. On physical examination, scleral icterus was noted. Workup revealed acutely elevated liver transaminases (>5 times the upper limit of normal), alkaline phosphatase, conjugated hyperbilirubinemia, and coagulopathy. Other etiologies, including viruses, common toxins, drugs, autoimmune, and copper-induced hepatitis, were considered. Bicalutamide was discontinued and the patient was managed with supportive care. He showed improvement of clinical and laboratory abnormalities within days. While rare, clinically significant and potentially life-threatening liver injury can result from use of bicalutamide. Prompt recognition and discontinuation of bicalutamide is necessary to avoid serious complications from this adverse reaction.

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

PubMed

Lieberman, Harris R; Tharion, William J; Shukitt-Hale, Barbara; Speckman, Karen L; Tulley, Richard

2002-11-01

When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

Pharmacologic Impact (aka "Breaking Bad") of Medications on Wound Healing and Wound Development: A Literature-based Overview.

PubMed

Beitz, Janice M

2017-03-01

Patients with wounds often are provided pharmacologic interventions for their wounds as well as for their acute or chronic illnesses. Drugs can promote wound healing or substantively hinder it; some medications cause wound or skin reactions. A comprehensive review of extant literature was conducted to examine the impact of drug therapy on wound healing and skin health. MEDLINE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for English-language articles published between 2000 and 2016 using the terms drugs, medications, drug skin eruptions, adverse skin reactions, wound healing, delayed wound healing, nonhealing wound, herbals, and herbal supplements. The search yielded 140 articles (CINAHL) and 240 articles (MEDLINE) for medications and wound healing. For medications and adverse skin effects, the search identified 256 articles (CINAHL) and 259 articles (MEDLINE). The articles included mostly narrative reviews, some clinical trials, and animal studies. Notable findings were synthesized in a table per pharmacological class and/or agent focusing on wound healing impact and drug-induced adverse skin reactions. The medications most likely to impair wound healing and damage skin integrity include antibiotics, anticonvulsants, angiogenesis inhibitors, steroids, and nonsteroidal anti-inflammatory drugs. Conversely, drugs such as ferrous sulfate, insulin, thyroid hormones, and vitamins may facilitate wound healing. Selected clinical practices, including obtaining a detailed medication history that encompasses herbal supplements use; assessing nutrition status especially protein blood levels affecting drug protein binding; and scrutinizing patient history and physical characteristics for risk factors (eg, atopy history) can help diminish and/or eliminate adverse integumentary outcomes. "Deprescribing" (discontinuing unnecessary medications) should be utilized when possible. Contemporary wound care clinicians must be cognizant of these mitigating clinical approaches.

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

PubMed

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

2013-01-01

To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. 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. 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 10(th), 20(th), and 30(th) 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 10(th) 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. Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Bowel Angioedema Associated With Iodinated Contrast Media: Incidence and Predisposing Factors.

PubMed

Seo, Nieun; Chung, Yong Eun; Lim, Joon Seok; Song, Mi Kyung; Kim, Myeong-Jin; Kim, Ki Whang

2017-09-01

Bowel angioedema is an acute adverse reaction to iodinated contrast media (CM) that involves the gastrointestinal tract. We aimed to investigate the incidence and predisposing factors of iodinated CM-associated bowel angioedema during computed tomography (CT) examinations. This study was approved by our institutional review board, and informed consent was waived due to its retrospective design. From July 2013 to July 2015, adult patients with a history of adverse reactions to iodinated CM during CT (group A, n = 427) and patients without adverse reactions matched for age and sex with the propensity-score matching method (group B, n = 427) were studied. Contrast media-associated bowel angioedema was determined when bowel wall thickness increased after contrast enhancement compared with the precontrast scan. Potential predisposing factors including patient demographics, symptoms and time of adverse reactions, and CM-related factors were compared between patients with and without angioedema in group A. In addition, the incidence of bowel angioedema was compared between groups A and B. The incidence of CM-associated bowel angioedema in group A was 3.3% (14/427) in the per-patient analysis and 2.6% (15/578) in the per-examination analysis. The CM-associated bowel angioedema involved the distal duodenum and/or proximal jejunum and showed long-segmental circumferential bowel wall thickening on CT. None of the studied predisposing factors was different between patients with and without bowel angioedema (P > 0.05). The incidence of CM-associated bowel angioedema in group B was 1.9% (8/427) and 1.7% (8/458) for per-patient and per-examination analyses, respectively, and these rates were not significantly different between groups A and B (P = 0.346 and P = 0.370, respectively). The incidence of CM-associated bowel angioedema during CT was 1.7% to 3.3%, and none of the studied predisposing factors was associated with bowel angioedema.

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

PubMed

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

2017-05-01

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

Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review.

PubMed

Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

2016-10-01

Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture.

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

PubMed Central

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

2011-01-01

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

Fish allergy in childhood.

PubMed

Pascual, Cristina Y; Reche, Marta; Fiandor, Ana; Valbuena, Teresa; Cuevas, Teresa; Esteban, Manuel Martin

2008-11-01

Fish and its derived products play an important role in human nutrition, but they may also be a potent food allergen. Fish can be an ingested, contact, and inhalant allergen. Gad c I, a Parvalbumin, the major allergen in codfish, is considered as fish and amphibian pan-allergen. Prevalence of fish allergy appears to depend on the amount of fish eaten in the local diet. In Europe, the highest consumption occurs in Scandinavian countries, Spain and Portugal. In Spain, fish is the third most frequent allergen in children under 2 yr of age after egg and cow's milk. An adverse reaction to fish may be of non-allergic origin, due to food contamination or newly formed toxic products, but the most frequent type of adverse reactions to fish are immunologic-mediated reactions (allergic reactions). Such allergic reactions may be both IgE-mediated and non-IgE-mediated. Most cases are IgE-mediated, due to ingestion or contact with fish or as a result of inhalation of cooking vapors. Some children develop non-IgE-mediated type allergies such as food protein induced enterocolitis syndrome. The clinical symptoms related to IgE-mediated fish allergy are most frequently acute urticaria and angioedema as well as mild oral symptoms, worsening of atopic dermatitis, respiratory symptoms such as rhinitis or asthma, and gastrointestinal symptoms such as nausea and vomiting. Anaphylaxis may also occur. Among all the species studied, those from the Tunidae and Xiphiidae families appear to be the least allergenic.

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

PubMed Central

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

2013-01-01

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. PMID:24098420

[Analysis of Kudiezi injection's security literature].

PubMed

Chang, Yan-Peng; Xie, Yan-Ming

2012-09-01

By retrieving the relevant database, aim was to achieve the security reported of Kudiezi injection (Yueanxin). To analysis the gender, age, underlying disease, medication dosage, solvent, adverse event/adverse reaction time of occurrence, clinical presentation of patients, It was found the adverse event/adverse reaction usually occur in older people, involving the organs and systems include skin and its appendages, digestive system, nervous system, circulatory system, respiratory system, systemic reaction, part of the adverse event/adverse reaction's cause were not according to the instructions. It was found on the adverse event/adverse reaction of the judgment on the lack of objective evidence, to produce certain effect for objective evaluation of security of Kudiezi injection (Yueanxin).

Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.

PubMed

Kaur, Kamaljeet; Fayad, Raja; Saxena, Arpit; Frizzell, Norma; Chanda, Anindya; Das, Suvarthi; Chatterjee, Saurabh; Hegde, Shweta; Baliga, Manjeshwar Shrinath; Ponemone, Venkatesh; Rorro, Matthew; Greene, Jennifer; Elraheb, Yasmine; Redd, Alan J; Bian, John; Restaino, John; Norris, LeAnn B; Qureshi, Zaina P; Love, Bryan L; Brookstaver, Brandon; Georgantopoulos, Peter; Sartor, Oliver; Raisch, Dennis W; Rao, Gowtham; Lu, Kevin; Ray, Paul; Hrusheshky, William; Schulz, Richard; Ablin, Richard; Noxon, Virginia; Bennett, Charles L

2016-02-01

The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists. To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability. 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA's MedWatch program. Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed "FQ-associated disability" (FQAD). Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin. Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised. ©2016 Frontline Medical Communications.

Post-marketing safety monitoring of shenqifuzheng injection: a solution made of dangshen (Radix Codonopsis) and huangqi (Radix Astragali Mongolici).

PubMed

Ai, Qinghua; Zhang, Wen; Xie, Yanming; Huang, Wenhua; Liang, Hong; Cao, Hui

2014-08-01

To identify the potential risk factors associated with Shenqifuzheng injection (SFI), a solution made of Dangshen (Radix Codonopsis) and Huangqi (Radix Astragali Mongolici), for the timely provision of information to regulatory authorities. A comprehensive analysis of the production process, quality standards, pharmacology, post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions (ADR), case analyses, and systematic reviews, intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital information system (HIS). Sub-acute toxicity tests suggesting that a dose of 15 mL/kg (concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85 per thousand. From March to November 2013, of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI at a dosage and a treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash, chills, feeling cold, palpitation, dyspnea, edema of a lower extremity, palpebral edema, and superficial vein inflammation, among others. This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors. It supports the safety of SFI for clinical, research,and production uses based on objective, reliable, and scientific information to provide safe medication.

Family Adversity and Resilience Measures in Pediatric Acute Care Settings.

PubMed

O'Malley, Donna M; Randell, Kimberly A; Dowd, M Denise

2016-01-01

Adverse childhood experiences (ACEs) impact health across the life course. The purpose of this study was to identify caregiver ACEs, current adversity, and resilience in families seeking care in pediatric acute care settings. Study aims included identifying demographic characteristics, current adversities, and resilience measures associated with caregiver ACEs ≥4. A cross-sectional survey study design was used and a convenience sample (n = 470) recruited at emergency and urgent care settings of a large Midwest pediatric hospital system. Measures were self-reported. The original 10-item ACEs questionnaire measured caregiver past adversity. Current adversity was measured using the 10-item IHELP. The six-item Brief Resiliency Scale measured resilience, and WHO-5 Well-Being Index was used to measure depressive affect. Compared to participants with ACEs score of 0-3 participants with ACEs ≥4 were more likely to have multiple current adversities, increased risk of depression, and lower resilience. Caregivers using pediatric acute care settings carry a high burden of ACEs and current adversities. Caregiver ACEs are associated with current child experiences of adversity. Caregivers socioeconomic status and education level may not be an accurate indicator of a family's risks or needs. Pediatric acute care settings offer opportunities to access, intervene, and prevent childhood adversity. © 2016 Wiley Periodicals, Inc.

A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen–UVA photochemical treatment

PubMed Central

Knutson, F; Osselaer, J; Pierelli, L; Lozano, M; Cid, J; Tardivel, R; Garraud, O; Hervig, T; Domanovic, D; Cukjati, M; Gudmundson, S; Hjalmarsdottir, I B; Castrillo, A; Gonzalez, R; Brihante, D; Santos, M; Schlenke, P; Elliott, A; Lin, J-S; Tappe, D; Stassinopoulos, A; Green, J; Corash, L

2015-01-01

Background and Objectives A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT-PLT transfusion. Results Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components. PMID:25981525

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section, significant...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section, significant...

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

2017-08-15

Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.

Longitudinal myelitis associated with yellow fever vaccination.

PubMed

Chaves, M; Riccio, P; Patrucco, L; Rojas, J I; Cristiano, E

2009-07-01

Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever vaccine-associated neurotropic disease. This terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. The objective of this communication is to report a patient who received a YF vaccine in Argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. A 56-year-old man began with progressive paraparesia, urinary retention, and constipation 48 h previous to admission. The patient received YF vaccine 45 days prior to the onset of the symptoms. There was no history of other immunization or relevant condition. MR of the spine showed longitudinal intramedullary hyperintense signal (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests for other flavivirus were negative. A diagnosis of longitudinal myelitis without encephalitis associated with YF vaccine was performed and symptoms improved 5 days later. This is the first report dealing with longitudinal myelitis as a serious adverse event associated with YF vaccination in which confirmation of the presence of antibodies in CSF was found. To date, it is also the first report with serological confirmation in Argentina and in South America. We consider that the present investigation will raise awareness in the region in the reporting of adverse events related to YF vaccine and improve our knowledge of adverse reactions to the vaccine.

[Clinical efficacy of flomoxef in the field of pediatrics].

PubMed

Ogura, H; Kubota, H; Murakami, N; Tomoda, T; Hamada, F; Matsumoto, K; Araki, K; Ogura, Y; Kurashige, T; Kitamura, I

1987-08-01

A new oxacephem antibiotic, flomoxef sodium (FMOX, 6315-S), was studied for its clinical efficacy in the field of pediatrics. The treated patients were infants and children ranging from 6 months to 14 years old suffering from bacterial pneumonia in 3 cases, acute tonsillitis in 2 cases, acute enterocolitis in 2 cases, and cellulitis and urinary tract infection in 1 case each, a total of 9 cases. FMOX was administered at (levels of) 57-150 mg/kg in daily dose with durations of treatment ranging from 5 to 18 days. Clinical efficacies of good or excellent results were obtained in all cases (excellent in 4, good in 5). As an adverse reaction, eosinophilia was observed in 1 patient. This elevation is, however, normalized with the cessation of the treatment.

Acute immune thrombocytopenic purpura as adverse reaction to oral polio vaccine (OPV).

PubMed

Jin, Cheng-qiang; Dong, Hai-xin; Sun, Zhuo-xiang; Zhou, Jian-wei; Dou, Cui-yun; Lu, Shu-hua; Yang, Rui-rui

2013-08-01

A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13×10(9)/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections.

Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

PubMed Central

Edwards, Beatrice J.; Usmani, Sarah; Raisch, Dennis W.; McKoy, June M.; Samaras, Athena T.; Belknap, Steven M.; Trifilio, Steven M.; Hahr, Allison; Bunta, Andrew D.; Abu-Alfa, Ali; Langman, Craig B.; Rosen, Steve T.; West, Dennis P.

2013-01-01

Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods: A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were “renal problems” and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted. Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 ± 10 years. Multiple myeloma (n = 220, 46%), breast cancer (n = 98, 20%), and prostate cancer (n = 24, 5%) were identified. Agents included ZOL (n = 411, 87.5%), pamidronate (n = 8, 17%), and alendronate (n = 36, 2%). Outcomes included hospitalization (n = 304, 63.3%) and death (n = 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs. Conclusion: AKI was identified in BP cancer clinical trials, although a safety signal for BPs and AKI within the FDA AERS was not detected. Our findings may be attributed, in part, to clinicians who believe that AKI occurs infrequently; ascribe the AKI to underlying premorbid disease, therapy, or cancer progression; or consider that AKI is a known adverse drug reaction of BPs and thus under-report AKI to the AERS. PMID:23814519

Adverse reactions to cosmetics and methods of testing.

PubMed

Nigam, P K

2009-01-01

Untoward reactions to cosmetics, toiletries, and topical applications are the commonest single reason for hospital referrals with allergic contact dermatitis. In most cases, these are only mild or transient and most reactions being irritant rather than allergic in nature. Various adverse effects may occur in the form of acute toxicity, percutaneous absorption, skin irritation, eye irritation, skin sensitization and photosensitization, subchronic toxicity, mutagenicity/genotoxicity, and phototoxicity/photoirritation. The safety assessment of a cosmetic product clearly depends upon how it is used, since it determines the amount of substance which may be ingested, inhaled, or absorbed through the skin or mucous membranes. Concentration of ingredients used in the different products is also important. Various test procedures include in vivo animal models and in vitro models, such as open or closed patch test, in vivo skin irritation test, skin corrosivity potential tests (rat skin transcutaneous electrical resistance test, Episkin test), eye irritation tests (in vivo eye irritancy test and Draize eye irritancy test), mutagenicity/genotoxicity tests (in vitro bacterial reverse mutation test and in vitro mammalian cell chromosome aberration test), and phototoxicity/photoirritation test (3T3 neutral red uptake phototoxicity test). Finished cosmetic products are usually tested in small populations to confirm the skin and mucous membrane compatibility, and to assess their cosmetic acceptability.

Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia.

PubMed

Gabor, Krisztina Mita; Schermann, Geza; Lautner-Csorba, Orsolya; Rarosi, Ferenc; Erdelyi, Daniel J; Endreffy, Emoke; Berek, Krisztina; Bartyik, Katalin; Bereczki, Csaba; Szalai, Csaba; Semsei, Agnes F

2015-04-01

Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P = 0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P = 0.0044, respectively). Our results indicate that DCK polymorphisms might be important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity. © 2015 Wiley Periodicals, Inc.

Worsening of Asthma with Systemic Corticosteroids

PubMed Central

Sheth, Ankur; Reddymasu, Savio; Jackson, Robert

2006-01-01

Despite widespread use for treatment of asthma and allergies, glucocorticoids may cause allergic reactions, even anaphylaxis. The incidence of adverse reactions to systemic glucocorticoids is 0.3%. The most commonly reported corticosteroids causing anaphylaxis like reactions are hydrocortisone, prednisone, and methylprednisolone. Most authors agree that allergic reactions to systemic corticosteroids are possibly immunoglobulin E mediated. We report a patient with asthma, aspirin allergy, and nasal polyps who developed bronchospasm following the administration of intravenous methylprednisolone sodium succinate during an acute asthmatic attack. We discuss the differential diagnosis of worsening asthma despite adequate treatment, and suggest corticosteroid-induced bronchospasm in our patient. Corticosteroid-induced bronchospasm should be considered when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy, particularly when a history of aspirin allergy is present. Teaching Point: Know the differential diagnosis for worsening of asthma despite adequate treatment.Consider corticosteroid-induced bronchospasm when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy.Corticosteroid-induced bronchospasm is more commonly seen in asthmatics with a history of aspirin allergy. PMID:16606375

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Adverse reactions and other factors that impact subsequent blood donation visits.

PubMed

Custer, Brian; Rios, Jorge A; Schlumpf, Karen; Kakaiya, Ram M; Gottschall, Jerome L; Wright, David J

2012-01-01

The importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. Six REDS-II blood centers provided data for this analysis. Summary minor and major adverse reaction categories were created. The influence of adverse reactions on donation was examined in two ways: Kaplan-Meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (AORs) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. Donors who had major reactions had longer times to return than donors with minor or no reactions. The AOR of returning for donors with major reactions was 0.32 (95% confidence interval [CI], 0.28-0.37) and with minor reactions 0.59 (95% CI, 0.56-0.62) when compared to donors who did not have reactions. Conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. Subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. Factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions. Having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. Factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction. © 2011 American Association of Blood Banks.

Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation

PubMed Central

Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

2017-01-01

ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. PMID:28538774

Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy.

PubMed

Asakura, Hidesaku; Takahashi, Hoyu; Tsuji, Hajime; Matsushita, Tadashi; Ninomiya, Hideyuki; Honda, Goichi; Mimuro, Jun; Eguchi, Yutaka; Kitajima, Isao; Sakata, Yoichi

2014-03-01

Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated. The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

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

Promoting adverse drug reaction reporting: comparison of different approaches.

PubMed

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

2016-01-01

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

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Treatment of Epidermal Growth Factor Receptor Inhibitors Associated Adverse Skin Reactions by Zhiyang Pingfu Liquid: a Clinical Study].

PubMed

Wang, Hong-yan; Zou, Chao; Cui, Hui-juan; Bai, Yan-ping; Li, Yuan; Tan, Huang-ying; Wang, Wei; Ju, Hai

2015-07-01

To study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin. All 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment. EGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05). ZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions.

[Efficacy and tolerance of fenspiride in adult patients with acute respiratory tract infections].

PubMed

Płusa, T; Nawacka, D

1998-12-01

Fenspiride is an antiinflammatory drug targeted for the respiratory tract. In our study clinical efficacy and tolerance of drug were evaluated in 392 adult patients with acute respiratory tract infections. According to clinical criteria all observed symptoms were classified as mild, moderate and severe. The most of observed patients were included into moderate symptom score. Cough and nose obturation were dominant symptoms. All noticed changes in the upper respiratory tract were decreased after fenspiride therapy in 7 days trial. In 168 observed patients systemic and in 60 local acting antibiotics were successfully applied. Excellent tolerance of fenspiride was documented in 59% and good tolerance --in 34% of patients. Observed adverse reactions were classified as mild and in 20 patients fenspiride was rejected. Authors suggest that fenspiride therapy is save and successful in patient with acute respiratory tract infection. Good results in patients with bronchitis in decreasing of bronchospasm indicate fenspiride as a good tool in bronchial infection.

[Efficacy of ivabradine in combination therapy for complicated acute coronary syndrome in patients with type 2 diabetes mellitus].

PubMed

Kondrat'ev, A I; Dolgikh, V T; Stotskiĭ, A O

2010-01-01

To study the effect of ivabradine (coraxan, Servier) as part of combination therapy on the clinical manifestations of acute left ventricular failure (ALVF) in Braunwald class II-IIIB unstable angina in patients with type 2 diabetes mellitus (T2DM). Thirty-six T2DM patients (mean age 56 + 4.3 years) with a diagnosis of acute coronary syndrome were examined. Eighteen healthy individuals were examined as an age- and gender-matched control group. Metabolic, hemodynamic, and electrophysiological parameters were studied in all the patients on hospital stay days I and S. Ivabradine used in combination therapy for unstable angina caused reductions in the clinical manifestations of ALVF, heart rate, the number of myocardial ischemic episodes. In the ivabradine-treated patients, left ventricular ejection fraction showed a significant trend for increase. No adverse reactions were recorded. Ivabradine therapy demonstrated antiischemic and antianginal efficiencies and a good tolerability, without leading to the development of tolerance and without being followed by the development of the withdrawal syndrome.

Sumatriptan/Naproxen Sodium: A Review in Migraine.

PubMed

Syed, Yahiya Y

2016-01-01

Sumatriptan/naproxen sodium (Treximet®) is a fixed-dose combination of a serotonin 5-HT1B/1D receptor agonist (sumatriptan) and an NSAID (naproxen sodium), approved in the USA for the acute treatment of migraine with or without aura in adolescents and adults. In a randomized, phase 3 trial in adolescents, significantly more sumatriptan/naproxen sodium than placebo recipients were pain-free at 2 h. Similarly, in a pair of randomized phase 3 trials in adults, significantly more sumatriptan/naproxen sodium than placebo recipients had relief from migraine symptoms at 2 h, and the combination was more effective than individual components in terms of sustained (2-24 h) pain-free response rate. Sumatriptan/naproxen sodium was generally well tolerated, with ≤11 % of adolescents and ≤22 % of adults reporting treatment-related adverse events in the key clinical trials. The most common adverse reactions were nasopharyngitis, hot flushes and muscle tightness in adolescents, and dizziness, pain or pressure sensations, nausea, somnolence, dry mouth, dyspepsia and paraesthesia in adults. Based on current data, sumatriptan/naproxen sodium is a useful option for the acute treatment of migraine in adolescents and adults. The fixed-dose combination may reduce pill burden and improve adherence in some patients.

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

PubMed

Bjånes, Tormod Karlsen

2011-03-04

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

40 CFR 717.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR... adverse reaction to health or the environment. (b) Firm or company means any person, that is subject to.... (i) Significant adverse reactions are reactions that may indicate a substantial impairment of normal...

40 CFR 717.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR... adverse reaction to health or the environment. (b) Firm or company means any person, that is subject to.... (i) Significant adverse reactions are reactions that may indicate a substantial impairment of normal...

The efficacy and adverse effects of dicobalt edetate in cyanide poisoning.

PubMed

Marrs, Timothy Clive; Thompson, John Paul

2016-09-01

Dicobalt edetate is one of a number of cobalt compounds that have been studied in the treatment of cyanide poisoning, their efficacy being based upon the fact that cyanide combines with cobalt to form relatively non-toxic complexes. Inorganic cobalt salts are quite toxic (cyanide and cobalt antagonise one another's toxicity) and complexes such as dicobalt edetate were studied with the aim of identifying compounds that were less acutely toxic, but which retained the antidotal properties of cobalt salts. The proprietary preparation, Kelocyanor™, contains free cobalt and glucose as well as dicobalt edetate. The aim of this study was to evaluate the published evidence for the efficacy and adverse effects of dicobalt edetate. A Pubmed search was undertaken for the period 1961-September 2015. The search terms were "dicobalt edetate", "cobalt edetate" and "Kelocyanor", which produced 24 relevant citations. A review of the references in four relevant books (L'intoxication cyanhydrique et son traitement, Clinical and Experimental Toxicology of Cyanides, Antidotes for Poisoning by Cyanide and Antidotes) produced three further relevant papers, making a total of 27 papers. Efficacy of dicobalt edetate: There is evidence from animal pharmacodynamic studies that dicobalt edetate is an effective cyanide antidote in experimental animals. Some 39 cases of human poisoning treated with dicobalt edetate have been reported, but in only nine cases were blood cyanide concentrations measured, although administration of dicobalt edetate procured survival in four of the seven patients with concentrations in the lethal range (>3.0 mg/L). It is unlikely that death in any of the adequately documented fatal cases was attributable to treatment failure with dicobalt edetate, as it is probable that they all had suffered anoxic brain damage before treatment could be initiated. Furthermore, in one case, acute gold toxicity contributed substantially to death. Adverse effects of dicobalt edetate: Adverse effects reported have included hypertension, tachycardia, nausea, retrosternal pain, sweating, palpebral, facial and laryngeal oedema, vomiting, urticaria and/or a feeling of impending doom. Such effects appear to be more prevalent where the antidote has been administered without evidence of substantial systemic poisoning or where other antidotes have been used which might have been expected also to combine with cyanide. Although the adverse effects observed were doubtless unpleasant, and some were severe, no fatal reactions were found. Dicobalt edetate is an effective cyanide antidote when given to patients with systemic cyanide poisoning, but it has the potential to give rise to adverse reactions, particularly when administered in the absence of intoxication.

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

PubMed Central

Miyaoka, Tsuyoshi; Tsuji, Seiichi; Inami, Yasushi; Nishida, Akira; Horiguchi, Jun

2010-01-01

Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. Data Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized. Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem. PMID:21494350

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

PubMed Central

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

2013-01-01

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

Unequal Sized Pupils Due to Escitalopram; Adverse Events to Dietary Supplements Causing Emergency Department Visits; Compulsive Masturbation Due to Pramipexole; Metformin-Induced Lactic Acidosis Masquerading As an Acute Myocardial Infarction.

PubMed

Mancano, Michael A

2016-05-01

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

Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning.

PubMed

Basher, A; Rahman, S H; Ghose, A; Arif, S M; Faiz, M A; Dawson, A H

2013-01-01

Acute organophosphorus (OP) poisoning is relatively common and a major cause of death from poisoning in developing countries. Magnesium has been shown to be of benefit in animal models. We conducted a phase II study of bolus doses of (MgSO4) in 50 patients with acute organophosphate poisoning. Patients eligible for inclusion had ingested OP and had cholinergic symptoms consistent with moderate or severe poisoning. All patients received standard care of atropinization titrated to control muscarinic symptoms and pralidoxime. The trial was run in 4 sequential groups of patients. Participants in each group received a different total dose of MgSO4 (20%) administered as intermittent bolus doses infused over 10-15 min or placebo. There was one control patient for every 4 patients who received MgSO4. Group A (16 patients) received a total of 4 gm MgSO4 as a single bolus, group B (8 patients) received 8 gm (in two 4 gm doses q4H), group C (8 patients) received 12 gm (in three 4 gm doses q4H) group D (8 patients) received 16 gm (in four 4 gm doses q4H) and control (10 patients) received placebo). Patients were closely monitored for any adverse reaction like significant clinical neuromuscular disturbance and respiratory depression. No adverse reactions to magnesium were observed. The 24 hour urinary magnesium concentration were statistically different between 16 gm (234.74 ± 74.18 mg/dl) and control (118.06 ± 30.76 mg/dl) (p = 0.019), while it was much lower than the 80% of the intravenous magnesium load. Six patients died in control group compared to 3 in 4 gm, 2 in 8 gm and 1 in 12 gm group. There was no mortality in 16 gm group. Magnesium was well tolerated in this study. Larger studies are required to examine for efficacy.

Probable fenofibrate-induced acute generalized exanthematous pustulosis.

PubMed

Power, Anna E; Graudins, Linda V; McLean, Catriona A; Hopper, Ingrid

2015-12-01

The case of a patient who experienced a severe adverse reaction requiring emergency treatment after a single dose of fenofibrate is described. A 58-year-old woman with type 1 diabetes was hospitalized for treatment of an extensive blistering rash on the buttocks and trunk accompanied by fever, hypotension, tachycardia, neutrophilia, impaired renal function, and liver enzyme abnormalities. She reported that two days previously she had developed fever and vomiting four hours after taking her first dose of fenofibrate (145 mg). The patient required vasopressor support and was initially treated with broad-spectrum antibiotics for 3 days and a course of immune globulin. On hospital day 4, histopathology returned results consistent with acute generalized exanthematous pustulosis (AGEP), and the patient was subsequently treated with topical steroids. Gradual resolution of AGEP was noted at the time of her discharge from the hospital on day 7 and at one-week follow-up. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. yielded a score of 5, indicating a probable association between fenofibrate use and AGEP development. AGEP is a predominantly drug-induced condition but is not typically associated with fenofibrate use. Cutaneous eruptions in AGEP are often accompanied by systemic symptoms (e.g., fever, leukocytosis), and the disorder can also be associated with impaired creatinine clearance and elevated aminotransaminase levels. A woman with type 1 diabetes developed AGEP after taking a single dose of fenofibrate. Her cutaneous symptoms began to resolve within days of discontinuation of fenofibrate use. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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

PubMed

Arnott, Janine; Hesselgreaves, Hannah; Nunn, Anthony J; Peak, Matthew; Pirmohamed, Munir; Smyth, Rosalind L; Turner, Mark A; Young, Bridget

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

Promoting adverse drug reaction reporting: comparison of different approaches

PubMed Central

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

2016-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Significant adverse reactions that must be recorded. 717.12 Section 717.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis

PubMed Central

Thornhill, Martin H.; Dayer, Mark J.; Prendergast, Bernard; Baddour, Larry M.; Jones, Simon; Lockhart, Peter B.

2015-01-01

Objectives Antibiotic prophylaxis (AP) administration prior to invasive dental procedures has been a leading focus of infective endocarditis prevention. However, there have been long-standing concerns about the risk of adverse drug reactions as a result of this practice. The objective of this study was to identify the incidence and nature of adverse reactions to amoxicillin and clindamycin prophylaxis to prevent infective endocarditis. Methods We obtained AP prescribing data for England from January 2004 to March 2014 from the NHS Business Services Authority, and adverse drug reaction data from the Medicines and Healthcare Products Regulatory Agency's Yellow Card reporting scheme for prescriptions of the standard AP protocol of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin for those allergic to penicillin. Results The reported adverse drug reaction rate for amoxicillin AP was 0 fatal reactions/million prescriptions (in fact 0 fatal reactions for nearly 3 million prescriptions) and 22.62 non-fatal reactions/million prescriptions. For clindamycin, it was 13 fatal and 149 non-fatal reactions/million prescriptions. Most clindamycin adverse drug reactions were Clostridium difficile infections. Conclusions AP adverse drug reaction reporting rates in England were low, particularly for amoxicillin, and lower than previous estimates. This suggests that amoxicillin AP is comparatively safe for patients without a history of amoxicillin allergy. The use of clindamycin AP was, however, associated with significant rates of fatal and non-fatal adverse drug reactions associated with C. difficile infections. These were higher than expected and similar to those for other doses, durations and routes of clindamycin administration. PMID:25925595

Systemic Allergy to Corticosteroids: Clinical Features and Cross Reactivity.

PubMed

Barbaud, Annick; Waton, Julie

2016-01-01

Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a systemic HS to CS. Acute or delayed urticaria can occur in immediate HS. Immediate HS can be due to excipients, mainly carboxymethylcellulose or to CS themselves. Delayed reactions, mainly maculopapular rash and acute generalized exanthematous pustulosis can occur. Skin tests with systemic CS have to be standardized. It is necessary to determine if IDT with CS frequently induce skin atrophy or not and if such skin atrophy is transient by doing prospective studies using an standardized method and a limited injected volume (0.02 ml). Patch tests can be done in delayed HS, with readings at day 2, 4 and 7. In SCD, the Baeck's classification of CS in 3 chemical groups could explain cross reactivity between systemic CS. However, this classification is not applicable to explain cross-reactions between in systemic HS. According to the literature, 52/79 patients had a HS reaction to a group confirmed by a positive allergological investigations, but had a negative provocation test with another CS belonging to the same group. In case of non-severe cutaneous adverse reactions and when skin tests are negative, provocation tests have to be performed to find an alternative CS, even if it belongs to the same chemical group as those responsible for the initial reaction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adverse drug reactions in hospitalized Colombian children.

PubMed

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

2016-09-30

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

21 CFR 1271.350 - Reporting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 1271.350 Reporting. (a) Adverse reaction reports. (1) You must investigate any adverse reaction... report to FDA an adverse reaction involving a communicable disease if it: (i) Is fatal; (ii) Is life... reactions that are the subject of these 15-day reports and must submit followup reports within 15 calendar...

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

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

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

Adverse Drug Reactions in Dental Practice

PubMed Central

Becker, Daniel E.

2014-01-01

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

Acute Effects of Pre-Event Lower Limb Massage on Explosive and High Speed Motor Capacities and Flexibility

PubMed Central

Arabaci, Ramiz

2008-01-01

The aim of this study was to examine the acute effects of pre- performance lower limb massage after warm-up on explosive and high-speed motor capacities and flexibility. Twenty-four physically active healthy Caucasian male subjects volunteered to participate in this study. All subjects were from a Physical Education and Sport Department in a large university in Turkey. The study had a counterbalanced crossover design. Each of the subjects applied the following intervention protocols in a randomised order; (a) massage, (b) stretching, and (c) rest. Before (pre) and after (post) each of the interventions, the 10 meter acceleration (AS), flying start 20 meter sprint (FS), 30 meter sprint from standing position (TS), leg reaction time (LR), vertical jump (VJ) and sit & reach (SR) tests were performed. A Wilcoxon’s signed rank test was used to compare before and after test values within the three interventions (massage, stretching and rest). The data showed a significant worsening, after massage and stretching interventions, in the VJ, LR (only in stretching intervention), AS and TS tests (p < 0.05), and significant improvement in the SR test (p < 0.05). In contrast, the rest intervention led only to a significant decrement in TS performance (p < 0.05). In conclusion, the present findings suggest that performing 10 minute posterior and 5 minute anterior lower limb Swedish massage has an adverse effect on vertical jump, speed, and reaction time, and a positive effect on sit and reach test results. Key pointsPerforming 10 minute posterior and 5 minute anterior lower limb Swedish massages has an adverse affect on vertical jump, speed, and reaction time and a positive effect on sit and reach test results.According to the present results, long duration massage should not be recommended for warm-ups.Larger subject pools are needed to verify these events. PMID:24149965

Systematic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Chinese Herbal Decoction for the Treatment of Gout

PubMed Central

Liu, Xiaoyu; Chen, Pinyi; Liu, Ling; Zhang, Yanqi; Wu, Yazhou; Pettigrew, Julia Christine; Cheng, Dixiang; Yi, Dong

2014-01-01

Background In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. Objectives In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. Methods We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. Results Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: −0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: −0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). Conclusions Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions. PMID:24465466

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

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

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

2007-11-05

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

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

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

PubMed Central

Loke, Yoon Kong; Derry, Sheena

2001-01-01

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

Apheresis platelets are more frequently associated with adverse reactions than pooled platelets both in recipients and in donors: a study from French hemovigilance data.

PubMed

Daurat, Aurélien; Roger, Claire; Gris, JeanChristophe; Daurat, Gérald; Feissel, Michel; Le Manach, Yannick; Lefrant, JeanYves; Muller, Laurent

2016-06-01

Controversy exists regarding the safety of the different types of platelet (PLT) concentrates. This study was aimed at comparing the rate of adverse reactions associated with apheresis PLT concentrates (APCs) and pooled PLT concentrates (PPCs) both in donors and in recipients. From the French national hemovigilance system, types and numbers of recipient adverse reactions were compared over a period from 2009 to 2011. Donor adverse reactions were available for 2010 and 2011. This study involved 23 of 26 French regions. Main outcomes were the rates of adverse reaction in recipients and serious adverse reaction in donors. There were 790,854 PLT transfusions during the study period (477,747 [60%] with APCs, 313,107 [40%] with PPCs). APCs were associated with more adverse reactions (6244 vs. 2469 per 1,000,000, p < 0.001) and more severe and life-threatening reactions (respectively, 241 vs. 131 per 1,000,000, p < 0.001; and 182 vs. 121 per 1,000,000, p = 0.04). Mortality rates due to an adverse transfusion reaction were similar (15 vs. 6 per 1,000,000, p = 0.5). In donors, the number of whole blood (WB) donations was 4,722,685 whereas 266,095 apheresis procedures were performed. Serious adverse reactions were more frequent for apheresis procedures than for WB donations (5445 vs. 803 per 1,000,000, p < 0.001). Our findings suggest that apheresis PLTs may be more hazardous than pooled PLTs both in recipients and in donors. This study calls for randomized trials to confirm or refute these results. © 2016 AABB.

Toxic epidermal necrolysis successfully treated with etanercept.

PubMed

Gubinelli, Emanuela; Canzona, Flora; Tonanzi, Tiziano; Raskovic, Desanka; Didona, Biagio

2009-03-01

Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.

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

PubMed

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

2017-11-15

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

Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

PubMed

Nakayama, Tetsuo; Onoda, Kazumasa

2007-01-05

General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in several cases suspected of being vaccine adverse events.

The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities

PubMed Central

Frangogiannis, Nikolaos G

2014-01-01

Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, resulting in activation of the Nuclear Factor (NF)-κB system and induction of chemokines, cytokines and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment and resolution of the post-infarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury. PMID:24072174

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

PubMed

Chaves, Marlén

2015-01-01

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

[Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and recurrent respiratory tract infection].

PubMed

Liao, Jia-Yi; Zhang, Tao

2014-05-01

To observe the clinical therapeutic effect of OM-85 BV(OM-85 Broncho-Vaxom) in children with asthma and recurrent respiratory tract infection, and the effect of OM-85 BV on human β-defensins 1 (hBD-1) and immunoglobulin levels. Sixty-two children with asthma and recurrent respiratory infection treated between 2011 January and December were divided into two groups by the randomized, double blind method: a treatment group and a control group. With inhaling corticosteroids, the treatment group was given OM-85 BV, and the control group was given a placebo. Clinical curative effects and adverse reactions were observed. Serum levels of hBD-1, IgA, IgG, IgM and urea and alanine aminotransferase (ALT) were measured before treatment and 6 months and 12 months after treatment. Compared with the control group and before treatment, the frequency of respiratory tract infection was reduced in the treatment group 6 months and 12 months after treatment (P<0.05), and serum levels of hBD-1, IgA and IgG in the treatment group increased significantly (P<0.05). There was no significant difference in serum levels of urea, ALT and IgM between the control and treatment groups (P>0.05). Mild adverse reactions occurred in 3 cases in the two groups, 2 cases of abdominal pain and 1 cases of constipation. OM-85 BV can improve serum levels of hBD-1, IgA and IgG, reduce the occurrence of acute respiratory tract infection and cause mild adverse reactions, suggesting its satisfactory therapeutic effect and safety in the treatment of asthma combined with recurrent respiratory tract infection in children.

The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning.

PubMed

Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

2016-03-01

Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning.Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370.Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)-especially rash (59.74%)-were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae.Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist-370 than with Isovue-370, but this difference is limited only to the mild AARs. The incidence of AARs could be affected by multiple factors.

The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

PubMed Central

Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

2016-01-01

Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist-370 than with Isovue-370, but this difference is limited only to the mild AARs. The incidence of AARs could be affected by multiple factors. PMID:27015204

Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial.

PubMed

Santini, Manuela Favarin; Rosa, Ricardo Abreu da; Ferreira, Maria Beatriz Cardoso; Fischer, Maria Isabel; Souza, Erick Miranda; Só, Marcus Vinícius Reis

2017-01-01

Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P<0.05). In the Tr/Ac group, the scores significantly decreased over time from time point 6 h (P<0.05). Comparing the pain at each time point, the groups were not significantly different (P>0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

Big Five Personality Traits and the General Factor of Personality as Moderators of Stress and Coping Reactions Following an Emergency Alarm on a Swiss University Campus.

PubMed

Hengartner, Michael P; van der Linden, Dimitri; Bohleber, Laura; von Wyl, Agnes

2017-02-01

We conducted an online survey including 306 participants aged 18-64 years to assess the general factor of personality (GFP) and Big Five personality traits in relation to individual stress and coping reactions following a shooting emergency alarm at a Swiss university campus. Although the emergency eventually turned out to be a false alarm, various witnesses showed pronounced distress owing to a vast police operation. The GFP structure was replicated using two alternative modelling approaches. Neuroticism related substantially to acute fear and traumatic distress as well as to more enduring maladaptive coping. Agreeableness was negatively associated with the coping strategy of medication use, whereas both agreeableness and conscientiousness related positively to social activity following the emergency. The GFP related moderately to peri-traumatic distress and showed a substantial negative association with medication use and a strong positive association with social activity. In conclusion, both the GFP and Big Five traits significantly moderate stress responses following a stressful life event. The GFP predominantly relates to socially adaptive coping, whereas in particular neuroticism accounts for acute stress reactions such as fear and traumatic distress. These findings support the notion that personality influences how persons react in the face of adversity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

Unequal Sized Pupils Due to Escitalopram; Adverse Events to Dietary Supplements Causing Emergency Department Visits; Compulsive Masturbation Due to Pramipexole; Metformin-Induced Lactic Acidosis Masquerading As an Acute Myocardial Infarction

PubMed Central

Mancano, Michael A.

2016-01-01

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) Med Watch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Med Watch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's Med Watchprogram and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner. PMID:27303087

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

PubMed

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

2015-12-01

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

The Identification of Seniors at Risk (ISAR) score to predict clinical outcomes and health service costs in older people discharged from UK acute medical units.

PubMed

Edmans, Judi; Bradshaw, Lucy; Gladman, John R F; Franklin, Matthew; Berdunov, Vladislav; Elliott, Rachel; Conroy, Simon P

2013-11-01

tools are required to identify high-risk older people in acute emergency settings so that appropriate services can be directed towards them. to evaluate whether the Identification of Seniors At Risk (ISAR) predicts the clinical outcomes and health and social services costs of older people discharged from acute medical units. an observational cohort study using receiver-operator curve analysis to compare baseline ISAR to an adverse clinical outcome at 90 days (where an adverse outcome was any of death, institutionalisation, hospital readmission, increased dependency in activities of daily living (decrease of 2 or more points on the Barthel ADL Index), reduced mental well-being (increase of 2 or more points on the 12-point General Health Questionnaire) or reduced quality of life (reduction in the EuroQol-5D) and high health and social services costs over 90 days estimated from routine electronic service records. two acute medical units in the East Midlands, UK. a total of 667 patients aged ≥70 discharged from acute medical units. an adverse outcome at 90 days was observed in 76% of participants. The ISAR was poor at predicting adverse outcomes (AUC: 0.60, 95% CI: 0.54-0.65) and fair for health and social care costs (AUC: 0.70, 95% CI: 0.59-0.81). adverse outcomes are common in older people discharged from acute medical units in the UK; the poor predictive ability of the ISAR in older people discharged from acute medical units makes it unsuitable as a sole tool in clinical decision-making.

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

PubMed

Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

2015-06-01

All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2010-01-01

Allergic reactions to insect bites are a global problem, the true incidence and prevalence of morbidity from adverse reactions to mosquito bites are unknown. To describe the adverse reactions to mosquito bites in school-age children of Monterrey, Nuevo Leon. 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. 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. Adverse reactions to mosquito bites occur frequently. Early detection is important to establish a prompt treatment.

[Food allergy or food intolerance?].

PubMed

Maître, S; Maniu, C-M; Buss, G; Maillard, M H; Spertini, F; Ribi, C

2014-04-16

Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.

Acute and long-term management of food allergy: systematic review.

PubMed

de Silva, D; Geromi, M; Panesar, S S; Muraro, A; Werfel, T; Hoffmann-Sommergruber, K; Roberts, G; Cardona, V; Dubois, A E J; Halken, S; Host, A; Poulsen, L K; Van Ree, R; Vlieg-Boerstra, B J; Agache, I; Sheikh, A

2014-02-01

Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts. Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized. Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration. Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Time-extended local rtPA infiltration for acutely thrombosed hemodialysis fistulas.

PubMed

Regus, Susanne; Lang, Werner; Heinz, Marco; Rother, Ulrich; Meyer, Alexander; Almási-Sperling, Veronika; Uder, Michael; Schmid, Axel

2018-01-01

This study describes results of a modified local thrombolysis technique for acutely thrombosed hemodialysis (HD) arteriovenous fistulas (AVF), which is characterized by prolonged recombinant tissue plasminogen activator (rtPA) local exposure times. Contrary to the standard lyse- and- wait (L&W) technique with local reaction times of 20-40 minutes, the modified protocol allows timing of challenging angioplasty maneuvers to the next regular working day. From February 2009 to April 2014, 84 patients on HD presented with 152 acutely thrombosed AVF. They proceeded to local thrombolysis including a single shot infiltration of rtPA, local reaction time up to 40 hours and finally percutaneous stenosis angioplasty. Success rates, major adverse events and need for temporary catheter placements (TCP) were retrospectively analyzed. The local thrombolysis time after single shot infiltration was 18.6 ± 6.2 (range 2-40) hours. Mean rtPA- dosage was 2.7 mg ± 1.2. The overall success rate was 89.5% and the major complication rate was 3.3%, whereas TCP was necessary in 12.5%. The PP/SP at 1, 3, 6, 12, 18, and 24 month were 86% ± 3%/95% ± 2%, 68% ± 4%/92% ± 2%, 43% ± 4%/90% ± 2%, 28% ± 4%/82% ± 3%, 12% ± 3%/82% ± 3%, 7% ± 2%/63% ± 4%, respectively. The modified L&W technique with prolonged local rtPA reaction times is a safe and effective declotting procedure. The need for TCP was not increased and therefore comparable to the standard technique. © 2017 International Society for Hemodialysis.

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

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

Contrast media use in the operating room.

PubMed

Bickham, Peggy; Golembiewski, Julie

2010-04-01

Iodinated contrast media is frequently used in the OR, but often is not well understood by health care providers who are administering it. Although used for diagnosis rather than treatment, contrast media is classified as a drug by the FDA, and has indications, contraindications, adverse effects, drug interactions, disease interactions, and laboratory interference issues related to its use. Iodinated contrast media is classified according to osmolarity and ionicity, and these characteristics contribute to potential for adverse effects and choice of agent. Financial and safety concerns are factors to be considered when selecting an appropriate agent. Adverse effects can range from mild and self-limited to severe and life threatening; potentially the most serious of these are anaphylactoid reactions and contrast-induced acute renal failure. Knowledge of risk factors and preventive strategies is vital, as are issues related to substitution of gadolinium-based contrast, an off-label use. It is important for the perianesthesia nurse to become familiar with these commonly used imaging medications. Copyright 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom.

PubMed

Clark, Richard F; McKinney, Patrick E; Chase, Peter B; Walter, Frank G

2002-06-01

Allergic reactions are the most commonly reported adverse events after administration of antivenoms. Conventional horse serum-based crotalid antivenom used in the United States (Antivenin [Crotalidae] polyvalent) can lead to both immediate and delayed hypersensitivity reactions. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) has recently been approved for use in the United States. Experience from premarketing trials of this product and in the administration of other types of Fab, such as in digoxin poisoning, has demonstrated these fragments to be safe and effective, with a low incidence of sequella; however, allergic reactions can occur when any animal-protein derivatives are administered to human subjects. We report in detail the nature and course of allergic reactions that occurred in 4 patients treated with FabAV. Cases of anaphylaxis, acute urticaria, angioedema, and delayed serum sickness are described. All reactions were easily treated with some combination of antihistamines, epinephrine, and steroids, with prompt resolution of signs and symptoms enabling further dosing of antivenom as required. Several of these cases may have resulted from batches of antivenom contaminated with Fc fragments. The overall incidence of immediate and delayed allergic reactions to this product appears so far to be lower than that reported with conventional whole-immunoglobulin G (IgG) antivenom, but postmarketing surveillance is warranted.

Controlled study of neuroprosthetic functional electrical stimulation in sub-acute post-stroke rehabilitation.

PubMed

Ring, Haim; Rosenthal, Nechama

2005-01-01

Assess the effects of daily neuroprosthetic (NESS Handmaster) functional electrical stimulation in sub-acute stroke. Controlled study, patients clinically stratified to 2 groups; no active finger movement, and partial active finger movements, and then randomized to control and neuroprosthesis groups. Observer blinded evaluations at baseline and completion of the 6-week study. 22 patients with moderate to severe upper limb paresis 3-6 months post-onset. Patients in day hospital rehabilitation, receiving physical and occupational therapy 3 times weekly. The neuroprosthesis group used the device at home. The neuroprosthesis group had significantly greater improvements in spasticity, active range of motion and scores on the functional hand tests (those with partial active motion). Of the few patients with pain and oedema, there was improvement only among those in the neuroprosthesis group. There were no adverse reactions. Supplementing standard outpatient rehabilitation with daily home neuroprosthetic activation improves upper limb outcomes.

Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.

PubMed

Macy, E; Burchette, R J

2002-12-01

Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare. Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures. In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005). Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

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

PubMed

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

2012-08-01

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

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

PubMed

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

2012-10-01

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

Risk factors for acute adverse events during ultrasound-guided central venous cannulation in the emergency department.

PubMed

Theodoro, Daniel; Krauss, Missy; Kollef, Marin; Evanoff, Bradley

2010-10-01

Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. The authors hypothesized that the technique has limitations among certain patients and clinical scenarios. The purpose of this study was to identify characteristics of adverse events surrounding US-guided central venous cannulation (CVC). The authors assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive internal jugular CVC with US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. The patients with catheters were followed until the catheters were removed based on radiographic evidence or hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self-reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome.   Physicians attempted 289 CVCs on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95% confidence interval [CI] = 15.5 to 24.7), the most common being 31 unsuccessful placements (11%, 95% CI = 7.7 to 14.8). Patients with a history of end-stage renal disease (odds ratio [OR] = 3.54, 95% CI = 1.59 to 7.89), and central lines placed by operators with intermediate experience (OR = 2.26, 95% CI = 1.19 to 4.32), were most likely to encounter adverse events. Previously cited predictors such as body mass index (BMI), coagulopathy, and pulmonary hyperinflation were not significant in our final model. Acute adverse events occurred in approximately one-fifth of US-guided internal jugular central line attempts. The study identified both patient (history of end-stage renal disease) and physician (intermediate experience level) factors that are associated with acute adverse events. © 2010 by the Society for Academic Emergency Medicine.

Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes.

PubMed

Lo Re, Vincent; Carbonari, Dena M; Saine, M Elle; Newcomb, Craig W; Roy, Jason A; Liu, Qing; Wu, Qufei; Cardillo, Serena; Haynes, Kevin; Kimmel, Stephen E; Reese, Peter P; Margolis, David J; Apter, Andrea J; Reddy, K Rajender; Hennessy, Sean; Bhullar, Harshvinder; Gallagher, Arlene M; Esposito, Daina B; Strom, Brian L

2017-01-01

To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. Cohort studies using 2009-2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible. There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis. Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings. NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results.

Zika Virus Infection and Differential Diagnosis in A Cohort of HIV-Infected Patients.

PubMed

Calvet, Guilherme Amaral; Brasil, Patricia; Siqueira, Andre Machado; Zogbi, Heruza Einsfeld; de Santis Gonçalves, Bianca; da Silva Santos, Aline; Lupi, Otilia; Valls de Souza, Rogerio; Santos Rodrigues, Cintia Damasceno Dos; da Silveira Bressan, Clarisse; Wakimoto, Mauymi Duarte; de Araújo, Eliane Saraiva; Santos, Ingrid Cardoso Dos; Georg, Ingebourg; Ribeiro Nogueira, Rita Maria; Veloso, Valdilea Gonçalves; Bispo de Filippis, Ana Maria

2018-06-14

BackgroundZika virus (ZIKV) emergence in South America revealed the lack of knowledge regarding clinical manifestations in HIV-infected individuals. We described the clinical characteristics, laboratory manifestations, differential diagnosis, and outcome of ZIKV infection in a large, single-center cohort of HIV-infected patients.MethodsHIV-infected patients aged ≥ 18 years with clinical suspected arboviral disease from an ongoing cohort were followed from February through December 2015. Acute serum samples were tested for ZIKV, DENV, and CHIKV by rRT-PCR, anti-DENV IgM/IgG, and syphilis assays; convalescent samples were tested for anti-DENV IgM/IgG; and urine samples were tested for ZIKV by rRT-PCR. ZIKV disease was defined according to the PAHO guidelines.ResultsOf 101 patients, ZIKV was confirmed in 43 cases and suspected in 34, and another diagnosis was assumed for 24 patients (dengue, secondary/latent syphilis, respiratory infections, human parvovirus B19, adverse drug reaction, musculoskeletal disorders, and acute gastroenteritis). ZIKV-confirmed and suspected patients reported similar signs and symptoms. Pruritic rash was the most common symptom, followed by myalgia, nonpurulent conjunctivitis, arthralgia, prostration, and headache. In the short-term follow-up [median 67.5 days (IQR: 32-104.5)], CD4 cell count (Z = -.831, p = 0.406) and HIV viral load (Z = -.447, p = 0.655) did not change significantly post ZIKV infection. There were no hospitalizations, complications, or deaths.ConclusionsAmong HIV-infected patients with suspected arboviral disease, 42.6% were ZIKV-infected. CD4 cell counts and HIV viral load were not different post ZIKV infection. Differential diagnosis with other diseases and adverse drug reaction should be evaluated.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized 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. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

77 FR 65192 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-25

... Component, data on adverse reactions and incidents associated with blood transfusions are used to provide national estimates of adverse reactions and incidents. The Long-Term Care Facility (LTCF) Component is used.... Laboratory Technologist. 57.304: Hemovigilance Adverse Reaction Medical/Clinical 500 120 10/60 Laboratory...

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms.

PubMed

Barrett, Frederick S; Bradstreet, Matthew P; Leoutsakos, Jeannie-Marie S; Johnson, Matthew W; Griffiths, Roland R

2016-12-01

Acute adverse psychological reactions to classic hallucinogens ("bad trips" or "challenging experiences"), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens. © The Author(s) 2016.

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

PubMed Central

Barrett, Frederick S.; Bradstreet, Matthew P.; Leoutsakos, Jeannie-Marie S.; Johnson, Matthew W.; Griffiths, Roland R.

2017-01-01

Acute adverse psychological reactions to classic hallucinogens (“bad trips”, or “challenging experiences”), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the 5-Dimensional Altered States of Consciousness questionnaire) in an internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire (CEQ). The stand-alone CEQ was then validated in a separate sample. Seven CEQ factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with the difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The CEQ provides a basis for future investigation of predictors and outcomes of challenging experiences with psilocybin, and should be explored as a measure of challenging experiences with the broad class of classic hallucinogens. PMID:27856683

75 FR 30841 - Advisory Commission on Childhood Vaccines; Request for Nominations for Voting Members

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... that result in fewer or no significant adverse reactions; surveying Federal, State, and local programs... childhood vaccines, including the adverse reaction reporting requirements of section 2125(b); advising the... frequency and severity of adverse reactions associated with childhood vaccines; consulting on the...

76 FR 66061 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... and Reporting Requirements for Allegations of Significant Adverse Reactions to Human Health or the... Adverse Reactions to Human Health or the Environment (TSCA Section 8(c))''. ICR numbers: EPA ICR No. 1031... of significant adverse reactions to health or the environment alleged to have been caused by such...

77 FR 42306 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

... Requirements for Allegations of Significant Adverse Reactions to Human Health or the Environment AGENCY... Requirements for Allegations of Significant Adverse Reactions to Human Health or the Environment; EPA ICR No... and Reporting Requirements for Allegations of Significant Adverse Reactions to Human Health or the...

[Suspected adverse reactions after vaccination. Results from the German Health Interview and Examination Survey for Children and Adolescents. Part 2: predictors of parental reporting of suspected adverse reactions after vaccinations].

PubMed

Poethko-Müller, C; Atzpodien, K; Schmitz, R; Schlaud, M

2011-03-01

Each method to monitor vaccine safety has strengths and limitations. Therefore, vaccine safety monitoring should rely on different types of data sources. Methods commonly rely on patient-reported adverse reactions. Little is, however, known about factors that may affect the probability with which patients report adverse reactions to vaccines. From 2003-2006, the representative National Health Interview and Examination Survey for Children and Adolescents ("Kinder- und Jugendgesundheitssurvey", KiGGS) retrospectively collected information about vaccines, vaccination dates, and suspected vaccine related adverse reactions from a total of 17,641 participants (<17 years). Poorly tolerated vaccinations were more likely reported from parents living in former West Germany compared to former East Germany (OR 1.61; 95% CI 1.08-2.39), parents of children with special health care needs (OR 1.49; 95% CI 1.08-2.04), and from parents reporting reservations against vaccinations (OR 3.29; 95% CI 2.28-4.75). Parental reporting of adverse vaccine reactions appears to be associated with parental perception and assessment of possible adverse vaccine reactions, as well as with the parents' attitude towards immunization in general.

BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis.

PubMed

Ismail, Eman Abdel Rahman; Mahmoud, Hanan Mohamed; Tawfik, Lamis Mohamed; Habashy, Deena Mohamed; Adly, Amira Abdel Moneam; El-Sherif, Nayera Hazaa; Abdelwahab, Mahmoud Ahmed

2012-02-01

Although BIRC6/Apollon seems to play a critical role as an antiapoptotic regulator, its clinical relevance in acute leukemia remains largely elusive. Therefore, we aimed to investigate BIRC6 gene expression in childhood acute leukemia in relation to clinicopathological characteristics at presentation, therapeutic response, and prognosis. BIRC6 expression level was assessed in 75 children with acute leukemia; 30 patients with acute myeloblastic leukemia (AML) and 45 patients with acute lymphoblastic leukemia (ALL) using real-time quantitative reverse transcriptase-polymerase chain reaction. The median level of BIRC6 expression did not differ significantly between AML and ALL patients. BIRC6 expression level was higher in patients with AML and ALL with extramedullary involvement, white blood cell (WBC) count ≥ 10 × 10(9) /L, and unfavorable cytogenetics at diagnosis. BIRC6 gene expression was higher in patients with unfavorable response to therapy at day 14, those who developed relapse or died in both leukemic groups. The best cutoff value of BIRC6 to predict therapeutic response and disease outcome was determined. AML and ALL patients with BIRC6 overexpression had significantly shorter overall and disease free survivals. This is the first report to study BIRC6 gene in pediatric ALL. Our results suggested that BIRC6 gene expression could be considered as an adverse risk factor in childhood acute leukemia and, hence, could be used to guide therapeutic regimens. © 2012 John Wiley & Sons A/S.

[Comparative study on four kinds of assessment methods of post-marketing safety of Danhong injection].

PubMed

Li, Xuelin; Tang, Jinfa; Meng, Fei; Li, Chunxiao; Xie, Yanming

2011-10-01

To study the adverse reaction of Danhong injection with four kinds of methods, central monitoring method, chart review method, literature study method and spontaneous reporting method, and to compare the differences between them, explore an appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection. Set down the adverse reactions' questionnaire of four kinds of methods, central monitoring method, chart review method, literature study method and collect the information on adverse reactions in a certain period. Danhong injection adverse reaction information from Henan Province spontaneous reporting system was collected with spontaneous reporting method. Carry on data summary and descriptive analysis. Study the adverse reaction of Danhong injection with four methods of central monitoring method, chart review method, literature study method and spontaneous reporting method, the rates of adverse events were 0.993%, 0.336%, 0.515%, 0.067%, respectively. Cyanosis, arrhythmia, hypotension, sweating, erythema, hemorrhage dermatitis, rash, irritability, bleeding gums, toothache, tinnitus, asthma, elevated aminotransferases, constipation, pain are new discovered adverse reactions. The central monitoring method is the appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection, which could objectively reflect the real world of clinical usage.

Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

PubMed

Kalaiselvan, Vivekanandan; Sharma, Surbhi; Singh, Gyanendra Nath

2014-09-01

Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

Adverse Reactions in Allogeneic Blood Donors: A Tertiary Care Experience from a Developing Country.

PubMed

Sultan, Sadia; Baig, Mohammad Amjad; Irfan, Syed Mohammed; Ahmed, Syed Ijlal; Hasan, Syeda Faiza

2016-03-01

Fragmented blood transfusion services along with an unmotivated blood donation culture often leads to blood shortage. Donor retention is crucial to meet the increasing blood demand, and adverse donor reactions have a negative impact on donor return. The aim of this study was to estimate adverse donor reactions and identify any demographic association.  . We conducted a prospective study between January 2011 and December 2013. A total of 41,759 healthy donors were enrolled. Professionally trained donor attendants drew blood and all donors were observed during and following donation for possible adverse events for 20 minutes. Blood donors were asked to report if they suffered from any delayed adverse consequences.  . Out of 41,759 blood donors, 537 (1.3%) experienced adverse reactions. The incidence was one in every 78 donations. The mean age of donors who experienced adverse events was 26.0±6.8 years, and all were male. Out of 537 donors, 429 (80%) developed vasovagal reaction (VVR), 133 (25%) had nausea, 63 (12%) fainted, 35 (6%) developed hyperventilation, 9 (2%) had delayed syncope, and 9 (2%) developed hematoma. Arterial prick, nerve injury, cardiac arrest, and seizures were not observed. Donors aged less than < 30 years and weighing < 70 kg were significantly associated with VVR, hyperventilation, and nausea (p < 0.005). Undergraduates and Urdu speaking donors also had a significant association with fainting and nausea, respectively (p < 0.05).  . The prevalence of adverse events was low at our tertiary center. A VVR was the predominant adverse reaction and was associated with age and weight. Our study highlights the importance of these parameters in the donation process. A well-trained and experienced phlebotomist and pre-evaluation counseling of blood donors could further minimize the adverse reactions.

Predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical Rockall Score.

PubMed

Tham, T C K; James, C; Kelly, M

2006-11-01

The Rockall risk scoring system uses clinical criteria and endoscopy to identify patients at risk of adverse outcomes after acute upper gastrointestinal haemorrhage. A clinical Rockall score obtained using only the clinical criteria may be able to predict outcome without endoscopy. To validate the clinical Rockall Score in predicting outcome after acute non-variceal upper gastrointestinal haemorrhage. A retrospective observational study of consecutive patients who were admitted with non-variceal acute upper gastrointestinal haemorrhage was undertaken. Medical records were abstracted using a standardised form. 102 cases were identified (51 men and 51 women; mean age 59 years). 38 (37%) patients considered to be at low risk of adverse outcomes (clinical Rockall Score 0) had no adverse outcomes and did not require transfusion. Patients with a clinical Rockall Score of 1-3 had no adverse outcomes, although 13 of 45 (29%) patients required blood transfusions. Clinical Rockall Scores >3 (n = 19) were associated with adverse outcomes (rebleeding in 4 (21%), surgery in 1 (5%) and death in 2 (10%)). The clinical Rockall Score without endoscopy may be a useful prognostic indicator in this cohort of patients with acute non-variceal upper gastrointestinal haemorrhage. This score may reduce the need for urgent endoscopy in low-risk patients, which can instead be carried out on a more elective outpatient basis.

[Irrational use of drugs as a source of drug - induced diseases].

PubMed

Woroń, Jarosław; Porebski, Grzegorz; Kostka-Trabka, Elzbieta; Goszcz, Aleksandra

2007-01-01

The irrational use of medication, by which we understand the administration of drugs for indications where their effectiveness has not been confirmed, the disregard of restrictions and warnings against their use, and the use of drug combinations which do not increase the therapeutic effect but to the contrary increase the risk of adverse drug reactions, is a serious problem encountered in paediatric pharmacotherapy. Each year the centres for monitoring of adverse drug reactions receive many reports, the analysis of which show that the reasons of occurrence of adverse drug reactions after drug administration, are specifically due to irrational use of medications. In order to prevent in an active way the occurrence, of adverse drug reactions following drug administration it is worthwhile to bring to attention the reasons for their occurrence which not infrequently bring about pathological effects. Our work which is based on reports received by the Regional Centre for Adverse Drug Reactions Monitoring in Krakow concerning the occurrence of adverse drug reactions in an attempt to bring to attention in our view important problems in current pharmacotherapy.

Application and assessment of Chinese arsenic drugs in treating malignant hematopathy in China.

PubMed

Hu, Xiao-mei; Liu, Feng; Ma, Rou

2010-08-01

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder and Realgar-Indigo naturalis formula, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continually elucidated.

Childhood lymphoblastic leukemia adverse drug reactions: study of risk factors and therapy prognosis by optical methods

NASA Astrophysics Data System (ADS)

Zyubin, A.; Lavrova, A.; Babak, S.; Malaschenko, V.; Borisova, A.; Opryshko, N.

2016-10-01

The treatment of acute lymphoblastic leukemia (ALL) can result in the side-effects such as kidney affection, hepatic failure and tissue hypoxia. We study dynamics of special biochemical marker of these pathologies - adenosine triphosphate, that is well-known substance of energy metabolism. We use methods of confocal microscopy for determining the cellular and mitochondrial concentration of adenosine triphosphate (ATP). Quantitative values of adenosine triphosphate were calculated for each patient and correlation with degree of side-effects had been done. The application of confocal microscopy for studying of side-effects and therapy of lymphoblastic leukemia is discussed.

Adverse drug reactions induced by valproic acid.

PubMed

Nanau, Radu M; Neuman, Manuela G

2013-10-01

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

Global Aesthetics Consensus: Avoidance and Management of Complications from Hyaluronic Acid Fillers—Evidence- and Opinion-Based Review and Consensus Recommendations

PubMed Central

Liew, Steven; Sundaram, Hema; De Boulle, Koenraad L.; Goodman, Greg J.; Monheit, Gary; Wu, Yan; Trindade de Almeida, Ada R.; Swift, Arthur; Vieira Braz, André

2016-01-01

Background: Although the safety profile of hyaluronic acid fillers is favorable, adverse reactions can occur. Clinicians and patients can benefit from ongoing guidance on adverse reactions to hyaluronic acid fillers and their management. Methods: A multinational, multidisciplinary group of experts in cosmetic medicine convened the Global Aesthetics Consensus Group to review the properties and clinical uses of Hylacross and Vycross hyaluronic acid products and develop updated consensus recommendations for early and late complications associated with hyaluronic acid fillers. Results: The consensus panel provided specific recommendations focusing on early and late complications of hyaluronic acid fillers and their management. The impact of patient-, product-, and technique-related factors on such reactions was described. Most of these were noted to be mild and transient. Serious adverse events are rare. Early adverse reactions to hyaluronic acid fillers include vascular infarction and compromise; inflammatory reactions; injection-related events; and inappropriate placement of filler material. Among late reactions are nodules, granulomas, and skin discoloration. Most adverse events can be avoided with proper planning and technique. Detailed understanding of facial anatomy, proper patient and product selection, and appropriate technique can further reduce the risks. Should adverse reactions occur, the clinician must be prepared and have tools available for effective treatment. Conclusions: Adverse reactions with hyaluronic acid fillers are uncommon. Clinicians should take steps to further reduce the risk and be prepared to treat any complications that arise. PMID:27219265

Acute effects of alemtuzumab infusion in patients with active relapsing-remitting MS

PubMed Central

Thomas, Katja; Eisele, Judith; Rodriguez-Leal, Francisco Alejandro; Hainke, Undine

2016-01-01

Objective: Alemtuzumab exerts its clinical efficacy by its specific pattern of depletion and repopulation of different immune cells. Beyond long-term immunologic and clinical data, little is known about acute changes in immunologic and routine laboratory parameters and their clinical relevance during the initial alemtuzumab infusion. Methods: Fifteen patients with highly active MS were recruited. In addition to parameters including heart rate, blood pressure, body temperature, and monitoring of adverse events, complete blood cell count, liver enzymes, kidney function, acute-phase proteins, serum cytokine profile, complement activation, peripheral immune cell distribution, and their potential of cytokine release were investigated prior to and after methylprednisolone and after alemtuzumab on each day of alemtuzumab infusion. Results: After the first alemtuzumab infusion, both the total leukocyte and granulocyte counts markedly increased, whereas lymphocyte counts dramatically decreased. In addition to lymphocyte depletion, cell subtypes important for innate immunity also decreased within the first week after alemtuzumab infusion. Although patients reported feeling well, C-reactive protein and procalcitonin peaked at serum levels consistent with septic conditions. Increases in liver enzymes were detected, although kidney function remained stable. Proinflammatory serum cytokine levels clearly rose after the first alemtuzumab infusion. Alemtuzumab led to impaired cytokine release ex vivo in nondepleted cells. Normal clinical parameters and mild adverse events were presented. Conclusions: Dramatic immunologic effects were observed. Standardized infusion procedure and pretreatment management attenuated infusion-related reactions. Alemtuzumab-mediated effects led to artificially altered parameters in standard blood testing. We recommend clinical decision-making based on primarily clinical symptoms within the first alemtuzumab treatment week. PMID:27213173

An Open Label, Randomized, Comparative, Parallel Group, Multicenter, Prospective, Interventional, Clinical Study to Evaluate Efficacy and Safety of "AHPL/AYTOP/0113" in Comparison with "Framycetin Sulphate Cream" in Acute Wounds.

PubMed

Nipanikar, Sanjay U; Gajare, Kamalakar V; Vaidya, Vidyadhar G; Kamthe, Amol B; Upasani, Sachin A; Kumbhar, Vidyadhar S

2017-01-01

The main objective of the present study was to assess efficacy and safety of AHPL/AYTOP/0113 cream, a polyherbal formulation in comparison with Framycetin sulphate cream in acute wounds. It was an open label, randomized, comparative, parallel group and multi-center clinical study. Total 47 subjects were randomly assigned to Group-A (AHPL/AYTOP/0113 cream) and 42 subjects were randomly assigned to Group-B (Framycetin sulphate cream). All the subjects were advised to apply study drug, thrice daily for 21 days or up to complete wound healing (whichever was earlier). All the subjects were called for follow up on days 2, 4, 7, 10, 14, 17 and 21 or up to the day of complete wound healing. Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. Group-A subjects took significantly less ( P < 0.05) i.e., (mean) 7.77 days than (mean) 9.87 days of Group-B subjects for wound healing. At the end of the study, statistically significant better ( P < 0.05) results were observed in Group-A than Group-B in mean wound surface area, wound healing parameters and pain associated with wound. Excellent overall efficacy and tolerability was observed in subjects of both the groups. No adverse event or adverse drug reaction was noted in any subject of both the groups. AHPL/AYTOP/0113 cream proved to be superior to Framycetin sulphate cream in healing of acute wounds.

[Evaluation of reporting quality of RCT on nephrotoxicity of Tripterygium wilfordii preparations according to CONSORT HARMs statement].

PubMed

Feng, Xue; Fang, Sai-Nan; Gao, Yu-Xin; Liu, Jian-Ping; Chen, Wei

2018-02-01

To evaluate the quality of randomized controlled trials(RCT) on nephrotoxicity of Tripterygium wilfordii preparations according to the CONSORT HARMs statement. The report quality of each included study was evaluated according to the CONSORT HARMs statement， and the number of entries that comply with CONSORT HARMs statement was calculated in each study to evaluate the report quality on nephrotoxicity-related adverse reactions of T. wilfordii preparations and summarize the problems in domestic studies on nephrotoxicity-related adverse reactions. A total of 16 RCTs were included， with an average of 7 entries complying with CONSORT HARMs statement per study. The report of the nephrotoxic-associated RCT of T. wilfordii preparations was of poor quality and the most non-repeating entries included the following ones： using validated tools to report adverse effects， standards for coding of the adverse reactions， describing how and when to collect data on adverse reactions in Method， describing how adverse reactions are attributed to T. wilfordii， clearly stating who has reported the adverse reactions， describing the analysis method of adverse reactions， describing the method of collecting recurrent adverse reaction data， describing any subgroup analysis and exploratory analysis associated with the hazard. We suggest that the studies on adverse reactions of traditional Chinese medicine should strictly report the entries according to the CONSORT HARMs statement， and take the characteristics of traditional Chinese medicine into account to report the details of the Chinese medicine like compositions， dose， taking time， combined medication and the dialectical typology of research objects. Copyright© by the Chinese Pharmaceutical Association.

Safety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Jawad, M.; Schoop, R.; Suter, A.; Klein, P.; Eccles, R.

2012-01-01

Objective. To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods. 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results. A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions). Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (P < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions. Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio. PMID:23024696

Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a patient with butane inhalation lung injury.

PubMed

Lee, Min-Young; Park, Kyong Ah; Yeo, So-Jeong; Kim, Shin-Hee; Goong, Hyeun-Jeong; Jang, An-Soo; Park, Choon-Sik

2011-10-01

Allergic reactions to local anesthetics are very rare and represent <1% of all adverse local anesthetics reactions. A 54-year-old man was admitted to the hospital in the winter because of shortness of breath. The patient reportedly had an inhalation lung injury due to butane gas fuel. On the fifth day, he developed an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol administration to prepare for bronchoscopy to confirm an acute inhalational lung injury diagnosis. Cardiopulmonary resuscitation was performed immediately after respiratory arrest, and the patient was admitted to the intensive care unit intubated and on a ventilator. He was extubated safely on the third post-cardiopulmonary resuscitation day. These observations suggest that aerosol lidocaine anesthesia may cause airway narrowing and anaphylactic shock. Practitioners should be aware of this potential complication. We report on this case with a brief review of the literature.

Tracking Silent Hypersensitivity Reactions to Asparaginase during Leukemia Therapy Using Single-Chip Indirect Plasmonic and Fluorescence Immunosensing.

PubMed

Charbonneau, David M; Breault-Turcot, Julien; Sinnett, Daniel; Krajinovic, Maja; Leclerc, Jean-Marie; Masson, Jean-François; Pelletier, Joelle N

2017-12-22

Microbial asparaginase is an essential component of chemotherapy for the treatment of childhood acute lymphoblastic leukemia (cALL). Silent hypersensitivity reactions to this microbial enzyme need to be monitored accurately during treatment to avoid adverse effects of the drug and its silent inactivation. Here, we present a dual-response anti-asparaginase sensor that combines indirect SPR and fluorescence on a single chip to perform ELISA-type immunosensing, and correlate measurements with classical ELISA. Analysis of serum samples from children undergoing cALL therapy revealed a clear correlation between single-chip indirect SPR/fluorescence immunosensing and ELISA used in clinical settings (R 2 > 0.9). We also report that the portable SPR/fluorescence system had a better sensitivity than classical ELISA to detect antibodies in clinical samples with low antigenicity. This work demonstrates the reliability of dual sensing for monitoring clinically relevant antibody titers in clinical serum samples.

Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.

PubMed

Matthews, Eric P

2015-01-01

Although the advent of nonionic low-osmolar contrast agents has reduced the probability of a reaction to radiopaque contrast media derived from tri-iodinated benzoic acid, reactions still occur. Radiologic technologists must understand and know how to manage adverse effects of contrast media. Prompt attention to patients who exhibit the early signs of an adverse reaction can help to ensure the reaction does not progress to become severe or life-threatening.

Infusion of a non-HLA-matched ex-vivo expanded cord blood progenitor cell product after intensive acute myeloid leukaemia chemotherapy: a phase 1 trial.

PubMed

Delaney, Colleen; Milano, Filippo; Cicconi, Laura; Othus, Megan; Becker, Pamela S; Sandhu, Vicky; Nicoud, Ian; Dahlberg, Ann; Bernstein, Irwin D; Appelbaum, Frederick R; Estey, Elihu H

2016-07-01

The intensive chemotherapy regimens used to treat acute myeloid leukaemia routinely result in serious infections, largely due to prolonged neutropenia. We investigated the use of non-HLA-matched ex-vivo expanded cord blood progenitor cells to accelerate haemopoietic recovery and reduce infections after chemotherapy. We enrolled patients with a diagnosis of acute myeloid leukaemia by WHO criteria and aged 18-70 years inclusive at our institution (Fred Hutchinson Cancer Research Center) into this phase 1 trial. The primary endpoint of the study was safety of infusion of non-HLA-matched expanded cord blood progenitor cells after administration of clofarabine, cytarabine, and granulocyte-colony stimulating factor priming. The protocol is closed to accrual and analysis was performed per protocol. The trial is registered with ClinicalTrials.gov, NCT01031368. Between June 29, 2010, and June 26, 2012, 29 patients with acute myeloid leukaemia (19 newly diagnosed, ten relapsed or refractory) were enrolled. The most common adverse events were fever (27 [93%] of 29 patients) and infections (25 [86%] of 29 patients). We observed one case of acute infusional toxicity (attributed to an allergic reaction to dimethyl sulfoxide) in the 29 patients enrolled, who received 42 infusions of expanded progenitor cells. The following additional serious but expected adverse events were observed (each in one patient): grade 4 atrial fibrillation, grade 4 febrile neutropenia, lung infection with grade 4 absolute neutrophil count, colon infection with grade 4 absolute neutrophil count, grade 4 changed mental status, and one death from liver failure. No unexpected toxicity or graft-versus-host disease was observed. There was no evidence of in-vivo persistence of the expanded progenitor cell product in any patient beyond 14 days or induced alloimmunisation. Infusion of the expanded progenitor cell product seemed safe and might provide a promising treatment method for patients with acute myeloid leukaemia. Biomedical Advanced Research and Development Authority in the US Department of Health and Human Services and Genzyme (Sanofi). Copyright © 2016 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Frequency and risk factors for donor reactions in an anonymous blood donor survey.

PubMed

Goldman, Mindy; Osmond, Lori; Yi, Qi-Long; Cameron-Choi, Keltie; O'Brien, Sheila F

2013-09-01

Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors. We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions. The response rate was 45.5%. A total of 32% of first-time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first-time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first-time donors with reactions found adverse effects information inadequate. This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management. © 2012 American Association of Blood Banks.

Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India

PubMed Central

Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N

2017-01-01

Background: Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. Objective: The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. Materials and Methods: An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Results: Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Conclusion: Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction. PMID:28584372

Susoctocog Alfa: A Review in Acquired Haemophilia A.

PubMed

Burness, Celeste B; Scott, Lesley J

2016-05-01

Intravenous susoctocog alfa (Obizur(®)) is a recombinant, B-domain deleted, porcine sequence antihaemophilic factor VIII (FVIII) product that has recently been approved for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). Intravenous susoctocog alfa was an effective and generally well tolerated treatment for serious bleeding episodes in adult patients with AHA in a multinational, phase II/III trial (n = 28 evaluable). Patients received an initial dose of susoctocog alfa 200 U/kg, with subsequent dosages based on target FVIII trough levels and clinical assessments. All patients had a positive haemostatic response (based on predefined criteria) of the primary bleed 24 h after the first infusion of susoctocog alfa, with the bleed successfully controlled at the time of final dosing in 86 % of patients. The most frequently reported adverse reaction (incidence >5 %) was the development of inhibitory antibodies against susoctocog alfa (porcine FVIII). Overall, 25 % of antibody naive patients developed anti-susoctocog alfa antibodies during the study. No serious treatment-related adverse events, thrombotic events or allergic reactions were reported during the trial. In conclusion, intravenous susoctocog alfa is a useful addition to the limited treatment options available for the management of acute bleeding episodes in adults with AHA.

Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013.

PubMed

Alniemi, Dema T; Wetter, David A; Bridges, Alina G; El-Azhary, Rokea A; Davis, Mark D P; Camilleri, Michael J; McEvoy, Marian T

2017-04-01

Acute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center. A retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted. Of 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty-four patients (86%) had a personal history of drug reactions before the development of AGEP. A previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new-onset non-AGEP skin eruptions within a few months of the resolution of AGEP. © 2017 The International Society of Dermatology.

Adverse reactions to skin prick testing in children - prevalence and possible risk factors.

PubMed

Norrman, Gunilla; Fälth-Magnusson, Karin

2009-05-01

Skin prick test (SPT) is usually considered to be a safe procedure, but recently there have been occasional case reports of generalized allergic reactions. This study was performed to delineate the prevalence of, and evaluate possible risk factors for, adverse reactions to SPT in a prospective study. Altogether 5,908 patients aged < or =18 yr from 11 different pediatric settings were included. The adverse reactions were classified into two groups: (1) Generalized allergic reactions (GAR), (2) Vasovagal reactions (VVR). Adverse reactions were observed in 14 out of 5,908 children examined with SPT. Seven of the adverse reactions were GARs and required medication, yielding a 0.12% risk for GAR. Seven of 14 were VVRs, giving the same risk, 0.12%. Identified risk factors for GAR were low age (<1 yr) (RR 6.28) and active eczema (RR 16.98). For VVR, the risk factors were female sex (RR 7.32) and multiple skin pricks performed on a single patient (p < 0.05). We conclude that GARs do occur, albeit rarely, so the need for proper emergency handling should always be acknowledged. The risk factors suggested may help to identify patients who need extra attention.

Patient preferences for medicine administration for acute agitation: results from an internet-based survey of patients diagnosed with bipolar disorder or schizophrenia in two Nordic countries.

PubMed

Jørgensen, Tine Rikke; Emborg, Charlotte; Dahlen, Karianne; Bøgelund, Mette; Carlborg, Andreas

2018-01-01

The objective was to elicit patient preferences for medicine administration method in the management of acute agitation episodes among patients diagnosed with bipolar disorder or schizophrenia. The patients' experiences of acute agitation episodes and their management of episodes were also explored. Data were collected via an anonymous, internet-based survey of residents in Denmark or Sweden with schizophrenia or bipolar disorder (October 2014 to December 2014). Inclusion criteria were having a diagnosis of schizophrenia or bipolar disorder, and being above 18 years of age. The questionnaire included questions about preferences for medication attributes, experiences with pharmacological treatment for agitation and involvement in treatment plans. A total of 237 diagnosed patients (61 with schizophrenia; 176 with bipolar disorder) completed the questionnaire. Agitation episodes were experienced by 90% of the respondents. In total, 83% of the respondents reported having received treatment with tablets. When patients were presented with the attributes of an inhalation method, respondents stated that the fast onset of action, low risk of adverse reactions and least invasive form of drug delivery were positive attributes of treatment with inhalation. Inhalation is a new delivery route for treatment of acute agitation in patients diagnosed with bipolar disorder or schizophrenia. Inhalation is the preferred treatment method for acute agitation among Danish and Swedish patients with bipolar disorder or schizophrenia.

Adverse reactions of trivalent influenza vaccine in HIV-infected individuals.

PubMed

Hajiabdolbaghi, Mahboube; Jam, Sara; SeyedAlinaghi, SeyedAhmad; Jafari, Sirous; Badie, Banafshe Moradmand; Sabzvari, Duman

2010-01-01

In this study, we assessed the adverse reactions to influenza vaccination in HIV-infected individuals. From November 2006 to January 2007, a total of 203 HIV-infected persons were recruited. Demographic data were collected. Subjects were evaluated 48 h and 15 days after vaccination for symptoms and significant health events as possible side effects. Participants were instructed to measure their temperature in the morning and evening for 2 days post-immunization and to assess injection site and systemic adverse reactions. 80.3% of the subjects were male. The mean age of the subjects was 36.9 +/- 7.9 years. Local and systemic reactions were reported by 61 (30%) and 62 (30.5%) persons, respectively. The most common adverse reactions to the influenza vaccine included skin redness (37 cases), induration (32 cases), and pain (55 cases) as local reactions, and fever (22 cases), myalgia (46 cases), headache (12 cases) and weakness (35 cases) as general reactions. 1.4 % of the subjects had fever over 38.5 degrees C. There were significant associations between myalgia and flushing with CD4 counts (P<0.05). We found no relationship between adverse reactions and sex, history of smoking, allergy, alcohol, and drug usage, stage of HIV infection, anti-retroviral therapies, anti-TB medication and previous vaccination. We concluded that inactivated influenza vaccine administered in HIV-infected adults did not result in potential adverse events in this study population.

Patient knowledge on reporting adverse drug reactions in Poland

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

PubMed

Valgimigli, Marco; Frigoli, Enrico; Leonardi, Sergio; Rothenbühler, Martina; Gagnor, Andrea; Calabrò, Paolo; Garducci, Stefano; Rubartelli, Paolo; Briguori, Carlo; Andò, Giuseppe; Repetto, Alessandra; Limbruno, Ugo; Garbo, Roberto; Sganzerla, Paolo; Russo, Filippo; Lupi, Alessandro; Cortese, Bernardo; Ausiello, Arturo; Ierna, Salvatore; Esposito, Giovanni; Presbitero, Patrizia; Santarelli, Andrea; Sardella, Gennaro; Varbella, Ferdinando; Tresoldi, Simone; de Cesare, Nicoletta; Rigattieri, Stefano; Zingarelli, Antonio; Tosi, Paolo; van 't Hof, Arnoud; Boccuzzi, Giacomo; Omerovic, Elmir; Sabaté, Manel; Heg, Dik; Jüni, Peter; Vranckx, Pascal

2015-09-10

Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Acute Generalized Erythrodermic Pustular Psoriasis Associated with Bupropion/Naltrexone (Contrave®).

PubMed

Singh, Priyanka A; Cassel, Kerry P; Moscati, Ronald M; Eckersley, David

2017-04-01

We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (Contrave®; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of psoriasis. A 55-year-old woman was transferred to our tertiary medical center from a community hospital for possible Stevens-Johnson syndrome 3 weeks after initiation of bupropion/naltrexone. The patient was admitted to the burn unit for wound treatment and hydration. She received intravenous cyclosporine during the admission that resulted in acute kidney injury and the therapy was discontinued. The skin biopsy ruled out Stevens-Johnson syndrome and was more consistent with generalized pustular psoriasis. After discharge, the patient followed up with her dermatologist. She was diagnosed with acute generalized and erythrodermic psoriasis and the patient was restarted on cyclosporine 100 mg twice a day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Few case reports of bupropion-induced generalized pustular psoriasis and erythrodermic psoriasis in patients with a history of psoriasis have been reported. To our knowledge, acute generalized erythrodermic pustular psoriasis associated with bupropion/naltrexone has not been reported in a patient without history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care providers should be aware of this possible severe adverse reaction. Published by Elsevier Inc.

Transfusion of Packed Red Blood Cells--The Indications Have Changed.

PubMed

Cook, Alan; Miller, Nate

2015-12-01

Whole blood/packed red blood cells (pRBC) units transfused in the U.S. totaled 13,785,000 in 2011. A single institution in South Dakota transfused 6,485 units of pRBC in 2013. Current thresholds for transfusion have changed and each transfusion has the risk of causing an adverse reaction; thus, it is important to ensure pRBCs are administered appropriately. Due to these changes and the potential risks associated with transfusion, we reviewed the literature regarding appropriate indications for transfusion of pRBC. Our review specifically focused on four disease entities: iron-deficiency anemia, acute upper gastrointestinal (GI) bleeding, acute coronary syndromes, and chronic ischemic heart disease. Based on our findings, we recommend utilizing an overall conservative approach to the transfusion of pRBC. In patients with iron-deficiency anemia, first try alternative methods to improve hemoglobin levels; in those with acute GI bleeding, transfuse for hemoglobin less than 7 g/dL; in patients with acute coronary syndromes, let symptoms/signs be your guide; and in patients with ischemic heart disease, transfuse for hemoglobin levels less than 8 g/dL or if they are symptomatic. Most importantly, be cautious to not fixate on numbers alone; always incorporate patients' symptoms and co-morbidities when considering whether to transfuse pRBCs.

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

PubMed

Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

2016-01-01

Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.

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

PubMed Central

Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

2016-01-01

Background Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. Methods and Findings We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Conclusions Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase. PMID:27119382

Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR).

PubMed

Sidoroff, A; Dunant, A; Viboud, C; Halevy, S; Bavinck, J N Bouwes; Naldi, L; Mockenhaupt, M; Fagot, J-P; Roujeau, J-C

2007-11-01

Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. To evaluate the risk for different drugs of causing AGEP. A multinational case-control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10-infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis.

Blood transfusion risks and alternative strategies in pediatric patients.

PubMed

Lavoie, Josée

2011-01-01

Although the safety of the blood supply has been greatly improved, there still remain both infectious and noninfectious risks to the patient. The incidence of noninfectious transfusion reactions is greater than that of infectious complications. Furthermore, the mortality associated with noninfectious risks is significantly higher. In fact, noninfectious risks account for 87-100% of fatal complications of transfusions. It is concerning to note that the majority of pediatric reports relate to human error such as overtransfusion and lack of knowledge of special requirements in the neonatal age group. The second most frequent category is acute transfusion reactions, majority of which are allergic in nature. It is estimated that the incidence of adverse outcome is 18:100,000 red blood cells issued for children aged less than 18 years and 37:100,000 for infants. The comparable adult incidence is 13:100,000. In order to decrease the risks associated with transfusion of blood products, various blood-conservation strategies can be utilized. Modalities such as acute normovolemic hemodilution, hypervolemic hemodilution, deliberate hypotension, antifibrinolytics, intraoperative blood salvage, and autologous blood donation are discussed and the pediatric literature is reviewed. A discussion of transfusion triggers, and algorithms as well as current research into alternatives to blood transfusions concludes this review. © 2010 Blackwell Publishing Ltd.

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

[Safety evaluation and risk control measures of Cassiae Semen].

PubMed

Zhao, Yi-Meng; Wu, Li; Zhang, Shuo; Zhang, Li; Gao, Xue-Min; Sun, Xiao-Bo; Wang, Chun

2017-11-01

In this study, the authors reviewed domestic and foreign literatures, conducted the textual research on origin and development of Cassia Semen, studied records in ancient books and ancient and modern literatures, clinical adverse reactions and relevant experimental studies in recent years, and summarized the clinical features and influencing factors related to the safety of Cassiae Semen. According to the findings,Cassia Semen's safety risks are mainly liver and kidney system damages, with the main clinical features of fatigue, anorexia, disgusting of oil, yellow urine and gray stool; digestive system injury, with the main clinical features of diarrhea, abdominal distension, nausea and loose stool; reproductive system damage, with the main clinical features of vaginal bleeding. Allergic reactions and clinical adverse events, with the main clinical features for numb mouth, itching skin, nausea and vomiting, diarrhea, wheezing and lip cyanosis were also reported. The toxicological studies on toxic components of Cassiae Semen obtusifolia were carried out through acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. Risk factors might include patients, compatibility and physicians. Physicians should strictly abide by the medication requirements in the Pharmacopoeia, pay attention to rational compatibility, appropriate dosage,correct usage and appropriate processing, control the dosage below 15 g to avoid excessive intake, strictly control the course of treatment to avoid accumulated poisoning caused by long-term administration. At the same time, clinicians should pay attention to the latest research progress, update the knowledge structure, quickly find the latest and useful materials from clinical practice, scientific research and drug information and other literatures, make evaluation and judgment for the materials, establish a traditional Chinese medicine intelligence information library, and strengthen the control over adverse effects with a pre-warning consciousness. The authors suggested standardizing clinical medication of Cassiae Semen, and avoiding misuse or excessive use; clinicians should prescribe it in strict accordance with there commended usage and dosage in the Pharmacopoeia, and focus on the safety signal accumulation in clinic, while strengthening studies for toxic substance basis and toxicity mechanism, in order to give full play to Cassiae Semen's clinical efficacy and reduce its adverse reactions. Copyright© by the Chinese Pharmaceutical Association.

An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

PubMed

Thong, C L; Lambros, M; Stewart, M G; Kam, P C A

2005-08-01

Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed.

All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis.

PubMed

Ogura, Takashi; Azuma, Arata; Inoue, Yoshikazu; Taniguchi, Hiroyuki; Chida, Kingo; Bando, Masashi; Niimi, Yuka; Kakutani, Shinichi; Suga, Moritaka; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-09-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting. We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data. Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months. This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Safety of infliximab in Crohn's disease: a large single-center experience.

PubMed

Hamzaoglu, H; Cooper, J; Alsahli, M; Falchuk, K R; Peppercorn, M A; Farrell, R J

2010-12-01

The aim of this study was to evaluate the short- and long-term safety experience of infliximab treatment in patients with Crohn's disease (CD) in clinical practice. The medical records of 297 consecutive patients with CD treated with infliximab at the Beth Israel Deaconess Medical Center were reviewed for demographic features and adverse events. The 297 patients received a total of 1794 infusions. Patients received a median of four infusions and had a median follow-up of 14.3 months. Forty-four patients (15%) experienced a serious adverse event, requiring the infusion to be stopped in 33 patients (11%). Acute infusion reactions occurred in 18 patients (6%) including respiratory problems in 10 patients (3%) and an anaphylactoid reaction in 1 patient (0.3%). Serum sickness-like disease occurred in one patient (0.3%) and three patients (1%) developed drug-induced lupus. One patient developed a probable new demyelination disorder. Eight patients (2.7%), all of whom were on concurrent immunosuppressants, developed a serious infection, one resulting in fatal sepsis. Six patients (2%) developed malignancies including two lymphomas and two skin cancers. A total of four (1.3%) deaths were observed (median age 72.5 years); two due to gastrointestinal bleeding, one due to sepsis, and one due to malignancy. While short- and long-term infliximab therapy was generally well tolerated, serious adverse events occurred in 15% of patients including drug-induced lupus, fatal sepsis, and malignancy. Concomitant immunosuppressants were significantly associated with infections and deaths, particularly among elderly patients. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Gelatin-containing diphtheria-tetanus-pertussis (DTP) vaccine causes sensitization to gelatin in the recipients.

PubMed

Kumagai, T; Ozaki, T; Kamada, M; Igarashi, C; Yuri, K; Furukawa, H; Wagatuma, K; Chiba, S; Sato, M; Kojima, H; Saito, A; Okui, T; Yano, S

2000-02-14

Gelatin-specific T cell response was performed to determine whether a series of vaccinations with gelatin-containing DTP is a primary sensitization process in gelatin allergy. Thirty-seven recipients with gelatin-containing DTP who developed adverse reactions after vaccination and eight recipients of DTP without gelatin who also developed adverse reactions were studied. In addition, 10 subjects receiving gelatin-containing vaccine and 10 subjects inoculated with non-gelatin vaccine who did not show any adverse reactions were also investigated. All subjects inoculated with gelatin-containing DTP vaccine showed positive T cell responses against gelatin, however, occurrence of adverse reactions did not correlate with T cell responses. We conclude that DTP vaccine containing gelatin induces sensitization to gelatin in the recipients, but the mechanism of local reactions remains unknown.

Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

PubMed Central

Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

2014-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

Kinetic studies of L-asparaginase from Penicillium digitatum.

PubMed

Shrivastava, Abhinav; Khan, Abdul Arif; Shrivastav, Archana; Jain, Sudhir K; Singhal, Pradeep K

2012-01-01

L-Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and other related malignancies. Its further use includes reduction of asparagine concentration in food products, which may lead to formation of acrylamide. Currently bacterial asparaginase is produced at industrial scale, but the enzyme isolated from bacterial origin is often associated with adverse reactions. These side effects require development of asparaginase from alternative sources. In the present study, Penicillium digitatum was explored for the production of extracellular L-asparaginase using modified Czapek-Dox media. The enzyme was purified about 60.95-fold and then kinetic study showed that the Km value of the enzyme was 1 × 10⁻⁵ M. The optimum pH and temperature for the enzyme were 7.0 and 30°C, respectively. The optimum incubation period for L-asparaginase was 15 min. This work concludes that this enzyme can be a suitable candidate due to its strong kinetic properties, and further research can usher into development of asparaginase formulation from fungal origin with less adverse effects.

Long working hours, occupational health and the changing nature of work organization.

PubMed

Johnson, Jeffrey V; Lipscomb, Jane

2006-11-01

The impact of long working hours on health has been of major concern since the late 19th Century. Working hours are again increasing in the US. An overview of historical, sociological, and health-related research presented at an international conference on long working hours is discussed as an introduction to a special section in this issue. Research indicates that long working hours are polarizing along class lines with professionals working regular though longer hours and less well-educated workers having fewer though more irregular hours. Extended and irregular hours are associated with acute reactions such as stress and fatigue, adverse health behavior such as smoking, and chronic outcomes such as cardiovascular and musculoskeletal disorders. Improved methodologies are needed to track exposure to long working hours and irregular shifts longitudinally. Research should focus on the adverse impact that sleep-deprived and stressed workers may have on the health of the public they serve. A variety of protective efforts should be undertaken and evaluated. Copyright (c) 2006 Wiley-Liss, Inc.

Advances in lipid-lowering therapy through gene-silencing technologies.

PubMed

Nordestgaard, Børge G; Nicholls, Stephen J; Langsted, Anne; Ray, Kausik K; Tybjærg-Hansen, Anne

2018-05-01

New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50-90% with 2-12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

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

Pichon, Baptiste; Campion, Loïc; Delpon, Grégory

Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence ofmore » spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.« less

Psychological burden of food allergy

PubMed Central

Teufel, Martin; Biedermann, Tilo; Rapps, Nora; Hausteiner, Constanze; Henningsen, Peter; Enck, Paul; Zipfel, Stephan

2007-01-01

One fifth of the population report adverse reactions to food. Reasons for these symptoms are heterogeneous, varying from food allergy, food intolerance, irritable bowel syndrome to somatoform or other mental disorders. Literature reveals a large discrepancy between truly diagnosed food allergy and reports of food allergy symptoms by care seekers. In most studies currently available the characterization of patient groups is incomplete, because they did not distinguish between immunologic reactions and other kinds of food reactions. In analysing these adverse reactions, a thorough physical and psychological diagnostic approach is important. In our qualitative review, we present those diagnostic measures that are evidenced-based as well as clinically useful, and discuss the various psychological dimensions of adverse reactions to food. It is important to acknowledge the complex interplay between body and mind: Adults and children suffering from food allergy show impaired quality of life and a higher level of stress and anxiety. Pavlovian conditioning of adverse reactions plays an important role in maintaining symptoms. The role of personality, mood, or anxiety in food reactions is debatable. Somatoform disorders ought to be identified early to avoid lengthy and frustrating investigations. A future task will be to improve diagnostic algorithms, to describe psychological aspects in clearly characterised patient subgroups, and to develop strategies for an optimized management of the various types of adverse reactions to food. PMID:17659692

Adverse reactions in a population of Sydney pet rabbits vaccinated against rabbit calicivirus.

PubMed

Tung, T; Phalen, D; Toribio, J-Alml

2015-11-01

To determine the general clinical presentation and incidence of adverse reactions to Cylap® RCD vaccinations, of a nature serious enough for veterinary attention, in a Sydney population of pet rabbits. A retrospective survey using hospital databases. Nine veterinary hospitals in Sydney participated in a database search for the number of rabbits vaccinated within a 2-year period. The hospitals involved had an identified interest in rabbit medicine and included general, specialist and teaching hospitals. Details of the rabbit, vaccination event and any possible reaction were collected and analysed. Of 933 events recorded in 705 rabbits, 17 (1.8%) adverse reactions were observed. Of the adverse events, local injection site reactions (alopecia, abrasions and scabbing) were most common. Other reactions, including systemic signs of gastrointestinal tract stasis, lethargy and forelimb lameness, were also documented. Overall, rabbits presented for vaccination were mostly male (57.7%) and desexed (71.3%), with an average age of 28.1 months (median 19.0, range 1.4-149.8 months) and an average weight at first vaccination of 2.12 kg (median 2.08 kg, range 0.18-5.6 kg). A significant association between increasing age and decreased incidence of adverse events was demonstrated (P value, 0.038). The benefits of vaccination against RCV outweigh the risks of an adverse reaction occurring. Data from this study show that adverse reactions occur infrequently, are generally mild and self-resolving, and decrease in incidence with increasing age. These results are similar to previous field research on wild rabbit colonies and reports from government and industry. © 2015 Australian Veterinary Association.

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

PubMed Central

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

2002-01-01

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

Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis.

PubMed

Luszczki, Jarogniew J; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanislaw J

2006-11-01

Isobolographic analysis was used to characterize the interactions between stiripentol (STP) and clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice. The anticonvulsant and acute adverse (neurotoxic) effects of STP in combination with the various conventional antiepileptic drugs (AEDs), at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the PTZ and chimney tests in mice using the isobolographic analysis. Additionally, protective indices (PI) and benefit indices (BI) were calculated to identify their pharmacological profiles so that a ranking in relation to advantageous combination could be established. Moreover, adverse-effect paradigms were determined by use of the step-through passive avoidance task (long-term memory), threshold for the first pain reaction, grip-strength test (neuromuscular tone), and the hot plate test (acute thermal pain). Brain AED concentrations were also measured so as to ascertain any pharmacokinetic contribution to the pharmacodynamic interactions. All AED combinations comprising of STP and CZP, ETS, PB, and VPA (at the fixed ratios of 1:3, 1:1 and 3:1) were additive in terms of clonic seizure suppression in the PTZ test. However, these interactions were complicated by changes in brain AED concentrations consequent to pharmacokinetic interactions. Thus STP significantly increased total brain ETS and PB concentrations, and decreased VPA concentrations, but was without effect on CZP concentrations. In contrast, PB significantly decreased and VPA increased total brain STP concentrations while CZP and ETS were without effect. Furthermore, while isobolographic analysis revealed that STP and CZP in combination, at the fixed ratios of 1:1 and 3:1, were supraadditive (synergistic; p < 0.05), the combinations of STP with CZP (1:3), ETS, PB, or VPA (at all fixed ratios of 1:3, 1:1, and 3:1) were barely additivity in terms of acute neurotoxic adverse effects in the chimney test. Additionally, none of the examined combinations of STP with conventional AEDs (CZP, ETS, PB, VPA--at their median effective doses from the PTZ-test) affected long-term memory, threshold for the first pain reaction, neuromuscular tone, and acute thermal pain. Based on BI values, the combination of STP with PB at the fixed ratio of 1:3 appears to be a particularly favourable combination. In contrast, STP and CZP or ETS (at the fixed ratios of 1:1 and 3:1) were unfavorable combinations. However, these conclusions are confounded by the fact that STP is associated with significant pharmacokinetic interactions. The remaining combinations of STP with PB (1:1 and 3:1), CZP (1:3), ETS (1:3), and VPA (at all fixed ratios of 1:3, 1:1, and 3:1) do not appear to be potential favorable AED combinations.

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

PubMed

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

2013-08-01

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.

Incidence of adverse events in ferrets vaccinated with distemper or rabies vaccine: 143 cases (1995-2001).

PubMed

Greenacre, Cheryl B

2003-09-01

To determine the incidence of adverse events in ferrets vaccinated with a modified-live avian cell culture canine distemper virus vaccine licensed for use in ferrets, an inactivated rabies vaccine licensed for use in ferrets, or both. Retrospective study. 143 ferrets. Medical records were reviewed to identify ferrets that had an adverse event after vaccination. Adverse events developed within 25 minutes after vaccination in 13 ferrets. One ferret developed an adverse event after receiving a distemper and a rabies vaccine simultaneously and developed a second adverse event the following year after receiving the rabies vaccine alone. Therefore, a total of 14 adverse events were identified. All adverse events were an anaphylactic reaction characterized by generalized hyperemia, hypersalivation, and vomiting. Ten of the 14 anaphylactic reactions occurred after ferrets received both vaccines, 3 occurred after ferrets received the distemper vaccine alone, and 1 occurred after a ferret received the rabies vaccine alone. Incidences of adverse events after administration of both vaccines, the distemper vaccine alone, and the rabies vaccine alone were 5.6, 5.9, and 5.6%, respectively. Ferrets that had an anaphylactic reaction were significantly older at the time of vaccination than were ferrets that did not. Results suggest that there may be a high incidence of anaphylactic reactions after vaccination of domestic ferrets. Ferrets should be observed for at least 25 minutes after vaccination, and veterinarians who vaccinate ferrets should be prepared to treat anaphylactic reactions.

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

PubMed

De Angelis, Alessia; Colaceci, Sofia; Giusti, Angela; Vellone, Ercole; Alvaro, Rosaria

2016-03-01

To describe and synthesise previous research on factors conditioning the spontaneous reporting of adverse drug reactions among nurses. Spontaneous reports of adverse drug reactions by health-care providers, are a main instrument for the continuous evaluation of the risk-benefit ratio of every drug. Under-reporting of adverse drug reactions by all health-care providers, in particular by nurses, is a major limitation to this system. An integrated review of the literature was conducted using MEDLINE, CINAHL, Embase, Scopus databases and Google Scholar. After evaluation for appropriateness related to inclusion/exclusion criteria, 16 studies were included in the final analysis and synthesis. Two factors emerged from the study: (1) intrinsic factors related to nurses' knowledge and attitudes; (2) extrinsic factors related to nurses' interaction with health-care organisations and to the relationship between nurses and physicians. Nurses' attitudes that hinder reporting include ignorance, insecurity, fear and lethargy. Nurses are not fully aware of their role in adverse drug reaction reporting. Nurses must acquire greater knowledge to implement specific skills into their daily clinical practice. To improve nurses' reporting of adverse drug reactions, it is necessary to develop management approaches that modify both intrinsic and extrinsic factors. © 2015 John Wiley & Sons Ltd.

Outbreak of Adverse Reactions Associated with Contaminated Heparin

PubMed Central

Blossom, David B.; Kallen, Alexander J.; Patel, Priti R.; Elward, Alexis; Robinson, Luke; Gao, Ganpan; Langer, Robert; Perkins, Kiran M.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Jones, Marilyn; Schillie, Sarah F.; Shehab, Nadine; Ketterer, Daniel; Venkataraman, Ganesh; Kishimoto, Takashi Kei; Shriver, Zachary; McMahon, Ann W.; Austen, K. Frank; Kozlowski, Steven; Srinivasan, Arjun; Turabelidze, George; Gould, Carolyn V.; Arduino, Matthew J.; Sasisekharan, Ram

2013-01-01

BACKGROUND In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case–control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak. PMID:19052120

Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

PubMed

Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

2017-12-19

Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

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

PubMed

Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2016-07-01

We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

A U.S. perspective on the adverse reactions from traditional Chinese medicines.

PubMed

Ko, Richard J

2004-03-01

Traditional Chinese medicines (TCM) are popular in the United States and Asian and non-Asian consumers are using the product for disease treatment and health prevention. As more people are using TCM products, there are increased reports on adverse reactions. This review will focus on adverse reactions due to TCM as reported in the literature. The review is based on MedLine search of literatures using keywords including: herbs, herbal, traditional Chinese medicines with toxicity, adverse effects, death, drug interaction and pharmacokinetic. In addition, specific searches were performed using the above keywords with the common name and the scientific name of the plant product. The causes of adverse reactions associated with TCM are diverse. They include variability in active/toxic ingredients due to growing conditions, use of inherent toxic herbs causing toxicity, overdose of herbs, drug-herb interactions especially with pharmaceuticals that have narrow therapeutic index, coexisting diseases, and idiosyncratic reactions like allergy, hepatitis and anaphylaxis. Other adverse reactions can be due to manufacturing and quality problems causing adulteration, misidentification, substitution of one herb with another, variability in the amount of active ingredients, use of pharmaceuticals without identifying on the labels, improper processing and preparation, and contamination. To minimize the adverse reactions from TCM and protect the public, there must be adequate laws and regulations to ensure that products are manufactured with the highest standards. Manufacturers should be licensed by regulatory agency and manufactured under good manufacturing practice. TCM products must be evaluated for their safety before marketing. Proper labeling and good surveillance systems shall ensure the protection of the consumers.

Toxicology of haloacetonitriles

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

Hayes, J.R.; Condie, L.W. Jr.; Borzelleca, J.F.

1986-11-01

Haloacetonitriles are by-products of water chlorination and may form in vivo from the reaction of residual chlorine with endogenous compounds such as amino acids. Dibromoacetonitrile (DBAN) was negative in selected mutagenic assays; dichloroacetonitrile (DCAN) was mutagenic in S. typhimurium, but not in S. cerevisiae. Both DBAN and DCAN may be carcinogenic. The studies described were conducted to determined the acute, subacute, and subchronic toxicity of DBAN and DCAN. The acute oral LD/sub 50/ values (mg/kg) in mice and rats are: DBAN, mice: 289 (M), 303 (F); DBAN, rats: 245 (M), 361 (F); DCAN, mice: 270 (M), 279 (F); DCAN, rats:more » 339 (M), 330 (F). Death was preceded by slowed respiration, depressed activity, prostration, and coma. There were no apparent compound-related gross pathological effects. DBAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 23, 45, 90, and 180 mg/kg/day or 6, 23, and 45 mg/kg/day, respectively. No consistent, significant, adverse compound-related effects on any of the parameters evaluated were evident. Possible target organs might be spleen, thymus, and liver. The no-observed adverse-effect level (NOAEL) for 14 days was 45 mg/kg/day and for 90 days was 23 mg/kg/day. DCAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 12, 23, 45, and 90 mg/kg/day or 8, 33, and 65 mg/kg/day, respectively. There were not deaths during the 14 day study. No consistent, significant adverse compound-related effects on any of the parameters evaluated were evident. The NOAEL for 14 days was 45 mg/kg/day and for 90 days was 9 mg/kg/day.« less

[Second victim : Critical incident stress management in clinical medicine].

PubMed

Schiechtl, B; Hunger, M S; Schwappach, D L; Schmidt, C E; Padosch, S A

2013-09-01

Critical incidents in clinical medicine can have far-reaching consequences on patient health. In cases of severe medical errors they can seriously harm the patient or even lead to death. The involvement in such an event can result in a stress reaction, a so-called acute posttraumatic stress disorder in the healthcare provider, the so-called second victim of an adverse event. Psychological distress may not only have a long lasting impact on quality of life of the physician or caregiver involved but it may also affect the ability to provide safe patient care in the aftermath of adverse events. A literature review was performed to obtain information on care giver responses to medical errors and to determine possible supportive strategies to mitigate negative consequences of an adverse event on the second victim. An internet search and a search in Medline/Pubmed for scientific studies were conducted using the key words "second victim, "medical error", "critical incident stress management" (CISM) and "critical incident stress reporting system" (CIRS). Sources from academic medical societies and public institutions which offer crisis management programs where analyzed. The data were sorted by main categories and relevance for hospitals. Analysis was carried out using descriptive measures. In disaster medicine and aviation navigation services the implementation of a CISM program is an efficient intervention to help staff to recover after a traumatic event and to return to normal functioning and behavior. Several other concepts for a clinical crisis management plan were identified. The integration of CISM and CISM-related programs in a clinical setting may provide efficient support in an acute crisis and may help the caregiver to deal effectively with future error events and employee safety.

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

PubMed

Wogoman, H; Steinberg, M; Jenkins, A J

1999-06-01

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.

[Psychotic Acute Episode and Rhabdomyolysis after Lovastatin Ingestion].

PubMed

Caamaño, Beatriz H; Díaz, Jairo M González; Bracho, Daniel Guerrero; Herrera, Harold; Samur, Manuel Castro

2012-09-01

Statins are the most prescribed drugs worldwide given the benefit and security they offer. However, they can cause severe neurological, gastrointestinal, renal and muscular side effects. To describe the clinical course of a female patient with adverse drug reaction to Lovastatin. Case report and literature review. 52-year old woman with sudden psychosis and rhabdomyolysis secondary to Lovastatin and ending after the drug suspension. The causal relationship was corroborated with a score of 6 (probable ADR) on Naranjo's Scale. The simultaneous manifestation of psychosis and rhabdomiolysis represents an atypical and unique case following Lovastatin ingestion. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c Targets in Patients with Type 2 Diabetes Mellitus.

PubMed

Bannister, Margaret; Berlanga, Jenny

2016-09-01

Type 2 diabetes is a progressive condition that may require the combination of three oral treatments to achieve optimal glycemic management to prevent microvascular and macrovascular complications whilst minimizing the risk of acute complications and side effects or adverse reactions to treatments. With the widening availability of treatment options and increasing importance of individualized treatment pathways, including personalized HbA1c targets, this article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions.

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

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

Supplemental vitamin A prevents the acute radiation-induced defect in wound healing

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

Levenson, S.M.; Gruber, C.A.; Rettura, G.

Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet (which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)) was supplemented with 150,000 IU vit. A/kg dietmore » beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation.« less

21 CFR 606.170 - Adverse reaction file.

Code of Federal Regulations, 2012 CFR

2012-04-01

... maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood product arising as a result of blood collection or transfusion. A thorough investigation of each reported adverse... the manufacturer or collecting facility. (b) When a complication of blood collection or transfusion is...

Medication errors: the role of the patient.

PubMed

Britten, Nicky

2009-06-01

1. Patients and their carers will usually be the first to notice any observable problems resulting from medication errors. They will probably be unable to distinguish between medication errors, adverse drug reactions, or 'side effects'. 2. Little is known about how patients understand drug related problems or how they make attributions of adverse effects. Some research suggests that patients' cognitive models of adverse drug reactions bear a close relationship to models of illness perception. 3. Attributions of adverse drug reactions are related to people's previous experiences and to their level of education. The evidence suggests that on the whole patients' reports of adverse drug reactions are accurate. However, patients do not report all the problems they perceive and are more likely to report those that they do perceive as severe. Patients may not report problems attributed to their medications if they are fearful of doctors' reactions. Doctors may respond inappropriately to patients' concerns, for example by ignoring them. Some authors have proposed the use of a symptom checklist to elicit patients' reports of suspected adverse drug reactions. 4. Many patients want information about adverse drug effects, and the challenge for the professional is to judge how much information to provide and the best way of doing so. Professionals' inappropriate emphasis on adherence may be dangerous when a medication error has occurred. 5. Recent NICE guidelines recommend that professionals should ask patients if they have any concerns about their medicines, and this approach is likely to yield information conducive to the identification of medication errors.

40 CFR 717.15 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.15 Recordkeeping requirements. (a... significant adverse reactions alleged to have been caused by chemical substances or mixtures manufactured or... structure. Records must be retrievable by the alleged cause of the significant adverse reaction, which cause...

40 CFR 717.15 - Recordkeeping requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.15 Recordkeeping requirements. (a... significant adverse reactions alleged to have been caused by chemical substances or mixtures manufactured or... structure. Records must be retrievable by the alleged cause of the significant adverse reaction, which cause...

Acute effects of an organic solvent mixture on the human central nervous system.

PubMed

Muttray, Axel; Martus, P; Schachtrup, S; Müller, E; Mayer-Popken, O; Konietzko, J

2005-09-12

At workplaces, organic solvents are often used as mixtures. Nevertheless, there is limited knowledge of their acute effects on human central nervous system. Here we report the effects of a toluene-acetone mixture. In a parallel design, subgroups of 12 healthy men each were exposed to a mixture containing 25 ppm acetone and 250 ppm toluene or to air (control) in an exposure chamber for 4.5 hours. Concentrations corresponded to the German TLV (TRGS 403). Concentrations of toluene and acetone in venous blood were measured by headspace gas chromatography. Subjects were sedentary. The following tests were performed before and at the end of exposure: Questionnaires, simple reaction time, vigilance, quantitative analysis of EEG with open and closed eyes and during the Color Word Stress test, and visual evoked potentials (VEP). Blood levels were 0.14 (+/- 0.04 SD) mg toluene/l and 5.43 (+/- 1.37 SD) mg acetone/l at the end of solvent exposure. Scores of neurotoxic and irritating symptoms were not elevated during solvent exposure. Exposed subjects performed as well as control subjects on the simple reaction time test and on the vigilance test, neither reaction time nor number of hits differed significantly. A general linear model on log transformed spectral power values showed insignificant changes in EEG. In the alpha subset2-band an average reduction to 86 % was observed in exposed as compared to non exposed subjects with closed eyes, a reduction to 88 % in the theta-band with open eyes, and a reduction to 92 % in the theta-band during the Color Word Stress test. VEP P 100 latencies and amplitudes did not change. The mixture consisting of toluene and acetone did not cause any adverse acute effect. With respect to EEG data, possible subclinical effects on central nervous system cannot be excluded.

[Delayed adverse reactions to blood donation: From haemovigilance data to specific studies].

PubMed

Py, J-Y; Durieux, S; Barnoux, M; Sapey, T

2016-11-01

Delayed adverse reactions to blood donation occur after the donor left donation site. Their intrinsic gravity and possible complications can be increased by the fact the donor is alone. This can also increase bad memories, leading to a donation giving up. Blood transfusion centre is only aware in case of donor feedback, hence an event underrating. We choose to compare our data upon delayed adverse donor reactions with those we could find in past studies. A first data level comes from French haemovigilance data while serious adverse reactions declaration is mandatory. But a second level can be reached using blood transfusion centre computerized data because all the donation reactions are saved whatever the gravity is. In both cases, delayed reactions are only those reported by donors. We try to make an exhaustive search of specific studies upon the real delayed reactions incidence so as to compare with our data. There were 1957 serious adverse reactions declared in our regional haemovigilance database between 2011 and 2015: 49 % occurring during donation, 40 % after it but before donor departure, and 11 % delayed events. There were 16,050 adverse reactions recorded during the first trimester of 2016 in mainland France, with 2.7 % delayed ones. Proportion of delayed events rises when gravity rises, until 27.6 % for the most serious ones. It varies between 2.2 % and 2.7 % for vasovagal reactions, haematomas, and other local reactions, and reaches 16.2 % for other general reactions. Data found in other studies with a spontaneous donor notification are of the same kind. But four studies soliciting specifically donor notification give a dramatically higher delayed reactions incidence, with an understatement greater than three out of four. Moreover, these studies found a majority of delayed reactions, which are not included in haemovigilance like fatigue or bruising. Occurrence of a delayed donor reaction is clearly underrated in standard haemovigilance. It remains to be seen whether it have the same impact on donor return as immediate reactions. Considering that delayed reactions are much larger, it might be interesting to take them into account in the evaluation of strategies dedicated to lower immediate reactions. Copyright © 2016. Published by Elsevier SAS.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

[Immediate analgesic effect of wrist-ankle acupuncture for acute lumbago: a randomized controlled trial].

PubMed

Su, Jiang-tao; Zhou, Qing-hui; Li, Rui; Zhang, Jie; Li, Wei-hong; Wang, Qiong

2010-08-01

To assess the immediate analgesic effect of wrist-ankle acupuncture on acute lumbago and the relationship between the analgesic effect and the expectation of patients. A randomized, single-blind, sham-controlled trial was designed. Sixty cases of acute lumbago were randomly divided into two groups, 30 cases in each one. In observation group, wrist-ankle acupuncture was adopted to the Lower 5 and Lower 6 bilaterally, no requirement of Deqi (arrival of qi). In control group, sham acupuncture was adopted. The treatment was applied once in either group, with the needles retained for 30 min. The Short-form McGill Pain Questionnaire (SF-MPQ) and the Modified-Modified Schober (MMS) test were used to assess the motion related pain and the situation of spinal flexion in 3 min before treatment and 5 min, 10 min, 15 min, during treatment and 30 min (needle removed), respectively. The Expectation and Treatment Credibility Scale (ETCS) was applied to analyze the relationship between the expectation of patients and the analgesic effect. The adverse reaction was recorded. There were no statistically significant differences in SF-MPQ, MMS and ETCS before treatment between two groups (all P>0.05). In 5 min after needles insertion, the scores of the items in SF-MPQ in observation group were lower than those in control group (P<0.05, P<0.01). In 10 min after needles insertion, the scores of SF-MPQ in observation group were lower than those in control group and the scores of MMS were higher than those in control group (P<0.05). In 15 min after needles insertion, except the sensory pain rating index, the scores of the rest items in SF-MPQ in observation group were all lower than those in control group (P<0.05, P<0.01). In 30 min (needles removed), the scores of affective pain rating index of SF-MPQ and Visual Analogue Scale (VAS) in observation group were lower than those in control group (P<0.05, P<0.01). The expectation before treatment was negatively correlated with VAS scores in 5 min, 10 min, 15 min and 30 min after needle insertion separately in observation group (P<0.05), while the correlation was not found in control group (P>0.05). No adverse reaction was reported. Wrist-ankle acupuncture can reduce acute lumbago immediately and significantly. The higher the expectation on the analgesic effect of wrist-ankle acupuncture the patients have, the better the analgesic effect will be. This therapy is highly safe in the treatment.

Homeopathic and conventional treatment for acute respiratory and ear complaints: A comparative study on outcome in the primary care setting

PubMed Central

Haidvogl, Max; Riley, David S; Heger, Marianne; Brien, Sara; Jong, Miek; Fischer, Michael; Lewith, George T; Jansen, Gerard; Thurneysen, André E

2007-01-01

Background The aim of this study was to assess the effectiveness of homeopathy compared to conventional treatment in acute respiratory and ear complaints in a primary care setting. Methods The study was designed as an international, multi-centre, comparative cohort study of non-randomised design. Patients, presenting themselves with at least one chief complaint: acute (≤ 7 days) runny nose, sore throat, ear pain, sinus pain or cough, were recruited at 57 primary care practices in Austria (8), Germany (8), the Netherlands (7), Russia (6), Spain (6), Ukraine (4), United Kingdom (10) and the USA (8) and given either homeopathic or conventional treatment. Therapy outcome was measured by using the response rate, defined as the proportion of patients experiencing 'complete recovery' or 'major improvement' in each treatment group. The primary outcome criterion was the response rate after 14 days of therapy. Results Data of 1,577 patients were evaluated in the full analysis set of which 857 received homeopathic (H) and 720 conventional (C) treatment. The majority of patients in both groups reported their outcome after 14 days of treatment as complete recovery or major improvement (H: 86.9%; C: 86.0%; p = 0.0003 for non-inferiority testing). In the per-protocol set (H: 576 and C: 540 patients) similar results were obtained (H: 87.7%; C: 86.9%; p = 0.0019). Further subgroup analysis of the full analysis set showed no differences of response rates after 14 days in children (H: 88.5%; C: 84.5%) and adults (H: 85.6%; C: 86.6%). The unadjusted odds ratio (OR) of the primary outcome criterion was 1.40 (0.89–2.22) in children and 0.92 (0.63–1.34) in adults. Adjustments for demographic differences at baseline did not significantly alter the OR. The response rates after 7 and 28 days also showed no significant differences between both treatment groups. However, onset of improvement within the first 7 days after treatment was significantly faster upon homeopathic treatment both in children (p = 0.0488) and adults (p = 0.0001). Adverse drug reactions occurred more frequently in adults of the conventional group than in the homeopathic group (C: 7.6%; H: 3.1%, p = 0.0032), whereas in children the occurrence of adverse drug reactions was not significantly different (H: 2.0%; C: 2.4%, p = 0.7838). Conclusion In primary care, homeopathic treatment for acute respiratory and ear complaints was not inferior to conventional treatment. PMID:17335565

Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia: rationale and study design of a randomized double-blind study with a focus on acute hypersensitivity reactions.

PubMed

Adkinson, N Franklin; Strauss, William E; Bernard, Kristine; Kaper, Robert F; Macdougall, Iain C; Krop, Julie S

2017-01-01

Intravenous (IV) iron is often used to treat iron deficiency anemia in patients who are unable to tolerate or are inadequately managed with oral iron. However, IV iron treatment has been associated with acute hypersensitivity reactions. The comparative risk of adverse events (AEs) with IV iron preparations has been assessed by a few randomized controlled trials, which are most often limited by small patient numbers, which lack statistical power to identify differences in low-frequency AE such as hypersensitivity reactions. Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (FIRM) is a randomized, double-blind, international, multicenter, Phase III study designed to compare the safety of ferumoxytol and ferric carboxymaltose (FCM). The study includes adults with hemoglobin <12.0 g/dL (females) or <14.0 g/dL (males), transferrin saturation ≤20% or ferritin ≤100 ng/mL within 60 days of dosing, and a history of unsatisfactory or nontolerated oral iron therapy or in whom oral iron therapy is inappropriate. Patients are randomized (1:1) to ferumoxytol 510 mg or FCM 750 mg, each given intravenously on days 1 and 8. Primary end points are the incidence of moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. All potential hypersensitivity and hypotensive reactions will be adjudicated by a blinded, independent Clinical Events Committee. A secondary safety end point is the composite frequency of moderate-to-severe hypersensitivity reactions, including anaphylaxis, serious cardiovascular events, and death. Secondary efficacy end points include mean change in hemoglobin and mean change in hemoglobin per milligram of iron administered from baseline to week 5. Urinary excretion of phosphorus and the occurrence of hypophosphatemia after IV iron administration will be examined as well as the mechanisms of such hypophosphatemia in a substudy. FIRM will provide data on the comparative safety of ferumoxytol and FCM, two IV iron preparations with similar dosing schedules, focusing on moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. The study plans to enroll 2000 patients and is expected to complete in 2017.

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia

PubMed Central

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

Background While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012–2013. Methods The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Findings Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Conclusions Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control. PMID:28339462

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia.

PubMed

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Neutrophilic dermatitis and immune-mediated haematological disorders in a dog: suspected adverse reaction to carprofen.

PubMed

Mellor, P J; Roulois, A J A; Day, M J; Blacklaws, B A; Knivett, S J; Herrtage, M E

2005-05-01

This report describes the clinical and pathological findings of a suspected idiosyncratic adverse drug reaction in a young dog. The patient presented with sudden onset, severe skin lesions together with episodes of collapse. Investigations revealed a neutrophilic dermatitis with vasculitis, immune-mediated haemolytic anaemia and thrombocytopenia. Similar pathology has been described in human cases of Sweet's syndrome. The chronology of events suggested an adverse drug reaction to carprofen, although two antibiotics had been prescribed within the dog's recent history. Lymphocyte transformation tests were performed and tended to exclude both antibiotics as the cause of the reaction. To the authors' knowledge, lymphocyte transformation tests have not previously been described with regard to drug hypersensitivity assessment in the veterinary literature, and this is the first peer-reviewed case report of neutrophilic dermatitis and vasculitis with immune-mediated haemolytic anaemia and thrombocytopenia occurring as a suspected adverse drug reaction to carprofen in the dog.

[Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System].

PubMed

Cuena Boy, R; Maciá Martínez, M A

1998-03-31

To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. Observational, longitudinal, retrospective and comparative study of two series of cases. The entire Spanish healthcare system. Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. None. 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021). There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.

Adverse reactions to sulfites

PubMed Central

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

1985-01-01

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. PMID:4052897

Problematic Internet Use, Excessive Alcohol Consumption, Their Comorbidity and Cardiovascular and Cortisol Reactions to Acute Psychological Stress in a Student Population

PubMed Central

Bibbey, Adam; Phillips, Anna C.; Ginty, Annie T.; Carroll, Douglas

2015-01-01

Background and Aims Problematic Internet use and excessive alcohol consumption have been associated with a host of maladaptive outcomes. Further, low (blunted) cardiovascular and stress hormone (e.g. cortisol) reactions to acute psychological stress are a feature of individuals with a range of adverse health and behavioural characteristics, including dependencies such as tobacco and alcohol addiction. The present study extended this research by examining whether behavioural dependencies, namely problematic Internet use, excessive alcohol consumption, and their comorbidity would also be associated with blunted stress reactivity. Methods A large sample of university students (N = 2313) were screened using Internet and alcohol dependency questionnaires to select four groups for laboratory testing: comorbid Internet and alcohol dependence (N = 17), Internet dependence (N = 17), alcohol dependence (N = 28), and non-dependent controls (N = 26). Cardiovascular activity and salivary cortisol were measured at rest and in response to a psychological stress protocol comprising of mental arithmetic and public speaking tasks. Results Neither problematic Internet behaviour nor excessive alcohol consumption, either individually or in combination, were associated with blunted cardiovascular or cortisol stress reactions. Discussion It is possible that problematic Internet behaviour and excessive alcohol consumption in a student population were not related to physiological reactivity as they may not reflect ingrained addictions but rather an impulse control disorder and binging tendency. Conclusions The present results serve to indicate some of the limits of the developing hypothesis that blunted stress reactivity is a peripheral marker of the central motivational dysregulation in the brain underpinning a wide range of health and behavioural problems. PMID:26014670

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

PubMed

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

2018-05-09

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

Spontaneously Reported Adverse Reactions for Herbal Medicinal Products and Natural Remedies in Sweden 2007-15: Report from the Medical Products Agency.

PubMed

Svedlund, Erika; Larsson, Maria; Hägerkvist, Robert

2017-06-01

In relation to the extensive use of herbal medicinal products in self-care, the safety information is limited and there is a need for improvement. This study describes spontaneously reported adverse reactions related to herbal medicinal products and natural remedies in Sweden. To evaluate the characteristics and frequency of adverse events recorded by the Swedish Medical Products Agency, where herbal medicinal products and natural remedies were suspected as causative agents. Adverse drug reactions reported to the Swedish Medical Product Agency during 2007-15 related to approved herbal medicinal products or natural remedies were included and analysed in the retrospective study. Reports had been assessed for causality when they were lodged and only reports that had been assessed as at least possible were included in the study. In total, 116 reports (concerning 259 adverse reactions) related to herbal medicinal products or natural remedies were found in the Swedish national pharmacovigilance database. The active ingredients most frequently suspected during the study period were black cohosh rhizome (15 reports), purple coneflower herb (14 reports) and a combination of extracts of pollen (13 reports). Adverse reactions related to skin and subcutaneous tissue were the most commonly reported reactions. No previously unknown safety problems have been discovered in the present study. This finding could be explained by a thorough pre-approval assessment of medicinal products and the fact that most herbal preparations in medicinal products have been in clinical use for many years (for traditional herbal medicinal products, the requirements are ≥30 years), i.e. adverse reactions are acknowledged and assessed before approval.

[Sodium valproate as a cause of acute pancreatitis: a case report].

PubMed

Barreda, Luís; Rosas, Johana; Milian, William; Valdivia, Duilio; Targarona, Javier

2006-01-01

Valproic acid (VPA) is a commonly used medication approved by the U.S. FDA for the treatment of epilepsy, migraines and bipolar disorders. Adverse effects associated with VPA are typically benign, but there are more serious effects that are less frequent. These effects include hepatotoxicity, teratogenicity, possible polycystic ovaries with a potential sterile effect and acute pancreatitis. Even though acute pancreatitis is an adverse effect of very low frequency, it is very important due to the high mortality rate of patients with acute pancreatitis as a consequence of the use of valproic acid. In medical literature, by 2005, 80 cases of acute pancreatitis caused by valproic acid were reported, 33 of these cases were patients under the age of 18. This is a description of the clinical case of a 16 year old patient with necrotic pancreatitis caused by VPA, who was treated at the Acute Pancreatitis Unit of Edgardo Rebagliati Martins National Hospital.

Leflunomide in active rheumatoid arthritis: a prospective study in daily practice.

PubMed

Van Roon, E N; Jansen, T L Th A; Mourad, L; Houtman, P M; Bruyn, G A W; Griep, E N; Wilffert, B; Tobi, H; Brouwers, J R B J

2004-06-01

We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. In the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.

Leflunomide in active rheumatoid arthritis: a prospective study in daily practice.

PubMed

Van Roon, E N; Jansen, T L Th A; Mourad, L; Houtman, P M; Bruyn, G A W; Griep, E N; Wilffert, B; Tobi, H; Brouwers, J R B J

2004-08-01

We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.

Prevention of Hospital-Acquired Adverse Drug Reactions in Older People Using Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment Criteria: A Cluster Randomized Controlled Trial.

PubMed

O'Connor, Marie N; O'Sullivan, David; Gallagher, Paul F; Eustace, Joseph; Byrne, Stephen; O'Mahony, Denis

2016-08-01

To determine whether use of the Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) criteria reduces incident hospital-acquired adverse drug reactions (ADRs), 28-day medication costs, and median length of hospital stay in older adults admitted with acute illness. Single-blind cluster randomized controlled trial (RCT) of unselected older adults hospitalized over a 13-month period. Tertiary referral hospital in southern Ireland. Consecutively admitted individuals aged 65 and older (N = 732). Single time point presentation to attending physicians of potentially inappropriate medications according to the STOPP/START criteria. The primary outcome was the proportion of participants experiencing one or more ADRs during the index hospitalization. Secondary outcomes were median length of stay (LOS) and 28-day total medication cost. One or more ADRs occurred in 78 of the 372 control participants (21.0%; median age 78, interquartile range (IQR) 72-84) and in 42 of the 360 intervention participants (11.7%; median age 80, IQR 73-85) (absolute risk reduction = 9.3%, number needed to treat = 11). The median LOS in the hospital was 8 days (IQR 4-14 days) in both groups. At discharge, median medication cost was significantly lower in the intervention group (€73.16, IQR €38.68-121.72) than in the control group (€90.62, IQR €49.38-162.53) (Wilcoxon rank test Z statistic = -3.274, P < .001). Application of STOPP/START criteria resulted in significant reductions in ADR incidence and medication costs in acutely ill older adults but did not affect median LOS. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes

PubMed Central

Carbonari, Dena M; Saine, M Elle; Newcomb, Craig W; Roy, Jason A; Liu, Qing; Wu, Qufei; Cardillo, Serena; Haynes, Kevin; Kimmel, Stephen E; Reese, Peter P; Margolis, David J; Apter, Andrea J; Reddy, K Rajender; Hennessy, Sean; Bhullar, Harshvinder; Gallagher, Arlene M; Esposito, Daina B; Strom, Brian L

2017-01-01

Objective To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. Research design and methods Cohort studies using 2009–2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible. Results There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis. Conclusions Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings. Trial registration number NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results. PMID:28878934

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

PubMed Central

2010-01-01

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

Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease.

PubMed

Bakker, Jaap A; Drent, Marjolein; Bierau, Jörgen

2007-09-01

Mercaptopurine therapy is increasingly important as immunosuppressive therapy in interstitial lung disease. We focus on human mercaptopurine metabolism and the defects in this metabolism causing adverse drug reactions. Defects in mercaptopurine metabolizing enzymes like thiopurine methyltransferase and inosine triphosphate pyrophosphohydrolase lead to severe adverse drug reactions, sometimes with fatal outcome. Other enzymes, still not thoroughly investigated, can give rise to toxic effects or decreased efficacy in mercaptopurine therapy when the activity of these enzymes is altered. Pharmacogenetic screening of potential patients for mercaptopurine therapy is important to avoid adverse drug reactions caused by inherited enzyme deficiencies in these metabolic pathways. Pretreatment screening for deficiencies of mercaptopurine metabolizing enzymes will significantly reduce the number of patients with an adverse drug reaction and concomitantly associated healthcare costs.

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions.

PubMed

Beck, O; Helander, A; Karlson-Stiber, C; Stephansson, N

1998-01-01

The use of mushrooms containing the hallucinogenic substance psilocybin for intentional intoxication is relatively common. Occasionally, this results in adverse reactions with typical tachycardia that is not evidently caused by psilocybin. This study demonstrates the presence of phenylethylamine in the species Psilocybe semilanceata using gas chromatography-mass spectrometry and shows that the amount of this substance may vary much more than that of psilocybin. The highest amount of phenylethylamine (146 microg/g wet weight) was observed in mushrooms from a case of three young men hospitalized because of adverse reactions. Comparison of the symptoms observed in clinical cases of magic mushroom intoxication with those after intake of pure psilocybin or phenylethylamine suggests that phenylethylamine might have a role in the development of adverse reactions to Psilocybe mushroom intake.

Tuberculin skin testing: Spectrum of adverse reactions.

PubMed

Praveen, Ramar; Bahuguna, Amit; Dhadwal, Bhumesh Singh

2015-01-01

Tuberculin skin testing (TST) is one of the primary diagnostic modalities recommended by the World Health Organization (WHO) and the National Institute for Health and Care Excellence (NICE) study conducted in the United Kingdom (UK) for diagnosing tuberculosis (TB). Even after acceptance as a diagnostic modality and stern standardization, TST has its own flaws that include a spectrum of adverse reactions. We report a series of cases with a spectrum of adverse reactions occurring with a higher frequency than present in the available evidence. The study has some demerits such as being a retrospective one with interobserver variation and lack of histopathological confirmation. The observation is presented to accentuate the fact that adverse reactions are not a rarity and that further studies are required to establish the cause and exact incidence of the same.

Embedding an enriched environment in an acute stroke unit increases activity in people with stroke: a controlled before-after pilot study.

PubMed

Rosbergen, Ingrid Cm; Grimley, Rohan S; Hayward, Kathryn S; Walker, Katrina C; Rowley, Donna; Campbell, Alana M; McGufficke, Suzanne; Robertson, Samantha T; Trinder, Janelle; Janssen, Heidi; Brauer, Sandra G

2017-11-01

To determine whether an enriched environment embedded in an acute stroke unit could increase activity levels in acute stroke patients and reduce adverse events. Controlled before-after pilot study. An acute stroke unit in a regional Australian hospital. Acute stroke patients admitted during (a) initial usual care control period, (b) an enriched environment period and (c) a sustainability period. Usual care participants received usual one-on-one allied health intervention and nursing care. The enriched environment participants were provided stimulating resources, communal areas for eating and socializing and daily group activities. Change management strategies were used to implement an enriched environment within existing staffing levels. Behavioural mapping was used to estimate patient activity levels across groups. Participants were observed every 10 minutes between 7.30 am and 7.30 pm within the first 10 days after stroke. Adverse and serious adverse events were recorded using a clinical registry. The enriched environment group ( n = 30, mean age 76.7 ± 12.1) spent a significantly higher proportion of their day engaged in 'any' activity (71% vs. 58%, P = 0.005) compared to the usual care group ( n = 30, mean age 76.0 ± 12.8). They were more active in physical (33% vs. 22%, P < 0.001), social (40% vs. 29%, P = 0.007) and cognitive domains (59% vs. 45%, P = 0.002) and changes were sustained six months post implementation. The enriched group experienced significantly fewer adverse events (0.4 ± 0.7 vs.1.3 ± 1.6, P = 0.001), with no differences found in serious adverse events (0.5 ± 1.6 vs.1.0 ± 2.0, P = 0.309). Embedding an enriched environment in an acute stroke unit increased activity in stroke patients.

Self-reported adverse reactions associated with mycoprotein (Quorn-brand) containing foods.

PubMed

Jacobson, Michael F; DePorter, Janna

2018-06-01

Mycoprotein, which is produced by a mold and is the basis of Quorn-brand meat substitutes, is a novel cause of allergic and gastrointestinal reactions, but little information has been available on its associated symptomatology. To describe the nature and frequency of adverse reactions to mycoprotein. Self-reports of adverse reactions to mycoprotein were collected via a Web-based questionnaire (www.quorncomplaints.org) and then analyzed. Analysis of 1,752 adverse reactions found that Quorn products caused allergic and gastrointestinal symptoms, with some people experiencing both. Allergic reactions, including urticaria and anaphylaxis, occurred within 4 hours of consumption in 312 people. Of those reactions, 45.8%, 1 fatal, began within 1 hour of exposure. Of those 312 individuals, 188 (60.3%) reported repeated reactions after repeated consumption of Quorn, and 2 people experienced 8 reactions (13 people did not say whether they experienced more than 1 reaction). Quorn foods caused gastrointestinal symptoms, including emesis and diarrhea, within 8 hours of consumption in 1,692 people. Of the gastrointestinal symptoms, 66.6% occurred 46 to 180 minutes after consumption of the products. Symptoms ranged from mild nausea to emesis severe enough to warrant medical attention. Mycoprotein may be causing numerous and sometimes life-threatening allergic and gastrointestinal reactions. The acceptance in the food supply of this nonessential ingredient deserves reconsideration. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

PubMed

McNulty, Caitlin M G; Park, Miguel A

2017-11-01

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

78 FR 61372 - Advisory Commission of Childhood Vaccines; Request for Nominations for Voting Members

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... reactions; surveying federal, state, and local programs and activities related to gathering information on injuries associated with the administration of childhood vaccines, including the adverse reaction reporting... using credible data related to the frequency and severity of adverse reactions associated with childhood...

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

PubMed

Cichocka-Jarosz, E; Sanak, M; Szczeklik, A; Brzyski, P; Gielicz, A; Pietrzyk, J J

2011-01-01

We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom.

PubMed

Cannon, Robert; Ruha, Anne-Michelle; Kashani, John

2008-04-01

Acute hypersensitivity reactions are well known to occur with the administration of the Antivenin (Crotalidae) Polyvalent (Wyeth Laboratories, Marietta, PA). Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV, Protherics, Inc., Brentwood, TN) was introduced in 2001, and early studies reported a hypersensitivity reaction rate up to 19%. We describe the incidence of acute hypersensitivity reactions to FabAV in patients bitten by rattlesnakes. This was a nonconcurrent observational cohort study, with data obtained by chart review of all patients admitted to our service for rattlesnake bites from July 2000 to June 2004. The study was conducted at an urban Level I trauma center and urban children's hospital. All patients treated with FabAV were included. Those who received no antivenom or who were treated with Antivenin (Crotalidae) Polyvalent were excluded. The main outcome variable was whether an acute hypersensitivity reaction developed. Ninety-three patients were included in the review (72 male and 21 female patients). The mean age was 34.5 years (range 16 months to 91 years), and the mean dose of antivenom was 12 vials (range 4 to 32 vials). The incidence of acute hypersensitivity reactions was 5 of 93, or 5.4%. Four patients developed a mild reaction that was easily treated and were able to finish the full course of antivenom. Only 1 patient developed a reaction that prevented further antivenom administration. FabAV appears to be associated with a lower incidence of acute hypersensitivity than initially reported. Most reactions are mild and easily treated and do not preclude further dosing of antivenom.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

PubMed Central

Navari, Rudolph M

2009-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first-generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation. PMID:21188135

40 CFR 717.1 - Scope and compliance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ACT RECORDS AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO... mixtures: (a) To keep “records of significant adverse reactions to health or the environment, as determined...

40 CFR 717.1 - Scope and compliance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ACT RECORDS AND REPORTS OF ALLEGATIONS THAT CHEMICAL SUBSTANCES CAUSE SIGNIFICANT ADVERSE REACTIONS TO... mixtures: (a) To keep “records of significant adverse reactions to health or the environment, as determined...

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

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

PubMed

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

2017-04-01

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

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

PubMed

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

2007-06-01

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

Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain

PubMed Central

Birnie, D H; Vickers, L E; Hillis, W S; Norrie, J; Cobbe, S M

2005-01-01

Objective: To assess whether antibodies to human heat shock protein 60 (anti-huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an adverse one year prognosis in patients admitted with acute cardiac chest pain. Design: Prospective observational study. Setting: Teaching hospital. Patients: 588 consecutive emergency admissions of patients with acute chest pain of suspected cardiac origin. Main outcome measures: Anti-huhsp60 and anti-mhsp65 titres were assayed on samples drawn on the morning after admission. The end points after discharge were coronary heart disease death, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain. Results: During follow up after discharge (mean of 304 days, range 1–788 days), 277 patients had at least one of the study outcomes. Patients with increased titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95% confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p  =  0.015). Anti-mhsp65 titres were not predictive. Conclusions: Patients admitted with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse one year prognosis. PMID:16103543

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

PubMed

Rossi, C; Reginelli, A; D'Amora, M; Di Grezia, G; Mandato, Y; D'Andrea, A; Brunese, L; Grassi, R; Rotondi, A

2014-01-01

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

National differences in publishing papers on adverse drug reactions

PubMed Central

Ferner, R E; Aronson, J K

2005-01-01

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

Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or "Innate Hypersensitivity"?

PubMed

Spoerl, David; Nigolian, Haig; Czarnetzki, Christoph; Harr, Thomas

2017-06-07

Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions.

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

PubMed

Hauben, Manfred; Aronson, Jeffrey K

2007-01-01

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

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

NASA Astrophysics Data System (ADS)

Wibroe, Peter Popp; Anselmo, Aaron C.; Nilsson, Per H.; Sarode, Apoorva; Gupta, Vivek; Urbanics, Rudolf; Szebeni, Janos; Hunter, Alan Christy; Mitragotri, Samir; Mollnes, Tom Eirik; Moghimi, Seyed Moein

2017-07-01

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

[Reactions to food].

PubMed

Halvorsen, R; Eggesb M; Botten, G

1995-12-10

Adverse reactions to food occur in about 1-2% of the population, but are reported more frequently by patients. Most reactions to food are not caused by allergy. IgE-mediated food reactions are well known and of major clinical significance owing to their potentially dangerous, even life-threatening character. Adverse reactions to food can also be caused by immunological mechanisms other than IgE-mediated reactions such as, enzyme deficiencies, active pharmacological substances in food and psychological mechanisms. Double-blind provocation is the only way to diagnose a positive reaction to a food item with some certainty. Regretably no objective measures for food reactions exist.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed

Mueller, R S; Unterer, S

2018-06-01

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

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

PubMed

Gist, Katja M; Kaufman, Jonathan; da Cruz, Eduardo M; Friesen, Robert H; Crumback, Sheri L; Linders, Megan; Edelstein, Charles; Altmann, Christopher; Palmer, Claire; Jalal, Diana; Faubel, Sarah

2016-04-01

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

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

Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.

PubMed

Calapai, G; Imbesi, S; Cafeo, V; Ventura Spagnolo, E; Minciullo, P L; Caputi, A P; Gangemi, S; Milone, L

2013-08-01

Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray. © 2013 John Wiley & Sons Ltd.

Patch-testing for the management of hypersensitivity reactions to second-line anti-tuberculosis drugs: a case report.

PubMed

Khan, Samsuddin; Andries, Aristomo; Pherwani, Asha; Saranchuk, Peter; Isaakidis, Petros

2014-08-15

The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management. A 17-year old Indian female multidrug-resistant tuberculosis patient co-infected with human immunodeficiency virus developed a hypersensitivity reaction after starting second-line anti-tuberculosis treatment in Mumbai, India. The patient was being treated with kanamycin, moxifloxacin, para-aminosalicylic acid, cycloserine, clofazimine, and amoxicillin-clavulanic acid. Twenty-four hours later, the patient developed generalized urticaria, morbilliform rash and fever. All drugs were suspended and the patient was hospitalised for acute management. Skin patch-testing was used to identify drugs that potentially caused the hypersensitivity reaction; results showed a strong reaction to clofazimine, moderate reaction to kanamycin and mild reaction to cycloserine. An interim second-line anti-tuberculosis regimen was prescribed; cycloserine and kanamycin were then re-challenged one-by-one using incremental dosing, an approach that allowed clinicians to re-introduce these drugs promptly and safely. The patient is currently doing well. This is the first case-report of a multidrug-resistant tuberculosis patient co-infected with the human immunodeficiency virus with hypersensitivity reaction to multiple second-line anti-tuberculosis drugs. Skin patch-testing and controlled re-challenge can be a useful management strategy in such patients. There is an urgent need for second-line anti-tuberculosis regimens that are more effective, safe and better tolerated.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Epidemiology of adverse drug reactions to phenformin and metformin.

PubMed Central

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

1978-01-01

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

Side and site of deep vein thrombosis in women using oral contraceptives.

PubMed

Kierkegaard, A

1985-01-01

The anatomy of the thrombus in acute deep vein thrombosis (DVT) in women using oral contraceptives was studied in 277 reports on DVT received by the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The study revealed a similarity between the anatomy of DVT in women on oral contraceptives and that of DVT in pregnant women, suggesting a pharmacologic influence of the hormones in the pill on the pathogenesis of DVT in women on oral contraceptives. The anatomy of DVT in women on low-estrogen pills was identical with that of DVT in women on high-estrogen pills, suggesting an identical pharmacologic influence of the two types of pill on the pathogenesis of DVT in women on oral contraceptives.

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

PubMed Central

Longhurst, Hilary

2018-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment. PMID:29594115

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus.

PubMed

Longhurst, Hilary

2017-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients' quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose-response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.

Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality

EPA Science Inventory

Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy.

PubMed

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-09-02

BACKGROUND This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. MATERIAL AND METHODS The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. RESULTS Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. CONCLUSIONS We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy

PubMed Central

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-01-01

Background This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. Material/Methods The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. Results Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. Conclusions We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy. PMID:28864818

The role of natural color additives in food allergy.

PubMed

Lucas, C D; Hallagan, J B; Taylor, S L

2001-01-01

A critical evaluation of the available information demonstrates that reactions to natural color additives are rare. Studies of turmeric and carotenoid pigments administered in mixtures with other food colorings failed to definitely identify reactions to either color additive. For carotenoids, the one case report of an adverse reaction was not conclusive. An anaphylactic reaction to saffron does suggest an IgE-mediated reaction, but the high use of saffron as compared with this single report of an adverse reaction suggests that sensitivity to saffron is extremely rare. Numerous reports of reactions to grapes or grape products have been reported in the literature, but no reports of sensitivities to grape skin extract or grape color extract were found. In rare cases, annatto dye may provoke a severe, adverse reaction in individuals with an uncommon hypersensitivity, and may aggravate the symptoms of patients suffering from recurrent urticaria. In its long history of use, there has been only one reported case of anaphylaxis resulting from the ingestion of annatto. Studies designed to investigate the role of annatto in recurrent urticaria sufferers were limited due to the absence of double-blind challenge and placebo controls. A number of cases of adverse reactions to carmine following ingestion have been reported in the literature. These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the reported cases, the cause of sensitization to carmine was topical exposure from the use of carmine-containing cosmetics or occupational exposure to carmine and not from ingestion of carmine-containing foods and beverages. Following sensitization, affected individuals would be sensitive to carmine and the amounts present in foods and beverages could elicit allergic reactions. It is not known whether all individuals with carmine sensitivity induced through topical use are sensitive to the ingestion of carmine in foods. However, reactions to carmine solely because of ingestion are likely to be exceedingly rare due to the low use levels of carmine in foods and beverages. Despite their widespread use in food products, few reports of allergic reactions following ingestion have been reported for the majority of natural color additives. It is concluded that the ingestion of natural color additives presents a very low risk of provoking adverse reactions.

Acute versus subacute community-acquired meningitis: Analysis of 611 patients.

PubMed

Sulaiman, Tarek; Salazar, Lucrecia; Hasbun, Rodrigo

2017-09-01

Community-acquired meningitis can be classified into acute and subacute presentations by the duration of illness of ≤ or >5 days, respectively. There are currently no studies comparing the clinical features, management decisions, etiologies, and outcomes between acute and subacute presentations.It is a retrospective study of adults with community-acquired meningitis hospitalized in Houston, TX between January 2005 and January 2010. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of ≤4.A total of 611 patients were identified, of which 458 (75%) were acute and 153 subacute (25%). The most common etiologies were unknown in 418 (68.4%), viral in 94 (15.4%), bacterial in 47 (7.7%), fungal in 42 patients (6.9%), and other noninfectious etiologies in 6 (1%). Patients with subacute meningitis were more likely to be immunosuppressed or have comorbidities, had fungal etiologies, and had higher rates of hypoglycorrachia and abnormal neurological findings (P <.05). Patients with an acute presentation were more likely to be treated empirically with intravenous antibiotics and had higher cerebrospinal fluid pleocytosis and serum white blood cell counts (P <.05). On logistic regression, age >65 years and abnormal neurological findings were predictive of an adverse clinical outcome in both acute and subacute meningitis, whereas fever was also a significant prognostic factor in acute meningitis. (P <.05).Acute and subacute meningitis differ in regards to clinical presentations, etiologies, laboratory findings, and management decisions, but did not differ in rates of adverse clinical outcomes. Future studies including thoroughly investigated patients with new diagnostic molecular methods may show different results and outcomes.

German guideline for the management of adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI).

PubMed

Reese, Imke; Ballmer-Weber, Barbara; Beyer, Kirsten; Fuchs, Thomas; Kleine-Tebbe, Jörg; Klimek, Ludger; Lepp, Ute; Niggemann, Bodo; Saloga, Joachim; Schäfer, Christiane; Werfel, Thomas; Zuberbier, Torsten; Worm, Margitta

2017-01-01

Adverse food reactions are far more often perceived than objectively verified. In our scientific knowledge on non-allergic adverse reactions including the so called histamine intolerance, there are large deficits. Due to the fact that this disorder is increasingly discussed in the media and the internet, more and more people suspect it to be the trigger of their symptoms. The scientific evidence to support the postulated link between ingestion of histamine and adverse reactions is limited, and a reliable laboratory test for objective diagnosis is lacking. This position paper by the "Food Allergy" Working Group of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Association of Allergologists (AeDA), the Society for Pediatric Allergology and Environmental Medicine (GPA), and the Swiss Society for Allergology and Immunology (SGAI) reviews the data on the clinical picture of adverse reactions to ingested histamine, summarizes important aspects and their consequences, and proposes a practical diagnostic and therapeutic approach.

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

Vural, Fisun; Ciftci, Seval; Vural, Birol

2015-01-01

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

Acute stress reactions after submarine accidents.

PubMed

Eid, Jarle; Johnsen, Bjørn Helge

2002-05-01

The aim of the present study was to explore contextual and individual factors associated with acute stress reactions in three Norwegian submarine crews exposed to different significant peacetime maneuver accidents. Approximately 2 to 3 weeks after the accidents, crew members completed the Coping Style Questionnaire, the General Health Questionnaire, the Impact of Event Scale, and the Post-Traumatic Symptom Scale. Although exposed subjects (N = 47) revealed more posttraumatic stress symptoms than nonexposed crew members on shore leave (N = 7), they showed less acute stress reactions than survivors from a surface ship accident in the Norwegian Navy. Inspection of individual cases revealed that 4% of the exposed submariners showed high loads of acute stress symptoms. Unit cohesion and habitual coping styles emerged as resilience factors, whereas previous exposure to critical incidents and personal experience of not coping in the accident situation emerged as vulnerability factors, explaining 32% of the acute stress reactions reported by submarine crew members.

Adverse events associated with single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

PubMed

Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

2015-10-13

This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews. To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults. We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews. Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth.For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.Most reviews did not report specific adverse events. Despite ongoing problems with the measurement, recording, and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.

PubMed

Isai, Alina; Durand, Julie; Le Meur, Steven; Hidalgo-Simon, Ana; Kurz, Xavier

2012-11-19

All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the most frequently discussed in association with A/H1N1 vaccination; reporting rates were generally within expected background rates. Copyright © 2012 Elsevier Ltd. All rights reserved.

RhIG for the treatment of immune thrombocytopenia: consensus and controversy

PubMed Central

Despotovic, Jenny M.; Lambert, Michele P.; Herman, Jay H.; Gernsheimer, Terry B.; McCrae, Keith R.; Tarantino, Michael D.; Bussel, James B.

2012-01-01

Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID:21981825

The restaurant syndromes.

PubMed

Settipane, G A

1987-01-01

The Restaurant syndromes can be caused by five major factors: food allergens, sulfites, monosodium glutamate (MSG), tartrazine, and scombroidosis (and other seafood poisoning). A history of atopy and ingestion of known food allergens such as peanuts, egg, fish, and walnuts, together with positive results of skin tests or RAST to these foods, will favor a diagnosis of food allergy. Allergic reactions to peanuts have produced fatalities in minutes through an IgE mediated reaction. An extremely rapid onset (minutes) of symptoms consisting of flushing, bronchospasm and hypotension is consistent with a sulfite reaction. Burning, pressure, and tightness or numbness in the face, neck, and upper chest following ingestion of Chinese food favors a diagnosis of adverse reaction to MSG. Also, development of late onset bronchospasm (up to 14 hours) may be related to MSG reactions. Bronchospasm and urticaria in a patient with a history of aspirin intolerance suggests tartrazine sensitivity. If everyone ingesting a fish meal develops flushing, urticaria, pruritus, gastrointestinal complaints, or bronchospasm, this implies scombroidosis, ciguatera, or other seafood poisoning. Finally, severe headache or hypertension can result from ingestion of naturally occurring amines, such as tyramine (cheese, red wine) and phenylethylamine (chocolate). A double-blind oral challenge test may be the only way of confirming the diagnosis for most of the etiological factors of the Restaurant syndromes. The treatment of choice for acute reaction is epinephrine followed by antihistamine. Proper labeling and avoidance of these ingredients in sensitive individuals are the best preventive measures.

Two approaches to the clinical dilemma of treating TTP with therapeutic plasma exchange in patients with a history of anaphylactic reactions to plasma.

PubMed

Sidhu, Davinder; Snyder, Edward L; Tormey, Christopher A

2017-06-01

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease caused by autoantibody-mediated deficiency in von Willebrand factor (VWF) cleaving protease, ADAMTS-13. The primary acute treatment is therapeutic plasma exchange (TPE). However, some patients can develop allergic/anaphylactic reactions to the replacement (i.e., donor) plasma over time. Two potential treatment strategies for patients with TTP who demonstrate severe allergic reactions to plasma used for exchange were examined. Two patients with TTP exacerbations who developed severe allergic reactions to donor plasma were identified. One patient's TPE was re-initiated with Octaplas, a lot-batched solvent and detergent treated, type-specific, pooled donor plasma product. The other patient was exchanged with primarily albumin, followed by slow incremental exposures to donor plasma to mitigate exposures and allergic risks. Both patients were assessed for anaphylaxis. Both treatment strategies were successful in preventing any further clinically significant allergic/anaphylactic reactions and facilitated both patients' TTP remissions. Based on our experience with two similar patients with TTP exacerbations and history of anaphylactic reactions to plasma during TPE, we have identified two possible treatment protocols to achieve remission in this clinical dilemma. Substituting Octaplas for standard plasma or, alternatively, using albumin with slowly increasing amounts of standard plasma may help to mitigate the risk of further anaphylactic adverse events. J. Clin. Apheresis 32:158-162, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Understanding recovery in children following traffic-related injuries: exploring acute traumatic stress reactions, child coping, and coping assistance.

PubMed

Marsac, Meghan L; Donlon, Katharine A; Hildenbrand, Aimee K; Winston, Flaura K; Kassam-Adams, Nancy

2014-04-01

Millions of children incur potentially traumatic physical injuries every year. Most children recover well from their injury but many go on to develop persistent traumatic stress reactions. This study aimed to describe children's coping and coping assistance (i.e., the ways in which parents and peers help children cope) strategies and to explore the association between coping and acute stress reactions following an injury. Children (N = 243) rated their acute traumatic stress reactions within one month of injury and reported on coping and coping assistance six months later. Parents completed a measure of coping assistance at the six-month assessment. Children used an average of five to six coping strategies (out of 10), with wishful thinking, social support, and distraction endorsed most frequently. Child coping was associated with parent and peer coping assistance strategies. Significant acute stress reactions were related to subsequent child use of coping strategies (distraction, social withdrawal, problem-solving, blaming others) and to child report of parent use of distraction (as a coping assistance strategy). Findings suggest that children's acute stress reactions may influence their selection of coping and coping assistance strategies. To best inform interventions, research is needed to examine change in coping behaviors and coping assistance over time, including potential bidirectional relationships between trauma reactions and coping.

Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets.

PubMed

Flinterman, A E; Knulst, A C; Meijer, Y; Bruijnzeel-Koomen, C A F M; Pasmans, S G M A

2006-03-01

Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens' current status. Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake.

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

PubMed

Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge

2006-03-01

Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.

Tolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in Benin.

PubMed

Denoeud-Ndam, Lise; Clément, Marie-Caroline; Briand, Valérie; Akakpo, Jocelyn; Agossou, Videhouenou K; Atadokpédé, Félix; Dossou-Gbété, Lucien; Komongui, Didier G; Afangnihoun, Aldric; Girard, Pierre-Marie; Zannou, Djimon-Marcel; Cot, Michel

2012-09-01

To investigate the tolerability of mefloquine intermittent preventive treatment (MQ IPTp) for malaria in HIV-infected pregnant women compared with HIV-negative women. Prospective cohort study comparing samples of HIV-negative and HIV-infected pregnant women from 2 clinical trials conducted in Benin. One hundred and three HIV-infected women from the ongoing PACOME trial were compared with 421 HIV-negative women from a former trial, both trials aiming to evaluate the efficacy and tolerability of MQ IPTp, administered at the dose of 15 mg/kg. Descriptive analysis compared the proportion of women reporting at least 1 adverse reaction, according to HIV status. Multilevel logistic regression identified factors associated with the probability of reporting an adverse reaction for each MQ intake. Dizziness and vomiting were the most frequent adverse reactions. Adverse reactions were less frequent in HIV-infected women (65% versus 78%, P = 0.009). In multilevel analysis, HIV infection [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.08 to 0.61] decreased the risk for adverse reactions, whereas detectable viral load (OR = 2.46, 95% CI = 1.07 to 5.66), first intake (versus further intakes, OR = 5.26, 95% CI = 3.70 to 7.14), older age (OR = 1.62, 95% CI = 1.13 to 2.32), and higher education level (OR = 1.71, 95% CI = 1.12 to 2.61) increased the risk. Moderate and severe adverse reactions were more frequent when antiretrovirals were started concomitantly with a MQ intake. This study provides reassuring data on the use of MQ IPTp in HIV-infected pregnant women. However frequent, adverse reactions remained moderate and did not impair adherence to MQ IPTp. In this high-risk group, MQ might be an acceptable alternative in case sulfadoxine-pyrimethamine loses its efficacy for intermittent preventive treatment.

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

PubMed

Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

2016-03-16

Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain.

PubMed

Saito, Mariko; Chakraborty, Goutam; Hui, Maria; Masiello, Kurt; Saito, Mitsuo

2016-08-16

Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy). Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7) mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

α-Lipoic acid treatment of aged type 2 diabetes mellitus complicated with acute cerebral infarction.

PubMed

Zhao, L; Hu, F-X

2014-01-01

This study aims to evaluate the efficacy and safety of α-lipoic acid in the treatment of aged type 2 diabetes mellitus (T2DM) complicated with acute cerebral infarction. 90 patients were randomly divided into two groups, on the basis of conventional treatment. The experiment group was administrated with α-lipoic acid, while only Vitamin C for the control group, for 3 consecutive weeks. Before and after the experiment, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels were measured and scored with the NIHSS (National Institutes of Health Stroke Scale), and the changes of blood glucose, insulin function and other indicators were observed. After the treatment, the plasma SOD and GSH-Px levels increased, while MDA decreased (p < 0.05), with statistical significance when compared with the control group (p < 0.01). NIHSS score, blood glucose, blood lipids and HOMA-IA of the experiment group decreased significantly (p < 0.01); and no significant adverse reactions were found in both groups. α-lipoic acid was safe and effective in the treatment of aged T2DM complicated with acute cerebral infarction, significantly reducing the patient's oxidative stress, blood glucose and lipid levels and being able to improve islet function.

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

PubMed

Akosman, Cengiz; Ordu, Cetin; Eroglu, Elif; Oyan, Basak

2015-01-01

Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

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

2011-01-01

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

Safety of benzathine penicillin for preventing congenital syphilis: a systematic review.

PubMed

Galvao, Tais F; Silva, Marcus T; Serruya, Suzanne J; Newman, Lori M; Klausner, Jeffrey D; Pereira, Mauricio G; Fescina, Ricardo

2013-01-01

To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis. We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses. From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low. Studies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

75 FR 29352 - Draft Guidance for Industry on Data Elements for Submission of Veterinary Adverse Event Reports...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-25

... filling out form FDA 1932, ``Veterinary Adverse Drug Reaction, Lack of Effectiveness, Product Defect... Drug Reaction, Lack of Effectiveness, Product Defect Report.'' II. Significance of Guidance This level...

75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...) prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia...

Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

PubMed Central

Lionberger, David R; Brennan, Michael J

2010-01-01

The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions. PMID:21197326

Antibiotics for the common cold and acute purulent rhinitis.

PubMed

Kenealy, Tim; Arroll, Bruce

2013-06-04

It has long been believed that antibiotics have no role in the treatment of common colds yet they are often prescribed in the belief that they may prevent secondary bacterial infections. To determine the efficacy of antibiotics compared with placebo for reducing general and specific nasopharyngeal symptoms of acute upper respiratory tract infections (URTIs) (common colds).To determine if antibiotics have any influence on the outcomes for acute purulent rhinitis and acute clear rhinitis lasting less than 10 days before the intervention.To determine whether there are significant adverse outcomes associated with antibiotic therapy for participants with a clinical diagnosis of acute URTI or acute purulent rhinitis. For this 2013 update we searched CENTRAL 2013, Issue 1, MEDLINE (March 2005 to February week 2, 2013), EMBASE (January 2010 to February 2013), CINAHL (2005 to February 2013), LILACS (2005 to February 2013) and Biosis Previews (2005 to February 2013). Randomised controlled trials (RCTs) comparing any antibiotic therapy against placebo in people with symptoms of acute upper respiratory tract infection for less than seven days, or acute purulent rhinitis less than 10 days in duration. Both review authors independently assessed trial quality and extracted data. This updated review included 11 studies. Six studies contributed to one or more analyses related to the common cold, with up to 1047 participants. Five studies contributed to one or more analyses relating to purulent rhinitis, with up to 791 participants. One study contributed only to data on adverse events and one met the inclusion criteria but reported only summary statistics without providing any numerical data that could be included in the meta-analyses. Interpretation of the combined data is limited because some studies included only children, or only adults, or only males; a wide range of antibiotics were used and outcomes were measured in different ways. There was a moderate risk of bias because of unreported methods details or because an unknown number of participants were likely to have chest or sinus infections.Participants receiving antibiotics for the common cold did no better in terms of lack of cure or persistence of symptoms than those on placebo (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.59 to 1.51, (random-effects)), based on a pooled analysis of six trials with a total of 1047 participants. The RR of adverse effects in the antibiotic group was 1.8, 95% CI 1.01 to 3.21, (random-effects). Adult participants had a significantly greater risk of adverse effects with antibiotics than with placebo (RR 2.62, 95% CI 1.32 to 5.18) (random-effects) while there was no greater risk in children (RR 0.91, 95% CI 0.51 to 1.63).The pooled RR for persisting acute purulent rhinitis with antibiotics compared to placebo was 0.73 (95% CI 0.47 to 1.13) (random-effects), based on four studies with 723 participants. There was an increase in adverse effects in the studies of antibiotics for acute purulent rhinitis (RR 1.46, 95% CI 1.10 to 1.94). There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults. There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis. Routine use of antibiotics for these conditions is not recommended.

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

PubMed

Gutiérrez Fernández, D; Moreno-Ancillo, A; Fernández Meléndez, S; Domínguez-Noche, C; Gálvez Ruiz, P; Alfaya Arias, T; Carballada González, F; Alonso Llamazares, A; Marques Amat, L; Vega Castro, A; Antolín Amérigo, D; Cruz Granados, S; Ruiz León, B; Sánchez Morillas, L; Fernández Sánchez, J; Soriano Gomis, V; Borja Segade, J; Dalmau Duch, G; Guspi Bori, R; Miranda Páez, A

2016-01-01

Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.

PubMed

Wells, Adam J; Hoffman, Jay R; Gonzalez, Adam M; Stout, Jeffrey R; Fragala, Maren S; Mangine, Gerald T; McCormack, William P; Jajtner, Adam R; Townsend, Jeremy R; Robinson, Edward H

2013-06-01

Phosphatidylserine (PS) may attenuate the adverse effects of physical fatigue. Therefore, we investigated the effects of a multi-ingredient supplement containing 400 mg/d PS and 100 mg/d caffeine (supplement [SUP]) for 2 weeks on measures of cognitive function (CF), reaction time (RT), and mood (MD) following an acute exercise stress. It is hypothesized that PS will maintain preexercise CF and RT scores, while attenuating postexercise fatigue. Participants completed 2 acute bouts of resistance exercise (T1 and T2) separated by 2-week ingestion of SUP or control (CON). Outcome measures were assessed pre- and postexercise. When collapsed across groups, a significant decrease in RT performance was seen in the 60-second reaction drill from pre- to postexercise at T1. All other RT tests were similar from pre- to postexercise at T1. Reaction time was not significantly changed by PS. When collapsed across groups, a significant increase in performance of the serial subtraction test was seen. A significant increase (8.9% and 7.1%) in the number of correct answers and a significant decrease (8.0% and 7.5%) in time to answer were seen from pre- to postworkout at T1 and T2, respectively. A significant increase in total MD score from pre- to postworkout was observed for CON but not for PS at T2. Phosphatidylserine significantly attenuated pre- to postexercise perception of fatigue compared to CON. Ingestion of SUP for 14 days appears to attenuate postexercise MD scores and perception of fatigue, but does not affect CF or RT, in recreationally trained individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2006-02-01

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

Guided surgical debridement: staining tissues with methylene blue.

PubMed

Dorafshar, Amir H; Gitman, Marina; Henry, Ginard; Agarwal, Shailesh; Gottlieb, Lawrence J

2010-01-01

Precise surgical debridement of wounds is required to achieve wound closure. The authors describe their experience with a technique using topical methylene blue to facilitate precise surgical debridement. In this technique, methylene blue dye is applied topically to the wound surface at the onset of surgery. The stained wound site is then wiped to remove dye from the surface of normal epithelium; eschar, nonviable tissue, and granulation tissue remain stained. The methylene blue-stained tissue is surgically removed, and the newly debrided surface of the wound is assessed for adequate vascularity and biopsied to verify presence of bacteriologic balance before closure. The authors have used this technique in more than 200 wound debridements during the past year, including acute surgical or traumatic wounds, acute and subacute burn wounds, chronic granulating wounds, partially epithelialized wounds, sinus tracts, and fistulae. No adverse reactions have been noted, even on patients undergoing multiple applications through serial operations. Topical application of methylene blue to wounds with mixed tissue content helps to distinguish between viable and nonviable tissue and between epithelialized and nonepithelialized areas, facilitating more precise and complete wound debridement.

Effect of submucosal application of tramadol on postoperative pain after third molar surgery.

PubMed

Gönül, Onur; Satılmış, Tülin; Bayram, Ferit; Göçmen, Gökhan; Sipahi, Aysegül; Göker, Kamil

2015-10-14

The aim of this study was to evaluate the effectiveness of submucosal application of tramadol, for acute postoperative facial pain, following the extraction of impacted third molar teeth. This prospective, double-blind, randomised placebo-controlled study included 60 ASA I-II patients undergoing impacted third molar surgery under local anaesthesia. Following the surgical procedure, patients were randomly divided into two groups; group T (1 mg/kg tramadol) and group S (2-mL saline). Treatments were applied submucosally after surgery. Pain after extraction was evaluated using a visual analogue scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 h postoperatively. The time at which the first analgesic drug was taken, the total analgesic dose used, and adverse tissue reactions were also evaluated. In group T, postoperative VAS scores were significantly lower compared to that in group S (p < 0.05). This study demonstrated that post-operative submucosal application of tramadol is an effective method for reducing acute post-operative facial pain after impacted third molar surgery.

Life-Threatening Atypical Case of Acute Generalized Exanthematous Pustulosis.

PubMed

Tajmir-Riahi, Azadeh; Wörl, Petra; Harrer, Thomas; Schliep, Stefan; Schuler, Gerold; Simon, Miklos

2017-01-01

Antibiotics are known to cause severe cutaneous adverse reactions, such as the rare acute generalized exanthematous pustulosis (AGEP). Unlike Stevens-Johnson syndrome or toxic epidermal necrolysis, AGEP is rarely life-threatening. Systemic involvement is not typical, and if present usually coincides with a mild elevation of the hepatic enzymes and a decrease in renal function. Hence, AGEP is known to have a good prognosis and to be life-threatening only in elderly patients or patients with chronic diseases. Herein, we report a case of AGEP in a young healthy male leading to systemic inflammatory response syndrome and to treatment in an intensive care unit after being treated with 5 different antibiotics. Initial symptoms were not indicative for AGEP and the patient's course of disease led promptly to critical cardiorespiratory symptoms and systemic inflammatory response syndrome. We assume that the administration of the 5 different antibiotics resulted in type IV allergy as well as secondary infection with Enterococcus faecium and Staphylococcus aureus, while the underlying periodontitis also contributed to the severity of this case. © 2017 S. Karger AG, Basel.

Hepatotoxicity due to red bush tea consumption: a case report.

PubMed

Reddy, Shamantha; Mishra, Pragnyadipta; Qureshi, Sana; Nair, Singh; Straker, Tracey

2016-12-01

Many conventional drugs used today, including isoniazid, dapsone, and acetaminophen, are well recognized culprits of hepatotoxicity. With increasing use of complementary and alternative medical therapies, several herbal medicines, such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins. Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies when taken in excessive quantities. A myriad of liver dysfunctions may occur including transient liver enzyme abnormalities due to acute and chronic hepatitis. These herbal products are often overlooked as the causal etiologic agent during the evaluation of a patient with elevated liver function tests. We describe a case of hepatotoxicity due to ingestion of red bush tea diagnosed during preoperative assessment of a patient scheduled for laparoscopic appendectomy. Elevated liver enzymes and thrombocytopenia detected in the patient's laboratory work up confounded the initial diagnosis of acute appendicitis and additional investigations were required to rule out cholecystitis and other causes of hepatitis. Open appendectomy was done uneventfully under spinal anesthesia without any further deterioration of hepatic function. Copyright © 2016. Published by Elsevier Inc.

Preclinical evaluation of zinc phthalocyanine tetrasulfonate-based PDT

NASA Astrophysics Data System (ADS)

Borgatti-Jeffreys, Antonella; Hooser, Stephen B.; Miller, Margaret A.; Thomas, Rose M.; deGortari, Amalia; Lucroy, Michael D.

2005-04-01

Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second-generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available. ZnPcS4 was given to Swiss Webster mice to assess acute toxicity. Doses >100 mg/kg were associated with acute toxicity and mortality, and doses >100 mg/kg resulted in renal tubular nephrosis, suggesting that the minimum toxic dose is approximately 100 mg/kg. Based on these data, a Phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs is underway, with ZnPcS4 doses up to 2 mg/kg producing no apparent toxicity. Tumor response has been observed after ZnPcS4-based PDT using doses as low as 0.25 mg/kg, suggesting that conventional phase I clinical trials may not be appropriate for PDT protocols.

[Clinical and pharmacokinetics evaluation of flomoxef in pediatrics].

PubMed

Higashino, H; Kobayashi, T; Shuto, K; Matsui, T; Hasui, M; Nogi, S; Adachi, Y; Kobayashi, Y; Araki, A; Sonoda, N

1987-08-01

Flomoxef (FMOX, 6315-S), a new parenteral oxacephem antibiotic was investigated for its clinical efficacy and pharmacokinetics. The results obtained are summarized below. 1. Twenty-eight patients were treated with 39-152 mg/kg per day of FMOX by intravenous administration. Diagnosis of patients were pneumonia in 15 patients, acute upper respiratory tract infection in 5, acute enterocolitis in 3, urinary tract infection in 2 and cholangitis, suppurative lymphadenitis and suspicious sepsis in 1 patient each. Clinical effect was excellent in 7 cases, good in 8, fair in 5, poor in 2 and 6 cases were excluded because therapy periods were too short and other antibiotics were used together. Efficacy rate was 68% and the rate of bacterial disappearance was 83%. 2. Rash was found in 5 cases and thrombocytosis was found in 1 out of 28 cases. However, no severe adverse reaction was encountered. 3. The peak serum level of FMOX was 51.0 micrograms/ml after 20 mg/kg of drip infusion for 30 minutes and the half-life was 17.2 minutes in alpha-phase and 58.2 minutes in beta-phase.

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

PubMed

Stang, P E; Fox, J L

1992-02-01

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

Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia.

PubMed

Paula, Francisco Danilo Ferreira; Elói-Santos, Silvana Maria; Xavier, Sandra Guerra; Ganazza, Mônica Aparecida; Jotta, Patricia Yoshioka; Yunes, José Andrés; Viana, Marcos Borato; Assumpção, Juliana Godoy

2015-01-01

Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. Seventy-four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan-Meier and multivariate Cox methods and the log-rank test were used for statistical analysis. Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1×10(-3) for precursor B-cell acute lymphoblastic leukemia and 1×10(-2) for T-cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1%±5.6% versus 41.7%±17.3%, respectively; p-value=0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. Copyright © 2015 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

[Allergy to ranitidine: one case report and literature review].

PubMed

Cuevas-Castillejos, Héctor; Cuevas-Castillejos, José Elihú; García-Murray, Oscar; Larenas-Linnemann, Désirée

2013-01-01

Ranitidine is a drug, which seldom causes adverse reactions, nevertheless, allergic reactions have been described varying in type and intensity after its administration. In contrast to other drugs, there are not many validated and standardized diagnostic tests in order to demonstrate this drug produces an allergic reaction. In this article we present a 9-months-old girl with a ranitidine allergic reaction with the diagnosis established by a non-intentional challenge test. We also provide information from the National Drug Surveillance Center in Mexico concerning ranitidine adverse drug reactions (including allergic reactions) in a 10-year period.

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

PubMed

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

2012-01-01

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

Acute gouty arthritis complicated with acute ST elevation myocardial infarction is independently associated with short- and long-term adverse non-fatal cardiac events.

PubMed

Liu, Kuan-Liang; Lee, Hsin-Fu; Chou, Shing-Hsien; Lin, Yen-Chen; Lin, Chia-Pin; Wang, Chun-Li; Chang, Chi-Jen; Hsu, Lung-An

2014-01-01

Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.

Children's disaster reactions: the influence of family and social factors.

PubMed

Pfefferbaum, Betty; Jacobs, Anne K; Houston, J Brian; Griffin, Natalie

2015-07-01

This review examines family (demographics, parent reactions and interactions, and parenting style) and social (remote effects, disaster media coverage, exposure to secondary adversities, and social support) factors that influence children's disaster reactions. Lower family socioeconomic status, high parental stress, poor parental coping, contact with media coverage, and exposure to secondary adversities have been associated with adverse outcomes. Social support may provide protection to children in the post-disaster environment though more research is needed to clarify the effects of certain forms of social support. The interaction of the factors described in this review with culture needs further exploration.

Beneficial Effect of Beraprost Sodium Plus Aspirin in the Treatment of Acute Ischemic Stroke.

PubMed

Chen, Siqia; Xie, Sisi; He, Wenzhen; Wei, Duncan; Li, Shunxian; Chen, Wenjie

2017-09-12

BACKGROUND To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). MATERIAL AND METHODS 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. RESULTS Initially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. CONCLUSIONS In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

International, prospective haemovigilance study on methylene blue-treated plasma.

PubMed

Noens, L; Vilariño, Ma D; Megalou, A; Qureshi, H

2017-05-01

Methylene blue is a phenothiazine dye, which in combination with visible light has virucidal and bactericidal properties, disrupting the replication of a broad range of enveloped viruses and some non-enveloped viruses. The study objective was to collect data on adverse reactions occurring with methylene blue plasma administered in a routine clinical practice environment and document their characteristics and severity. This was an open label, multicentre, non-controlled, non-randomized, non-interventional study. Patients who receive a methylene blue plasma transfusion were observed for any signs and symptoms (adverse reactions) within 24 h safter the start of the transfusion, in different hospitals for a study duration of at least 1 year. A total of 19 315 methylene blue plasma units were transfused. There were eight patients with adverse reactions recorded during the study, one of them serious. Two had more than one reaction (two and four, respectively). Three patients had previous transfusions with methylene blue plasma only. Methylene blue plasma has a very acceptable safety profile with a rate of serious adverse reactions of 0·5/10 000 units. © 2017 International Society of Blood Transfusion.

Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

PubMed

Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

2017-12-19

Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]). Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

Short-term effects of air pollution, markers of endothelial activation, and coagulation to predict major adverse cardiovascular events in patients with acute coronary syndrome: insights from AIRACOS study.

PubMed

Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Rodríguez, Sergio; Avanzas, Pablo; Juarez-Prera, Ruben A

2017-07-01

The aim of this study was to determine whether markers of inflammation and coagulation are associated with short-term particulate matter exposure and predict major adverse cardiovascular events at 360 d in patients with acute coronary syndrome (ACS). We included 307 consecutive patients, and assessed the average concentrations of data on atmospheric pollution in ambient air and meteorological variables from 1 d up to 7 d prior to admission. In patients with ACS, the markers of endothelial activation and coagulation, but not black carbon exposure, are associated with major adverse cardiovascular events at one-year follow-up.

Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

PubMed Central

Makowska, Joanna S.

2015-01-01

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management. PMID:25749768

Hypersensitivity reaction to β-lactam antibiotics in patients with adult T-cell leukemia/lymphoma treated with mogamulizumab
.

PubMed

Yasu, Takeo; Imai, Yoichi; Ohno, Nobuhiro; Uchimaru, Kaoru; Kurokawa, Yosuke; Tojo, Arinobu

2017-10-01

Mogamulizumab (MOG) is a humanized anti-CCR4 monoclonal antibody that is highly cytotoxic for adult T-cell leukemia/lymphoma (ATL) cells. Most non-hematological adverse events are cutaneous adverse reactions in ATL patients. We reviewed the medical records of 24 patients with CCR4-positive aggressive ATL who had received MOG treatment. The incidence of MOG-induced cutaneous adverse reactions (MCARs) was 25% (6 patients). Four patients with MCAR had an interesting clinical course, compared with MCARs reported in previous reports. The factors causing MCAR were suspected to be cefepime, cefozopran, and piperacillin/tazobactam. We consider that hypersensitivity reaction to β-lactam antibiotics is involved in a significant proportion of MCARs.
.

Short term safety assessment of cilazapril.

PubMed

Coulter, D M

1993-11-24

To undertake an event monitoring study of cilazapril in general practice during the early marketing period, to provide some comparisons with other angiotensin converting enzyme inhibitors and to assess the monitoring method. The monitoring was undertaken in the Intensive Medicines Monitoring Programme. Cilazapril was prescribed for mild to moderate hypertension in 996 patients at a recommended dose of 2.5-5.0 mg daily. The monitoring period was six months and practitioners were asked to report all adverse events. A reaction profile was prepared and compared with profiles for lisinopril, enalapril and captopril. The chi-square test was applied to differences in proportions. There were 84 (8.4%) reports describing 133 adverse events; 124 (93%) were assessed as reactions. Withdrawals totalled 53 (5.3%). The most common reactions were cough (2.9%), nausea and vomiting (1.3%) and lethargy (1.1%). Cilazapril had a higher proportion of neurological reactions (p < 0.001) (mainly headache) but a lower proportion of skin reactions (p = 0.001) than the other ACE inhibitors. It also had relatively less diarrhoea and there were differences in the patterns of psychiatric reactions. Cilazapril has a similar reaction profile to other ACE inhibitors but this paper shows differences, some not previously reported, that may assist selection when prescribing. Although there was a high rate of reporting of known adverse reactions, other events were reported at a very low rate and spontaneous reporting is thus confirmed as an unreliable method of monitoring for unexpected adverse reactions.

The role of maladaptive appraisals in child acute stress reactions.

PubMed

Salmon, Karen; Sinclair, Emma; Bryant, Richard A

2007-06-01

To test the prediction of cognitive models of trauma that negative, catastrophic appraisals central to the development of psychopathological stress reactions. A cross-sectional, concurrent design was used. Sixty-six children (aged 7-13 years), who were hospitalized after traumatic injury were assessed within 4 weeks of their trauma for acute stress disorder, depression, and administered the Child Post-traumatic Cognitions Inventory (cPTCI). Parental acute stress was also assessed. Children's negative appraisals of their ongoing vulnerability accounted for 44% of the variance of acute stress reactions in children. Injury severity, depression, age, and parental acute stress levels did not account for significant additional variance. The findings provide support for cognitive models of trauma adaptation and highlight the importance of assessing children's appraisals of their traumatic experience in order to develop effective interventions.

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

PubMed

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

2015-06-01

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

Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents.

PubMed

McWilliam, Vicki L; Koplin, Jennifer J; Field, Michael J; Sasaki, Mari; Dharmage, Shyamali C; Tang, Mimi L K; Sawyer, Susan M; Peters, Rachel L; Allen, Katrina J

2018-03-01

Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

PubMed

Lehloenya, R J; Todd, G; Wallace, J; Ngwanya, M R; Muloiwa, R; Dheda, K

2016-07-01

The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied. To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection. Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated. Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions. In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings. © 2016 British Association of Dermatologists.

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

PubMed

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

2009-08-01

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

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

PubMed Central

Nikfarjam, Azadeh; Gonzalez, Graciela H.

2011-01-01

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

Adversomics: a new paradigm for vaccine safety and design

PubMed Central

Whitaker, Jennifer A.; Ovsyannikova, Inna G.; Poland, Gregory A.

2015-01-01

Summary Despite the enormous population benefits of routine vaccination, vaccine adverse events and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance—and thus to infectious disease prevention—worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine adverse events, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term “adversomics” was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine adverse events/reactions, and outline a plan for the further development of this emerging research field. PMID:25937189

Evaluation of the in-hospital hemovigilance by introduction of the information technology-based system.

PubMed

Fujihara, Harumi; Yamada, Chiaki; Furumaki, Hiroaki; Nagai, Seiya; Shibata, Hiroki; Ishizuka, Keiko; Watanabe, Hiroko; Kaneko, Makoto; Adachi, Miwa; Takeshita, Akihiro

2015-12-01

Hemovigilance is an important aspect of transfusion medicine. However, the frequency of the adverse reactions often varies using different reporters. Recently, we have employed a new information technology (IT)-based in-hospital hemovigilance system. Here, we evaluated changes in practice after implementation of an IT-based reporting system. We compared the rate of frequency and details of blood transfusion-related adverse reactions 3 years before and after introduction of the IT-based reporting system. Contents and severity of the adverse reactions were reported in a paper-based reporting system, but input by selecting items in an IT-based reporting system. The details of adverse reactions are immediately sent to the blood transfusion unit online. After we introduced the IT-based reporting system, the reported rate of transfusion-related adverse reactions increased approximately 10-fold from 0.20% to 2.18% (p < 0.001), and frequencies of urticaria, pruritus, rash, fever (p < 0.001), hypertension (p = 0.001), tachycardia (p = 0.003), and nausea and vomiting (p = 0.010) increased significantly. Although there was no error report in the paper-based reporting, incorrect reports were observed in 90 cases (0.52%) in the IT-based reporting (p < 0.001). The advantages of IT-based reporting were: 1) a significant increase in the frequency of adverse reaction reporting and 2) a significant decrease in underreporting, although the true frequency has yet to be clarified. The disadvantage of the IT-based reporting was an increased incidence of incorrect inputs, all of which was unnoticed by the reporters. Our results showed several important points in need of monitoring after introduction of an IT-based reporting system. © 2015 AABB.

[Reasonable and safe application of Shuxuetong injection and intravenous medication's combined application in acute cerebral infarction's therapy].

PubMed

Li, Ming-Quan; Xie, Yan-Ming; Zhao, Jian-Jun

2012-09-01

Shuxuetong injection is a kind of compound injection which is made from traditional Chinese medicine Hirudo and Pheretime, which has a clear anticoagulant, fibrinolytic promoting, blood rheology improving, blood lipids regulating and cell protecting effect, and the injection has been widely used in clinical. Especially, the injection has often been combined with other Chinese and modern medicine in the treatment of cerebral infarction disease. However, there are still many non-standard and irrational aspects in clinical practice so as to make a more reasonable and safer use of Shuxuetong injection. In order to avoid the occurrence of adverse reactions to provide a reference for regulating the use of the injection,the paper systematically expounds the Shuxuetong injection's main clinical problems and the reasonable combination.

Four cases of investigational therapy with interleukin-11 against acute myocardial infarction.

PubMed

Nakagawa, Masashi; Owada, Yasuko; Izumi, Yasukatsu; Nonin, Shinichi; Sugioka, Kenichi; Nakatani, Daisaku; Iwata, Shinichi; Mizutani, Kazuki; Nishimura, Satoshi; Ito, Asahiro; Fujita, Suwako; Daimon, Takashi; Sawa, Yoshiki; Asakura, Masanori; Maeda, Makiko; Fujio, Yasushi; Yoshiyama, Minoru

2016-09-01

We describe four cases of the patients with ST-elevation myocardial infarction (STEMI) that were treated with interleukin-11 (IL-11), a cardioprotective cytokine. Recombinant human IL-11 (rhIL-11), was intravenously administered to two cases at low dose (6 µg/kg) and to two at high dose (25 µg/kg). The cytokine administration started just after the coronary occlusion was confirmed by coronary angiography (CAG), taking 3 h. Following CAG, percutaneous coronary intervention (PCI) was performed as a standard therapy. No serious adverse drug reactions were observed. All the cases left the hospital without the symptom of heart failure. We discuss the possibility of the clinical use of rhIL-11 as an adjunct therapy to PCI for the STEMI patients.

Risk factors for repeat adverse asthma events in children after visiting an emergency department.

PubMed

To, Teresa; Wang, Chengning; Dell, Sharon; Fleming-Carroll, Bonnie; Parkin, Patricia; Scolnik, Dennis; Ungar, Wendy

2008-01-01

The aim of this study was to identify risk factors for long-term adverse outcomes in children with asthma after visiting the emergency department (ED). A prospective observational study was conducted at the ED of a pediatric tertiary hospital in Ontario, Canada. Patient outcomes (ie, acute asthma episodes and ED visits) were measured at baseline and at 1- and 6-months post-ED discharge. Time trends in outcomes were assessed using the generalized estimating equations method. Multiple conditional logistic regressions were used to model outcomes at 6 months and examine the impact of drug insurance coverage while adjusting for confounders. Of the 269 children recruited, 81.8% completed both follow-ups. ED use significantly reduced from 39.4% at baseline to 26.8% at 6 months (P < .001), whereas the level of acute asthma episodes remained unchanged. Children with drug insurance coverage were less likely to have acute asthma episodes (adjusted odds ratio [AOR] = 0.36; 95% CI, 0.15-0.85; P < .02) or repeat ED visits (AOR = 0.45; 95% CI, 0.20-0.99; P < .05) at 6 months. Other risk factors for adverse outcomes included previous adverse asthma events and certain asthma triggers (eg, cold/sinus infection). Washing bed linens in hot water weekly was protective against subsequent acute asthma episodes. Our study demonstrated significant improvements in long-term outcomes in children seeking acute care for asthma in the ED. Future efforts remain in targeting the sustainability of improved outcomes beyond 6 months. Risk factors identified can help target vulnerable populations for proper interventions, which may include efforts to maximize insurance coverage for asthma medications and strategies to improve asthma self-management through patient and provider education.

Acute Normal Tissue Reactions in Head-and-Neck Cancer Patients Treated With IMRT: Influence of Dose and Association With Genetic Polymorphisms in DNA DSB Repair Genes

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

Werbrouck, Joke; Ruyck, Kim de; Duprez, Frederic

2009-03-15

Purpose: To investigate the association between dose-related parameters and polymorphisms in DNA DSB repair genes XRCC3 (c.-1843A>G, c.562-14A>G, c.722C>T), Rad51 (c.-3429G>C, c.-3392G>T), Lig4 (c.26C>T, c.1704T>C), Ku70 (c.-1310C>G), and Ku80 (c.2110-2408G>A) and the occurrence of acute reactions after radiotherapy. Materials and Methods: The study population consisted of 88 intensity-modulated radiation therapy (IMRT)-treated head-and-neck cancer patients. Mucositis, dermatitis, and dysphagia were scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into a CTC0-2 and CTC3+ group for the analysis of each acute effect. The influence of the dose on critical structures was analyzed using dose-volumemore » histograms. Genotypes were determined by polymerase chain reaction (PCR) combined with restriction fragment length polymorphism or PCR-single base extension assays. Results: The mean dose (D{sub mean}) to the oral cavity and constrictor pharyngeus (PC) muscles was significantly associated with the development of mucositis and dysphagia, respectively. These parameters were considered confounding factors in the radiogenomics analyses. The XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes were significantly associated with the development of severe dysphagia (CTC3+). No association was found between the investigated polymorphisms and the development of mucositis or dermatitis. A risk analysis model for severe dysphagia, which was developed based on the XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes and the PC dose, showed a sensitivity of 78.6% and a specificity of 77.6%. Conclusions: The XRCC3c.722C>T and Ku70c.-1310C>G polymorphisms as well as the D{sub mean} to the PC muscles were highly associated with the development of severe dysphagia after IMRT. The prediction model developed using these parameters showed a high sensitivity and specificity.« less

Correction to: Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials.

PubMed

Ballow, Mark; Wasserman, Richard L; Jolles, Stephen; Chapel, Helen; Berger, Mel; Misbah, Siraj A

2018-04-27

The article Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials, written by Mark Ballow, Richard L. Wasserman, Stephen Jolles, Helen Chapel, Mel Berger, Siraj A. Misbah, was originally published Online First without open access.

Bioabsorbable poly-L/D-lactide (96/4) scaffold arthroplasty (RegJoint™) for trapeziometacarpal osteoarthritis: a 3-year follow-up study.

PubMed

Mattila, Simo; Ainola, Mari; Waris, Eero

2018-05-01

The poly-L/D-lactide joint scaffold (RegJoint™) has recently been associated with adverse tissue reactions and osteolysis after partial trapeziectomy for trapeziometacarpal osteoarthritis. Twenty-two of 23 patients previously operated on with this scaffold were re-examined at a mean follow-up of 3.3 years (range 36-53 months). Overall, the results showed an unacceptably high rate of adverse tissue reactions related to the degradation process of the implant, resulting in a revision procedure in three patients. At final follow-up, at which point the implant had completely degraded, there were no signs of ongoing adverse tissue reactions. There was a significant decrease in pain, increase in strength and subjective improvement in function at final follow-up compared with the pre-operative results in patients who had not undergone revision surgery. However, owing to the high incidence of adverse tissue reactions, the use of the implant has been discontinued in the treatment of trapeziometacarpal osteoarthritis. IV.

Chemical research on red pigments after adverse reactions to tattoo.

PubMed

Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

2016-03-01

Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

The effect of vitamin E on acute skin reaction caused by radiotherapy.

PubMed

Dirier, A; Akmansu, M; Bora, H; Gurer, M

2007-09-01

Ionizing radiation affects healthy organs and tissues as well as diseased tissues during radiation therapy. Skin reactions varying from acute erythema to necrosis can be seen. It has been found that vitamin E can prevent mutagenic and/or carcinogenic effects of ionizing radiation in both animals and cell cultures. This study investigated the preventative effect of antioxidant vitamin E on irradiation-induced acute skin reactions. No protective effect of vitamin E was demonstrated. It is possible that the vehicle induced free radical exposure in the irradiated skin.

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

PubMed

Bobes, Julio; Rejas, J; Garcia-Garcia, M; Rico-Villademoros, F; García-Portilla, M P; Madrigal, M; Hernández, G

2002-09-01

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ 2 ) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ 2 : p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ 2 : p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ 2 : p < 0.05). Olanzapine, quetiapine and risperidone also showed a lower risk of EPS than haloperidol when adjusting by dose. Our results suggest that the atypical antipsychotics studied are less likely to induce extrapyramidal adverse reactions compared with haloperidol in stabilised patients, although these reactions are still common.

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

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

Paravati, Anthony J., E-mail: Anthony.J.Paravati@dartmouth.edu; Russo, Andrea L.; Aitken, Candice

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

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

PubMed

Pande, Sushil

2018-01-01

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

Potential Therapeutic Effects of Psilocybin.

PubMed

Johnson, Matthew W; Griffiths, Roland R

2017-07-01

Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

Reevaluation of the post-marketing safety of Shuxuening injection based on real-world and evidence-based evaluations.

PubMed

Wang, Can; Shi, Qing-Ping; Ding, Feng; Jiang, Xiao-Dong; Tang, Wei; Yu, Mei-Ling; Zhu, Jian-Hua

2018-01-01

To evaluate the factors influencing suspected hypersensitivity and adverse systemic reactions after Shuxuening injection and to provide innovative ideas and methods for the reevaluation of post-marketing safety of Shuxuening. This study used a prospective, nested case-control study design, combined with a prescription sequence analysis design method. It classified patients who exhibited trigger signals after administration of Shuxuening injection as suspected allergic patients and made comparisons with patients who did not report adverse effects to calculate the correlation between relevant risk factors and suspected allergic reactions. Randomized controlled studies and cohort studies of the adverse drug reaction (ADR) of Shuxuening were performed using a computer database. Data retrieval was carried out by the foundation governing the individual database. Meta-analysis was performed by using R3.2.3 software to evaluate the ADRs of Shuxuening. The results of real-world study showed that administration of Shuxuening in combination with potassium aspartate and magnesium, atorvastatin calcium, Shengmai injection, pantoprazole sodium, or high-dose medication was a risk factor for suspected allergic reactions. Meta-analysis showed that the incidence of adverse events was 5.84% (95% CI 0.0499; 0.0674), and serious adverse reaction rate was 4.36% (95% CI 0.0188; 0.0760) when Shuxuening was used in combination with these drugs. The incidence of allergic reaction was also influenced by the vehicle, duration of treatment, single dose, and indicated vs off-label use. Risk factors for adverse reaction following the use of Shuxuening injection in patients are associated with a single dose, vehicle, type of disease, and combination with potassium aspartate, atorvastatin calcium, Shengmai injection, injection with pantoprazole sodium, and other drugs. Physicians should be careful to follow guidelines when administering this drug. We further propose that the unique methodology used in this study may be useful for reevaluation of the safety of other traditional Chinese medicines.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions.

PubMed

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions.

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

Cutaneous drug reaction case reports: from the world literature.

PubMed

2003-01-01

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

An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine.

PubMed

Wauters, Robert H; Hernandez, Camellia L; Petersen, Maureen M

2017-09-19

Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

From a Viewpoint of Clinical Settings: Pharmacoepidemiology as Reverse Translational Research (rTR).

PubMed

Kawakami, Junichi

2017-01-01

Clinical pharmacology and pharmacoepidemiology research may converge in practise. Pharmacoepidemiology is the study of pharmacotherapy and risk management in patient groups. For many drugs, adverse reaction(s) that were not seen and/or clarified during research and development stages have been reported in the real world. Pharmacoepidemiology can detect and verify adverse drug reactions as reverse translational research. Recently, development and effective use of medical information databases (MID) have been conducted in Japan and elsewhere for the purpose of post-marketing safety of drugs. The Ministry of Health, Labour and Welfare, Japan has been promoting the development of 10-million scale database in 10 hospitals and hospital groups as "the infrastructure project of medical information database (MID-NET)". This project enables estimation of the frequency of adverse reactions, the distinction between drug-induced reactions and basal health-condition changes, and usefulness verification of administrative measures of drug safety. However, because the database information is different from detailed medical records, construction of methodologies for the detection and evaluation of adverse reactions is required. We have been performing database research using medical information system in some hospitals to establish and demonstrate useful methods for post-marketing safety. In this symposium, we aim to discuss the possibility of reverse translational research from clinical settings and provide an introduction to our research.

In silico design, chemical synthesis and toxicological evaluation of 1,3-thiazolidine-2,4-dione derivatives as PPARγ agonists.

PubMed

Alemán-González-Duhart, Diana; Tamay-Cach, Feliciano; Correa-Basurto, José; Padilla-Martínez, Itzia Irene; Álvarez-Almazán, Samuel; Mendieta-Wejebe, Jessica Elena

2017-06-01

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the metabolism of lipids and carbohydrates. The exogenous ligands of these receptors are thiazolidinediones (TZDs), which are used to treat type 2 diabetes mellitus (DM2). However, drugs from this group produce adverse effects such as hepatic steatosis. Hence, the aim of this work was to design a set of small molecules that can activate the γ isoform of PPARs while minimizing the adverse effects. The derivatives were designed containing the polar head of TZD and an aromatic body, serving simultaneously as the body and tail. Two ligands were selected out of 130 tested. These compounds were synthesized in a solvent-free reaction and their physicochemical properties and toxicity were examined. Acute oral toxicity was determined by administering these compounds to female Wistar rats in increasing doses (as per the OECD protocol 425). The median lethal dose (LD50) of the compound substituted with a hydroxyl heteroatom was above 2000 mg/kg, and that of the compound substituted with halogens was 700-1400 mg/kg. The results suggest that the compounds can interact with PPARγ and elicit biological responses similar to other TZDs, but without showing adverse effects. The compounds will be subsequently evaluated in a DM2 animal model. Copyright © 2017. Published by Elsevier Inc.

78 FR 41412 - Advisory Commission of Childhood Vaccines; Request for Nominations for Voting Members

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

... Services Administration, HHS. ACTION: Notice. SUMMARY: The Health Resources and Services Administration... that result in fewer or no significant adverse reactions; surveying federal, state, and local programs... childhood vaccines, including the adverse reaction reporting requirements of section 2125(b); advising the...

Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

2007-01-01

Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.

PubMed

Muraro, A; Werfel, T; Hoffmann-Sommergruber, K; Roberts, G; Beyer, K; Bindslev-Jensen, C; Cardona, V; Dubois, A; duToit, G; Eigenmann, P; Fernandez Rivas, M; Halken, S; Hickstein, L; Høst, A; Knol, E; Lack, G; Marchisotto, M J; Niggemann, B; Nwaru, B I; Papadopoulos, N G; Poulsen, L K; Santos, A F; Skypala, I; Schoepfer, A; Van Ree, R; Venter, C; Worm, M; Vlieg-Boerstra, B; Panesar, S; de Silva, D; Soares-Weiser, K; Sheikh, A; Ballmer-Weber, B K; Nilsson, C; de Jong, N W; Akdis, C A

2014-08-01

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Treatment of toxic epidermal necrolysis with moisture-retentive ointment: a case report and review of the literature.

PubMed

Atiyeh, Bishara S; Dham, Ruwayda; Yassin, M Fayez; El-Musa, Kusai A

2003-02-01

Toxic epidermal necrolysis (TEN) is a rare condition that was described by Lyell in 1956. It is a severe, acute, adverse, primarily drug-induced, potentially fatal, cutaneous reaction that is characterized by large areas of skin desquamation and sloughing, similar in many aspects to second-degree burns. The treatment of cutaneous drug reactions rests essentially on immediate diagnosis and recognition of the disease process, accurate history, thorough physical examination, prompt discontinuation of the offending drug, and supportive care. TEN patients are best managed in specialized burn units. Nevertheless, the management remains very much individualized, based on the clinical setting. Topical wound care remains an essential factor in the treatment of burn-like syndromes and is a main determining parameter for morbidity and mortality. As the value of moist environment in wound healing is being fully appreciated, we report on the use of a newly introduced ointment, the Moist Exposed Burn Ointment (Julphar; Gulf Pharmaceutical industries, Ras El-Khaymah, United Arab of Emirutes), a moisture-retentive ointment, in the successful management of a case of TEN.

Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population.

PubMed

Ontiveros, Noe; López-Gallardo, Jesús A; Vergara-Jiménez, Marcela J; Cabrera-Chávez, Francisco

2015-07-21

The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9-13.5) and 7.8 (6.4-9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7-4.8), wheat allergy 0.72% (0.38-1.37); celiac disease 0.08% (0.01-0.45), and NCGS 0.97% (0.55-1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49-1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice.

Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population

PubMed Central

Ontiveros, Noe; López-Gallardo, Jesús A.; Vergara-Jiménez, Marcela J.; Cabrera-Chávez, Francisco

2015-01-01

The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9–13.5) and 7.8 (6.4–9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7–4.8), wheat allergy 0.72% (0.38–1.37); celiac disease 0.08% (0.01–0.45), and NCGS 0.97% (0.55–1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49–1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice. PMID:26197336

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries

PubMed Central

Lev-Ran, Shaul

2017-01-01

Background Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Objective Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. Methods We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration’s Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Results Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). Conclusions These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. PMID:29074469

Afamelanotide for Erythropoietic Protoporphyria.

PubMed

Langendonk, Janneke G; Balwani, Manisha; Anderson, Karl E; Bonkovsky, Herbert L; Anstey, Alexander V; Bissell, D Montgomery; Bloomer, Joseph; Edwards, Chris; Neumann, Norbert J; Parker, Charles; Phillips, John D; Lim, Henry W; Hamzavi, Iltefat; Deybach, Jean-Charles; Kauppinen, Raili; Rhodes, Lesley E; Frank, Jorge; Murphy, Gillian M; Karstens, Francois P J; Sijbrands, Eric J G; de Rooij, Felix W M; Lebwohl, Mark; Naik, Hetanshi; Goding, Colin R; Wilson, J H Paul; Desnick, Robert J

2015-07-02

Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly reduced quality of life. We evaluated the safety and efficacy of an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease pain and improve quality of life. We conducted two multicenter, randomized, double-blind, placebo-controlled trials of subcutaneous implants containing 16 mg of afamelanotide. Patients in the European Union (74 patients) and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to receive a subcutaneous implant containing either afamelanotide or placebo every 60 days (a total of five implants in the European Union study and three in the U.S study). The type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded over the respective 180-day and 270-day study periods. Quality of life was assessed with the use of validated questionnaires. A subgroup of U.S. patients underwent photoprovocation testing. The primary efficacy end point was the number of hours of direct exposure to sunlight without pain. In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug. Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.).

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

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2018-06-07

Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

PubMed

Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

2009-11-01

To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

Patient Safety Learning Laboratory: Making Acute Care More Patient-Centered

ClinicalTrials.gov

2017-03-22

Central Line-Associated Bloodstream Infection (CLABSI); Venous Thromboembolism; Patient Fall; Catheter-Associated Infection; Severe Hypoglycemia; Opioid-Related Severe Adverse Drug Event; Hospital Acquired Pressure Ulcer; Adverse Drug Event; Severe Hospital Acquired Delerium; Rapid Response Related to Arrhythmia

Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type

PubMed Central

Kane, Alice E.; Mitchell, Sarah J.; Mach, John; Huizer-Pajkos, Aniko; McKenzie, Catriona; Jones, Brett; Cogger, Victoria; Le Couteur, David G.; de Cabo, Rafael; Hilmer, Sarah N.

2018-01-01

Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice. PMID:26615879

Renal failure as a suspected adverse reaction to benoxaprofen

PubMed Central

Fine, Wilfred; Tallis, R. C.; Osman, K. M.

1982-01-01

A 77-year-old woman suffering from osteoarthritis was treated with benoxaprofen. She developed diarrhoea, skin rash and renal failure. Renal failure has not been reported before as an adverse reaction to benoxaprofen. The case is discussed in the context of multisystem and immunological response to benoxaprofen. PMID:6213949

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

PubMed

Kim, Seonji; Park, Kyounghoon; Kim, Mi-Sook; Yang, Bo Ram; Choi, Hyun Jin; Park, Byung-Joo

2017-10-01

Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals. Copyright © 2017 Elsevier B.V. All rights reserved.

A double-blind, randomized, controlled trial on N-acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Ataei, Sara; Hadjibabaie, Molouk; Moslehi, Amirhossein; Taghizadeh-Ghehi, Maryam; Ashouri, Asieh; Amini, Elham; Gholami, Kheirollah; Hayatshahi, Alireza; Vaezi, Mohammad; Ghavamzadeh, Ardeshir

2015-06-01

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9 and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan-Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients. Copyright © 2014 John Wiley & Sons, Ltd.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

PubMed

Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

2015-06-26

Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Infectious mononucleosis complicated by acute haemolytic anaemia with a positive Donath-Landsteiner reaction

PubMed Central

Wishart, M. M.; Davey, M. G.

1973-01-01

A patient with infectious mononucleosis complicated by acute haemolytic anaemia is described. The patient had, in addition to non-specific cold agglutinins in the serum, a positive Donath-Landsteiner reaction in the absence of syphilis. The association of a positive Donath-Landsteiner reaction with haemolytic anaemia in infectious mononucleosis has been described only once before. PMID:4714957

Safe use of iodinated and gadolinium-based contrast media in current practice in Japan: a questionnaire survey.

PubMed

Tsushima, Yoshito; Ishiguchi, Tsuneo; Murakami, Takamichi; Hayashi, Hiromitsu; Hayakawa, Katsumi; Fukuda, Kunihiko; Korogi, Yukunori; Sugimoto, Hideharu; Takehara, Yasuo; Narumi, Yoshifumi; Arai, Yasuaki; Kuwatsuru, Ryohei; Yoshimitsu, Kengo; Awai, Kazuo; Kanematsu, Masayuki; Takagi, Ryo

2016-02-01

To help establish consensus on the safe use of contrast media in Japan. Questionnaires were sent to accredited teaching hospitals with radiology residency programs. The reply rate was 45.4% (329/724). For contrast-induced nephropathy (CIN), chronic and acute kidney diseases were considered a risk factor in 96.7 and 93.6%, respectively, and dehydration in 73.9%. As preventive actions, intravenous hydration (89.1%) and reduction of iodinated contrast media dose (86.9%) were commonly performed. For nephrogenic systemic fibrosis (NSF), chronic and acute kidney diseases were considered risk factors in 98.5 and 90.6%, respectively, but use of unstable gadolinium-based contrast media was considered a risk factor in only 55.6%. A renal function test was always (63.5% in iodinated; 65.7% in gadolinium) or almost always (23.1; 19.8%) performed, and estimated glomerular filtration rate (eGFR) was the parameter most frequently used (80.8; 82.6%). For the patients with risk factors for acute adverse reaction (AAR), steroid premedication or/and change of contrast medium were frequent preventive actions, but intravenous steroid administration immediately before contrast media use was still performed. Our questionnaire survey revealed that preventive actions against CIN were properly performed based on patients' eGFR. Preventive actions against NSF and AAR still lacked consensus.

Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

PubMed

Böhm, Ruwen; Cascorbi, Ingolf

2016-01-01

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

Acute stress responses: A review and synthesis of ASD, ASR, and CSR.

PubMed

Isserlin, Leanna; Zerach, Gadi; Solomon, Zahava

2008-10-01

Toward the development of a unifying diagnosis for acute stress responses this article attempts to find a place for combat stress reaction (CSR) within the spectrum of other defined acute stress responses. This article critically compares the diagnostic criteria of acute stress disorder (ASD), acute stress reaction (ASR), and CSR. Prospective studies concerning the predictive value of ASD, ASR, and CSR are reviewed. Questions, recommendations, and implications for clinical practice are raised concerning the completeness of the current acute stress response diagnoses, the heterogeneity of different stressors, the scope of expected outcomes, and the importance of decline in function as an indicator of future psychological, psychiatric, and somatic distress. PsycINFO Database Record 2009 APA.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions

PubMed Central

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions. PMID:29755394

Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis

PubMed Central

Jeon, Tae Joo; Park, Ji Young

2017-01-01

AIM To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. METHODS We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. RESULTS Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. CONCLUSION Elevated baseline NLR correlates with severe acute pancreatitis and organ failure. PMID:28638228

Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis.

PubMed

Jeon, Tae Joo; Park, Ji Young

2017-06-07

To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. Elevated baseline NLR correlates with severe acute pancreatitis and organ failure.

[Vigilance for veterinary medicinal products: Reports of adverse reactions in the year 2015].

PubMed

Müntener, C; Kupper, J; Naegeli, H; Gassner, B

2016-11-01

A total of 292 adverse reactions to veterinary medicinal products were reported during the year 2015. This represents an increase of 9% compared to the previous year (268 reports). Similar to previous years, most of the reactions reported were linked to the use of antiparasitics (55.1%), non-steroidal anti-inflammatory products (8.9%) or antiinfectives (9.3%). The affected animal species were primarily dogs (198 reports) and cats (42 reports), followed by cattle (31 reports) and horses (8 reports). Additional 42 reports were provided within the frame of consultations with Tox Info Suisse in Zürich and involved mainly the excessive intake of flavored tablets. Eight signals were identified from the reports received or the periodic safety update reports. They resulted in revisions of the product information in sections addressing contraindications, adverse reactions or withdrawal times.

How Safe Are Common Analgesics for the Treatment of Acute Pain for Children? A Systematic Review.

PubMed

Hartling, Lisa; Ali, Samina; Dryden, Donna M; Chordiya, Pritam; Johnson, David W; Plint, Amy C; Stang, Antonia; McGrath, Patrick J; Drendel, Amy L

2016-01-01

Background . Fear of adverse events and occurrence of side effects are commonly cited by families and physicians as obstructive to appropriate use of pain medication in children. We examined evidence comparing the safety profiles of three groups of oral medications, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, to manage acute nonsurgical pain in children (<18 years) treated in ambulatory settings. Methods . A comprehensive search was performed to July 2015, including review of national data registries. Two reviewers screened articles for inclusion, assessed methodological quality, and extracted data. Risks (incidence rates) were pooled using a random effects model. Results . Forty-four studies were included; 23 reported on adverse events. Based on limited current evidence, acetaminophen, ibuprofen, and opioids have similar nausea and vomiting profiles. Opioids have the greatest risk of central nervous system adverse events. Dual therapy with a nonopioid/opioid combination resulted in a lower risk of adverse events than opioids alone. Conclusions . Ibuprofen and acetaminophen have similar reported adverse effects and notably less adverse events than opioids. Dual therapy with a nonopioid/opioid combination confers a protective effect for adverse events over opioids alone. This research highlights challenges in assessing medication safety, including lack of more detailed information in registry data, and inconsistent reporting in trials.

Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low osmolar contrast media in high-risk patients.

PubMed

Jung, Jae-Woo; Choi, Young Hun; Park, Chang Min; Park, Heung Woo; Cho, Sang-Heon; Kang, Hye-Ryun

2016-09-01

Corticosteroid prophylaxis has been widely adopted for the prevention of acute allergic-like reactions to iodinated contrast media, but its use is still controversial because there is no strong evidence supporting its efficacy before administration of nonionic low osmolar contrast media (LOCM). To assess the outcomes of premedication in patients with previous acute allergic-like reactions to LOCM in clinical practice. A retrospective study was performed on 322 high-risk patients who were reexposed to LOCM after premedication composed of antihistamines and/or systemic corticosteroids because of a previous history of acute allergic-like reactions to LOCM. After premedication, 275 patients (85.4%) did not experience any reaction, but 47 patients (14.6%) still experienced a breakthrough reaction. The premedication rate and amount of corticosteroid administered were significantly higher in the nonrecurrence group than in the recurrence group (P = .04 and P = .04, respectively), and a linear trend was observed in the use of corticosteroid premedication and the efficacy of prevention (P for trend = .02). Multivariate binary logistic regression revealed that corticosteroid premedication was effective in preventing recurrence (odds ratio, 0.284; 95% confidence interval, 0.103-0.784). Nonetheless, despite corticosteroid premedication, 3.4% of high-risk patients still experienced moderate to severe reactions, and 14.3% of patients with a severe index reaction again had a severe reaction. Premedication with corticosteroids seems to be helpful in reducing the overall rate of recurrence of acute allergic-like reactions to LOCM in high-risk patients, but patients with severe index reactions are still at risk of developing severe reactions despite corticosteroid premedication. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Adverse drug reaction, patent blue V dye and anaesthesia.

PubMed

Tripathy, Swagata; Nair, Priya V

2012-11-01

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

Acute adverse events associated with the administration of Crotalidae polyvalent immune Fab antivenom within the North American Snakebite Registry.

PubMed

Kleinschmidt, Kurt; Ruha, Anne-Michelle; Campleman, Sharan; Brent, Jeffrey; Wax, Paul

2018-04-24

Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.

Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

PubMed

Kularatne, Senanayake A M; Weerakoon, Kosala; Silva, Anjana; Maduwage, Kalana; Walathara, Chamara; Rathnayake, Ishani; Medagedara, Senal; Paranagama, Ranjith; Mendis, Suresh; Kumarasiri, P V R

2016-09-15

The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the timing, rate or severity of adverse drug reactions to antivenom when administered simultaneously and up to 4 h prior to antivenom. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improving education for the management of contrast reactions: an online didactic model.

PubMed

Niell, Bethany L; Vartanians, Vartan M; Halpern, Elkan P

2014-02-01

Radiologists could improve their knowledge of contrast reaction management. The aim of this study was to evaluate to what degree the implementation of a didactic module resulted in improved technologist, nurse, and physician knowledge and comfort levels regarding the appropriate management of adverse reactions to contrast media. After institutional review board approval was obtained, nurses, technologists, and physicians involved in contrast administration were required to complete the educational module. Premodule and postmodule assessments were designed online. Each assessment included knowledge-based questions regarding the appropriate management of different types of contrast reactions, as well as questions regarding each respondent's comfort level with the treatment of various types of adverse contrast reactions. Comfort level was measured using a 6-point, Likert-type scale. Premodule and postmodule assessment scores were compared using McNemar's test. After module completion, physicians demonstrated a statistically significant improvement in knowledge regarding the proper administration route, concentration, and dose of intramuscular epinephrine. Physicians demonstrated significantly increased comfort with the administration of intramuscular epinephrine to adult and pediatric patients after module completion (P < .05). Module completion resulted in statistically significant improvements in respondents' comfort levels with the treatment of an adverse reaction to contrast media, although 19% of personnel still reported feeling uncomfortable after completing the module. Didactic instruction in contrast reaction management results in improved knowledge and comfort levels for physicians, nurses, and technologists. However, a significant percentage of personnel still reported feeling uncomfortable treating an adverse contrast reaction after module completion, suggesting that didactic instruction alone may be inadequate. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins.

PubMed

Schaer, Dominik J; Buehler, Paul W; Alayash, Abdu I; Belcher, John D; Vercellotti, Gregory M

2013-02-21

Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) product in Japan and more recent preclinical animal studies suggest that the natural Hb and the hemin-scavenger proteins Hp and hemopexin have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as RBC transfusion, sickle cell disease, sepsis, and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis.

Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

PubMed

Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

2013-01-01

One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery.

Adverse drug events in the oral cavity.

PubMed

Yuan, Anna; Woo, Sook-Bin

2015-01-01

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Embolia cutis medicamentosa: an unusual adverse reaction to terlipressin

PubMed Central

Gatos-Gatopoulos, Polychronis; Kostantoudakis, Stephanos; Panayiotides, Ioannis G.; Dimitriadis, George D.; Triantafyllou, Konstantinos

2017-01-01

Terlipressin is a synthetic long-acting analog of vasopressin widely used to control variceal bleeding by lowering portal venous pressure. We report an unusual adverse reaction to terlipressin in a 78-year-old patient with esophageal variceal bleeding who developed skin necrosis soon after treatment initiation. Skin biopsy revealed embolia cutis medicamentosa. PMID:29118569

21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Contraindications Warnings and Precautions Adverse Reactions Drug Interactions Use in Specific Populations Full... Adverse Reactions 7 Drug Interactions 8 Use in Specific Populations 8.1 Pregnancy 8.2 Labor and delivery 8... action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 Nonclinical Toxicology 13.1 Carcinogenesis...

Deep vein thrombosis and the oestrogen content in oral contraceptives. An epidemiological analysis.

PubMed

Kierkegaard, A

1985-01-01

Epidemiological studies have pointed to a correlation between the oestrogen content of oral contraceptives and the risk of deep vein thrombosis (DVT). The correlation has been strongest in studies which partially consisted of adverse drug reaction reports to the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The present study analyzes the epidemiological basis of the adverse drug reaction reports on DVT in women on oral contraceptives to SADRAC. It verifies the reported correlation between the oestrogen content of the pills and the risk of DVT but it also demonstrates that this correlation probably was secondary to differences in the diagnostic standard of DVT, to differences in reporting policies to SADRAC and to an age difference between women on low-oestrogen-pills and those on high-oestrogen pills and is thus due to bias. It is concluded that adverse drug reaction reporting on oral contraceptives has been very unreliable, for which reason it cannot support any epidemiological conclusion concerning the relative thrombogenicity of high-oestrogen pills compared with that of low-oestrogen pills.

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

PubMed

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

2013-09-01

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

Dietary trials with a commercial chicken hydrolysate diet in 63 pruritic dogs.

PubMed

Loeffler, A; Lloyd, D H; Bond, R; Kim, J Y; Pfeiffer, D U

2004-04-24

The owners of 63 pruritic dogs were instructed to feed them a chicken hydrolysate diet exclusively for six weeks as part of diagnostic investigations into non-seasonal pruritus. Ectoparasitism and microbial infections were eliminated during the dietary trial. The dogs' skin lesions, gastrointestinal signs and frequency of defecation were assessed and scores for pruritus were assigned before they started the diet and before and after they resumed their original diet. An adverse food reaction was diagnosed if the pruritus resolved while they were on the diet, but recurred when they resumed their original food regimen. Seventeen of the 63 dogs were withdrawn from the trial, including four which found the diet unpalatable; however, its palatability was reported to be good or excellent in 48 of the dogs. An adverse food reaction alone was diagnosed in nine (19.6 per cent) of the 46 dogs and another nine had an adverse food reaction and atopy. There were gastrointestinal signs in six of the nine dogs with an adverse food reaction, which resolved on the trial diet but recurred when they resumed their original diet.

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Flow Microscopy Imaging Is Sensitive to Characteristics of Subvisible Particles in Peginesatide Formulations Associated With Severe Adverse Reactions.

PubMed

Daniels, Austin L; Randolph, Theodore W

2018-05-01

The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relationships are unknown. Images recorded by flow imaging microscopy reflect information about particle morphology, but flow microscopy is typically used to determine only particle size distributions, neglecting information on particle morphological features that may be immunologically relevant. We recently developed computational techniques that utilize the Kullback-Leibler divergence and multidimensional scaling to compare the morphological properties of particles in sets of flow microscopy images. In the current work, we combined these techniques with expectation maximization cluster analyses and used them to compare flow imaging microscopy data sets that had been collected by the U.S. Food and Drug Administration after severe adverse drug reactions (including 7 fatalities) were observed in patients who had been administered some lots of peginesatide formulations. Flow microscopy images of particle populations found in the peginesatide lots associated with severe adverse reactions in patients were readily distinguishable from images of particles in lots where severe adverse reactions did not occur. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

iADRs: towards online adverse drug reaction analysis.

PubMed

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

2012-12-01

Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

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

PubMed

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

2014-10-23

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

Acute and Subchronic Toxicological Evaluations of Allium rotundum L.: A Dietary Plant from Iran.

PubMed

Hosseinzadeh, Leila; Farhangian, Sajad; Hajialyani, Marziyeh; Bahari, Arash; Farzaei, Mohammad Hosein

2018-04-25

Allium rotundum L. is a dietary plant with diverse nutritional and herbal applications. According to its widespread application in Iranians' diets, understanding the possible adverse effects and toxic activities could be of major importance. The aim of this study was to establish the acute and subchronic toxicity profile of the hydroalcoholic extract of Allium rotundum on male and female Wistar rats. The acute study indicated no adverse effect or toxic activity after administration of the extract, suggesting that the LD 50 value is up to 5,000 mg/kg body weight for the extract. The subchronic study at three doses (250, 500, and 750 mg/kg body weight/day) supported the results of acute study and revealed that no abnormal change or toxicity was induced by the extract in both male and female Wistar rats. All the biochemical and hematological parameters of the treated rats were in historical range after long-term administration of the extract. The histopathological examination also revealed no lesion or alteration in the tissue of vital organs (kidney, liver, heart, lung, and spleen). The NOAEL (no observed adverse effect level) value was high enough (greater than 750 mg/kg body weight/ day) to conclude the nontoxic nature of this extract. The safety of this extract was affirmed by the acute and subchronic toxic studies and suggested that this plant could be a proper and effective dietary plant due to its high nutritive value and inherent therapeutic properties.

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

PubMed

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

2016-02-01

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

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru.

PubMed

Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

2011-01-01

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89), anemia (OR = 2.10; IC95%: 1.13-3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6), and smoking (OR = 2.00; 95%CI: 1.03-3.87) were independently associated with adverse drug reactions. Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries.

PubMed

Yom-Tov, Elad; Lev-Ran, Shaul

2017-10-26

Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R 2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. ©Elad Yom-Tov, Shaul Lev-Ran. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.10.2017.

[Hypersensitivity reaction to radio contrast media: diagnosis, prevention and treatment].

PubMed

Mahlab-Guri, Keren; Herskovitz, Pearl; Sthoeger, Zev

2012-07-01

More than 70 million radiographic examinations with radio contrast media are performed worldwide each year. The incidence of adverse reactions to radio contrast media is 5-13%. Adverse reactions include hypersensitivity reactions, chemotoxic reactions and renal toxicity. Hypersensitivity reactions to radio contrast media range from mild pruritus to life-threatening emergency. The differential diagnosis between hypersensitivity reaction to radio contrast media and chemotoxic reaction is challenging. The incidence of chemotoxic reactions is mainly affected by the chemical structure of the radio contrast media and the rate of infusion. The incidence of hypersensitivity radio contrast media reaction is affected by age and by the presence of asthma and other atopic diseases. The diagnosis of hypersensitivity reaction to radio contrast media is based on clinical manifestations. The additional value of laboratory tests is limited and questionable. In case of hypersensitivity radio contrast reaction, the infusion should be stopped immediately, airways should be protected and fluids, oxygen and drugs should be given. Prophylactic treatment before its administration may prevent hypersensitivity reactions to radio contrast media.

Safety assessment of sandalwood oil (Santalum album L.).

PubMed

Burdock, George A; Carabin, Ioana G

2008-02-01

Sandalwood (Santalum album L.) is a fragrant wood from which oil is derived for use in food and cosmetics. Sandalwood oil is used in the food industry as a flavor ingredient with a daily consumption of 0.0074 mg/kg. Over 100 constituents have been identified in sandalwood oil with the major constituent being alpha-santalol. Sandalwood oil and its major constituent have low acute oral and dermal toxicity in laboratory animals. Sandalwood oil was not mutagenic in spore Rec assay and was found to have anticarcinogenic, antiviral and bactericidal activity. Occasional cases of irritation or sensitization reactions to sandalwood oil in humans are reported in the literature. Although the available information on toxicity of sandalwood oil is limited, it has a long history of oral use without any reported adverse effects and is considered safe at present use levels.

The application of computer image analysis in life sciences and environmental engineering

NASA Astrophysics Data System (ADS)

Mazur, R.; Lewicki, A.; Przybył, K.; Zaborowicz, M.; Koszela, K.; Boniecki, P.; Mueller, W.; Raba, B.

2014-04-01

The main aim of the article was to present research on the application of computer image analysis in Life Science and Environmental Engineering. The authors used different methods of computer image analysis in developing of an innovative biotest in modern biomonitoring of water quality. Created tools were based on live organisms such as bioindicators Lemna minor L. and Hydra vulgaris Pallas as well as computer image analysis method in the assessment of negatives reactions during the exposition of the organisms to selected water toxicants. All of these methods belong to acute toxicity tests and are particularly essential in ecotoxicological assessment of water pollutants. Developed bioassays can be used not only in scientific research but are also applicable in environmental engineering and agriculture in the study of adverse effects on water quality of various compounds used in agriculture and industry.

Mortality due to acute adverse drug reactions in Galicia: 1997-2011.

PubMed

Miguel-Arias, Domingo; Pereiro Gómez, César; Bermejo Barrera, Ana M; López de Abajo Rodríguez, Benito; Sobrido Prieto, María

2016-03-02

The aim of this research is to study all people who died in the Autonomous Community of Galicia from acute death after drugconsumption (ADR) in which there was judicial intervention during the period from 1997 to 2011, according to inclusion and exclusión criteria established by the National Drug Plan for the entire national territory. Sociodemographic and clinical characteristics of deceased subjects were studied, in order to identify key risk factors and/or vulnerable populations.A total of 805 deaths were recorded. The distribution by provinces and municipalities corresponds to the areas of greatest population, incidence of consumption and proximity to the coast. The average age of these patients was 34.34 years, with a gradual increase over years. Most of them were male (91.2%) and single (47.7). 43.5% of the deceased habitually used the parenteral route of administration and 36.4% had positive HIV serology. The most frequently-detected substances corresponded to opiates (heroin: 61.3%, methadone: 35.6%), followed by cocaine (53.7%), although the most common pattern was that of poly-consumption. ADR mortality figures remain relatively stable throughout the study period. The predominant pattern is that of males, opiates and a long history of consumption.

Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant.

PubMed

Snipelisky, David F; Kurklinsky, Andrew K; Chirila, Razvan

2015-12-01

Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion.

[Acute lymphoblastic leukemia: a genomic perspective].

PubMed

Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids.

PubMed

Gable, Robert S

2007-01-01

To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyltryptamine and beta-carboline brew (ayahuasca/hoasca) used in religious ceremonies. A systematic literature search, supplemented by interviews with ceremony participants. No laboratory animal models were located that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no evidence that ayahuasca has substantial or persistent abuse potential. Long-term psychological benefits have been documented when ayahuasca is used in a well-established social context. A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.

Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

PubMed

Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

2014-01-01

The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

Subglottic injury, gastric juice, corticosteroids, and peptide growth factors in a porcine model.

PubMed

Yellon, R F; Szeremeta, W; Grandis, J R; Diguisseppe, P; Dickman, P S

1998-06-01

To study the effects of mucosal injury, gastric juice, and corticosteroids and to determine the presence of peptide growth factors in the subglottic mucosa in a porcine model. Prospective cohort animal study. In this model of subglottic injury, five groups (n = 5 each) of piglets were used. Injury was induced by electrocautery (acute), electrocautery plus repeated saline application (chronic), electrocautery plus repeated gastric juice application (chronic plus gastric juice), or repeated gastric juice application (gastric). Control piglets had normal saline applied repeatedly. Histopathologic findings for the gastric juice group included basal cell hyperplasia (80%), squamous metaplasia (80%), and mucosal ulceration (40%). Control piglets showed squamous metaplasia (80%) but no basilar hyperplasia or ulceration. Immunohistochemistry detected peptide growth factors and epidermal growth factor receptor (EGFR) in all groups. Decreased staining was most frequent in the acute injury group. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) documented lower expression of EGFR in the gastric juice group (P = .01). These findings suggest that peptide growth factors and EGFR are part of normal subglottic mucosal turnover. Noxious stimuli decrease production of these factors. Gastric juice had adverse effects documented by histopathology and molecular techniques.

Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

PubMed

Alehashem, Maryam; Baniasadi, Shadi

2018-01-01

A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p < 0.05), dose, and the number of prepared drugs (r = 0.46, p < 0.01 and 0.39, p < 0.05), and working hours in different locations of oncology setting for six weeks (preparation room: r = 0.38, P < 0.05, treatment room: r = 0.46, P < 0.01, patient room: r = 0.63, P < 0.01, and station: r = 0.68, P < 0.01). Due to inadequate control measures, oncology health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

PubMed

Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

2005-02-01

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients.

PubMed

Ann, Heawon; Kim, Ki Hyon; Choi, Hyun Young; Chang, Hyun Ha; Han, Sang Hoon; Kim, Kye Hyung; Lee, Jin Soo; Kim, Yeon Sook; Park, Kyung Hwa; Kim, Young Keun; Sohn, Jang Wook; Yun, Na Ra; Lee, Chang Seop; Choi, Young Wha; Lee, Yil Seob; Kim, Shin Woo

2017-09-01

Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea. Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy

Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

PubMed

Lew, Daniel; Yoon, Soon Man; Yan, Xiaofei; Robbins, Lori; Haritunians, Talin; Liu, Zhenqiu; Li, Dalin; McGovern, Dermot Pb

2017-10-28

To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA ( P = 0.04) and IgG-ASCA ( P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions ( P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic , and pathways associations.

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

PubMed

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

2007-01-01

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

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

PubMed

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

2018-05-01

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

Intradermal reactions to purified protein derivative in patients with diabetes mellitus.

PubMed

Nwabudike, L C; Ionescu-Tîrgovişte, C

2005-01-01

Diabetes mellitus is known to adversely affect the immune system. Immune dysfunction is also associated with the etiology of diabetes mellitus. Immune dysfunction is associated with diminished chemotactic, phagocytic and monocyte activity. There is also increased T-cell activity. All these are associated with acute hyperglycemia. We investigated the cellular arm of the immune system of patients with diabetes mellitus using intradermal reactions (IDR) to purified protein derivative (PPD). Both groups high blood glucose [HBG] vs. low blood glucose [LBG]) were homogeneous in terms of size and sex and average age (24. vs. 22.; 21 F vs 25 M; 56.5yrs. vs. 54.5 yrs.). The LBG had a greater average duration of diabetes (13.6 yrs vs. 9.3 yrs), which suggests an increased tendency to complications of diabetes mellitus. The results showed an average blood glucose and IDR (HBG vs. LBG) of 235.8 +/- 46.5 mg/dl vs. 144.3 +/- 26.7 mg/dl and 18.5 +/- 8.5 mm vs. 12.2 +/- 7.0 mm respectively. These results showed that IDR is significantly affected by hyperglycemia. This increased IDR may be a consequence of the synergy between interferon-gamma and tumor necrosis factor alpha which is a significant factor in diabetes. Also, there is an accentuation of this synergy following injection of PPD. It appears to be clear that IDR to PPD may be influenced by the diabetic state, especially acute hyperglycemia. However, it also appears that IDR to PPD may not be an adequate method for assessing cutaneous cell-mediated immunity.

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

PubMed

Borroni, Riccardo G

2015-01-01

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

Excipients in topical corticosteroid preparations in Canada.

PubMed Central

Searles, G E; DesGroseilliers, J P

1989-01-01

Topical corticosteroids are widely used for the treatment of dermatoses in Canada. The effects of the various nontherapeutic components of these formulations are less well known than those of the active ingredients and may cause adverse reactions. Information on the components is fragmentary and is scattered throughout the literature. We have attempted to consolidate this information into one source. Recent provincial legislation requiring the generic substitution of interchangeable products and the nondisclosure of all ingredients in product labelling hinder the search for an excipient that has caused an adverse reaction. Practitioner participation in the Cutaneous Adverse Reaction Registry of the Canadian Dermatology Association will identify sensitizing excipients and will support efforts by the profession to obtain more effective and safer products. PMID:2766179

Impact of reducing the threshold for acetylcysteine treatment in acute paracetamol poisoning: the recent United Kingdom experience.

PubMed

Bateman, D N; Dear, J W; Carroll, R; Pettie, J; Yamamoto, T; Elamin, M E M O; Peart, L; Dow, M; Coyle, J; Gray, A; Dargan, P I; Wood, D M; Eddleston, M; Thomas, S H L

2014-01-01

On 3 September 2012, the licensed indication for acetylcysteine was changed in the United Kingdom (UK) so that all patients with a plasma paracetamol concentration above a "100 mg/L" (4 h post ingestion) nomogram treatment line after an acute paracetamol (acetaminophen) overdose should be treated. This is a lower threshold than that used in the United States, Canada, Australia, and New Zealand. Here we report the impact of this change in the UK on the management of patients with acute overdose in different paracetamol concentration ranges. This is a cohort study, consisting of a retrospective analysis conducted on prospectively collected audit data in three UK hospitals. Following appropriate ethical and data protection authority approval, data for patients presenting within 24 h of an acute timed single paracetamol overdose were extracted. Numbers of admissions and use of antidote in relation to different paracetamol concentration bands (< 100 mg/L; 100-149 mg/L; 150-199 mg/L; and ≥ 200 mg/L at 4 h) were analyzed for one-year periods before and after the change. Comparing the year before with the year after the change, there was no change in the numbers of patients presenting to hospital within 24 h of acute timed paracetamol overdose (1246 before and 1251 after), but more patients were admitted (759 before and 849 after) and treated with acetylcysteine (389 before and 539 after). Of the 150 additional patients treated with acetylcysteine in the year following the change, 114 (76%, 95% CI: 68.4-82.6) were in the 100-149 group and 9 (6.0%, 95% CI: 2.8-11.1) in the 150-199 group. Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100-149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions.

Smallpox vaccination and adverse reactions. Guidance for clinicians.

PubMed

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

2003-02-21

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.

The clinical safety of high-dose piracetam--its use in the treatment of acute stroke.

PubMed

De Reuck, J; Van Vleymen, B

1999-03-01

Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.

Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections.

PubMed

Schuetz, Philipp; Wirz, Yannick; Mueller, Beat

2018-03-06

Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care? Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.

Continuous active surveillance of adverse events following immunisation using SMS technology.

PubMed

Westphal, Darren W; Williams, Stephanie A; Leeb, Alan; Effler, Paul V

2016-06-17

On-going post-licensure surveillance of adverse events following immunisation (AEFI) is critical to detecting and responding to potentially serious adverse events in a timely manner. SmartVax is a vaccine safety monitoring tool that uses automated data extraction from existing practice management software and short message service (SMS) technology to follow-up vaccinees in real-time. We report on childhood vaccine safety surveillance using SmartVax at a medical practice in Perth, Western Australia. Parents of all children under age five years who were vaccinated according to the Australian National Immunisation Schedule between November 2011 and June 2015 were sent an SMS three days post administration to enquire whether the child had experienced a suspected vaccine reaction. Affirmative replies triggered a follow-up SMS requesting details of the reaction(s) via a link to a survey that could be completed using a smartphone or the web. Rates of reported AEFI including fever, headache, fatigue, rash, vomiting, diarrhoea, rigours, seizures, and local reactions were calculated by vaccination time point. Overall, 239 (8.2%; 95% CI 7.2-9.2%) possible vaccine reactions were reported for 2897 vaccination visits over the 44 month time period. The proportion of children experiencing a possible AEFI, mostly local reactions, was significantly greater following administration of diphtheria-tetanus-pertussis-poliomyelitis vaccine at 4 years of age (77/441; 17.5%; 95% CI 13.9-21.0%) compared to the vaccinations given at 2-18 months (p<0.001). Across all time points, local reactions and fatigue were the most frequently reported AEFI. Automated SMS-based reporting can facilitate sustainable, real-time, monitoring of adverse reactions and contribute to early identification of potential vaccine safety issues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

PubMed

Rossini, Roberta; Iorio, Annamaria; Pozzi, Roberto; Bianco, Matteo; Musumeci, Giuseppe; Leonardi, Sergio; Lettieri, Corrado; Bossi, Irene; Colombo, Paola; Rigattieri, Stefano; Dossena, Cinzia; Anzuini, Angelo; Capodanno, Davide; Senni, Michele; Angiolillo, Dominick J

2017-02-01

There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical decision and not because of hypersensitivity reactions. A standard rapid desensitization protocol is safe and effective across a broad spectrum of patients, irrespective of the type of aspirin sensitivity manifestation, with indications to undergo coronary angiography with intent to perform percutaneous coronary intervention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02848339. © 2017 American Heart Association, Inc.

Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

PubMed

Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

2017-11-15

OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

Adverse reactions, psychological factors, and their effect on donor retention in men and women.

PubMed

Veldhuizen, Ingrid; Atsma, Femke; van Dongen, Anne; de Kort, Wim

2012-09-01

This study investigates the effect of a vasovagal reaction (VVR) or needle reaction (NR) on the risk of stopping as a blood donor, taking into account variables from the Theory of Planned Behavior (TPB). Is stopping risk solely related to the adverse reaction itself, or do the TPB variables play a role as well? Emphasis is placed on possible sex differences. TPB variables were assessed within 12,051 whole blood donors. Also, donors reported the occurrence of adverse reactions during or after their last donation. Blood bank records were used to determine whether donors stopped donating within the next 2 years. Logistic regression analyses were performed to estimate the effect of self-reported adverse reactions on stopping risk, adjusting for the TPB variables. Analyses were performed separately for both sexes. Men have a lower odds of reporting a NR or a VVR than women (odds ratio [OR] 0.34, 95% confidence interval [CI], 0.28-0.43; and OR 0.26, 95% CI 0.19-0.36, for NR and VVR, respectively). For both sexes, only a VVR was associated with stopping risk, which is higher in men (men, OR 3.95, 95% CI 2.19-7.11; women, OR 1.78, 95% CI 1.35-2.35). After adjusting for the TPB variables both ORs declined (men, OR 3.38, 95% CI 1.86-6.15; women, OR 1.58, 95% CI 1.17-2.14). Also, self-efficacy and affective attitude are negatively associated with adverse reactions. Female donors report more VVRs than male donors, but male donors have a higher stopping risk after a VVR than female donors. Coping differences and possible reporting tendencies might play a role. For donor retention purposes, prevention and coping techniques should take sex differences into account. © 2012 American Association of Blood Banks.

Optical diagnostics of vascular reactions triggered by weak allergens using laser speckle-contrast imaging technique

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

Kuznetsov, Yu L; Kalchenko, V V; Astaf'eva, N G

2014-08-31

The capability of using the laser speckle contrast imaging technique with a long exposure time for visualisation of primary acute skin vascular reactions caused by a topical application of a weak contact allergen is considered. The method is shown to provide efficient and accurate detection of irritant-induced primary acute vascular reactions of skin. The presented technique possesses a high potential in everyday diagnostic practice, preclinical studies, as well as in the prognosis of skin reactions to the interaction with potentially allergenic materials. (laser biophotonics)

Nuclear transit study in children with chronic faecal soiling after Hirschsprung disease (HSCR) surgery has revealed a group with rapid proximal colonic treatment and possible adverse reactions to food.

PubMed

Stathopoulos, Lefteris; King, Sebastian K; Southwell, Bridget R; Hutson, John M

2016-08-01

Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food. Patients (n = 10, all males, 9.6 year; 4.25-15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed. Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients. Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption.

Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

PubMed

Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

2016-05-01

Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

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

PubMed

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

2008-05-01

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

SOCIAL MEDIA MINING SHARED TASK WORKSHOP.

PubMed

Sarker, Abeed; Nikfarjam, Azadeh; Gonzalez, Graciela

2016-01-01

Social media has evolved into a crucial resource for obtaining large volumes of real-time information. The promise of social media has been realized by the public health domain, and recent research has addressed some important challenges in that domain by utilizing social media data. Tasks such as monitoring flu trends, viral disease outbreaks, medication abuse, and adverse drug reactions are some examples of studies where data from social media have been exploited. The focus of this workshop is to explore solutions to three important natural language processing challenges for domain-specific social media text: (i) text classification, (ii) information extraction, and (iii) concept normalization. To explore different approaches to solving these problems on social media data, we designed a shared task which was open to participants globally. We designed three tasks using our in-house annotated Twitter data on adverse drug reactions. Task 1 involved automatic classification of adverse drug reaction assertive user posts; Task 2 focused on extracting specific adverse drug reaction mentions from user posts; and Task 3, which was slightly ill-defined due to the complex nature of the problem, involved normalizing user mentions of adverse drug reactions to standardized concept IDs. A total of 11 teams participated, and a total of 24 (18 for Task 1, and 6 for Task 2) system runs were submitted. Following the evaluation of the systems, and an assessment of their innovation/novelty, we accepted 7 descriptive manuscripts for publication--5 for Task 1 and 2 for Task 2. We provide descriptions of the tasks, data, and participating systems in this paper.

Projected Real-World Effectiveness of Using Aggressive Low-Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada.

PubMed

Alter, David A; Tu, Jack V; Koh, Maria; Jackevicius, Cynthia A; Austin, Peter C; Rezai, Mohammad R; Bhatia, R Sacha; Johnston, Sharon; Udell, Jacob A; Ko, Dennis T

2018-05-12

The extent to which outcome benefits may be achieved through the implementation of aggressive low-density lipoprotein (LDL) cholesterol targets in real world settings remains unknown, especially among elderly statin users following acute coronary syndromes. A population-based cohort study consisting of 19 544 post-acute coronary syndrome statin-users aged ≥66 years between January 1, 2017 and March 31, 2014 was used to project the number of adverse outcome events (acute myocardial infarction or death from any cause) that could be prevented if all post-acute coronary syndrome elderly statin users were treated to 1 of 2 LDL cholesterol target levels (≤50 and ≤70 mg/dL). The number of preventable adverse outcomes was estimated by using model-based expected event probabilities as derived from Cox Proportional hazards models. In total, 61.6% and 25.5% of the elderly patients met LDL cholesterol targets of ≤70 and ≤50 mg/dL, respectively, based on current management. No more than 2.3 adverse events per 1000 elderly statin users (95% confidence interval: -0.7 to 5.4, P =0.62) could be prevented over 8.1 years if all patients were to be treated from current LDL cholesterol levels to either of the 2 LDL cholesterol targets of 70 or 50 mg/dL. The number of acute myocardial infarctions or death that could be prevented through the implementation of LDL cholesterol targets with statins is negligible among an elderly post-acute coronary syndrome population. Such findings may have implications for the applicability of newer agents, such as proprotein convertase subtilisin/kexin type-9- inhibitors. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

PubMed

Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

2016-06-01

In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.