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Sample records for adverse patient reactions

  1. Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management

    PubMed Central

    Drummond, James; Tran, Phong; Fary, Camdon

    2015-01-01

    Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID:26132653

  2. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

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

  3. Interpreting adverse drug reaction (ADR) reports as hospital patient safety incidents

    PubMed Central

    Davies, Emma C; Green, Christopher F; Mottram, David R; Pirmohamed, Munir

    2010-01-01

    AIM In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications. METHODS ADRs identified in a 6-month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA. RESULTS Seven hundred and thirty-three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as ‘low’ (minor treatment), 181 (24.7%) as ‘moderate’ (moderate increase in treatment, no permanent harm), 14 (1.91%) as ‘severe’ (permanent harm) and 1 (0.14%) was categorized as ‘catastrophic’ (direct cause of death). In terms of impact on the organization, none was categorized as ‘no harm/ no risk’, 508 (69.3%) as ‘insignificant’, 188 (25.6%) as ‘minor’, 25 (3.4%) as ‘moderate’, 12 (1.6%) as ‘major’ and none was classed as ‘catastrophic’. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection. CONCLUSIONS Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card System. A consistent message needs to be sent to prospective reporters of ADRs; the availability of more than one system is likely to confuse reporters and does not aid patient safety. PMID:20642552

  4. 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

  5. A Prospective Study Evaluating Metabolic Capacity of Thiopurine and Associated Adverse Reactions in Japanese Patients with Inflammatory Bowel Disease (IBD)

    PubMed Central

    Odahara, Shunichi; Uchiyama, Kan; Kubota, Takahiro; Ito, Zensho; Takami, Shinichiro; Kobayashi, Hiroko; Saito, Keisuke; Koido, Shigeo; Ohkusa, Toshifumi

    2015-01-01

    Azathioprine (AZA) is frequently used in patients with inflammatory bowel disease (IBD). However, toxic adverse reactions frequently develop and limit the clinical benefits. Currently, the precise mechanisms underlying thiopurine-related toxicity are not well understood. To investigate the relationship between the extent of thiopurine metabolism and adverse reactions in Japanese IBD patients, we prospectively observed 48 IBD patients who received AZA. We analyzed the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) gene mutations and measured the concentrations of 6-thioguanine nucleotide (6-TGN) continuously for 52 weeks. All patients possessed wild-type TPMT gene sequences. The ITPA 94C>A mutation was detected in 19 patients (39.6%). Adverse reactions developed in 14 of the 48 patients (29.2%), including leukopenia in 10 patients (20.8%). In the leukopenia group, the percentages of patients with 94C>A were higher than those in the without-leukopenia group (70.0% vs. 31.6%, P < 0.05). The average concentrations of 6-TGN in the patients with 94C>A were generally higher than those in the patients without 94C>A, however, there were no significant differences. Only 3 out of 10 patients with leukopenia exhibited high 6-TGN levels (30.0%). No negative correlations between white blood cell (WBC) counts and 6-TGN concentrations were observed. The cumulative incidence of leukopenia were higher for patients with 94C>A. Seven out of 19 patients (36.8%) with the ITPA 94C>A mutation developed leukopenia; however, this mutation may not unequivocally increase the risk of developing leukopenia. In addition, there are factors other than increased 6-TGN levels that are involved in the onset of leukopenia. PMID:26360046

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

    PubMed Central

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

    2015-01-01

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

  7. Adverse reactions of Achilles tendon xanthomas in three hypercholesterolemic patients after treatment intensification with niacin and bile acid sequestrants.

    PubMed

    Lakey, Wanda C; Greyshock, Nicole; Guyton, John R

    2013-01-01

    Multiple cholesterol-reducing therapies have been shown to induce the regression of tendon xanthoma in patients with familial hypercholesterolemia. We present 3 cases of adverse reactions in Achilles tendon xanthomas after the addition of niacin and bile acid sequestrants to ongoing statin therapy. Reduction in tendon dimensions and marked softening of xanthomas were interpreted as cholesterol removal from heavily infiltrated tissue sites. In 2 cases, changes in the xanthomas occurred despite only minor lipoprotein improvements, raising the possibility of direct drug effects in cholesterol-infiltrated tissue. Intriguingly, recent studies have described niacin receptor-mediated effects in macrophages. In summary, although adverse reactions in Achilles tendon xanthomas appear to be infrequent, clinicians should be aware of this phenomenon in their patients after intensifying lipid treatments, especially with the use of niacin in patients with familial hypercholesterolemia. Xanthoma responses may provide clues to new pharmacologic effects in cholesterol-infiltrated tissues. PMID:23415439

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

    PubMed Central

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

    2011-01-01

    AIM To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme. METHODS Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents. RESULTS There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme's independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals. CONCLUSION Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals. PMID:21496066

  9. 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…

  10. Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy

    PubMed Central

    Sadiq, Shamiya; Khajuria, Vijay; Mahajan, Annil; Singh, Jang B.

    2015-01-01

    Background and Objectives Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). Materials and Methods A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. Results Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. Conclusion The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID:26557538

  11. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

    PubMed

    Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

    2014-12-01

    This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients. PMID:25711751

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

    Dubus, Jean-Christophe; Bavoux, Françoise; Boyer-Gervoise, Marie-José; Jean-Pastor, Marie-Josèphe; Chalumeau, Martin

    2011-01-01

    Objective To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. Design The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Setting Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. Patients The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. Results The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n?=?27), worsening of respiratory distress during respiratory tract infection (n?=?35), dyspnoea (n?=?18), cough aggravation or prolongation (n?=?11), and bronchospasm (n?=?1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Conclusion Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence. PMID:21818391

  16. Adverse reactions to injectable soft tissue fillers.

    PubMed

    Requena, Luis; Requena, Celia; Christensen, Lise; Zimmermann, Ute S; Kutzner, Heinz; Cerroni, Lorenzo

    2011-01-01

    In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler. PMID:21167403

  17. Adverse drug reactions in hospitalized pediatric patients of Saudi Arabian University Hospital and impact of pharmacovigilance in reporting ADR

    PubMed Central

    Khan, Lateef M.; Al-Harthi, Sameer E.; Saadah, Omar I.

    2012-01-01

    Objectives Children are more vulnerable to ADRs, and this susceptibility is compounded due to hospitalization. There is a lack of local data regarding the potential risk of ADRs in hospitalized pediatric patients. Therefore, this study is designed to identify the frequent nature, severity of adverse drug reactions, drugs implicated and factors influencing ADRs. Methods Intensive monitoring study of ADRs was done in hospitalized pediatric patients of King Abdulaziz University Hospital, Jeddah from January to December 2011, with an analogous retrospective study for the preceding year to determine incidence rate, demographic aspects, causality appraisal, polypharmacy, body organs/systems involved and drugs implicated in ADR. Comparison of the two data was done to determine the impact of pharmacovigilance. Results Incidence rate of ADRs in retrospective study was (4.50%) and (8.2%) in prospective study. ADR was more in patients who received 5–6 drugs, which was (15.5%) in retrospective study and (22.1%) in prospective study. Regarding age, it was the highest in patients of 0–1 year of age which was (40.7%) in retrospective study and (38.8%) in prospective study. Anti-infective agents were the most frequently involved in ADR (40.8%) in prospective study and (48.2%) and retrospective study. This study also demonstrated that, there was high susceptibility of the skin to the ADR which was (37%) in retrospective study and (42.9%) in prospective study. None of the ADRs proved to be fatal. Conclusion Well premeditated intensive monitoring approach in pharmacovigilance amplifies the ADR detection, which can persuade healthcare providers into more drug safety. PMID:23960842

  18. 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

  19. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200?mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20?mg and 30?mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1? and tumor necrosis factor-? and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  20. Patient-reported adverse drug reactions and their influence on adherence and quality of life of chronic myeloid leukemia patients on per oral tyrosine kinase inhibitor treatment

    PubMed Central

    Kekäle, Meri; Peltoniemi, Marikki; Airaksinen, Marja

    2015-01-01

    Purpose To evaluate adverse drug reactions (ADRs) experienced by chronic myeloid leukemia (CML) patients during per oral tyrosine kinase inhibitor (TKI) treatment and correlation of ADR symptoms with medication adherence and perceived quality of life (QoL). Patients and methods Eighty-six adult, chronic-phase CML patients who had been on TKI treatment (79% on imatinib, 10.5% dasatinib, and 10.5% nilotinib) for at least 6 months participated in the study (mean age: 57.8 years, 52% males). The mean time from diagnosis was 5.1 years. All patients were interviewed, and patient-reported ADRs were obtained using a structured list. Adherence was assessed using Morisky’s 8-item Medication Adherence Scale (MMAS). The symptoms’ interference with patient’s daily QoL was measured by asking patients about the influence of symptom(s) on their mood, general condition, enjoyment of life, walking, relationships, and work. Results Ninety-seven percent of the patients were suffering from at least one ADR. The mean number of different symptoms was seven (range: 0–15, median 6). The most commonly perceived ADRs were muscle soreness or cramp (69/86, 80%); swelling of hands, legs, feet, or around the eyes (59/86, 69%); and fatigue (43/86, 50%). No correlation was found between adherence and ADRs, because symptoms were equally common in each MMAS adherence class. Half of the patients felt that the ADRs had a negative influence on their daily QoL. A quarter of the patients reported that ADRs affected either their mood, general condition, or enjoyment of life. The incidence of almost all ADRs was much higher among patients reporting negative influence of ADRs on their daily life compared to total study population (P=0.016). Conclusion TKI-related ADRs were common among CML patients irrespective of patient’s adherence level. Patients who reported that ADRs had a negative influence on their daily QoL perceived more ADRs than those who did not experience a negative influence. PMID:26677317

  1. Determinants of adverse reaction following postoperative T-tube cholangiogram.

    PubMed Central

    Dellinger, E P; Kirshenbaum, G; Weinstein, M; Steer, M

    1980-01-01

    The incidence, nature, and mechanisms of adverse reaction following postoperative T-tube cholangiogram have received little attention in the medical literature. This paper presents the experience at one hospital over a 30-month period (1975--1977) covering 139 patients who had 170 cholangiograms. Factors examined included intraoperative and postoperative cultures of bile, the use of antibiotics prior to the performance of the cholangiogram, the technique of cholangiography, the interval between operation and cholangiogram. Eleven (6.5%) cholangiograms were followed by an adverse reaction. Two of these reactions were severe, manifested by signs of septic shock. The administration of antibiotics was not associated with a reduction in adverse reactions. The cholangiographic technique of gravity infusion of dye, which effectively limits the amount of pressure generated during the study, was associated with a significant reduction in adverse reactions. No severe reactions occurred following any study performed by the gravity technique. There was no significant correlation between the age of the patient or the number of days postoperative with adverse reaction. A review of the literature suggests that the mechanism for these severe reactions is cholangiovenous reflux. The avoidance of high intraductal pressures (above 25 cm of water) during the performance of postoperative T-tube cholangiogram should significantly reduce the incidence of adverse reactions. PMID:7369805

  2. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

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

  3. Diagnosis and Management of Adverse Local Tissue Reactions Secondary to Corrosion at the Head-Neck Junction in Patients With Metal on Polyethylene Bearings.

    PubMed

    Plummer, Darren R; Berger, Richard A; Paprosky, Wayne G; Sporer, Scott M; Jacobs, Joshua J; Della Valle, Craig J

    2016-01-01

    We reviewed 27 patients who underwent revision for an adverse local tissue reaction (ALTR) secondary to corrosion at the head-neck junction with MoP bearings. Serum cobalt and chromium levels were elevated in all cases, with a mean cobalt of 11.2ppb and chromium of 2.2ppb. Patients underwent modular bearing exchange, including a ceramic head with a titanium sleeve in 23 of 27 cases with only one recurrence of ALTR in one of the four patients not treated with a ceramic head. The diagnosis of ALTR secondary to corrosion is associated with cobalt levels of >1ppb with cobalt levels elevated above chromium. Retention of a well-fixed stem and modular exchange to a ceramic head leads to resolution of symptoms and decreases in metal levels. PMID:26321628

  4. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 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...

  5. 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...

  6. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 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...

  7. The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

    PubMed

    Liu, Hui; Ding, Liang; Zhang, Fangbin; Zhang, Yu; Gao, Xiang; Hu, Pinjin; Bi, Huichang; Huang, Min

    2015-10-01

    Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*-105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022-0.709, P = 0.0012). The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs. PMID:26432087

  8. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

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

  9. ADRIS - The Adverse Drug Reactions Information Scheme.

    PubMed

    Hug, Hubert; Bagatto, Dario; Dannecker, Robert; Schindler, Richard; Horlacher, Oliver; Gut, Joseph

    2004-01-01

    Under the Adverse Drug Reactions Information Scheme (ADRIS) data and knowledge relevant to the etiology of adverse drug reactions (ADRs) such as chemical structure of parent compounds, metabolites, covalent adducts, nucleic acid and protein sequences, protein structures, pharmaco-, toxico- and enzyme kinetics, pharmaco- and toxicodynamics, protein interactions, molecular pathways and complexes, as well as toxicological and clinical outcomes, are collected and logically and semantically related. ADRIS reflects the ontological prerequisite for the creation of databases and knowledge discovery systems for the abstraction and visualization of theragenomic concepts. A final outcome is the prediction of ADRs based on a profound knowledge of drug function and the molecular basics for personalized drug safety and eventually, personalized medicine. 2004 PMID:15090937

  10. 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...

  11. Cutaneous adverse reactions to acyclovir: case reports.

    PubMed Central

    Robinson, G E; Weber, J; Griffiths, C; Underhill, G S; Jeffries, D J; Goldmeir, D

    1985-01-01

    Intravenous, oral, and topical formulations of acyclovir have been successful in treating genital herpes. We report on two patients who developed skin reactions while taking acyclovir, which resolved when treatment was stopped. PMID:2935482

  12. The pattern and risk factors associated with adverse drug reactions induced by Reteplase in patients with acute ST-elevation myocardial infarction: The first report from Iranian population

    PubMed Central

    Aslanabadi, Naser; Safaie, Naser; Shadfar, Faezeh; Taban-Sadeghi, Mohammad Reza; Feizpour, Hossein; Mashayekhi, Simin Ozar; Hamishehkar, Hadi; Aghdam, Naser Khezerlou; Dousti, Samaneh; Namdar, Hossein; Entezari-Maleki, Taher

    2015-01-01

    Objective: Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Reteplase is a fibrin-specific thrombolytic which is used in the treatment of AMI. There is a limited number of studies reporting the postmarketing adverse drug reactions (ADRs) induced by reteplase. This study was aimed to examine the reteplase pattern of ADR and its associated risk factors in patients with acute ST-elevation myocardial infarction. Methods: A cross-sectional, prospective study in an 8-month period was done at the University affiliated referral cardiovascular center. The Naranjo probability scale and World Health Organization criteria for severity of ADRs were used for assessing the ADRs. The linear regression and logistic regression tests were used to evaluate the correlation between ADRs and risk factors. Findings: The all 20 patients who received reteplase during the study period were entered. The majority of patients (n = 17) experienced at least one ADR. The results showed that the incidence of ADRs was mainly associated with gender and age, and the number of ADRs was associated with the history of diabetes and taking anti-diabetic agents. The gender was the main predictor in the occurrence of ADRs (odds ratio: 32, 95% confidence interval: 1.38–737.45; P = 0.030). Conclusion: The results showed that gender, age, diabetes mellitus, and using of anti-diabetes medications are the risk factors associated with the incidence of ADRs by reteplase.

  13. Systemic adverse drug reactions secondary to anti-VEGF intravitreal injection in patients with neovascular age-related macular degeneration.

    PubMed

    Semeraro, Francesco; Morescalchi, F; Parmeggiani, Francesco; Arcidiacono, Barbara; Costagliola, Ciro

    2011-09-01

    The wet form of age related macular degeneration (AMD), known also as exudative or neovascular, is characterized by the formation of a pathological choroidal neovascular membrane (CNV) responsible for most cases of severe blindness. Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein acting as a growth factor selective for endothelial cells; it regulates angiogenesis and enhances vascular permeability and plays a leading role in this disorder. The consistent association between CNV and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular AMD. The importance of VEGF for the development of AMD-related CNV has led to the development of a strategy able to block its pathologic effects. The rationale is that a blockade of VEGF actions could be effective in arresting choroidal angiogenesis and also reducing the vascular permeability, which is frequently the main cause of visual acuity deterioration. However, VEGF has also important functions in vascular physiology. The effects of anti-VEGF therapy may inhibit these functions. Herein we report the systemic adverse events secondary to intravitreal administration of these compounds i.e. the main cardiovascular effects (thrombosis, hemorrhage, hypertension, proteinuria), as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thrombophlebitis. PMID:21470108

  14. Revisiting cutaneous adverse reactions to pemetrexed

    PubMed Central

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

    2011-01-01

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

  15. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  16. 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

  17. Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis

    PubMed Central

    Liu, Yue-Ping; Xu, Han-Qing; Li, Ming; Yang, Xiang; Yu, Shu; Fu, Wei-Ling; Huang, Qing

    2015-01-01

    Purpose Azathioprine (AZA) is widely used as an immunosuppressive drug in autoimmune diseases, but its use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating AZA therapy. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and AZA-induced ADRs using meta-analysis. Methods We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and AZA-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in patients with autoimmune diseases were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using Revman 5.3 software. Results Eleven published studies, with a total of 651 patients with autoimmune diseases, investigated associations between TPMT polymorphisms and AZA-induced ADRs, were included in this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with AZA-induced overall ADRs, bone marrow toxicity and gastric intolerance; pooled ORs were 3.12 (1.48–6.56), 3.76 (1.97–7.17) and 6.43 (2.04–20.25), respectively. TPMT polymorphisms were not associated with the development of hepatotoxicity; the corresponding pooled OR was 2.86 (95%CI: 0.32–25.86). However, the association in GI subset could be driven by one single study. After this study was excluded, the OR was 2.11 (95%CI: 0.36–12.42); namely, the association became negative. Conclusions Our meta-analysis demonstrated an association of TPMT polymorphisms with overall AZA-induced ADRs, bone marrow toxicity and gastric intolerance, but not with hepatotoxicity. The presence of the normal TPMT genotypes cannot preclude the development of ADRs during AZA treatment, TPMT genotyping prior to commencing AZA therapy cannot replace, may augment, the current practice of regular monitoring of the white blood cell. Because of small sample sizes, large and extensive exploration was required to validate our findings. PMID:26633017

  18. 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

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

    PubMed

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

    2013-01-01

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

  20. Completeness of adverse drug reactions reports of the Saudi adverse event reporting system

    PubMed Central

    Alshammari, Thamir M.; Al-Kathiri, Wa’ad H.; Louet, Hervé Le; Aljadhey, Hisham S.

    2015-01-01

    Objectives: To assess completeness of reports in the Saudi Adverse Event Reporting System (SAERS), which is a part of the Saudi Food and Drug Authority pharmacovigilance system for monitoring the safety of medications. Methods: A cross-sectional study was conducted in Riyadh, Saudi Arabia using the reports that were received between December 2009 and June 2012 in the SAERS. The completeness was assessed by reviewing the components of the adverse drug reactions (ADRs) form, and how many fields were completed. Descriptive statistics are reported. Result: There were 14,783 reports during the study period. Eighty percent of these reports were spontaneous reports. Information related to the drug (99%) and adverse events (98%) of the reports were completed. While the patient’s demographic data were completed only in 38% of all reports, the least completed item in the ADRs form was the reporter information (15%). The most reported drug class was tumor necrosis factor inhibitors (7%), whereas events involving the respiratory organ system were the most frequently reported (4.5%). Conclusion: Although the SAERS is considered new, it has a high number of reports. More efforts are needed to improve the completeness of the SAERS to be a good source to assess the signals between events and suspected drugs, especially when there is a high number of reports. PMID:26108586

  1. 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

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

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

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

  3. Adverse reaction to metal debris after Birmingham hip resurfacing arthroplasty

    PubMed Central

    Junnila, Mika; Seppänen, Matti; Mokka, Jari; Virolainen, Petri; Pölönen, Tuukka; Vahlberg, Tero; Mattila, Kimmo; Tuominen, Esa K J; Rantakokko, Juho; Äärimaa, Ville; Itälä, Ari; Mäkelä, Keijo T

    2015-01-01

    Background and purpose Concern has emerged about local soft-tissue reactions after hip resurfacing arthroplasty (HRA). The Birmingham Hip Resurfacing (BHR) was the most commonly used HRA device at our institution. We assessed the prevalence and risk factors for adverse reaction to metal debris (ARMD) with this device. Patients and methods From 2003 to 2011, BHR was the most commonly used HRA device at our institution, with 249 implantations. We included 32 patients (24 of them men) who were operated with a BHR HRA during the period April 2004 to March 2007 (42 hips; 31 in men). The mean age of the patients was 59 (26–77) years. These patients underwent magnetic resonance imaging (MRI), serum metal ion measurements, the Oxford hip score questionnaire, and physical examination. The prevalence of ARMD was recorded, and risk factors for ARMD were assessed using logistic regression models. The mean follow-up time was 6.7 (2.4–8.8) years. Results 6 patients had a definite ARMD (involving 9 of the 42 hips). 8 other patients (8 hips) had a probable ARMD. Thus, there was definite or probable ARMD in 17 of the 42 hips. 4 of 42 hips were revised for ARMD. Gender, bilateral metal-on-metal hip replacement and head size were not factors associated with ARMD. Interpretation We found that HRA with the Birmingham Hip Resurfacing may be more dangerous than previously believed. We advise systematic follow-up of these patients using metal ion levels, MRI/ultrasound, and patient-reported outcome measures. PMID:25582189

  4. Adverse drug reactions in special populations - the elderly.

    PubMed

    Davies, E A; O'Mahony, M S

    2015-10-01

    The International Conference on Harmonization considers older people a 'special population', as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  5. Precautions and Adverse Reactions during Blood Transfusion

    MedlinePLUS

    ... More serious allergic reactions may be treated with hydrocortisone or even with epinephrine . Treatments are available that ... Name Select Brand Names acetaminophen TYLENOL epinephrine ADRENALIN hydrocortisone CORTEF, SOLU-CORTEF Blood Transfusion Overview of Blood ...

  6. Severe cutaneous adverse reaction to telaprevir.

    PubMed

    Shuster, Marina; Do, Daihung; Nambudiri, Vinod

    2015-01-01

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

  7. Precautions and Adverse Reactions during Blood Transfusion

    MedlinePLUS

    ... the transfused blood after it is collected. In addition to an increase in temperature, the person has chills and sometimes headache or back pain. Sometimes the person also has symptoms of an allergic reaction such as itching or a rash. Usually, acetaminophen ...

  8. Assessment of Adverse Drug Reactions Based on Spontaneous Signals at Secondary Care Public Hospital

    PubMed Central

    Ponnusankar, S.; Tejaswini, M.; Chaitanya, M.

    2015-01-01

    Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program.

  9. Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions

    PubMed Central

    KARIMZADEH, Parvaneh; BAKRANI, Vahid

    2013-01-01

    Objective According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. Material & Methods In this descriptive study, children less than 14 years old with AED side effects referred to the Children’s Medical Center and Mofid Childeren’s Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. Results A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). Conclusion In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions. PMID:24665302

  10. Adverse reactions to food constituents: allergy, intolerance, and autoimmunity.

    PubMed

    Kitts, D; Yuan, Y; Joneja, J; Scott, F; Szilagyi, A; Amiot, J; Zarkadas, M

    1997-04-01

    Food allergies and intolerance represent important health concerns to consumers who are predisposed to these illnesses. Unlike many current food safety issues, food sensitivities are complicated by both complex and multiple individual adverse reactions, which can vary from emotional to pathophysiological ailments. In some instances, the underlying mechanisms that result in the development of food allergies or intolerance have marked differences but produce common symptoms. The present-day diagnosis of these disorders can be impeded by intrinsic limitations in generating accurate information from patient history and biochemical, physicochemical, and immunochemical tests. Oral challenge tests represent effective methods for confirming and testing food allergens and food intolerance; however, these procedures are often restricted to clinical trials. It is important to be able to distinguish among food allergy, intolerance, and autoimmune disease in the management of these disorders. The role of food in the development of autoimmune disease may be exemplified by celiac disease, a food-induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley. Various wheat and soy protein sources, including the soy protein isolates used to make infant formulas, have been related to juvenile or insulin-dependent diabetes mellitus (IDDM), a common chronic disease of childhood. Employing food process technologies to eliminate food constituents with potential for intolerance in some individuals is a potentially viable approach for reducing risk to food-related disorders. Finally, the development of food labelling regulations that require the identification of potential food allergens or agents for intolerance in the ingredient declaration on prepackaged food is a positive step toward the prevention of severe adverse reactions in hypersensitive individuals. PMID:9196849

  11. [Adverse cutaneous reactions induced by exposure to woods].

    PubMed

    Chomiczewska-Skóra, Dorota

    2013-01-01

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

  12. Energy drink use and adverse effects among emergency department patients.

    PubMed

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

    2012-10-01

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

  13. Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors

    PubMed Central

    Lupu, I; Voiculescu, VM; Bacalbasa, N; Prie, BE; Cojocaru, I; Giurcaneanu, C

    2015-01-01

    Classical antineoplastic therapy is encumbered by extensively studied adverse reactions, most often of systemic nature. The emergence of new generations of anticancer treatments, including epidermal growth factor receptor inhibitors, besides improving the response to treatment and the survival rate, is accompanied by the occurrence of new specific side effects, incompletely studied. These side effects are most often cutaneous (hand foot syndrome, acneiform reactions), and in some cases are extremely severe, requiring dose reduction or drug discontinuation. The prevention of the cutaneous adverse effects and their treatment require a close collaboration between the oncologist and the dermatologist. The occurrence of some of these skin adverse effects may be a favorable prognostic factor for the response to the cancer treatment and the overall survival. Abbreviations: EGFR = epidermal growth factor receptors; EGFRI = epidermal growth factor receptors inhibitors PMID:26361513

  14. [Viscum album L. (Iscador) in the cat: tolerance, adverse reactions and indications].

    PubMed

    Glardon; Pache; Magnenat; Pin; Parvis

    2014-08-01

    In this retrospective study, the tolerance to subcutaneus mistletoe injections (Viscum album L.), adverse reactions and possible indications have been evaluated in feline patients of a small animal clinic. Among the 22 cats treated between 2008 and 2013, 4 did not accept the injections done by the owner, 7 showed slight short time adverse reactions, that disappeared spontaneously. No long term (more than 70 days) adverse reaction directly related to the Viscum album treatment could be identified. This study shows that Iscador(®) can be injected subcutaneously without a risk of worsening of the clinical signs or exacerbation of tumors. The antitumoral, but also immune-modulating and anti-inflammatory properties offer interesting treatment opportunities for dermatologic, odonto-stomatologic or allergic patients. PMID:25082635

  15. Different reactions to adverse neighborhoods in games of cooperation.

    PubMed

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

    2012-01-01

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

  16. 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

  17. Physician access to drug profiles to reduce adverse reactions

    NASA Astrophysics Data System (ADS)

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

    1995-10-01

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

  18. Perception of Nigerian medical students on adverse drug reaction reporting

    PubMed Central

    Abubakar, Abdullahi Rabiu; Chedi, Bashir A. Z.; Mohammed, Khalid Garba; Haque, Mainul

    2015-01-01

    Spontaneous reporting (SPR) and intensive monitoring are the conventional systems used for detecting, recording, and reporting adverse drug reactions (ADRs). Using spontaneous reporting a lot of successes has been made as existing ADRs were identified and new ones prevented through this methods. The aim of this appraisal was to evaluate the knowledge, attitude, and the practice of medical students with regards to ADRs reporting and to see if differences exist between the level of study and genders. The questionnaire was adopted, modified, and validated from previous studies. It comprised of 25 questions. It was administered year-IV and V medical students of Bayero University Kano, Nigeria. The data collected were coded and analyzed using the Statistical Package for the Social Sciences (SPSS) version 20, currently known as IBM SPSS Statistics. The response rate was 74%. Among the 108 participants, 80% got the definition of ADRs correct; 63% of them knew the precise functions of pharmacovigilance (PV). In addition, 82% strongly agreed that ADR reporting is health care workers responsibility; 82% also said PV should be taught in detail. Meanwhile, 99% have noticed patient experiencing ADRs; 67% said even mild ADRs should be reported. The outcome of this study showed good knowledge and attitude with respect to ADRs and PV among the medical students surveyed. Unfortunately, the practice of medical students was found to be unsatisfactory. There is a need to upgrade the students teaching the curriculum with respect to ADRs monitoring.

  19. Dietary aspects of adverse reactions to foods in adults.

    PubMed Central

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

    1988-01-01

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

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

    SciTech Connect

    Ishikawa, Atsuko; Suga, Tomo; Shoji, Yoshimi; Kato, Shingo; Ohno, Tatsuya; Ishikawa, Hitoshi; Yoshinaga, Shinji; Ohara, Kiyoshi; Ariga, Hisanori; Nomura, Kuninori; Shibamoto, Yuta; Ishikawa, Ken-Ichi; Moritake, Takashi; Michikawa, Yuichi; Iwakawa, Mayumi; Imai, Takashi

    2011-11-15

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

  1. 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. PMID:23420567

  2. Cytotoxic Proteins and Therapeutic Targets in Severe Cutaneous Adverse Reactions

    PubMed Central

    Su, Shih-Chi; Chung, Wen-Hung

    2014-01-01

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

  3. Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions.

    PubMed

    Su, Shih-Chi; Chung, Wen-Hung

    2014-01-01

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

  4. ADRIS--The Adverse Drug Reactions Information Scheme.

    PubMed

    Hug, Hubert; Bagatto, Dario; Dannecker, Robert; Schindler, Richard; Horlacher, Oliver; Gut, Joseph

    2003-12-01

    Under the Adverse Drug Reactions Information Scheme (ADRIS) data and knowledge relevant to the etiology of adverse drug reactions (ADRs) such as chemical structure of parent compounds, metabolites, covalent adducts, nucleic acid and protein sequences, protein structures, pharmaco-, toxico- and enzyme kinetics, pharmaco- and toxicodynamics, protein interactions, molecular pathways and complexes, as well as toxicological and clinical outcomes, are collected and logically and semantically related. ADRIS reflects the ontological prerequisite for the creation of databases and knowledge discovery systems for the abstraction and visualization of theragenomic concepts. A final outcome is the prediction of ADRs based on a profound knowledge of drug function and the molecular basics for personalized drug safety and eventually, personalized medicine. PMID:14646695

  5. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions.

    PubMed

    Hung, Shuen-Iu; Chung, Wen-Hung; Jee, Shiou-Hwa; Chen, Wen-Chieh; Chang, Yun-Ting; Lee, Woan-Ruoh; Hu, Shu-Ling; Wu, Meng-Tse; Chen, Gwo-Shing; Wong, Tak-Wah; Hsiao, Pa-Fan; Chen, Wei-Hsuan; Shih, Han-Yu; Fang, Wu-Hsiang; Wei, Chun-Yu; Lou, Yi-Hui; Huang, Yau-Li; Lin, Juei-Jueng; Chen, Yuan-Tsong

    2006-04-01

    The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific. PMID:16538176

  6. Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital

    PubMed Central

    Palaniappan, Muthiah; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan

    2015-01-01

    Background Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. Aim To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Settings and Design Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. Materials and Methods All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. Statistical Analysis used The study used descriptive statistics and the values were expressed in numbers and percentages. Results During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo’s scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be enalapril (17.5%), atorvastatin (14.9%), aspirin (8.4%) and metoprolol (8.4%). Conclusion The cardiovascular drug related adverse effects constituted 18.1% of the total ADRs reported during the study period. Cough, gastritis, fatigue and myalgia by enalapril, aspirin, ?-blockers and atorvastatin respectively were found to be the most commonly reported ADRs among the cardiovascular drugs. PMID:26675485

  7. 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

  8. [Knowledge creation about adverse drug reactions in the paediatric population].

    PubMed

    Aagaard, Lise

    2013-02-01

    Knowledge of adverse drug reactions (ADRs) from medicine use in children is limited. We analyzed 4,500 ADRs submitted for children from ages 0 to 17 years to the Danish National ADR Database in the period from 1998 to 2007 with respect to occurrence, seriousness and type of reported ADRs, therapeutic group, age, gender and reporter. 40 per cent of the reported ADRs were serious, and fatal cases were found. Half of the ADRs were reported in children from 0 up to 2 years of age. The majority of the ADRs were reported for immunization therapies, antibiotics and psychotropic medicine. Physicians reported 90% of all ADRs. PMID:23402239

  9. Nurse-perceived Patient Adverse Events and Nursing Practice Environment

    PubMed Central

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

    2014-01-01

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

  10. Reactions of Psychiatric Patients to Telepsychiatry

    PubMed Central

    Campbell, Robbie; O’Gorman, Jennifer; Cernovsky, Zack Z.

    2015-01-01

    Telepsychiatry could offer a viable medical service to remote or isolated social communities if it does not generate adverse reactions such as delusional ideation, particularly in patients in settlements without adequate exposure to mainstream culture and internet. We examined subjective reactions to telepsychiatry of randomly selected 84 psychiatric patients from remote locations in Ontario, Canada. They rated the quality of their teleconferencing sessions via 10 item questionnaire and were asked about advantages and disadvantages of telepsychiatry. The majority of patients indicated that they were able to communicate as if physically present (92.9%) and were comfortable with telepsychiatric service (95.2%). They found the sessions as beneficial as direct meetings with their psychiatrist (84.5%) and would use this service again (98.8%). There were no instances of telepsychiatry being associated with adverse reactions in patients from remote communities with inadequate exposure to modern mainstream culture and internet.

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

    PubMed

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

    2014-10-01

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

  12. Oral adverse reactions after injection of cosmetic fillers: report of three cases.

    PubMed

    Feio, P S Q; Gouvêa, A F; Jorge, J; Lopes, M A

    2013-04-01

    The use of injectable cosmetic fillers in orofacial tissues has increased in the past few years. Although a wide variety of agents are available on the market and satisfactory results have been achieved, adverse reactions can be observed. The authors report three new cases of oral reactions in three women who received injections of different cosmetic fillers in the perioral area. In two cases, the lesions presented as nodules on the lip mucosa, and in the last case, as an intraoral ulcer with submental swelling. Considering the concern of patients about malignancies in these lesions, clinicians and pathologists should be aware of these adverse reactions and a detailed history should be made to diagnose these conditions. PMID:22749542

  13. A study of cutaneous adverse drug reactions at a tertiary center in Jammu, India

    PubMed Central

    Sharma, Rohini; Dogra, Devraj; Dogra, Naina

    2015-01-01

    Aim: The aim was to study various morphological patterns of cutaneous adverse drug reactions (CADRs) and identify the culprit drug or drugs by establishing a causal link using Naranjo adverse drug reaction probability scale. Materials and Methods: The study was carried out between November 2010 and November 2011 at the Department of Dermatology, Government Medical College, Jammu. A total of 150 patients with CADR reporting to the dermatology department or referred from other departments were evaluated. Detailed history, clinical examination, hematological, and biochemical investigations were recorded. The venereal disease research laboratory test, HIV (ELISA), and histopathological examination were done wherever indicated. Results: A total of 150 patients were evaluated after applying the inclusion and exclusion criteria. The mean age of the patients with CADRs was 33.26 years. A majority of patients (30.6%) were in the age group of 21–30 years. The male to female ratio was 1.7:1.2. The most common CADRs were fixed drug eruption in 33.3% of patients followed by urticaria in 17.3%, and maculopapular rash in 13.3%. The most common classes of drugs implicated were antimicrobials in 40% of patients followed by nonsteroidal antiinflammatory drugs in 35.3%. The Naranjo adverse drug reaction probability scale indicated probable association of 77.3%, highly probable association of 12.6%, and 1% possible association with the implicated drugs. Conclusion: The pattern of CADRs and the drugs causing them is remarkably different in our population. Knowledge of these drug reactions, their causative drugs, and prognostic indicators is essential for the clinician. PMID:26009710

  14. A time-indexed reference standard of adverse drug reactions

    PubMed Central

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

    2014-01-01

    Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance. PMID:25632348

  15. Causality assessment of adverse drug reaction in Pulmonology Department of a Tertiary Care Hospital

    PubMed Central

    Khan, Amer; Adil, Mir S.; Nematullah, K.; Ihtisham, S.; Aamer, K.; Aamir, Syed

    2015-01-01

    Background: Adverse drug reaction (ADR) is considered to be the sixth leading cause of death. The incidence rate estimates approximately 2% of hospital admissions are due to ADRs. Objective: To monitor ADRs in Pulmonology department of a tertiary care hospital patient with pulmonary diseases in an inpatient department of pulmonology. Materials and Methods: A prospective, single centered, observational and open labeled study was carried out in Princess Esra Hospital. The patient population was broadly divided into four categories based on diagnosis - chronic obstructive pulmonary disease, Infections, Asthma and Others. Suspected ADRs were reported, analyzed, and causality assessment was carried out using Naranjo's algorithm scale. Results: A total of 302 patients were observed, of which 98 patients experienced ADRs, which accounted for 32.23% of the incidence and totally 160 ADEs were observed. Adult Patients were found to have higher incidence (32.09%) while the incidence rate was slightly greater in geriatric patients (32.39%). The highest incidence of ADEs were found in others group (78.57%). Majority of ADRs were suspected to be due to theophylline (19.39%). Gastrointestinal system (38.75%) was the most common organ system affected due to ADRs. Drug was withdrawn in 12 patients, and specific treatment was administered to 32 patients in view of clinical status. Specific treatment for the management of suspected reaction was administered in 32.65% of ADR reports. Conclusion: A relatively high incidence of adverse drug events (32.2%) have been recorded which shows that not only Geriatric patients, but also adults are more susceptible to adverse drug effects. A number of drugs in combination were used, and ADEs often get multiplied. Careful therapeutic monitoring and dose individualization is necessary. PMID:26229344

  16. Adverse Drug Reactions in Children—A Systematic Review

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Gabrilovich, Evgeniy

    2013-01-01

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

  18. Adverse reactions following routine anticholinergic eye drops in a paediatric population: an observational cohort study

    PubMed Central

    van Minderhout, Helena M; Joosse, Maurits V; Grootendorst, Diana C

    2015-01-01

    Objectives To investigate the presence, nature and relationship to age, sex, ethnicity and body mass index (BMI) of adverse reactions following routine cycloplegic eye drops in children. Design Prospective observational cohort study. Setting Ophthalmology outpatient clinic Dutch metropolitan hospital; February, March and April 2009. Participants Children aged 3–14-year-old children receiving two drops of cyclopentolate 1% (C+C) or one drop of cyclopentolate 1% and one drop of tropicamide 1% (C+T). Patients were categorised by age (3–6, 7–10 and 11–14?years), sex, ethnicity and body mass index (BMI) (low, normal or high). Outcome measures Rate and nature of adverse reactions reported at 45?min following treatment. Crude and adjusted ORs for reporting an adverse reaction using stepwise regression analysis with BMI, age, ethnicity and sex. Results 912 of 915 eligible patients participated (99.7%). Adverse reactions were reported for C+C in 10.3% and in C+T in 4.8% (42/408 and 24/504, p=0.002), respectively. Central effects were present in 95% in C+C and in 92% in C+T. Compared to C+T, an increased risk was present in C+C (crude OR 2.3 (1.4 to 3.9), p=0.002). Forward adjustment showed BMI to be an influencing factor in treatment (OR 3.1 (1.7 to 5.6), p<0.001). In a multivariate model, a dose of cyclopentolate remained associated with adverse reactions. Analysis per BMI and regime and age category and regime, indicated associations with low BMI (OR C+C 21.4 (6.7 to 67.96), p<0.001, respectively, C+T 5.2 (2.1 to 12.8), p<0.001) and young age (OR C+C 8.1 (2.7 to 24.8), p<0.001). Conclusions Adverse reactions were common and almost exclusively involved the central nervous system. Both presence and severity were associated with repeated instillation of cyclopentolate 1%, low BMI and young age. In specific paediatric populations, a single dose of cyclopentolate must be considered. Vital function monitoring facilities are advisable. Adjustment of guidelines is recommended. PMID:26700273

  19. Cutaneous adverse drug reactions in Indian population: A systematic review

    PubMed Central

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

    2014-01-01

    Background: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. Aims: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. Materials and Methods: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing “definite” and “probable” categories of causality analysis were labeled as “definite and probable causality (DPC) studies”. The other included studies were labeled as “non-DPC studies”. Results: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), ?-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS/TEN, and exfoliative dermatitis were 1.71%, 16.39%, and 3.57%, respectively. “Definitely preventable”, “probably preventable” and “not preventable” categories CADRs were 15.64%, 63.14%, and 34.64%, respectively. Conclusion: Antimicrobials, NSAIDs and antiepileptic are common causative agents of CADRs in India. Antiepileptic agents show high rates of severe cutaneous reactions. PMID:25593813

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

    PubMed Central

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

    2012-01-01

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

  1. An EAACI “European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI)”: the methodology

    PubMed Central

    2014-01-01

    At present, there is no European report on clinically relevant systemic reactions due to the regular use of allergen immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a “harmonised terminology” according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated “national coordinator” was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed. PMID:25075276

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

    PubMed Central

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

    2007-01-01

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

  3. [Adverse events in patients from a pediatric hospital.

    PubMed

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

    2013-01-01

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

  4. Pharmacovigilance on Twitter? Mining Tweets for Adverse Drug Reactions

    PubMed Central

    O’Connor, Karen; Pimpalkhute, Pranoti; Nikfarjam, Azadeh; Ginn, Rachel; Smith, Karen L; Gonzalez, Graciela

    2014-01-01

    Recent research has shown that Twitter data analytics can have broad implications on public health research. However, its value for pharmacovigilance has been scantly studied – with health related forums and community support groups preferred for the task. We present a systematic study of tweets collected for 74 drugs to assess their value as sources of potential signals for adverse drug reactions (ADRs). We created an annotated corpus of 10,822 tweets. Each tweet was annotated for the presence or absence of ADR mentions, with the span and Unified Medical Language System (UMLS) concept ID noted for each ADR present. Using Cohen’s kappa1, we calculated the inter-annotator agreement (IAA) for the binary annotations to be 0.69. To demonstrate the utility of the corpus, we attempted a lexicon-based approach for concept extraction, with promising success (54.1% precision, 62.1% recall, and 57.8% F-measure). A subset of the corpus is freely available at: http://diego.asu.edu/downloads. PMID:25954400

  5. Frequency and Pattern of Noninfectious Adverse Transfusion Reactions at a Tertiary Care Hospital in Korea

    PubMed Central

    Cho, Jooyoung; Choi, Seung Jun; Kim, Sinyoung; Alghamdi, Essam

    2016-01-01

    Background Although transfusion is a paramount life-saving therapy, there are multiple potential significant risks. Therefore, all adverse transfusion reaction (ATR) episodes require close monitoring. Using the computerized reporting system, we assessed the frequency and pattern of non-infectious ATRs. Methods We analyzed two-year transfusion data from electronic medical records retrospectively. From March 2013 to February 2015, 364,569 units of blood were transfused. Of them, 334,582 (91.8%) records were identified from electronic nursing records. For the confirmation of ATRs by blood bank physicians, patients' electronic medical records were further evaluated. Results According to the nursing records, the frequency of all possible transfusion-related events was 3.1%. After the blood bank physicians' review, the frequency was found to be 1.2%. The overall frequency of febrile non-hemolytic transfusion reactions (FNHTRs) to red blood cells (RBCs), platelet (PLT) components, and fresh frozen plasmas (FFPs) were 0.9%, 0.3%, and 0.2%, respectively, and allergic reactions represented 0.3% (RBCs), 0.9% (PLTs), and 0.9% (FFPs), respectively. The pre-storage leukocyte reduction significantly decreased the frequency of FNHTRs during the transfusion of RBCs (P<0.01) or PLTs (P?0.01). Conclusions The frequency of FNHTRs, allergic reactions, and "no reactions" were 22.0%, 17.0%, and 60.7%, respectively. Leukocyte-reduction was associated with a lower rate of FNHTRs, but not with that of allergic reactions. The development of an effective electronic reporting system of ATRs is important in quantifying transfusion-related adverse events. This type of reporting system can also accurately identify the underlying problems and risk factors to further the quality of transfusion care for patients. PMID:26522757

  6. Bias in Spontaneous Reporting of Adverse Drug Reactions in Japan

    PubMed Central

    Matsuda, Shinichi; Aoki, Kotonari; Kawamata, Takuya; Kimotsuki, Tetsuji; Kobayashi, Takumi; Kuriki, Hiroshi; Nakayama, Terumi; Okugawa, Seigo; Sugimura, Yoshihiko; Tomita, Minami; Takahashi, Yoichiro

    2015-01-01

    Background Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan’s unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time. Methods A manufacturer’s database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio. Results For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period. Conclusions Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan. PMID:25933226

  7. Detect adverse drug reactions for drug Simvastatin Yihui Liu1,2

    E-print Network

    Aickelin, Uwe

    Detect adverse drug reactions for drug Simvastatin Yihui Liu1,2 1 Institute of Intelligent Department of Computer Science, University of Nottingham, UK Abstract--Adverse drug reaction (ADR) is widely feature matrix and feature selection. The experiments are carried out on the drug Simvastatin. Major side

  8. Detect adverse drug reactions for drug Alendronate Yihui Liu1,2

    E-print Network

    Aickelin, Uwe

    Detect adverse drug reactions for drug Alendronate Yihui Liu1,2 1 Institute of Intelligent Department of Computer Science, University of Nottingham, UK Abstract--Adverse drug reaction (ADR) is widely feature matrix and feature selection. The experiments are carried out on the drug Alendronate. Major side

  9. Detect adverse drug reactions for drug Atorvastatin Yihui Liu1,2

    E-print Network

    Aickelin, Uwe

    Detect adverse drug reactions for drug Atorvastatin Yihui Liu1,2 1 Institute of Intelligent Department of Computer Science, University of Nottingham, UK Abstract--Adverse drug reaction (ADR) is widely feature matrix and feature selection. The experiments are carried out on the drug Atorvastatin. Major side

  10. Detect adverse drug reactions for drug Pioglitazone Yihui Liu1,2

    E-print Network

    Aickelin, Uwe

    Detect adverse drug reactions for drug Pioglitazone Yihui Liu1,2 1 Institute of Intelligent Department of Computer Science, University of Nottingham, UK Abstract--Adverse drug reaction (ADR) is widely feature matrix and feature selection. The experiments are carried out on the drug Pioglitazone. Major side

  11. 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…

  12. Abnormal splicing of NEDD4 in myotonic dystrophy type 2: possible link to statin adverse reactions.

    PubMed

    Screen, Mark; Jonson, Per Harald; Raheem, Olayinka; Palmio, Johanna; Laaksonen, Reijo; Lehtimäki, Terho; Sirito, Mario; Krahe, Ralf; Hackman, Peter; Udd, Bjarne

    2014-08-01

    Myotonic dystrophy type 2 (DM2) is a multisystemic disorder caused by a (CCTG)n repeat expansion in intron 1 of CNBP. Transcription of the repeats causes a toxic RNA gain of function involving their accumulation in ribonuclear foci. This leads to sequestration of splicing factors and alters pre-mRNA splicing in a range of downstream effector genes, which is thought to contribute to the diverse DM2 clinical features. Hyperlipidemia is frequent in DM2 patients, but the treatment is problematic because of an increased risk of statin-induced adverse reactions. Hypothesizing that shared pathways lead to the increased risk, we compared the skeletal muscle expression profiles of DM2 patients and controls with patients with hyperlipidemia on statin therapy. Neural precursor cell expressed, developmentally downregulated-4 (NEDD4), an ubiquitin ligase, was one of the dysregulated genes identified in DM2 patients and patients with statin-treated hyperlipidemia. In DM2 muscle, NEDD4 mRNA was abnormally spliced, leading to aberrant NEDD4 proteins. NEDD4 was down-regulated in persons taking statins, and simvastatin treatment of C2C12 cells suppressed NEDD4 transcription. Phosphatase and tensin homologue (PTEN), an established NEDD4 target, was increased and accumulated in highly atrophic DM2 muscle fibers. PTEN ubiquitination was reduced in DM2 myofibers, suggesting that the NEDD4-PTEN pathway is dysregulated in DM2 skeletal muscle. Thus, this pathway may contribute to the increased risk of statin-adverse reactions in patients with DM2. PMID:24907641

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Health Risks and Adverse Reactions to Functional Foods.

    PubMed

    Ameratunga, Rohan; Crooks, Christine; Simmons, Greg; Woon, See-Tarn

    2016-01-25

    Functional foods have become increasingly popular with consumers anxious to mitigate the effects of an unhealthy lifestyle or aging. In spite of attractive health claims, these products do not have legal or regulatory status in most countries and are regulated through their health claims. Regulation of functional foods by health claims does not address health risks and adverse effects of these products. In this essay regulatory aspects of functional foods are reviewed along with adverse effects published in the peer-reviewed literature. We detail why the lack of an internationally accepted definition of functional foods places consumers at risk of adverse outcomes. Our review will assist regulatory agencies, manufacturers and consumer groups to assess the benefits and reduce the risks associated with these products. PMID:25163007

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

    PubMed Central

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

    2015-01-01

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

  17. Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity.

    PubMed

    Wiley, Laura K; Moretz, Jeremy D; Denny, Joshua C; Peterson, Josh F; Bush, William S

    2015-01-01

    It is unclear the extent to which best practices for phenotyping disease states from electronic medical records (EMRs) translate to phenotyping adverse drug events. Here we use statin-induced myotoxicity as a case study to identify best practices in this area. We compared multiple phenotyping algorithms using administrative codes, laboratory measurements, and full-text keyword matching to identify statin-related myopathy from EMRs. Manual review of 300 deidentified EMRs with exposure to at least one statin, created a gold standard set of 124 cases and 176 controls. We tested algorithms using ICD-9 billing codes, laboratory measurements of creatine kinase (CK) and keyword searches of clinical notes and allergy lists. The combined keyword algorithms produced were the most accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms, addition of ICD9 codes or laboratory data did not appreciably increase algorithm accuracy. We conclude that phenotype algorithms for adverse drug events should consider text based approaches. PMID:26306287

  18. Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity

    PubMed Central

    Wiley, Laura K.; Moretz, Jeremy D.; Denny, Joshua C.; Peterson, Josh F.; Bush, William S.

    2015-01-01

    It is unclear the extent to which best practices for phenotyping disease states from electronic medical records (EMRs) translate to phenotyping adverse drug events. Here we use statin-induced myotoxicity as a case study to identify best practices in this area. We compared multiple phenotyping algorithms using administrative codes, laboratory measurements, and full-text keyword matching to identify statin-related myopathy from EMRs. Manual review of 300 deidentified EMRs with exposure to at least one statin, created a gold standard set of 124 cases and 176 controls. We tested algorithms using ICD-9 billing codes, laboratory measurements of creatine kinase (CK) and keyword searches of clinical notes and allergy lists. The combined keyword algorithms produced were the most accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms, addition of ICD9 codes or laboratory data did not appreciably increase algorithm accuracy. We conclude that phenotype algorithms for adverse drug events should consider text based approaches. PMID:26306287

  19. Automatic Detection Of Vaccine Adverse Reactions By Incorporating Historical Medical Conditions

    E-print Network

    Karypis, George

    Automatic Detection Of Vaccine Adverse Reactions By Incorporating Historical Medical Conditions This paper extends the state of art by bringing the historical medical conditions into the vaccine adverse with certain vaccines. We propose a novel measure called dual-lift for this task. It is shown that the dual

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

    E-print Network

    Baral, Chitta

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

  1. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  2. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  3. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  4. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  5. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  6. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...regarding each unit of blood or blood product arising as a result of blood collection or transfusion...b) When a complication of blood collection or transfusion...collecting facility in the event of a donor reaction, or by the...

  7. The genetics of pro-arrhythmic adverse drug reactions

    PubMed Central

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

    2014-01-01

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

  8. Oral Sedation Postdischarge Adverse Events in Pediatric Dental Patients.

    PubMed

    Huang, Annie; Tanbonliong, Thomas

    2015-01-01

    The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment. This prospective study involved 51 patients needing dental treatment under oral conscious sedation. Each patient received one of various regimens involving combinations of a narcotic (ie, morphine or meperidine), a sedative-hypnotic (ie, chloral hydrate), a benzodiazepine (ie, midazolam or diazepam), and/or an antihistamine (ie, hydroxyzine HCl). Nitrous oxide and local anesthesia were used in conjunction with all regimens. After written informed consent was obtained, each guardian was contacted by phone with specific questions in regard to adverse events following the dental appointment. Out of 51 sedation visits, 46 were utilized for analysis including 23 boys and 23 girls ranging from 2 years 2 months to 10 years old (mean 5.8 years). 60.1% of patients slept in the car on the way home, while 21.4% of that group was difficult to awaken upon reaching home. At home, 76.1% of patients slept; furthermore, 85.7% of patients who napped following the dental visit slept longer than usual. After the appointment, 19.6% exhibited nausea, 10.1% vomited, and 7.0% experienced a fever. A return to normal behavior was reported as follows: 17.4% in <2 hours, 39.1% in 2-6 hours, 28.3% in 6-10 hours, and 15.2% in >10 hours. Postdischarge excessive somnolence, nausea, and emesis were frequent complications. The time to normality ranged until the following morning demonstrating the importance of careful postdischarge adult supervision. PMID:26398124

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

    PubMed Central

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

    2009-01-01

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

  10. Adverse surgical outcomes among patients with cognitive impairments.

    PubMed

    Bernstein, G M; Offenbartl, S K

    1991-11-01

    To determine the factors that contributed to adverse outcomes, the records of 59 cognitively impaired patients with nonfatal complications (n = 23) or death (n = 36) on a general surgery teaching service over a 30-month period were examined retrospectively. Specific complications are reported. Patient, disease, and management factors related to mortality and morbidity are identified. Patients with cognitive impairments had a higher mortality rate (9.6 vs 6.3%) and approximately the same rate of nonfatal complications (6.1 vs 7.6%) when compared with general surgery patients as a whole. Patient characteristics including age over 70, dementia, nursing home residence, contractures, inability to communicate, need for total care, and gross malnutrition were associated with fatal outcomes. Vascular, colonic, esophageal, gastric, or duodenal conditions, emergency admission, urgent operation, and admission APACHE II scores greater than or equal to 15 were disease-related factors associated with mortality. Management risk factors were prehospital or inpatient diagnostic delays and technical or judgmental errors of surgical management. Twenty-four of 36 deaths were directly related either to a diagnostic delay (11), an operative technical error (11), or a judgmental error of postoperative airway management (2). Eighty-five per cent of diagnostic delays (11/13) and 37 per cent (11/30) of technical errors resulted in mortality. Suggestions for improving the care of these patients are discussed. PMID:1746775

  11. Adverse events in total knee arthroplasty: Results of a physician independent survey in 260 patients

    PubMed Central

    2010-01-01

    Purpose Identification of all common and potentially avoidable adverse events is crucial to further improve the quality of medical care. The intention of the current study was to evaluate a standardized physician independent survey format on adverse events in total knee arthroplasty. The protocol for reporting adverse drug events following the International Conference of Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) was adopted for adverse events occurring during surgical interventions. Material and methods Data of a prospective sequential cohort trial introducing a clinical pathway for total knee arthroplasty was analysed. Reporting of adverse events was done by a physician independent study nurse using the modified ICH-Good Clinical Practice (GCP) format (Structure and Content of Clinical study reports - E3) in 260 patients. The adverse events were graded to their severity and their potential relation to surgical treatment. Results A total of 55 patients (21%) suffered from an adverse event and 16 (6%) from a serious adverse event. In 38 patients' one adverse event occurred, 12 patients showed 2 adverse events and 5 patients suffered from a combination of an adverse and a serious adverse event. A serious adverse event alone occurred in 11 patients. The incidence of adverse events (Fisher p = 0.448) and serious adverse (p = 0.126) events showed no significant difference between the two cohorts. The most common adverse events were deep vein thrombosis (8% and 5%) followed by wound healing problems (1% and 0%) and haematoma (1% and 3%). A wide range of non surgical adverse events were recorded with low incidence levels. Conclusion The use of the modified ICH-GCP format supports standardization of adverse event reporting. Routine assessment of adverse events by a study nurse revealed higher incidence rates of adverse events in total knee arthroplasty. We recommend the implementation of trained paramedical staff for the documentation of adverse events in routine clinical care. PMID:20699004

  12. Influence of Adverse Drug Reactions on Treatment Success: Prospective Cohort Analysis of HIV-Infected Individuals Initiating First-Line Antiretroviral Therapy in India

    PubMed Central

    Shet, Anita; Antony, Jimmy; Arumugam, Karthika; Kumar Dodderi, Sunil; Rodrigues, Rashmi; DeCosta, Ayesha

    2014-01-01

    Introduction Adverse drug reactions related to antiretroviral therapy (ART) remain a challenge in resource-limited settings, often causing significant morbidity and impaired adherence leading to treatment failure. This 2-year prospective study aimed to describe patterns and predictors of adverse reactions to first-line ART and assess the impact of these events on treatment success. Methods Between 2010–2013, 321 ART-naïve eligible adults were enrolled at two clinics in southern India. ART regimens included zidovudine or stavudine plus lamivudine, plus nevirapine or efavirenz. Pill count adherence, immunological and virological monitoring, and laboratory-based adverse drug reactions were measured prospectively and analyzed. Results Among 321 patients in the study, 289 (90.0%) patients experienced at least 1 adverse reaction, and 85 (26.5%) experienced at least 1 severe reaction. The incidence rate was 52 and 15 per 100 person-years for all reactions and severe reactions respectively. The cumulative incidence of zidovudine-induced anemia was 37.1% over 2 years. At 12 and 24 months, the proportion of patients with optimal adherence, undetectable viral load and CD4 counts >350 cells/mm3 were similar between patients who experienced or did not experience severe adverse drug reactions. Conclusions Our results highlight the high frequency of ART-related adverse drug reactions among individuals initiating first-line ART in India, underscoring the importance of detailed counseling and monitoring for maintaining ART durability. Severe drug-induced anemia needs to be addressed urgently with alternative first-line agents, and close laboratory surveillance. High treatment efficacy despite decreased drug safety seen here may be because patients have limited treatment options. Our results support the use of currently recommended safer first-line ART regimens that minimize the risk of severe life-threatening toxicities and provide for a better quality of life. Trial registration ISRTCN Registry: ISRCTN79261738. PMID:24614165

  13. Methodological framework to identify possible adverse drug reactions using population-based administrative data

    PubMed Central

    Sauer, Brian; Nebeker, Jonathan; Shen, Shuying; Rupper, Randall; West, Suzanne; Shinogle, Judith A.; Xu, Wu; Lohr, Kathleen N.; Samore, Matthew

    2014-01-01

    Purpose: We present a framework for detecting possible adverse drug reactions (ADRs) using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs): known reactions (gastrointestinal, psychological disturbances), potential reactions (respiratory disturbance), novel reactions (hepatic, hematological disturbances), and death. Methods: Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression. Results: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6) in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3). Conclusions: We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential ADEs and generate hypotheses for future investigations. Early findings, or signal detection, are considered hypothesis generating since confirmatory studies must be designed to determine if the signal represents a true drug safety problem. PMID:26180631

  14. Patterns of Adverse Drug Reactions in Different Age Groups: Analysis of Spontaneous Reports by Community Pharmacists

    PubMed Central

    Yu, Yun Mi; Shin, Wan Gyoon; Lee, Ju-Yeun; Choi, Soo An; Jo, Yun Hee; Youn, So Jung; Lee, Mo Se; Choi, Kwang Hoon

    2015-01-01

    Purpose To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age. Methods ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female. Results Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively. Conclusions According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups. PMID:26172050

  15. Adverse reactions in cattle to a capripox vaccine.

    PubMed

    Yeruham, I; Perl, S; Nyska, A; Abraham, A; Davidson, M; Haymovitch, M; Zamir, O; Grinstein, H

    1994-10-01

    Capripox vaccine (strain 0240) caused severe generalised skin reactions in vaccinated dairy cattle in two herds, whereas beef cattle did not develop reactions. All the reacting animals developed lumpy skin disease-like lesions. The incidence of skin lesions in first-lactation cows in herd A was 22.9 per cent and in herd B 29.3 per cent, mainly in the post-calving period. In older cows, the incidence was 10 per cent in herd A and 12.4 per cent in herd B. In herd B the high-yielding lactating cows were the most severely affected. There was a decrease of 3.5 per cent in milk production in each herd over a period of 12 days, and six first calving animals (3.5 per cent) and six cows (1.5 per cent) were slaughtered. A capripox virus was isolated from the animals with severe lesions, and was also demonstrated by electron microscopy. The histopathological lesions were similar to those of lumpy skin disease. The extent of the lesions appeared to be stress-related and, to a lesser degree, correlated with age and breed. PMID:7825272

  16. Blood transfusion safety: A study of adverse reactions at the blood bank of a tertiary care center

    PubMed Central

    Negi, Gita; Gaur, Dushyant Singh; Kaur, Rajveer

    2015-01-01

    Background: An adverse transfusion reaction (ATR) is an unfavorable reaction to the transfused unit, the severity of which may be different among individuals depending upon the type of reaction and the patient's susceptibility. Transfusion reactions may be immediate or delayed type depending on the onset and immune or nonimmune type depending on the pathogenesis. A study was conducted to study the frequency of various transfusion reactions and the associated morbidity. Materials and Methods: All ATRs occurring over a period of 3 years at a tertiary care health center were studied in detail according to the institute's protocol. Results: Of 38,013 units of blood and components that had been issued, 101 (0.2%) cases had an ATR. The most common reaction was allergic - 34/101 (33.6%) followed by febrile - 26/101 (25.7%). Other reactions included transfusion-related acute lung injury in 6/101 (5.9%) cases, and immune reactions were seen in 19/101 (18.8%) cases. Conclusion: Allergic and febrile reactions are most common and least harmful, but fatal reactions can also occur, and preventive measures must be taken to avoid such reactions. PMID:26682203

  17. Defining targets for investigating the pharmacogenomics of adverse drug reactions to antifungal agents.

    PubMed

    Meletiadis, Joseph; Chanock, Stephen; Walsh, Thomas J

    2008-05-01

    Adverse drug reactions (ADRs) associated with antifungal therapy are major problems in patients with invasive fungal infections. Whether by clinical history or patterns of genetic variation, the identification of patients at risk for ADRs should result in improved outcomes while minimizing deleterious side effects. A major contributing factor to ADRs with antifungal agents relates to drug distribution, metabolism and excretion. Genetic variation in key genes can alter the structure and expression of genes and gene products (e.g., proteins). Thus far, the effort has focused on identifying polymorphisms with either empirical or predicted in silico functional consequences; the best candidate genes encode phase I and II drug-metabolizing enzymes (e.g., CYP2C19 and N-acetyltransferase), plasma proteins (albumin and lipoproteins) and drug transporters (P-glycoprotein and multidrug resistance proteins), which can affect the disposition of antifungal agents, eventually leading to dose-dependent (type A) toxicity. Less is known regarding the key genes that interact with antifungal agents, resulting in idiosyncratic (type B) ADRs. The possible role of certain gene products and genetic polymorphisms in the toxicities of antifungal agents are discussed in this review. The preliminary data address the following: low-density lipoproteins and cholesteryl ester transfer protein in amphotericin B renal toxicity; toll-like receptor 1 and 2 in amphotericin B infusion-related ADRs; phosphodiesterase 6 in voriconazole visual adverse events; flavin-containing monooxygenase, glutathione transferases and multidrug resistance proteins 1 and 2 in ketoconazole and terbinafine hepatotoxicity; CYP enzymes and P-glycoprotein in drug interactions between azoles and coadministered medications; multidrug resistance proteins 8 and 9 on 5-flucytosine bone marrow toxicity; and mast cell activation in caspofungin histamine release. This will focus on high-priority candidate genes, which could provide a starting point for molecular studies to elucidate the potential mechanisms for understanding toxicity associated with antifungal drugs as well as identifying candidate genes for large population prospective genetic association studies. PMID:18466103

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

    PubMed

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

    2015-06-01

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

  19. Adverse Drug Reactions of Spontaneous Reports in Shanghai Pediatric Population

    PubMed Central

    Du, Wen-Min; Xu, Jin-Fang; Zhang, Xin-Ji; He, Jia

    2014-01-01

    Background Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009. Methodology and Principal Findings Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter. Results A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (?2?=?15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors. Conclusions In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China. PMID:24587066

  20. 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

  1. 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

  2. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... referenced by the licensed manufacturer's patient identification number, adverse reaction term(s), and date... of the licensed manufacturer's patient identification number and adverse reaction term(s)); and (C)...

  3. Influence of dexmedetomidine on incidence of adverse reactions introduced by hemabate in postpartum hemorrhage during cesarean section

    PubMed Central

    Liu, Yang; Chen, Hong-Xia; Kang, Dao-Lin; Kuang, Xiao-Hua; Liu, Wen-Xing; Ni, Jin

    2015-01-01

    Objective: The purpose of our study was to observe the influence of dexmedetomidine on complications caused by hemabate in patients undergoing caesarean section. Methods: A total of 120 females (age range, 20-40 years) at 35-40 weeks gestation who delivered by cesarean between September, 2014 and December, 2014 were enrolled in our study. Patients were randomly allocated into three groups that received intravenously physiological saline 20 mL (placebo group), lower dose (0.5 ?g kg-1) of dexmedetomidine (low-dex gruop) and higher dose (1 ?g kg-1) of dexmedetomidine (high-dex group) during cesarean section, following the delivery of the infant and intramuscular hemabate injection. Results: Nausea, vomiting, chest congestion and elevated blood pressure were the most common adverse events of placebo group. Compared with placebo group, the above mentioned adverse reactions decreased significantly in both low-dex group and high-dex group (P<0.05), whereas there were no significant difference between low-dex group and high-dex group (P>0.05). As to patient satisfaction score, low-dex group and high-dex group were all higher than placebo group (P<0.05). Furthermore, there were more patients satisfied with high-dex group than low-dex group (P<0.05). Conclusion: Dexmedetomidine (0.5 ?g kg-1 and 1 ?g kg-1) were all effective in preventing adverse reactions introduced by hemabate and improve parturients’ satisfaction in patients undergoing cesarean delivery. And higher dose (1 ?g kg-1) of dexmedetomidine is superior to lower dose (0.5 ?g kg-1) in patient satisfaction. PMID:26550325

  4. Hematopoietic Stem Cell Transplantation with Cryopreserved Grafts: Adverse Reactions after Transplantation and Cryoprotectant Removal Prior to Infusion

    PubMed Central

    Shu, Zhiquan; Heimfeld, Shelly; Gao, Dayong

    2015-01-01

    Transplantation of hematopoietic stem cells (HSC) has been successfully developed as a part of treatment protocols for a large number of clinical indications, and cryopreservation of both autologous and allogeneic sources of HSC grafts is increasingly being employed to facilitate logistical challenges in coordinating the collection, processing, preparation, quality control testing and release of the final HSC product with delivery to the patient. Direct infusion of cryopreserved cell products into patients has been associated with the development of adverse reactions, ranging from relatively mild symptoms to much more serious, life-threatening complications, including allergic/gastrointestinal/cardiovascular/neurological complications, renal/hepatic dysfunctions, etc. In many cases the cryoprotective agent (CPA) used — which is typically dimethyl sulfoxide (DMSO), is believed to be the main causal agent of these adverse reactions and thus many studies recommend depletion of DMSO before cell infusion. In this paper, we will briefly review the history of HSC cryopreservation, the side effects reported after transplantation, along with advances in strategies for reducing the adverse reactions, including methods and devices for removal of DMSO. Strategies to minimize adverse effects include medication before and after transplantation, optimizing the infusion procedure, reducing the DMSO concentration or using alternative CPAs for cryopreservation, and removing DMSO prior to infusion. For DMSO removal, besides the traditional and widely applied method of centrifugation, new approaches have been explored in the last decade, such as filtration by spinning membrane, stepwise dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction in microfluidic channels, dialysis and dilution-filtration through hollow-fiber dialyzers, and some instruments (CytoMate™, Sepax S-100, Cobe 2991, microfluidic channels, dilution-filtration system, etc.) as well. However, challenges still remain: development of the optimal (fast, safe, simple, automated, controllable, effective, and low-cost) methods and devices for CPA removal with minimum cell loss and damage remains an unfilled need. PMID:24076548

  5. An observational study of cutaneous adverse drug reactions in a teaching hospital.

    PubMed

    Chopra, Deepti; Sharma, Vibha; Kapoor, Rohan; Dwivedi, Shridhar

    2015-12-01

    Background Pharmacotherapy is often impeded by adverse drug reactions (ADRs). Among these ADRs cutaneous reactions are the major class being easily identified and reported. If not noted early it has potential to develop into serious lesions. Objective To evaluate the clinical patterns of various drug induced cutaneous reactions. Setting A Teaching hospital in India. Methods All suspected cutaneous reactions to systemic drugs which were submitted to the ADR monitoring centre during a 6-month period (March 2014-August 2014) were analysed. Causality relationship, severity assessment and preventability assessment was also done. Results Out of 134 cutaneous ADRs, 56 % occurred in females, majority of cases were found in the age group of 41-50 years. The most common type of ADR was maculopapular rash (46.3 %) and majorly implicated drug class was antibiotics (51.3 %). Most (72.3 %) were mild. Polypharmacy and multiple comorbid conditions were important predisposing factors. Over half of the cases (58 %) were not preventable. Conclusion Cutaneous adverse reaction patterns and their causes vary as the result of changing use of drugs. In India, antibiotics are responsible for the majority of the cutaneous adverse drug reactions, and maculopapular rash is the side effect that is most reported. PMID:26238222

  6. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... normal activities experienced by all or most of the persons exposed at one time. (4) An impairment of normal activities which is experienced each time an individual is exposed. (b) Firms are not required to... are not required to record a significant adverse reaction to the environment if the alleged cause...

  7. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... normal activities experienced by all or most of the persons exposed at one time. (4) An impairment of normal activities which is experienced each time an individual is exposed. (b) Firms are not required to... are not required to record a significant adverse reaction to the environment if the alleged cause...

  8. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... normal activities experienced by all or most of the persons exposed at one time. (4) An impairment of normal activities which is experienced each time an individual is exposed. (b) Firms are not required to... are not required to record a significant adverse reaction to the environment if the alleged cause...

  9. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... normal activities experienced by all or most of the persons exposed at one time. (4) An impairment of normal activities which is experienced each time an individual is exposed. (b) Firms are not required to... are not required to record a significant adverse reaction to the environment if the alleged cause...

  10. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... normal activities experienced by all or most of the persons exposed at one time. (4) An impairment of normal activities which is experienced each time an individual is exposed. (b) Firms are not required to... are not required to record a significant adverse reaction to the environment if the alleged cause...

  11. Multi-task and Multi-view Learning for Predicting Adverse Drug Reactions

    E-print Network

    Zhang, Jintao

    2012-12-31

    Adverse drug reactions (ADRs) present a major concern for drug safety and are a major obstacle in modern drug development. They account for about one-third of all late-stage drug failures, and approximately 4% of all new chemical entities...

  12. Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005

    PubMed Central

    Patel, Hitesh; Bell, Derek; Molokhia, Mariam; Srishanmuganathan, Janakan; Patel, Mitesh; Car, Josip; Majeed, Azeem

    2007-01-01

    Background Adverse drug reactions (ADRs) are a frequent cause of mortality and morbidity to patients worldwide, with great associated costs to the healthcare providers including the NHS in England. We examined trends in hospital admissions associated with adverse drug reaction in English hospitals and the accuracy of national reporting. Methods Data from the Hospital Episode Statistics database (collected by the Department of Health) was obtained and analysed for all English hospital episodes (1998–2005) using ICD-10 codes with a primary (codes including the words ('drug-induced' or 'due to') or secondary diagnosis of ADR (Y40–59). More detailed analysis was performed for the year 2004–2005 Results Between 1998 and 2005 there were 447 071 ADRs representing 0.50% of total hospital episodes and over this period the number of ADRs increased by 45%. All ADRs with an external code increased over this period. In 2005 the total number of episodes (all age groups) was 13,706,765 of which 76,692 (0.56%) were drug related. Systemic agents, which include anti-neoplastic drugs, were the most implicated class (15.7%), followed by analgesics (11.7%) and cardiovascular drugs (10.1%). There has been a 6 fold increase in nephropathy secondary to drugs and a 65% decline in drug induced extra-pyramidal side effects. 59% of cases involving adverse drug reactions involved patients above 60 years of age. Conclusion ADRs have major public health and economic implications. Our data suggest that national Hospital Episode Statistics in England have recognised limitations and that consequently, admissions associated with adverse drug reactions continue to be under-recorded. External causes of ADR have increased at a greater rate than the increase in total hospital admissions. Improved and more detailed reporting combined with educational interventions to improve the recording of ADRs are needed to accurately monitor the morbidity caused by ADRs and to meaningfully evaluate national initiatives to reduce adverse drug reactions. PMID:17894876

  13. Correlation between expression of epidermal growth factor receptor and adverse reactions after chemotherapy of advanced non-small-cell lung cancer

    PubMed Central

    Hao, Zerui; Tian, Chunyan; Yang, Futang; Zhang, Jihong

    2015-01-01

    Objective: To analyze the correlation between expression of epidermal growth factor receptor (EGFR) and adverse reactions after chemotherapy of advanced non-small-cell lung cancer (NSCLC). Methods: A total of 120 NSCLC patients who were treated in our hospital from August 2009 to September 2011 were selected as an observation group, and another 120 healthy subjects were selected as a control group. EGFR expressions in both groups were detected. The observation group was subjected to combination chemotherapy, and their shorter- and long-term prognostic outcomes, adverse reactions and mortality were recorded. Meanwhile, correlation analysis was performed. Results: The observation group had significantly higher percentage and positive rate in EGFR expression than those of the control group (P<0.05). With increasing stage and lymphatic metastasis, the positive expression rate of EGFR rose significantly (P<0.05). In the observation group, the response rate of treatment was 62.5%, and the incidence rate of adverse reactions after chemotherapy was 28.3% (34/120). The 1-, 2- and 3-year survival rates were 38.3%, 15.0% and 10.0% respectively. Multiple Logistic regression analysis showed that TNM stage, lymphatic metastasis and positive EGFR expression were the main independent risk factors for post-chemotherapy adverse reactions (P<0.05). Conclusion: Advanced NSCLC was commonly accompanied by high EGFR expression. Although chemotherapy was able to improve the prognosis and survival rate, adverse reactions were also induced, being associated with the pathological characteristics and EGFR expressions of patients.

  14. Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

    PubMed Central

    Moore, Nicholas; Pollack, Charles; Butkerait, Paul

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. PMID:26203254

  15. Pediatric hospital admission due to adverse drug reactions: Report from a tertiary center

    PubMed Central

    Gholami, Kheirollah; Babaie, Fatemeh; Shalviri, Gloria; Javadi, Mohammad Reza; Faghihi, Toktam

    2015-01-01

    Objective: Adverse drug reactions (ADRs) are known as a cause of hospital admission. We have carried out a prospective study to characterize and assess the frequency, probability, preventability, and severity of ADRs, which lead to hospital admission in children. Methods: In a prospective observational study, a cohort of children admitted to a tertiary pediatric hospital was randomly screened to assess ADR as the cause of admission from June 2014 to January 2015. ADRs causing admissions were detected based on patients’ records, interviewing their parents, and confirmation by medical team. The probability of the ADRs was assessed based on WHO criteria and Naranjo tool. The preventability assessment was performed using Schumock and Thornton questionnaire. Findings: Of the 658 evaluated emergency admissions, 27 were caused by an ADR giving an incidence of 4.1%. Among ADRs, 37.1% were estimated to be preventable. Antibiotics were the most common medication class which caused hospital admission. Conclusion: Pediatric pharmacotherapy still needs evidence-based strategies to improve child care including education, monitoring, planning for medications after ADR occurrence, and implementing preventive measures when applicable.

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

    PubMed

    Takahashi, Haruo

    2009-01-01

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

  17. Recent advances of pharmacogenomics in severe cutaneous adverse reactions: immune and nonimmune mechanisms

    PubMed Central

    Dao, Ro-Lan; Su, Shih-Chi

    2015-01-01

    Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse reactions (SCAR) which are majorly caused by drugs. Though the incidence rate is low, SCAR sometimes can be life-threatening and leads to lifelong sequelae. Many pharmacogenomic associations in immune and nonimmune related genes with the development of SCAR have been discovered recently and the pharmacogenetic tests have been applied to prevent specific drug-induced SCAR. In this review, we discuss the recent advances of pharmacogenomics in SCAR. PMID:25938070

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

    PubMed Central

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

    2014-01-01

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

  19. Adverse drug reactions - examples of detection of rare events using databases.

    PubMed

    Chan, Esther W; Liu, Kirin Q L; Chui, Celine S L; Sing, Chor-Wing; Wong, Lisa Y L; Wong, Ian C K

    2015-10-01

    It is recognised that randomised controlled trials are not feasible for capturing rare adverse events. There is an increasing trend towards observational research methodologies using large population-based health databases. These databases offer more scope for adequate sample sizes, allowing for comprehensive patient characterisation and assessment of the associated factors. While direct causality cannot be established and confounders cannot be ignored, databases present an opportunity to explore and quantify rare events. The use of databases for the detection of rare adverse events in the following conditions, sudden death associated with attention deficit hyperactivity disorder (ADHD) treatment, retinal detachment associated with the use of fluoroquinolones and toxic epidermal necrolysis associated with drug exposure, are discussed as examples. In general, rare adverse events tend to have immediate and important clinical implications and may be life-threatening. An understanding of the causative factors is therefore important, in addition to the research methodologies and database platforms that enable the undertaking of the research. PMID:25060360

  20. Comparative analysis of pharmacovigilance methods in the detection of adverse drug reactions using electronic medical records

    PubMed Central

    Liu, Mei; McPeek Hinz, Eugenia Renne; Matheny, Michael Edwin; Denny, Joshua C; Schildcrout, Jonathan Scott; Miller, Randolph A; Xu, Hua

    2013-01-01

    Objective Medication  safety requires that each drug be monitored throughout its market life as early detection of adverse drug reactions (ADRs) can lead to alerts that prevent patient harm. Recently, electronic medical records (EMRs) have emerged as a valuable resource for pharmacovigilance. This study examines the use of retrospective medication orders and inpatient laboratory results documented in the EMR to identify ADRs. Methods Using 12?years of EMR data from Vanderbilt University Medical Center (VUMC), we designed a study to correlate abnormal laboratory results with specific drug administrations by comparing the outcomes of a drug-exposed group and a matched unexposed group. We assessed the relative merits of six pharmacovigilance measures used in spontaneous reporting systems (SRSs): proportional reporting ratio (PRR), reporting OR (ROR), Yule's Q (YULE), the ?2 test (CHI), Bayesian confidence propagation neural networks (BCPNN), and a gamma Poisson shrinker (GPS). Results We systematically evaluated the methods on two independently constructed reference standard datasets of drug–event pairs. The dataset of Yoon et al contained 470 drug–event pairs (10 drugs and 47 laboratory abnormalities). Using VUMC's EMR, we created another dataset of 378 drug–event pairs (nine drugs and 42 laboratory abnormalities). Evaluation on our reference standard showed that CHI, ROR, PRR, and YULE all had the same F score (62%). When the reference standard of Yoon et al was used, ROR had the best F score of 68%, with 77% precision and 61% recall. Conclusions Results suggest that EMR-derived laboratory measurements and medication orders can help to validate previously reported ADRs, and detect new ADRs. PMID:23161894

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

    PubMed Central

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

    2013-01-01

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

  2. Dermatological adverse reactions during anti-TNF treatments: focus on inflammatory bowel disease.

    PubMed

    Mocci, Giammarco; Marzo, Manuela; Papa, Alfredo; Armuzzi, Alessandro; Guidi, Luisa

    2013-11-01

    The clinical introduction of tumour necrosis factor (TNF) inhibitors has deeply changed the treatment of inflammatory bowel diseases (IBD). It has demonstrated impressive efficacy as compared to alternative treatments, allowing for the chance to achieve near-remission and long-term improvement in function and quality of life and to alter the natural history of Crohn's disease (CD) and ulcerative colitis (UC). As a consequence of longer follow-up periods the number of side effects which may be attributed to treatment with biologics is growing significantly. Cutaneous reactions are among the most common adverse reactions. These complications include injection site reactions, cutaneous infections, immune-mediated complications such as psoriasis and lupus-like syndrome and rarely skin cancers. We review the recent literature and draw attention to dermatological side effects of anti-TNF therapy of inflammatory bowel disease. PMID:23453887

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

    PubMed Central

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

    2014-01-01

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

  4. Adverse local tissue reactions in metal-on-polyethylene total hip arthroplasty due to trunnion corrosion: the risk of misdiagnosis.

    PubMed

    Whitehouse, M R; Endo, M; Zachara, S; Nielsen, T O; Greidanus, N V; Masri, B A; Garbuz, D S; Duncan, C P

    2015-08-01

    Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation. We present a consecutive series of 17 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series. The clinical presentation was pain, swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head-neck junction was noted in all cases. No bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts were noted in nine cases. Adverse soft-tissue reactions can occur in MoP THA owing to corrosion products released from the head-neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange. PMID:26224816

  5. [Psychopathologic reactions in orthopedic patients].

    PubMed

    Lesi?, Aleksandar; Opali?, Petar

    2003-01-01

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

  6. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial. PMID:26496172

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

    PubMed

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

    2014-07-16

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

  8. Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

    PubMed Central

    Venkataraman, Aishwarya; Yusuff, Michael; Liebeschuetz, Susan; Riddell, Anna; Prendergast, Andrew J.

    2015-01-01

    Background Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. Aim To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. Methods All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. Results Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. Conclusions Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. PMID:26275478

  9. Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review

    PubMed Central

    Bellet, Florelle; Asfari, Hadyl; Souvignet, Julien; Texier, Nathalie; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Burgun, Anita; Bousquet, Cédric

    2015-01-01

    Background The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients’ experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance. Objective A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance. Methods Daubt et al’s recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2. Results Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified. Conclusions This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding extraction, no study proposed a generic approach to easily adding a new site or data source. Additional studies are required to precisely determine the role of social media in the pharmacovigilance system. PMID:26163365

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

    Cancer.gov

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

  11. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    PubMed

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. PMID:26141794

  12. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    PubMed

    Stevenson, D D

    1984-10-01

    Aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) share common pharmacologic effects in the prevention of inflammation, at least in part through inhibition of prostaglandin formation. ASA and NSAIDs have predictable side effects such as gastric pain, ecchymosis, and tinnitus. They also cause anaphylactoid shock, urticaria/angioedema, nephropathy, and hepatitis in individuals who appear to be normal and in whom prediction of such reactions cannot be made. Two selected populations of patients are likely to experience hypersensitivity reactions to both ASA and NSAIDs. Patients with asthma have an 8% to 20% chance of experiencing asthmatic attacks after ingesting ASA and NSAID. If such patients have associated rhinosinusitis (polyps), prevalence increases to 30% to 40%. Patients with chronic urticaria/angioedema have a 21% to 30% chance of experiencing an urticarial flare after ingesting ASA and NSAIDs. PMID:6436354

  13. [Visualization and analysis of adverse reactions of molecularly targeted anticancer agents using the self-organizing map (SOM)].

    PubMed

    Hamamoto, Tomoyuki; Serizawa, Ayaka; Ohtsuki, Kaori; Kawakami, Junko; Sato, Kenichi

    2014-01-01

    Molecularly targeted anticancer agents cause a variety of adverse reactions compared with conventional anticancer agents because of their unique mechanisms of action. Sources of drug information such as package inserts (PIs) provide primarily document-based and numerical information. Therefore it is not easy to obtain a complete picture of drugs with similar effects, or to understand differences among drugs. In this study we used the self-organizing map (SOM) technique to visualize the adverse reactions indicated on PIs of 23 molecularly targeted anticancer agents as of March 2013. In both the presence/absence version and the frequency version, SOM was divided into domains according to mechanism of action, antibody drug or low-molecular weight drug, and molecular target. The component planes of the 753 adverse reaction items in the frequency version enabled us to grasp all available information and differences among the drugs. In some component planes in the presence/absence version, an adverse reaction that had not been reported for a drug but had already been reported for its proximally positioned drug(s) as of March 2013, was found to be reported thereafter by the Drug Safety Update (DSU) or the Adverse Event Report Search System "CzeekV," which is based on FDA Adverse Event Reporting System (FAERS). Our results suggest that visualization of the adverse reactions of molecularly targeted anticancer agents by the SOM technique is useful not only to acquire all available information and differences among drugs, but also to predict the appearance of adverse reactions. PMID:25274218

  14. The problems of anticholinergic adverse effects in older patients.

    PubMed

    Feinberg, M

    1993-01-01

    The old saying 'red as a beet, dry as a bone, blind as a bat, hot as a hare, mad as a hatter' is often quoted when describing the autonomic effects of drugs that block the muscarinic cholinergic system. These effects may be subtle or dramatic, yet can be overlooked or discounted as a natural consequence of old age. Elderly patients can be particularly sensitive to the anticholinergic action of drugs because of physiological and pathophysiological changes that often accompany the aging process. The use of multiple drugs, a common finding in older patients, may result in pharmacodynamic and pharmacokinetic drug interactions that heighten anticholinergic effects. While the classic anticholinergic problems of decreased secretions, slowed gastrointestinal motility, blurred vision, increased heart rate, heat intolerance, sedation and possibly mild confusion, may be uncomfortable for a younger patient in relatively good health, these effects can be disastrous for older patients. Even the most common peripheral anticholinergic complaint of dry mouth can reduce the ability to communicate, predispose to malnutrition, promote mucosal damage, denture misfit or dental caries, and increase the risk of serious respiratory infection secondary to loss of antimicrobial activity of saliva. Mydriasis and the inability to accommodate will impair near vision and may precipitate narrow angle glaucoma in predisposed patients, but less obviously could lead to an increased risk of accidents, including falls. Somatic complaints of constipation and urinary hesitancy, could, in the presence of anticholinergic challenge, result in faecal impaction or urinary retention. Cardiac effects may be poorly tolerated. Increases in heart rate may precipitate or worsen angina. Finally, thermoregulatory impairment induced by anticholinergics, which block the ability to sweat, may lead to life threatening hyperthermia. Central anticholinergic effects range from sedation, mild confusion and inability to concentration to frank delirium. Even mild effects can reduce function and increase dependency. At any level of care, the loss of independence increases the caregiver burden, costs, and most importantly, can negatively affect quality of life. Many age-related and disease-related conditions may predispose elderly patients to anticholinergic drug toxicity. Careful attention to anticholinergic effects when prescribing drugs, patient education, regular review of the entire drug regimen, and familiarity with the signs and symptoms of anticholinergic toxicity will help to reduce the risk of drug-induced problems. PMID:8369593

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

    ERIC Educational Resources Information Center

    Bisgaier, Joanna; Rhodes, Karin V.

    2011-01-01

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

  16. Nevirapine: Most Common Cause of Cutaneous Adverse Drug Reactions in an Outpatient Department of a Tertiary Care Hospital

    PubMed Central

    Pawar, Mayur Popat; Pore, Shraddha Milind; Pradhan, Shekhar Nana; Bhoi, Umesh Yedu; Ramanand, Sunita Jaiprakash

    2015-01-01

    Introduction Skin is the most commonly involved organ in adverse drug reactions. Most of the cutaneous adverse drug reactions (CADRs) being of mild to moderate severity are likely to be diagnosed and treated in an outpatient setting. Consequently, knowledge regarding morphological pattern, severity and drugs implicated in causation of these CADRs has important implications for healthcare personnel. Aim To determine the current clinical pattern of CADRs and to assess their causality and severity with the help of standard scales. Study design and setting A prospective, observational study was conducted in the outpatient department of skin and venereal disease in a tertiary care hospital. Materials and Methods Patients with suspected CADR after consumption of systemic drug(s) were enrolled in the study. Data regarding demographics, clinical manifestations of CADR, drug history preceding the reaction, concomitant illness, relevant laboratory investigations etc was obtained. This data was then analysed for morphological pattern, causality and severity. CADRs with causality assessment possible and above on the basis of World Health Organization-Uppsala Monitoring Centre causality assessment system were considered for analysis. Statistics Descriptive statistics were used to express results of pattern, severity and causality of CADRs. Results Ninety patients were enrolled in the study. Male to female ratio for CADRs was 1:2.33. Maculopapular rash was most commonly encountered CADR in 76.67% cases followed by urticaria (8.89%), Stevens-Johnson syndrome (4.4%) and fixed dose eruptions (3.33%). Antiretrovirals were implicated in 75.56% (68/90) of CADRs. Nevirapine was suspected in 52 out of 90 (57.77%) cases of CADRs which included 39 cases of maculopapular rash, five cases of urticaria, four cases of Stevens-Johnson syndrome, and two cases each of pustular rash and angioedema respectively. Antimicrobials, antiepileptics and Non-steroidal Anti-inflammatory Drugs (NSAIDs) were other suspected drugs. Conclusion Antiretrovirals especially nevirapine was implicated in variety of CADRs ranging from maculopapular rash to life-threatening reactions like Stevens-Johnson syndrome in an outpatient setting. Women were twice as susceptible as men for CADRs. PMID:26672558

  17. Assessment of individual radiosensitivity in human lymphocytes of cancer patients and its correlation with adverse side effects to radiation therapy

    E-print Network

    Di Giorgio, M; Busto, E; Mairal, L; Menendez, P; Roth, B; Sardi, M; Taja, M R; Vallerga, M B

    2003-01-01

    Background and purpose: Individual radiosensitivity is an inherent characteristic, associated with an increased reaction to ionizing radiation on the human body. Biological endpoints such as clonogenic survival, chromosome aberration formation and repair capacity of radiation-induced damage have been applied to evaluate individual radiosensitivity in vitro. 5%-7% of cancer patients develop adverse side effects to radiation therapy in normal tissues within the treatment field, which are referred as 'clinical radiation reactions' and include acute effects, late effects and cancer induction. It has been hypothesized that the occurrence and severity of these reactions are mainly influenced by genetic susceptibility to radiation. Additionally, the nature of the genetic disorders associated with hypersensitivity to radiotherapy suggests that DNA repair mechanisms are involved. Consequently, the characterization of DNA repair in lymphocytes through cytokinesis blocked micronucleus (MN) and alkaline single-cell micro...

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

    PubMed Central

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

    2014-01-01

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

  19. Adverse drug reactions to self-medication: a study in a pharmacovigilance database.

    PubMed

    Berreni, Aurélia; Montastruc, François; Bondon-Guitton, Emmanuelle; Rousseau, Vanessa; Abadie, Delphine; Durrieu, Geneviève; Chebane, Leila; Giroud, Jean-Paul; Bagheri, Haleh; Montastruc, Jean-Louis

    2015-10-01

    Although self-medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self-medication recorded in the Midi-Pyrénées PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of drugs. PMID:26215671

  20. Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model

    PubMed Central

    Cao, D-S; Xiao, N; Li, Y-J; Zeng, W-B; Liang, Y-Z; Lu, A-P; Xu, Q-S; Chen, AF

    2015-01-01

    Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug–ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug–ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug–ADR interactions. PMID:26451329

  1. Corrosion and Adverse Local Tissue Reaction in One Type of Modular Neck Stem.

    PubMed

    Ghanem, Elie; Ward, Daniel M; Robbins, Claire E; Nandi, Sumon; Bono, James V; Talmo, Carl T

    2015-10-01

    Modular neck stems allow for optimization of joint biomechanics by restoring anteversion, offset, and limb length. A potential disadvantage is the generation of metal ions from fretting and crevice corrosion. We identified 118 total hip arthroplasty implanted with one type of dual-modular femoral component. Thirty-six required revision due to adverse local tissue reaction. Multivariate analysis isolated females and low offset necks as risk factors for failure. Kaplan-Meir analysis revealed small stem sizes failed at a higher rate during early follow-up period. Although the cobalt/chrome levels were higher in the failed group, these tests had low diagnostic accuracy for ALTR, while MRI scan was more sensitive. We conclude that the complications related to the use of dual modular stems of this design outweigh the potential benefits. PMID:26027523

  2. Adverse events in older patients undergoing ERCP: a systematic review and meta-analysis

    PubMed Central

    Day, Lukejohn W.; Lin, Lisa; Somsouk, Ma

    2014-01-01

    Background and study aims: Biliary and pancreatic diseases are common in the elderly; however, few studies have addressed the occurrence of adverse events in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Our objective was to determine the incidence rates of specific adverse events in this group and calculate incidence rate ratios (IRRs) for selected comparison groups. Patients and methods: Bibliographical searches were conducted in Medline, EMBASE, and Cochrane library databases. The studies included documented the incidence of adverse events (perforation, pancreatitis, bleeding, cholangitis, cardiopulmonary adverse events, mortality) in patients aged???65 who underwent ERCP. Pooled incidence rates were calculated for each reported adverse event and IRRs were determined for available comparison groups. A parallel analysis was performed in patients aged???80 and???90. Results: Our literature search yielded 7429 articles, of which 69 studies met our inclusion criteria. Pooled incidence rates for adverse events (per 1000 ERCPs) in patients aged???65 were as follows: perforation 3.8 (95?%CI 1.8?–?7.0), pancreatitis 13.1 (95?%CI 11.0?–?15.5), bleeding 7.7 (95?%CI 5.7?–?10.1), cholangitis 16.1 (95?%CI 11.7?–?21.7), cardiopulmonary events 3.7 (95?%CI 1.5?–?7.6), and death 7.1 (95?%CI 5.2?–?9.4). Patients???65 had lower rates of pancreatitis (IRR 0.3, 95?%CI 0.3?–?0.4) compared with younger patients. Octogenarians had higher rates of death (IRR 2.4, 95?%CI 1.3?–?4.5) compared with younger patients, whereas nonagenarians had increased rates of bleeding (IRR 2.4, 95?%CI 1.1?–?5.2), cardiopulmonary events (IRR 3.7, 95?%CI 1.0?–?13.9), and death (IRR 3.8, 95?%CI 1.0?–?14.4). Conclusions ERCP appears to be safe in elderly patients, except in the very elderly who are at higher risk of some adverse events. These data on adverse event rates can help to inform clinical decision-making, the consent process, and comparative effectiveness analyses. PMID:26134610

  3. Psychosocial Working Environment and Risk of Adverse Cardiac Events in Patients Treated for Coronary Heart Disease.

    PubMed

    Biering, Karin; Andersen, Johan Hviid; Lund, Thomas; Hjollund, Niels Henrik

    2015-12-01

    Introduction During the last decades a possible association between psychosocial working environment and increased risk of coronary heart disease (CHD) has been debated and moderate evidence supports that high psychological demands, lack of social support and iso-strain (the combination of high job strain and lack of social support) is associated with primary CHD. Whether psychosocial working environment plays a role as risk factor for new cardiac events and readmissions in patients with existing cardiovascular disease is less studied. Methods A cohort of patients <67 years treated with percutaneous coronary intervention (PCI) was established in 2006. Three months after PCI patients answered a questionnaire about their psychosocial working environment. Patients were followed in the Danish National Patient Registry and the Danish Civil Registration System for 3+ years to identify adverse cardiac events and death. We analysed the association between psychosocial working environment and adverse cardiac events by Cox Regression. Results A number of 528 patients had returned to work 12 weeks after PCI, while 97 were still sick-listed. We identified 12 deaths and 211 other events during follow-up. We found no statistically significant associations between psychosocial working environment and risk of adverse cardiac events and readmissions or mortality. Conclusion The psychosocial working environment was not associated with adverse cardiac events. PMID:26044947

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

    SciTech Connect

    Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David

    2010-06-15

    Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.

  5. A patient-initiated voluntary online survey of adverse medical events: the perspective of 696 injured patients and families

    PubMed Central

    Southwick, Frederick S; Cranley, Nicole M; Hallisy, Julia A

    2015-01-01

    Background Preventable medical errors continue to be a major cause of death in the USA and throughout the world. Many patients have written about their experiences on websites and in published books. Methods As patients and family members who have experienced medical harm, we have created a nationwide voluntary survey in order to more broadly and systematically capture the perspective of patients and patient families experiencing adverse medical events and have used quantitative and qualitative analysis to summarise the responses of 696 patients and their families. Results Harm was most commonly associated with diagnostic and therapeutic errors, followed by surgical or procedural complications, hospital-associated infections and medication errors, and our quantitative results match those of previous provider-initiated patient surveys. Qualitative analysis of 450 narratives revealed a lack of perceived provider and system accountability, deficient and disrespectful communication and a failure of providers to listen as major themes. The consequences of adverse events included death, post-traumatic stress, financial hardship and permanent disability. These conditions and consequences led to a loss of patients’ trust in both the health system and providers. Patients and family members offered suggestions for preventing future adverse events and emphasised the importance of shared decision-making. Conclusions This large voluntary survey of medical harm highlights the potential efficacy of patient-initiated surveys for providing meaningful feedback and for guiding improvements in patient care. PMID:26092166

  6. Adverse Respiratory Events Associated With Hypnotics Use in Patients of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Chung, Wei-Sheng; Lai, Ching-Yuan; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD). We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD. The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database. Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group. Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex. Patients who had used hypnotics within 1 month meant active users. The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models. Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively. After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11–17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68–14.2) compared with the adjusted ORs of those who never used hypnotics. The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. PMID:26166105

  7. ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis.

    PubMed

    Barbet, Joy L; Snook, Tara; Gay, John M; Mealey, Katrina L

    2009-04-01

    Twenty-two dogs diagnosed with generalized demodicosis were treated with milbemycin oxime (MO) because of poor response to previous therapies or because the dog was a breed known to be susceptible to ivermectin toxicosis. Fifteen of the 22 dogs were herding breeds. Doses of MO ranged from 1.0 to 2.2 mg kg(-1) day(-1) per os. Cheek swab samples were obtained in order to determine each dog's ABCB1 genotype. Adverse drug reactions were recorded for each dog by the owners and/or veterinarians. The ABCB1-1 Delta genotype was significantly associated with the development of an adverse reaction (neurological toxicity) after treatment with MO. None of the 19 dogs with the wild-type ABCB1 allele experienced adverse reactions, whereas two dogs homozygous for the ABCB1-1 Delta mutation developed ataxia. Assessing the ABCB1-1 Delta genotype prior to MO administration may prevent neurological toxicity in these patients. PMID:19171022

  8. 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. PMID:17477341

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

    PubMed Central

    Ekor, Martins

    2014-01-01

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

  10. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  11. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions

    PubMed Central

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2–10 months for known ADRs and 19–44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0–122.5 days and 185.5–306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

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

    PubMed

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

    2014-06-01

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

  13. Adverse Reaction of Sodium Hypochlorite during Endodontic Treatment of Primary Teeth

    PubMed Central

    Panse, Amey Manohar; Gawali, Pritesh Namdeo

    2015-01-01

    ABSTRACT Sodium hypochlorite (NaOCl) is the most common and effective intracanal medicament used in root canal treatments, because of its low-cost and a very effective antimicrobial activity against microbiota of infected root canals. Sodium hypochlorite is an effective intracanal irrigant and is used in concentrations ranging from 0.5 to 5.25%. At these concentrations, it is highly hypertonic and strongly alkaline with pH 11 to 13. Despite its safe properties, serious complications can result from inadvertent use due to its cytotoxic features. Most of the complications are the result of accidental extrusion of the solution from the apical foramen or accessory canals or perforations into the periapical area. Although it is an effective solution for disinfection of root canal system, fewer incidence of complications are reported, especially in primary teeth. Present article highlights one of such cases of NaOCl accident and its successful management in a 4-year-old child. How to cite this article: Chaugule VB, Panse AM, Gawali PN. Adverse Reaction of Sodium Hypochlorite during Endo-dontic Treatment of Primary Teeth. Int J Clin Pediatr Dent 2015;8(2):153-156. PMID:26379387

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

    PubMed Central

    Zeng, Zhi-Ping; Jiang, Jian-Guo

    2010-01-01

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

  15. Designing a national combined reporting form for adverse drug reactions and medication errors.

    PubMed

    Tanti, A; Serracino-Inglott, A; Borg, J J

    2015-04-01

    The Maltese Medicines Authority was tasked with developing a reporting form that captures high-quality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. This paper describes the process of introducing the first combined ADR/medication error reporting form in the EU for health-care professionals, the analysis of reports generated by it and the promotion of the system. A review of existing ADR forms was carried out and recommendations from the European Medicines Agency and World Health Organization audits integrated. A new, combined ADR/medication error reporting form was developed and pilot tested based on case studies. The Authority's quality system (ISO 9001 certified) was redesigned and a promotion strategy was deployed. The process used in Malta can be useful for countries that need to develop systems relative to ADR/medication error reporting and to improve the quality of data capture within their systems. PMID:26077519

  16. Systematic Analysis of the Associations between Adverse Drug Reactions and Pathways

    PubMed Central

    Chen, Xiaowen; Wang, Yanqiu; Wang, Pingping; Lian, Baofeng; Li, Chunquan; Wang, Jing; Li, Xia; Jiang, Wei

    2015-01-01

    Adverse drug reactions (ADRs) are responsible for drug candidate failure during clinical trials. It is crucial to investigate biological pathways contributing to ADRs. Here, we applied a large-scale analysis to identify overrepresented ADR-pathway combinations through merging clinical phenotypic data, biological pathway data, and drug-target relations. Evaluation was performed by scientific literature review and defining a pathway-based ADR-ADR similarity measure. The results showed that our method is efficient for finding the associations between ADRs and pathways. To more systematically understand the mechanisms of ADRs, we constructed an ADR-pathway network and an ADR-ADR network. Through network analysis on biology and pharmacology, it was found that frequent ADRs were associated with more pathways than infrequent and rare ADRs. Moreover, environmental information processing pathways contributed most to the observed ADRs. Integrating the system organ class of ADRs, we found that most classes tended to interact with other classes instead of themselves. ADR classes were distributed promiscuously in all the ADR cliques. These results reflected that drug perturbation to a certain pathway can cause changes in multiple organs, rather than in one specific organ. Our work not only provides a global view of the associations between ADRs and pathways, but also is helpful to understand the mechanisms of ADRs. PMID:26495310

  17. Management of adverse events in the treatment of patients with immunoglobulin therapy: A review of evidence.

    PubMed

    Cherin, Patrick; Marie, Isabelle; Michallet, Mauricette; Pelus, Eric; Dantal, Jacques; Crave, Jean-Charles; Delain, Jean-Christophe; Viallard, Jean-François

    2016-01-01

    Immunoglobulin (IG) therapy is actually used for a broad range of diseases including primary and secondary immunodeficiency disorders, and autoimmune diseases. This therapy is available for intravenous (IV) and subcutaneous (SC) administration. The efficacy of the IG therapy has been demonstrated in numerous studies and across different diseases. Generally, IG infusions are well tolerated; however some well-known adverse reactions, ranging from mild to severe, are associated with the therapy. The most common adverse reactions including headache, nausea, myalgia, fever, chills, chest discomfort, skin and anaphylactic reactions, could arise immediately during or after the infusion. Delayed events could be more severe and include migraine headaches, aseptic meningitis, haemolysis renal impairment and thrombotic events. This paper reviews all the potential adverse events related to IG therapy and establishes a comprehensive guideline for the management of these events. Moreover it resumes the opinions and clinical experience of expert endorsers on the utilization of the treatment. Published data were classified into levels of evidence and the strength of the recommendation was given for each intervention according to the GRADE system. PMID:26384525

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

    PubMed Central

    2013-01-01

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

  19. Decline in adverse outcomes and death in tuberculosis patients in Malawi: association with HIV interventions

    PubMed Central

    Kanyerere, H.; Mganga, A.; Tayler-Smith, K.; Zachariah, R.; Jahn, A.; Chimbwandira, F. M.; Mpunga, J.

    2015-01-01

    Between 2000 and 2012, the annual numbers of patients treated for tuberculosis (TB) in Malawi declined by 28%, from 28 234 to 20 463. During this time, the proportion of TB patients tested for the human immunodeficiency virus (HIV) increased from 6% to 87%. Most HIV-infected patients received cotrimoxazole preventive therapy, and the proportion receiving antiretroviral therapy increased to 88%. Between 2000 and 2008 there was a significant decline in all adverse outcomes (from 31% to 14%), and particularly in deaths (from 23% to 10%) and loss to follow-up (from 5.2% to 1.9%, P < 0.001). After 2008, there was no decrease in any adverse outcome. Ways to further reduce TB-associated mortality are discussed. PMID:26400381

  20. Pattern of Adverse Drug Reactions in Children Attending the Department of Pediatrics in a Tertiary Care Center: A Prospective Observational Study

    PubMed Central

    Digra, Kishour Kumar; Pandita, Aakash; Saini, GS; Bharti, Rajni

    2015-01-01

    AIM To study the pattern of various adverse drug reactions (ADRs) occurring in children attending the Department of Pediatrics, SMGS Hospital, Jammu over 1 year. SUBJECTS AND METHODS This was a prospective study, with study population of patients attending Department of Pediatrics over a period of 1 year. A structured format was used to enroll the participants. A pilot study was conducted to test the suitability of the format and feasibility of the study. The study was carried out to review various pattern of ADRs by using the Naranjo probability scale, and severity was assessed by using the Hartwig severity scale. ADRs were classified according to the classification used by the Adverse Drug Reaction Monitoring Center, Central Drugs Standard Control Organization, New Delhi, India. RESULTS In the present study, 104 patients were found to have developed acute drug reactions. Among these, 83.6% were type B, 14.42% type A, and 1.92% were type U. Furthermore, 25.96% ADRs were due to anticonvulsants, followed by antibiotics (22.11%), antipyretics (11.53%), vaccination (8.65%), steroids (6.73%), decongestants (5.67%), snake antivenom and antiemetics (3.84%), and fluids, insulin, and antacids (1.92%). The patients’ dermatological system was involved in 67.30%, followed by the central nervous system (CNS) in 11.53% patients. Renal system was involved in 6.73% patients. Cardiac, musculoskeletal, metabolic, and other systems were involved in 4.80%, 3.84%, 2.88%, and 0.96%, respectively. According to the Hartwig severity scale of ADRs, 64.4% patients had moderate ADRs, 29.8% patients had severe ADRs, and 5.76% had mild ADRs. In the present study, 64.4% patients expressed moderate severity, whereas 29.8% expressed high severity and 5.76% expressed mild ADRs. CONCLUSION ADRs were seen in 71% of the patients between 1 and 5 years of age, 26% in the age group of 5–10 years, and 3% were more than 10 years old. Anticonvulsants (25.96%) and antibiotics (22.11%) were responsible for majority of ADRs. Rash (55.76%) was the most common presentation of ADR. Owing to the high number of ADRs, the present study points to the need for rigid adverse drug monitoring among pediatric patients to ensure the safety of drug therapy. PMID:26309424

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-08-01

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

  3. Adverse reactions to suxamethonium and other muscle relaxants under general anesthesia

    SciTech Connect

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

    1983-06-01

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

  4. Is researching adverse events in hospital deaths a good way to describe patient safety in hospitals: a retrospective patient record review study

    PubMed Central

    Baines, Rebecca J; Langelaan, Maaike; de Bruijne, Martine C; Wagner, Cordula

    2015-01-01

    Objective Adverse event studies often use patient record review as a way to assess patient safety. As this is a time-consuming method, hospitals often study inpatient deaths. In this article we will assess whether this offers a representative view of the occurrence of adverse events in comparison to patients who are discharged while still living. Design Retrospective patient record review study. Setting and participants A total of 11?949 hospital admissions; 50% of inpatient deaths; the other half of patients discharged while alive. The data originated from our two national adverse event studies in 2004 and 2008. Main outcome measures Overall adverse events and preventable adverse events in inpatient deaths, and in admissions of patients discharged alive. We looked at size, preventability, clinical process and type of adverse events. Results Patients who died in hospital were on an average older, had a longer length of stay, were more often urgently admitted and were less often admitted to a surgical unit. We found twice as many adverse events and preventable adverse events in inpatient deaths than in patients discharged alive. Consistent with the differences in patient characteristics, preventable adverse events in inpatient deaths were proportionally less and were often related to the surgical process. Most types of adverse events and preventable adverse events occur in inpatient deaths as well as in patients discharged alive; however, these occur more often in inpatient deaths and are differently distributed. Conclusions Reviewing patient records of inpatient deaths is more efficient in identifying preventable AEs than reviewing records of those discharged alive. Although many of the same types of adverse events are found, it does not offer a representative view of the number or type of adverse events. PMID:26159451

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Association between the rs342293 polymorphism and adverse cardiac events in patients undergoing percutaneous coronary intervention.

    PubMed

    Siller-Matula, Jolanta M; Arbesu, Iciar; Jilma, Bernd; Maurer, Gerald; Lang, Irene M; Mannhalter, Christine

    2014-06-01

    The single nucleotide polymorphism (SNP) rs342293 has been shown to influence platelet number and mean platelet volume (MPV). We investigated the association between the rs342293 polymorphism and cardiovascular outcome in a prospective cohort study. The rs342293 polymorphism was analysed in 404 patients with coronary artery disease undergoing percutaneous coronary intervention. The rates of cardiac adverse events were recorded during two years of follow-up. The polymorphism was associated with MPV (median 10.1 fL, interquartile range [IQR]: 9.6 to 10.6 in patients with the CC-allele vs 10.4 fL, IQR: 9.9 to 11.1 in G>C SNP carriers; p<0.001), but not with platelet count. Survival analysis indicated that carriers of the rs342293 G variant had a substantially higher risk to develop cardiac adverse events compared with wild type carriers during two years of follow-up (33% vs 22%; adjusted hazard ratio = 1.63, 95% confidence interval = 1.06-2.52, p=0.027). The rs342293 SNP could explain 2.9% of the variability in MPV (p=0.01). In conclusion, patients undergoing coronary stenting who carry the G-variant of the rs342293 SNP which is associated with larger MPV are at higher risk for adverse cardiovascular outcome. PMID:24652536

  8. Anaphylaxis and other adverse reactions to blue dyes: a case series.

    PubMed

    Howard, J D; Moo, V; Sivalingam, P

    2011-03-01

    We report three cases of anaphylaxis during anaesthesia confirmed on intradermal testing to be related to patent blue V dye (Guerbet - Chemical Abstract Service 3536-49-0). All three cases were associated with moderate to severe hypotension. Two cases had delayed onset, and two were associated with a rash. None of the cases were associated with bronchospasm. In all three patients the interference with pulse oximetry readings contributed to difficulties in management. We recommend the use of a test dose of blue dye prior to surgery, as suggested in the manufacturer's product information. We also recommend high vigilance for possible allergic reactions when patent blue dyes are used for sentinel lymph node mapping, because the presentations may be atypical and the reduced pulse oximetry readings may be a distraction. PMID:21485680

  9. Patient views of adverse events: comparisons of self-reported healthcare staff attitudes with disclosure of accident information.

    PubMed

    Itoh, Kenji; Andersen, Henning Boje; Madsen, Marlene Dyrløv; Østergaard, Doris; Ikeno, Masaaki

    2006-07-01

    In the present paper, we report results of surveys in 2003 in Japan and Denmark about patients' views about adverse events, focusing on the actions of healthcare staff involved in a medical accident. Results show that patients were more likely to indicate negative expectations to a doctor's reactions after a medical accident when asked in general terms than when asked in relation to concrete case stories. When asked in general terms, 66% (47%) of Japanese (Danish) respondents expected that doctors sometimes hold back on providing information to patients about a medical accident, while 37% (7%) did so when asked about a concrete, mild-outcome case. We examine some possible reasons for the relatively high level of distrust of Japanese patients, and we discuss whether the seemingly lower level of disclosure in Japan than in Denmark and the negative stories in the Japanese press may have an impact. We also suggest some implications for introducing a patient-centred or customer-centred approach to risk management in healthcare and other domains. PMID:16759631

  10. Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use.

    PubMed

    Van Tyle, J H

    1984-01-01

    Ketoconazole is a well-tolerated oral antifungal agent with a broad spectrum of activity in vitro, but in vitro testing has not yet been correlated to in vivo results. In addition, many variables that can alter in vitro test results have been identified. The drug shows effectiveness in the treatment of paracoccidioidomycosis, chronic mucocutaneous candidiasis, oral thrush, coccidioidomycosis and histoplasmosis. It was recently approved for use in blastomycosis. It is not yet approved for use in dermatophyte infections, but a large body of literature exists supporting this application. Ketoconazole has several reported drug interactions, including lower bioavailability with cimetidine, accumulation of cyclosporin during concurrent therapy and a possible disulfiram-like reaction with alcohol. It is highly protein bound to albumin and is extensively metabolized. Dosage adjustment is not required in renal failure. The main side effects are gastrointestinal and occur in 5-10% of the patients. Rare side effects include gynecomastia and hepatotoxicity. The latter is reported to occur in 1 of 12,000 patients. Ketoconazole impairs testosterone synthesis, and therefore it is recommended that administration more than once daily be avoided in men. The usual dosage is 200-400 mg administered once daily. Few comparative or controlled studies have been published thus far. How it compares to amphotericin B is not known. The optimum dosage and the optimum duration of therapy are not established. PMID:6151171

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

    PubMed

    Elzagallaai, Abdelbaset A; Rieder, Michael J

    2015-10-01

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

  12. An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients With Community-Acquired Pneumonia

    PubMed Central

    Chen, Po-Chuan; Liao, Wen-I.; Wang, Ying-Chuan; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Ying-Hsin; Tsai, Shih-Hung

    2015-01-01

    Abstract Several studies argue against the association between admission hyperglycemia and adverse outcomes in infected diabetic patients. When investigating the association, it is necessary to consider preexisting hyperglycemia. The objective of this study was to assess whether stress-induced hyperglycemia, determined by the glycemic gap between admission glucose levels and A1c-derived average glucose levels adversely affects outcomes in diabetic patients admitted to hospital with community-acquired pneumonia (CAP). We retrospectively analyzed the glycemic gap and adverse outcomes of diabetic patients hospitalized because of CAP from June 1, 2007 to August 31, 2012 in single medical center in Taiwan. A total of 203 patients admitted with principal diagnosis of CAP and available data of glycemic gap. Patients with glycemic gaps ?40?mg/dL had greater AUROC values for the development of adverse outcomes compared with acute hyperglycemia and long-term glycemic controls. Patients with an elevated glycemic gap had an odds ratio of 3.84 for the incidence of combined adverse outcomes. Incorporation of the glycemic gap into pneumonia severity index, CURB-65 or SMART-COP scores, increased the discriminative performance of predicting the development of adverse outcomes. Glycemic gaps were associated with adverse outcomes of diabetic CAP patients. The discriminative performance of the calculated glycemic gaps was comparable with those of current clinical scoring systems and may further increase the AUROC of each system. PMID:26313809

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2015-01-01

    Aim: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. Materials and Methods: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. Results: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. Conclusion: UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting. PMID:25821314

  15. Assessment of three systems to empower the patient and decrease the risk of adverse drug events.

    PubMed

    Lawton, Kitta; Skjoet, Peter

    2011-01-01

    One way to reduce adverse drug events (ADEs) is to empower the patient to participate in the control of medication. This empowerment can be supported in different ways by making knowledge and information available to the patient. This study examines the usefulness and safety of two different systems on the background of a paper-based medication list presenting prescribed medicine presently used in hospitals in Copenhagen. Each of the systems examined aims to reduce ADEs but presents information in different levels of detail, and anticipates different level of prior knowledge from the patient: a Web-based prototype presenting medication, lab-results and alerts, and a cell phone-based prototype presenting alerts. Six patients were introduced to each of the systems by performing small tasks and subsequently interviewed. The patients found the paper-based medication list useful and comprehensive for control of own prescribed medication. The Web-based prototype also proved to be useful, but drug and lab values were hard to correlate, and the alerts were hard to understand. The cell phone-based prototype proved less useful as the patients were challenged to vision the applicability of the system. Furthermore, it is a safety issue that the information the alert is based upon, stems from the patient alone. We conclude that, in order for the Web-based system as well as the cell phone system to empower patient and increase patient safety, further development of the systems is necessary. PMID:21685630

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

    PubMed

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

    2015-05-01

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

  17. Adverse events and outcomes of procedural sedation and analgesia in major trauma patients

    PubMed Central

    Green, Robert S.; Butler, Michael B.; Campbell, Samuel G.; Erdogan, Mete

    2015-01-01

    Context: Trauma patients requiring procedural sedation and analgesia (PSA) may have increased risk of adverse events (AEs) and poor outcomes. Aims: To determine the incidence of AEs in adult major trauma patients who received PSA and to evaluate their postprocedural outcomes. Settings and Design: Retrospective analysis of adult patients (age >16) who received PSA between 2006 and 2014 at a Canadian academic tertiary care center. Materials and Methods: We compared the incidence of PSA-related AEs in trauma patients with nontrauma patients. Postprocedural outcomes including Intensive Care Unit admission, length of hospital stay, and mortality were compared between trauma patients who did or did not receive PSA. Statistical Analysis Used: Descriptive statistics and multivariable logistic regression. Results: Overall, 4324 patients received PSA during their procedure, of which 101 were trauma patients (107 procedures). The majority (77%) of these 101 trauma patients were male, relatively healthy (78% with American Society of Anesthesiologists Physical Status [ASA-PS] 1), and most (85%) of the 107 procedures were orthopedic manipulations. PSA-related AEs were experienced by 45.5% of the trauma group and 45.9% of the nontrauma group. In the trauma group, the most common AEs were tachypnea (23%) and hypotension (20%). After controlling for age, gender, and ASA-PS, trauma patients were more likely than nontrauma patients to develop hypotension (odds ratio 1.79; 95% confidence interval 1.11-2.89). Conclusion: Although trauma patients were more likely than nontrauma patients to develop hypotension during PSA, their outcomes were not worse compared to trauma patients who did not have PSA.

  18. Prevention of exercise-related injuries and adverse events in patients with type 2 diabetes.

    PubMed

    Mendes, Romeu; Sousa, Nelson; Reis, Victor Machado; Themudo-Barata, José Luís

    2013-12-01

    Physical activity is widely recommended as an essential non-pharmacological therapeutic strategy to the prevention and control of type 2 diabetes and cardiovascular risk. Microvascular and macrovascular complications associated with the natural progression of the disease and typical age and anthropometric profile of individuals with type 2 diabetes may expose these patients to an increased risk of injury and acute adverse events during exercise. These injuries and adverse events can lead to fear of new injury and consequent physical inactivity. Preventative measures are essential to reduce risk, increase safety and avoid the occurrence of exercise-related injuries in people with type 2 diabetes. This population can exercise safely if certain precautions are taken and if exercise is adapted to complications and contraindications of each individual. Conditions such as diabetic foot, diabetic retinopathy, diabetic nephropathy, diabetic autonomic neuropathy, cardiovascular risk factors, musculoskeletal disorders, hypoglycaemia, hyperglycaemia, dehydration and interactions between medication and exercise should be taken into consideration when prescribing exercise. PMID:24194555

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

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

    2001-01-01

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

  1. Endothelial Dysfunction Is Associated With Major Adverse Cardiovascular Events in Peritoneal Dialysis Patients

    PubMed Central

    Lee, Mi Jung; Han, Seung Hyeok; Lee, Jung Eun; Choi, Hoon Young; Yoon, Chang-Yun; Kim, Eun Jin; Han, Jae Hyun; Han, Ji Suk; Oh, Hyung Jung; Park, Jung Tak; Kang, Shin-Wook; Yoo, Tae-Hyun

    2014-01-01

    Abstract Endothelial dysfunction is implicated in increased cardiovascular risk in nondialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients. We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation [FMD]) in 143 nondiabetic PD patients and 32 controls. Primary outcome was a major adverse cardiac and cerebrovascular event (MACCE). Brachial FMD was significantly lower in PD patients than in controls (2.9% [1.3–4.7] vs 6.2% [5.4–8.3], P?patients (17.5%). When patients were dichotomized by the median value of FMD (2.9%), incidence rates of MACCEs were significantly higher in the group with lower FMD compared with higher FMD (7.2 vs 3.0/100 person-years, P?=?0.03). In multivariate Cox analysis, low FMD (?2.9%) was a significant independent predictor of MACCEs (hazard ratio?=?2.73, 95% confidence interval?=?1.03–7.22, P?=?0.04). Furthermore, multivariate fractional polynomial analysis showed that the risk of MACCE decreased steadily with higher FMD values. Impaired brachial FMD was a significant independent predictor of MACCEs in PD patients. Estimating endothelial dysfunction by brachial FMD could be useful for stratifying cardiovascular risk in these patients. PMID:25192486

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

    E-print Network

    Burdess, Anne

    2014-07-05

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

  3. Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction

    PubMed Central

    2011-01-01

    Background Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process. Methods The inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients. Results Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model. Conclusion Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate. PMID:21794175

  4. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

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

  5. Metabotropic Glutamate Receptor 5 Negative Modulation in Phase I Clinical Trial: Potential Impact of Circadian Rhythm on the Neuropsychiatric Adverse Reactions—Do Hallucinations Matter?

    PubMed Central

    Bruggeman, Richard; Baljé-Volkers, Corine

    2014-01-01

    Metabotropic Glutamate Receptor 5 (mGluR5) negative allosteric modulators (NAMs) may play a role in some psychiatric disorders such as anxiety and depression. The pharmacokinetic profile and pharmacodynamics effects of mGluR5-NAMs have been previously reported. We performed a post hoc analysis of pharmacological and clinical data obtained from 18 young healthy female subjects who received a mGluR5-NAM in the context of a phase I drug-drug interaction study between a mGluR5 NAM and a monophasic oral contraceptive. mGluR5-NAM was administered in an escalating bidaily dose level design. There was no interaction between the OC and mGluR5-NAM. Higher morning mGluR5-NAM plasma concentrations were found compared to evening concentrations. Most of the observed clinically significant neuropsychiatric adverse reactions occurred nocturnally and included visual (pseudo) hallucinations, insomnia accompanied by secondary behavioural disorders, and cognitive dysfunction symptoms of sufficient severity to interfere with daily functioning. Circadian rhythm-related physiological variations in drug absorption and disposition may explain this pharmacokinetics-pharmacodynamics apparently disproportionate relationship. We suggest that clinical trials evaluating basic pharmacokinetic properties of psychiatric medications consider potential drug's chronopharmacokinetics. This may assist with dose optimization and minimize serious neuropsychiatric adverse reactions in the vulnerable psychiatric patient. PMID:24729909

  6. Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong

    PubMed Central

    Woo, Peter Yat-Ming; Chan, Danny Tat-Ming; Chan, Kwong-Yau; Wong, Wai-Kei; Po, Yin-Chung; Kwok, John Ching-Kong; Poon, Wai-Sang

    2015-01-01

    Aim The aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients. Patients and Methods A multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed. Results A total of 198 patients, with a mean age of 55?years (range: 18–88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8?months, and 11?months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8?months postoperatively (range: 1?day–75?months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21–4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49–6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32–8.40). Conclusions Antiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy are at risk. We suggest, contrary to present practice, that primary seizure prophylaxis be given only during the perioperative period and resumed when they occur. We also recommend avoidance of aromatic AED due to their association with idiosyncratic adverse effects. PMID:26097495

  7. Cognitive adverse events of topiramate in patients with epilepsy and intellectual disability.

    PubMed

    Brandt, Christian; Lahr, Denise; May, Theodor W

    2015-04-01

    Topiramate (TPM) is an effective antiepileptic drug (AED). A high proportion of patients, however, experiences cognitive adverse events (CAEs), especially in verbal fluency, memory spans, and working memory. To our knowledge, CAEs of TPM have not been studied systematically in patients with intellectual disability (ID). This may be due to the fact that many of those patients are not able to follow test instructions properly and that neuropsychological instruments are not validated for that group. Cognitive deterioration in patients with ID may thus easily be overlooked. Topiramate is in frequent use in persons with ID. We included 26 consecutive patients with epilepsy and ID in this observational study who had undergone neuropsychological examinations as part of clinical routine before and after the introduction of TPM into the therapeutic regimen (n=4) or before and after the withdrawal of TPM (n=22). Examinations under TPM showed reduced cognitive speed, reduced verbal memory, reduced verbal fluency, and reduced flexibility compared to examinations without TPM. Despite some limitations (especially small sample size, high interindividual variation of the results dependent on the degree of ID, effects of other - limited - changes in the therapeutic regimen), our study indicates that TPM in persons with epilepsy and ID may lead to CAEs comparable to those in persons with normal intelligence. Neuropsychological testing is mandatory in order not to miss CAEs that might severely impair quality of life. PMID:25843340

  8. Adverse events associated with complementary and alternative medicine use in ovarian cancer patients

    PubMed Central

    Sweet, Erin S.; Standish, Leanna J.; Goff, Barbara; Andersen, M. Robyn

    2015-01-01

    Many women with ovarian cancer are choosing to include complementary and alternative medicine (CAM) substances in conjunction with their conventional treatment for ovarian cancer. A 2004 study by Navo et al., found between 44% and 53% of women with ovarian cancer use some form of CAM. Many oncologists express concern about the concomitant use of CAM during conventional treatment, particularly during chemotherapy. Specifically, some providers theorize that the adjunct use of CAM substances may be detrimental to the achievement of therapeutic levels of chemotherapy by inhibiting or inducing cytochrome P450 enzyme activity leading to increases in drug toxicity, under-treatment of disease or other adverse events. Chemotherapeutic agents have complex pharmacological profiles and narrow therapeutic windows and many factors can affect the pharmacodynamics of these drugs. In an effort to ascertain the extent of the potential problem with simultaneous use of CAM with conventional treatment we undertook comprehensive systematic review of published case reports describing CAM-related adverse events among ovarian cancer patients. Study design This article describes a systematic literature review. Methods The Natural Medicines Comprehensive Database (NMCD). PubMed, EMBASE® and the Cochrane Central Register of Controlled Trials (CCTR) were systematically reviewed for research articles pertaining to known CYP mediated CAM-drug interactions; case reports describing adverse events in patients, and clinical trials which examined the effects of herbs and supplements used during cancer treatment. Results Only one case report and one clinical trial were identified which met our inclusion criteria and were relevant to the current investigation. Conclusion Although there are concerns about the potential for adverse events related to concurrent use of CAM substances during conventional treatment we found few case reports and clinical trials in the literature which support this. However, CAM substances have the potential to affect the action of pharmacological agents through the modulation of elements of the P450 enzyme system. Therefore, it is prudent to assume that herbs and drugs using the same isoforms in the CYP450 pathway may be contraindicated for simultaneous use. However, there are few human studies evaluating herb-CYP interactions and additional research is needed as these precautions may not be necessary. PMID:23625025

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

    PubMed Central

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

    2015-01-01

    Over-the-counter products rarely cause unwanted reactions in the oral cavity. Oral reactions to these agents are not specific and might present with various clinical oral findings. Detailed medical history is a key to the proper diagnosis of these lesions and fortunately other diagnostic procedures are rarely needed. Lesions are usually managed with elimination of the offending agent and with topical steroids. In more severe cases systemic steroids should be applied. PMID:25883811

  10. Nitrate-induced paradoxical ischemia predicts adverse outcomes in elderly patients with healed myocardial infarcts

    PubMed Central

    Carboni, Gian Piero

    2013-01-01

    BACKGROUND: It is well known that nitrates can induce paradoxical myocardial ischemia. METHODS AND RESULTS: Fifty patients (median age 73 years; range 67 to 78 years; 80% male) with healed myocardial infarcts were selected. All patients underwent resting single-photon emission computed tomography (SPECT) and resting baseline gated-SPECT using sestamibi or thallium-201 after the sublingual administration of 5 mg isosorbide dinitrate (ISD). Forty-eight per cent (24 of 50) of the patients demonstrated ISD-induced peri-infarct ischemia as observed by SPECT. Compared with patients without ISD-induced ischemia, patients with ISD-induced ischemia presented larger infarcts as determined by the extent of perfusion defects (mean [± SD] 27±12 pixels versus 11±9 pixels; P<0.0001), lower ejection fractions (39±17% versus 50±15%; P<0.02) and a higher incidence of severe coronary artery disease (P<0.04). At five years, the survival probability on Kaplan-Meier analysis was 42% and 96% for patients with and without ISD-induced ischemia, respectively (HR 5.6 [95% CI 1.6 to 20]; P=0.009). CONCLUSIONS: Nitrates may have low efficacy in improving blood flow through the coronary vessels that supply large myocardial infarcts with high-resistance microvascular damage. At the same time, nitrates induce dilation and blood pressure decrease in remotely patent or mildly stenotic vessels. The blood pressure gradient elicited between the high- and low-resistance coronary vessels may provide the force for a blood flow steal from the viable zones of the infarct toward the healthy myocardium. The resultant nitrate-induced paradoxical ischemia could be a silent marker of myocardial instability and adverse outcomes in elderly patients with healed myocardial infarcts. PMID:23940452

  11. Reducing Adverse Polypharmacy in Patients With Borderline Personality Disorder: An Empirical Case Study

    PubMed Central

    Oldham, John M.; Gonzalez, Sylvia; Fowler, J. Christopher

    2015-01-01

    Objective: Polypharmacy is common and especially challenging in the context of borderline personality disorder in light of impulsivity and self-harm associated with the disorder, risk of adverse drug-drug interactions, and financial burden. Reduction in polypharmacy could be conceptualized as a high priority in the treatment of borderline personality disorder. This case aims to demonstrate that potential. Method: This case report presents outcomes data for an individual with borderline personality disorder during the course of an extended psychiatric hospitalization. Symptomatic change is based on the Patient Health Questionnaire Somatic, Anxiety, and Depression Symptoms scales and World Health Organization 5-Item Well-Being Index. Change in polypharmacy is presented both in terms of absolute number and complexity of the medication regimen. Clinical outcomes data are provided at 2, 12, and 24 weeks postdischarge. Results: During a 56-day hospitalization, the patient demonstrated clinical improvement across clinical domains—all occurred within the context of reduced number (43%) and complexity (40%) of her medication regimen. Symptomatic improvement was sustained up to 6 months postdischarge. Conclusions: Despite good intentions, polypharmacy can be associated with iatrogenic harm and contribute to functional impairment, especially in the context of borderline personality disorder, in which symptomatic fluctuations are part of the illness itself. A reduction in the patient’s high-risk polypharmacy during treatment represents a noteworthy treatment outcome in and of itself. Additional measures of medication risk and liability have the potential to become markers of clinical effectiveness. PMID:26693036

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. Adverse reactions to metal debris in metal-on-polyethylene total hip arthroplasty using a titanium-molybdenum-zirconium-iron alloy stem.

    PubMed

    Kiran, Manish; Boscainos, Petros J

    2015-02-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  16. Identification and prevalence of adverse drug events caused by potentially inappropriate medication in homebound elderly patients: a retrospective study using a nationwide survey in Japan

    PubMed Central

    Onda, Mitsuko; Imai, Hirohisa; Takada, Yurina; Fujii, Shingo; Shono, Takako; Nanaumi, Yoko

    2015-01-01

    Objectives A nationwide large-scale survey was conducted to identify the prevalence and causal medications of adverse drug events (ADEs) that are caused by potentially inappropriate medications (PIMs) given to homebound elderly patients, factors associated with ADEs, and measures taken by pharmacists to manage ADEs and their effects on ADEs. Settings A questionnaire was mailed to 3321 pharmacies nationwide. It asked about the details of PIMs and ADEs of up to 5 patients for whom home visits were provided by a pharmacist. Questionnaire forms were filled in by pharmacists who visited the patients. Design and participants Between 23 January and 13 February 2013, comprehensive assessment forms were sent to 3321 pharmacies. Data collected from 1890 pharmacies including data of 4815 patients were analysed and 28 patients of unknown sex were excluded. Their average age was 82.7?years. PIMs were identified based on the 2003 Beers Criteria Japan. Results There were 600 patients who did not provide valid answers regarding the medications. In the remaining 4243 patients, one or more medications that were considered to be PIMs had been prescribed to 48.4% of patients. PIM-induced ADEs were found in 8% of these patients by pharmacists during home visits. The top ADE-inducing medications were strong anticholinergic antihistamines, benzodiazepines, sulpiride and digoxin. The most common ADEs associated with benzodiazepines were frequent lightheadedness, somnolence and sleepiness, which increase the risk of falls and subsequent fractures in elderly patients. The following factors associated with ADEs were identified: sex, pharmacist awareness of prescription issues, frequency of visits and time spent at patients’ homes, and the frequency of detailed checks for patient adverse reactions by pharmacists. Conclusions The PIM prevalence associated with home healthcare in Japan was relatively high, as reported in previous studies. The present study suggests that pharmacists could reduce the incidence of PIMs and consequent ADEs. PMID:26260347

  17. Adverse childhood experiences influence white matter microstructure in patients with schizophrenia.

    PubMed

    Poletti, Sara; Mazza, Elena; Bollettini, Irene; Locatelli, Clara; Cavallaro, Roberto; Smeraldi, Enrico; Benedetti, Francesco

    2015-10-30

    Integrity of brain white matter (WM) tracts in adulthood could be detrimentally affected by exposure to adverse childhood experiences (ACE). Changes of diffusion tensor imaging (DTI) measures suggesting WM disruption have been reported in patients with schizophrenia together with a history of childhood maltreatment. We therefore hypothesized that ACE could be associated with altered DTI measures of WM integrity in patients with schizophrenia. We tested this hypothesis in 83 schizophrenia patients using whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial, and mean diffusivity (MD), and fractional anisotropy (FA). We observed an inverse correlation between severity of ACE and DTI measures of FA, and a positive correlation with MD in several WM tracts including corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus. Lower FA and higher MD are indexes of a reduction in fibre coherence and integrity. The association of ACE to reduced FA and increased MD in key WM tracts contributing to the functional integrity of the brain suggests that ACE might contribute to the pathophysiology of schizophrenia through a detrimental action on structural connectivity in critical cortico-limbic networks. PMID:26341951

  18. Adverse Event Management of Oral Mucositis in Patients with Breast Cancer

    PubMed Central

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

    2014-01-01

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

  19. Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab.

    PubMed

    Tirumani, Sree Harsha; Ramaiya, Nikhil H; Keraliya, Abhishek; Bailey, Nancy D; Ott, Patrick A; Hodi, F Stephen; Nishino, Mizuki

    2015-10-01

    Ipilimumab is a promising novel immunotherapy agent and is associated with a variety of immune-related adverse events (irAE). The purpose of this study was to investigate the manifestations of irAEs on body imaging in patients with advanced melanoma treated with ipilimumab. One-hundred forty-seven patients with advanced melanoma (59 women, 88 men; median age, 64.5 years) treated with ipilimumab were studied. All patients had the baseline and at least one follow-up chest/abdomen/pelvis CT or PET/CT during therapy, which were reviewed by a consensus of two radiologists blinded to the clinical data. Findings indicative of individual types of irAEs were assessed, including thyroiditis, sarcoid-like lymphadenopathy, pneumonitis, hepatitis, pancreatitis, and colitis. Among the 147 patients, 46 (31%) had radiologically identified irAEs. The time interval from the initiation of therapy to the development of irAEs was less than 3 months in 76% (35 of 46) of the patients (range, 0.2-9.1 months). Clinical characteristics did not differ between patients with and without irAEs (P > 0.18). Among the individual types of irAEs, colitis was most common (n = 28; 19%), followed by sarcoid-like lymphadenopathy (n = 8; 5%) and pneumonitis (n = 8; 5%). Hepatitis (n = 3), thyroiditis (n = 2), and pancreatitis (n = 1) were less common. The resolution of irAEs was noted in 32 of 36 patients (89%) with further follow-up scans, with a median time of 2.3 months after the detection of irAE. In conclusion, irAEs were noted on body imaging in 31% of patients with melanoma treated with ipilimumab. Colitis was the most common, followed by sarcoid-like lymphadenopathy and pneumonitis. The results call for an increased awareness of irAEs, given the expanding role of cancer immunotherapy. Cancer Immunol Res; 3(10); 1185-92. ©2015 AACR. PMID:26100356

  20. Rates of Cardiovascular Disease and Major Adverse Cardiovascular Events in Patients With Psoriatic Arthritis Compared to Patients Without Psoriatic Arthritis

    PubMed Central

    Li, Lin; Hagberg, Katrina Wilcox; Peng, Michael; Shah, Kamal; Paris, Maria; Jick, Susan

    2015-01-01

    Background Few studies report estimates of cardiovascular disease (CVD) or major adverse cardiovascular events (MACE) in patients with psoriatic arthritis (PsA). Objective To estimate rates of incident CVD and MACE in patients with PsA compared to patients without PsA. Methods Using the Clinical Practice Research Datalink, we conducted 2 cohort studies of patients with PsA compared to patients without PsA or psoriasis matched on age, sex, general practice, and calendar time: 1 study of CVD and 1 study of MACE. In each study, we excluded patients who had a study outcome before cohort entry. Cases were patients with a first-time diagnosis of CVD or MACE recorded during follow-up. We estimated incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (95% CI) and stratified results in the PsA cohort by exposure to systemic PsA treatments. Results The IR of CVD was higher in the patients with PsA compared to those without PsA (12.8/1000 person-years [PYs] [95% CI, 11.9–13.7] and 9.6/1000 PYs [95% CI, 9.3–9.0]; IRR, 1.33 [95% CI, 1.23–1.44]). The IR of MACE was slightly higher in the PsA compared to the non-PsA cohort (4.6/1000 PYs [95% CI, 4.1–5.1] and 3.5/1000 PYs [95% CI, 3.4–3.7]; IRR, 1.30 [95% CI, 1.15–1.47]). Among the patients with PsA, IRs were higher for those who received PsA treatments for both outcomes but did not differ significantly by type of treatment received. Conclusions The rates of CVD and MACE were slightly higher in the patients with PsA compared to the patients without PsA. Among the patients with PsA, rates of both outcomes were higher among those who received prescriptions for systemic PsA treatments. PMID:26406567

  1. Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding

    PubMed Central

    Niikura, Ryota; Nagata, Naoyoshi; Shimbo, Takuro; Sakurai, Toshiyuki; Aoki, Tomonori; Moriyasu, Shiori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Yokoi, Chizu; Yamada, Atsuo; Hirata, Yoshihiro; Koike, Kazuhiko; Akiyama, Junichi; Uemura, Naomi

    2015-01-01

    Background There are limited data on the safety of colonoscopy in patients with lower gastrointestinal bleeding (LGIB). We examined the various adverse events associated with colonoscopy in acute LGIB compared with non-GIB patients. Methods Emergency hospitalized LGIB patients (n = 161) and age- and gender-matched non-GIB controls (n = 161) were selected. Primary outcomes were any adverse events during preparation and colonoscopy procedure. Secondary outcomes were five bowel preparation-related adverse events–hypotension, systolic blood pressure <100 mmHg, volume overload, vomiting, aspiration pneumonia and loss of consciousness–and four colonoscopy-related adverse events–including hypotension, perforation, cerebrocardiovascular events and sepsis. Results During bowel preparation, 16 (9%) LGIB patients experienced an adverse event. None of the LGIB patients experienced volume overload, aspiration pneumonia or loss of consciousness; however, 12 (7%) had hypotension and 4 (2%) vomited. There were no significant differences in the five bowel preparation-related adverse events between LGIB and non-GIB patients. During colonoscopy, 25 (15%) LGIB patients experienced an adverse event. None LGIB patient had perforation or sepsis; however, 23 (14%) had hypotension and 2 (1%) experienced a cerebrocardiovascular event. There was no significant difference in the four colonoscopy-related adverse events between LGIB and non-GIB patients. In addition, no significant difference in any of the nine adverse events was found among subgroups: patients aged ?65 years, those with comorbidities, and those with antithrombotic drug use. Conclusions Adverse events in bowel preparation and colonoscopy among acute LGIB patients were low. No significant difference was found in adverse events between LGIB and non-GIB patients. These adverse events were also low in elderly LGIB patients, as well as in those with co-morbidities and antithrombotic drug use, suggesting that colonoscopy performed during acute LGIB did not increase adverse events. PMID:26368562

  2. Do Longer Intervals between Challenges Reduce the Risk of Adverse Reactions in Oral Wheat Challenges?

    PubMed Central

    Yanagida, Noriyuki; Imai, Takanori; Sato, Sakura; Ebisawa, Motohiro

    2015-01-01

    Background The use of oral food challenges (OFCs) in clinics is limited because they are complicated and associated with anaphylactic symptoms. To increase their use, it is necessary to develop novel, effective, and safe methods. However, the effectiveness of different OFCs has not been compared. Objective To investigate the effect of ingestion methods on wheat allergy symptoms and treatment during OFCs. Method Without changing the total challenge dose, we changed the administration method from a 5-installment dose titration every 15 min (15-min interval method) to 3 installments every 30 min (30-min interval method). We retrospectively reviewed and compared the results of 65 positive 15-min interval wheat challenge tests conducted between July 2005 and February 2008 and 87 positive 30-min interval tests conducted between March 2008 and December 2009. Results A history of immediate symptoms was more common for the 30-min interval method; however, no difference between methods was observed in other background parameters. Switching from the 15-min to the 30-min interval method did not increase symptoms or require treatment. The rate of cardiovascular symptoms (p = 0.032), and adrenaline use (p = 0.017) was significantly lower with the 30-min interval method. The results did not change after adjusting for the effects of immediate symptom history in multivariate analysis. Conclusion This study suggests that the 30-min interval method reduces the risk of adverse events, compared to the 15-min interval method. PMID:26624006

  3. Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis

    PubMed Central

    Kuo, Te-Hui; Tseng, Chien-Tzu; Lin, Wei-Hung; Chao, Jo-Yen; Wang, Wei-Ming; Li, Chung-Yi; Wang, Ming-Cheng

    2015-01-01

    Abstract The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case–control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI]?=?1.186–1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure–response trend (P?patients with ?3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE. PMID:26131808

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. PMID:25576362

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

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

  9. A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

    PubMed

    Liu, Xiao; Chen, Hsinchun

    2015-12-01

    Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. PMID:26518315

  10. Social dominance orientation predicts heterosexual men's adverse reactions to romantic rejection.

    PubMed

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

    2015-05-01

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

  11. Death by Cystine: an Adverse Emergent Property from a Beneficial Series of Reactions.

    PubMed

    Reitzer, Larry

    2015-12-01

    In this issue of the Journal of Bacteriology, Chonoles Imlay et al. (K. R. Chonoles Imlay, S. Korshunov, and J. A. Imlay, J Bacteriol 197:3629-3644, 2015, http://dx.doi.org/10.1128/JB.00277-15) show that oxidative stress kills sulfur-restricted Escherichia coli grown with sublethal H2O2 when challenged with cystine. Killing requires rapid and seemingly unregulated cystine transport and equally rapid cystine reduction to cysteine. Cysteine export completes an energy-depleting futile cycle. Each reaction of the cycle could be beneficial. Together, a cystine-mediated vulnerability emerges during the transition from a sulfur-restricted to a sulfur-replete environment, perhaps because of complexities of sulfur metabolism. PMID:26369582

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

    PubMed Central

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

    2012-01-01

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

  13. Adverse Outcomes after Major Surgery in Patients with Pressure Ulcer: A Nationwide Population-Based Retrospective Cohort Study

    PubMed Central

    Chou, Chia-Lun; Lee, Woan-Ruoh; Yeh, Chun-Chieh; Shih, Chun-Chuan

    2015-01-01

    Background Postoperative adverse outcomes in patients with pressure ulcer are not completely understood. This study evaluated the association between preoperative pressure ulcer and adverse events after major surgeries. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 17391 patients with preoperative pressure ulcer receiving major surgery in 2008-2010. With a propensity score matching procedure, 17391 surgical patients without pressure ulcer were selected for comparison. Eight major surgical postoperative complications and 30-day postoperative mortality were evaluated among patients with pressure ulcer of varying severity. Results Patients with preoperative pressure ulcer had significantly higher risk than controls for postoperative adverse outcomes, including septicemia, pneumonia, stroke, urinary tract infection, and acute renal failure. Surgical patients with pressure ulcer had approximately 1.83-fold risk (95% confidence interval 1.54-2.18) of 30-day postoperative mortality compared with control group. The most significant postoperative mortality was found in those with serious pressure ulcer, such as pressure ulcer with local infection, cellulitis, wound or treatment by change dressing, hospitalized care, debridement or antibiotics. Prolonged hospital or intensive care unit stay and increased medical expenditures were also associated with preoperative pressure ulcer. Conclusion This nationwide propensity score-matched retrospective cohort study showed increased postoperative complications and mortality in patients with preoperative pressure ulcer. Our findings suggest the urgency of preventing and managing preoperative pressure ulcer by a multidisciplinary medical team for this specific population. PMID:26000606

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

    PubMed Central

    Koh, Yvonne; Yap, Chun Wei

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    1985-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  17. Systematic review of adverse events of buprenorphine patch versus fentanyl patch in patients with chronic moderate-to-severe pain.

    PubMed

    Wolff, Robert F; Reid, Kim; di Nisio, Marcello; Aune, Dagfinn; Truyers, Carla; Hernandez, Adrian V; Misso, Kate; Riemsma, Rob; Kleijnen, Jos

    2012-07-01

    SUMMARY This systematic review compares convenience of administration, adverse events and tolerability of buprenorphine patch with fentanyl patch in patients with chronic pain. Methods of quantitative and qualitative research were combined. Seventeen databases were searched up to December 2010. A total of 49 unique trials (56 publications) were included. Patients regarded the use of patches, both transdermal buprenorphine and fentanyl, as easy and convenient. Compared with buprenorphine patch, fentanyl can cause more cases of constipation and could lead to a higher number of serious adverse events. There were no differences between buprenorphine patch and fentanyl patch regarding dizziness, somnolence, nausea and treatment discontinuation. Overall, transdermal administration of buprenorphine and fentanyl can be seen as an alternative pathway for delivering these drugs. Use of transdermal buprenorphine might be favorable in certain groups of patients, such as renally impaired, elderly and immunosuppressed patients. PMID:24654721

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

    PubMed Central

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

    2012-01-01

    OBJECTIVE To determine racial/ethnic differences in perinatal outcomes among women with gestational diabetes mellitus (GDM). STUDY DESIGN Retrospective cohort study of 32,193 singleton births among GDMs in California from 2006, using Vital Statistics Birth and Death Certificate and Patient Discharge Data. Women were divided by race/ethnicity: White, Black, Hispanic, or Asian. Multivariable logistic regression analyzed associations between race/ethnicity and adverse outcomes, controlling for potential confounders. Outcomes included: primary cesarean, preeclampisa, neonatal hypoglycemia, preterm delivery, macrosomia, fetal anomaly, respiratory distress syndrome (RDS). RESULTS Compared to other races, Black women had higher odds of preeclampsia [aOR=1.57, 95%CI(1.47-1.95)], neonatal hypoglycemia [aOR=1.79, 95%CI(1.07-3.00)], and preterm delivery <37 weeks [aOR=1.56, 95%CI(1.33-1.83)]. Asians had the lowest odds of primary cesarean [aOR=0.75, 95%CI(0.69-0.82)], large for gestational age infants [aOR=0.40, 95%CI(0.33-0.48)], and neonatal RDS [aOR=0.54, 95%CI(0.40-0.73)]. CONCLUSION Perinatal outcomes among women with GDM differ by race/ethnicity and may be attributed to inherent sociocultural differences that may impact glycemic control, the development of chronic co-morbidities, genetic variability, and variation in access to as well as quantity and quality of prenatal care. PMID:22818875

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Anaphylactoid reactions to protamine: an often lethal complication in insulin-dependent diabetic patients undergoing vascular surgery.

    PubMed

    Gupta, S K; Veith, F J; Ascer, E; Wengerter, K R; Franco, C; Amar, D; el-Gaweet, E S; Gupta, A

    1989-02-01

    Protamine is used routinely at our institution during arterial surgery to reverse the anticoagulant effect of heparin. Adverse fatal reactions to protamine are generally believed to be rare. However, major anaphylactoid reactions occurred in 11 of the last 1150 patients receiving this drug at our institution. Nine of these reactions occurred in 325 insulin-dependent diabetic patients (incidence, 3%), whereas only two occurred in the 825 patients not receiving insulin (incidence, 0.2%) (p less than 0.001). Ten of these reactions occurred within 10 minutes of protamine administration (15 to 35 mg), whereas one reaction occurred immediately after administration of a 5 mg test dose of protamine. Systolic blood pressure fell below 60 mm Hg in all of the 11 patients, and three patients had to be resuscitated with closed-chest massage. Initial treatment with epinephrine and steroids was successful in seven cases. Four patients required further resuscitative measures, including closed-chest massage. However, one of the patients died as a result of ventricular fibrillation resistant to treatment. Ten of the 11 patients, including the patient who died, had significant preexisting cardiac disease; six of the surviving 10 patients (60%) had perioperative myocardial infarctions and three died. Thus the total mortality rate was 36% (4/11). These data support the implication that neutral protamine Hagedorn (NPH) insulin produces an adverse reaction through immunologic presensitization of the patient. These data also show that, in the older vascular surgery population with a high incidence of significant cardiac disease, protamine reactions can be potentially lethal. Thus routine use of protamine should be avoided in diabetic patients receiving insulin. PMID:2645443

  2. Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

    PubMed Central

    Spindelegger, Christoph Josef; Papageorgiou, Konstantinos; Grohmann, Renate; Engel, Rolf; Greil, Waldemar; Konstantinidis, Anastasios; Agelink, Marcus Willy; Bleich, Stefan; Ruether, Eckart; Toto, Sermin

    2015-01-01

    Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings. PMID:25522416

  3. EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

    PubMed Central

    Khan, M. Amer; Khan, M. Nematullah; Sultan, Ihtisham; Khan, M. Aamer; Ali, S. Amir; Farooqui, Afroze

    2015-01-01

    Introduction Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). Aim The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. Materials and Methods A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. Result All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein ?2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti-cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. Conclusion Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID:26675667

  4. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

    PubMed Central

    Kumbhani, Dharam J.; Steg, Ph. Gabriel; Cannon, Christopher P.; Eagle, Kim A.; Smith, Sidney C.; Goto, Shinya; Ohman, E. Magnus; Elbez, Yedid; Sritara, Piyamitr; Baumgartner, Iris; Banerjee, Subhash; Creager, Mark A.; Bhatt, Deepak L.

    2014-01-01

    Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ?18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. PMID:24585266

  5. [Epidemiology of the hospital adverse events in Catalonia, Spain: a first step for the patient safety improvement].

    PubMed

    Bañeres, Joaquim; Orrego, Carola; Navarro, Laura; Casas, Lidia; Banqué, Marta; Suñol, Rosa

    2014-07-01

    It has been published that hospital adverse events are an important source of morbidity and mortality in different countries and settings. The aim of this study was to evaluate the frequency, magnitude, distribution and degree of preventability of adverse events in the Autonomous Community of Catalonia (Spain). We conducted a retrospective cohort study of 4,790 hospital discharges that were selected by simple random sampling after stratified multistage sampling in 15 hospitals in Catalonia. 38.25% of patients had positive risk criteria (screening phase). We identified 356 cases of adverse events, which represent a 7.4% (95%CI: 6.7% to 8.1%). Of these, 43.5% (155 cases) were considered preventable. This study confirms that adverse events in hospitals in Catalonia are frequent, and generate a significant impact on morbidity and mortality. As in other studies, corroborated that a high proportion of these adverse events are considered preventable. It was possible to identify priority areas to focus improvement efforts. PMID:25128353

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

    PubMed Central

    Aagaard, Lise; Hansen, Ebba Holme

    2011-01-01

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

  7. On the assessment of adverse drug reactions from spontaneous reporting systems: the influence of under-reporting on odds ratios.

    PubMed

    van der Heijden, Peter G M; van Puijenbroek, Eugène P; van Buuren, Stef; van der Hofstede, Jacques W

    2002-07-30

    A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting odds ratios. We will show that certain under-reporting problems play no role in assessing ADRs from SRSs: the results from the analyses turn out to be biased by some specific under-reporting problems, but not by others. SRS data can be particularly useful for the assessment of drug-drug interactions. If the assumption holds that there is an under-reporting problem for a first drug, and an under-reporting problem for a second drug, but that these two under-reporting problems do not influence each other, then reporting odds ratios estimated from SRSs are useful for signalling drug-drug interactions in the ADR-experiencing population. Similar results hold for covariate-drug interactions. We illustrate our results using two examples. PMID:12111885

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

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

  10. Determining Adverse Events in Patients with Neck Pain Receiving Orthopaedic Manual Physiotherapy: A Pilot and Feasibility Study

    PubMed Central

    Macdermid, Joy C.; Santaguida, P. Lina; Thabane, Lehana

    2013-01-01

    ABSTRACT Purpose: To pilot and determine the feasibility of estimating adverse events in patients with neck pain treated with cervical manipulation/mobilization by Canadian orthopaedic manual physiotherapists (OMPTs) using an online data-collection system to provide estimates for a future larger multi-centre international study. Methods: In a prospective multi-site two-group cohort study, participants received usual care and either (a) combined manipulation and mobilization or (b) mobilization only. Study feasibility objectives and criteria for success were set a priori. Data were analyzed using descriptive statistics. Results: A total of 20 patients were recruited from 6 of 16 participating centres, 17 to the mobilization group and 3 to the combined group. Barriers to data collection included low recruitment, difficulties in using the online data-collection system, and clinicians' and patients' being too busy to participate. Missing data for the primary outcome averaged 28.5%. A total of 69 symptom occurrences were reported during the treatment phase, all benign and transient. Most began within 0–12 hours after treatment (66/69, 95.6%) and lasted for 0–2 days (56/69, 81.2%). Kappa estimates of agreement between therapists and patients on reporting of adverse symptoms across visits 1–5 was substantial (?=0.68; 95% CI, 0.52–0.84; p<0.01). Conclusions: This pilot study demonstrates substantial challenges in conducting a large multi-centre trial. Brief, benign, and transient adverse events were common; no substantial adverse events were observed. PMID:24403696

  11. High risk of adverse events in hospitalised hip fracture patients of 65?years and older: results of a retrospective record review study

    PubMed Central

    Merten, Hanneke; Johannesma, Paul C; Lubberding, Sanne; Zegers, Marieke; Langelaan, Maaike; Jukema, Gerrolt N; Heetveld, Martin J; Wagner, Cordula

    2015-01-01

    Objectives Hip fracture patients of 65?years and older are a complex patient group who often suffer from complications and difficult rehabilitation with disappointing results. It is unknown to what extent suboptimal hospital care contributes to these poor outcomes. This study reports on the scale, preventability, causes and prevention strategies of adverse events in patients, aged 65?years and older, admitted to the hospital with a primary diagnosis of hip fracture. Design, setting and outcome measures A retrospective record review study was conducted of 616 hip fracture patients (?65?years) admitted to surgical or orthopaedic departments in four Dutch hospitals in 2007. Experienced physician reviewers determined the presence and preventability of adverse events, causes and prevention strategies using a structured review form. The main outcome measures were frequency of adverse events and preventable adverse events in hospitalised hip fracture patients of 65?years and older, and strategies to prevent them in the future. Results 114 (19%) of the 616 patients in the study experienced one or more adverse events; 49 of these were preventable. The majority of the adverse events (70%) was related to the surgical procedure and many resulted in an intervention or additional treatment (67%). Human causes contributed to 53% of the adverse events, followed by patient-related factors (39%). Training and close monitoring of quality of care and the health professional's performance were the most often selected strategies to prevent these adverse events in the future. Conclusions The high percentage of preventable adverse events found in this study shows that care for older hospitalised hip fracture patients should be improved. More training and quality assurance is required to provide safer care and to reduce the number of preventable adverse events in this vulnerable patient group. PMID:26346870

  12. 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

    2015-07-01

    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

  13. 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

  14. An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting in a tertiary care teaching hospital of Sikkim

    PubMed Central

    Datta, Supratim; Sengupta, Shramana

    2015-01-01

    Aim: Spontaneous voluntary adverse drug reaction (ADR) reporting is paramount to the success of the Pharmacovigilance Programme of India. There has however been minimal and sporadic voluntary reporting of ADR's at the ADR Monitoring Centre (AMC) Gangtok, Sikkim. Knowledge, perception, attitude, and awareness of health professionals are determinants of reporting practices. This questionnaire study aims at evaluating these indicators in the teaching hospital attached to the Medical Institute and find out methods to improve existing reporting practices. Materials and Methods: This is a cross-sectional questionnaire-based observational study carried out in the Medical, Surgical and Pathology Departments of the Teaching Hospital, Gangtok, Sikkim over a period of 2 months. The questionnaires were filled by the respondents and returned back to us within the next 24 h. Data obtained from filled questionnaires were thereby analyzed. Results: The overall correct response rate to the knowledge-based questions was 56.3%. While 97% of respondents were of the view that ADR reporting was necessary, 35% of the respondents felt that the difficulty in deciding the causality of an ADR discouraged them from reporting. 79% of the respondents were not aware of the presence of an AMC affiliated to the hospital, and 87% of the respondents admitted that they were not sending filled ADR forms to the AMC. Conclusions: The study indicates that the respondents have an average knowledge and positive attitude toward ADR reporting and pharmacovigilance. There is however a lack of awareness and poor ADR reporting practices. Efforts are required to enhance awareness and attitude toward pharmacovigilance and ADR reporting.

  15. Automatic Identification of Messages Related to Adverse Drug Reactions from Online User Reviews using Feature-based Classification

    PubMed Central

    LIU, Jingfang; ZHANG, Pengzhu; LU, Yingjie

    2014-01-01

    Abstract Background User-generated medical messages on Internet contain extensive information related to adverse drug reactions (ADRs) and are known as valuable resources for post-marketing drug surveillance. The aim of this study was to find an effective method to identify messages related to ADRs automatically from online user reviews. Methods We conducted experiments on online user reviews using different feature set and different classification technique. Firstly, the messages from three communities, allergy community, schizophrenia community and pain management community, were collected, the 3000 messages were annotated. Secondly, the N-gram-based features set and medical domain-specific features set were generated. Thirdly, three classification techniques, SVM, C4.5 and Naïve Bayes, were used to perform classification tasks separately. Finally, we evaluated the performance of different method using different feature set and different classification technique by comparing the metrics including accuracy and F-measure. Results In terms of accuracy, the accuracy of SVM classifier was higher than 0.8, the accuracy of C4.5 classifier or Naïve Bayes classifier was lower than 0.8; meanwhile, the combination feature sets including n-gram-based feature set and domain-specific feature set consistently outperformed single feature set. In terms of F-measure, the highest F-measure is 0.895 which was achieved by using combination feature sets and a SVM classifier. In all, we can get the best classification performance by using combination feature sets and SVM classifier. Conclusion By using combination feature sets and SVM classifier, we can get an effective method to identify messages related to ADRs automatically from online user reviews. PMID:26060719

  16. Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors.

    PubMed

    Mahmoudpour, Seyed Hamidreza; Asselbergs, Folkert W; de Keyser, Catherine E; Souverein, Patrick C; Hofman, Albert; Stricker, Bruno H; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

    2015-12-01

    Background Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. Objective To identify a proxy for ACEI-induced ADRs in prescription databases. Setting The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. Methods All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. Results Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. Conclusions Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases. PMID:26159317

  17. CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma.

    PubMed

    Chuang, Wen-Yu; Chang, Hung; Shih, Lee-Yung; Wang, Po-Nan; Chang, Yu-Sun; Lin, Tung-Liang; Hung, Yu-Shin; Yeh, Chi-Ju; Ueng, Shir-Hwa; Tang, Tzung-Chih; Kuo, Ming-Chung; Dunn, Po; Wu, Jin-Hou; Kao, Hsiao-Wen; Ou, Che-Wei; Wan, Yung-Liang; Hsueh, Chuen

    2015-11-01

    Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Age over 60 years is one of the five parameters of the International Prognostic Index (IPI), which is the most important clinical prognostic predictor in DLBCL. A previous study on German DLBCL patients over 60 years of age showed that immunoblastic morphology, but not germinal center B cell-like (GCB)/non-GCB subtype, correlated with short survival. We collected 174 DLBCL cases over 60 years of age in Taiwan and performed immunophenotyping and detection of Epstein-Barr virus (EBV)-encoded RNA (EBER) by in situ hybridization. Of the cases, 5.2 % were positive for CD5 and 5.7 % positive for EBER. Neither immunoblastic morphology nor GCB/non-GCB subtype correlated with survival. In univariate analysis, adverse prognostic factors included IPI???3 (P?adverse prognostic factor (HR?=?3.16; 95 % CI?=?1.34-7.47; P?=?0.0087) in addition to IPI???3 (HR?=?3.07; 95 % CI?=?1.84-5.11; P?=?0.000018). Surprisingly, despite an overall 5.2 % incidence of central nervous system (CNS) relapse in our patients, none of the CD5+ cases experienced CNS relapse (P?=?1.00). This is in stark contrast to the more frequent CNS relapse in Japanese CD5+ DLBCL patients. EBER positivity was associated with IPI???3 (P?=?0.010), stage III-IV (P?=?0.0082), and B symptoms (P?=?0.011). In multivariate analysis, EBER positivity was not an independent adverse prognostic factor (P?=?0.81), its effect being due likely to accompanying adverse clinical parameters. PMID:26369546

  18. Prolonged Emergency Department Length of Stay as a Predictor of Adverse Outcomes in Patients with Intracranial Hemorrhage

    PubMed Central

    Jones, Erica M.; Boehme, Amelia K.; Aysenne, Aimee; Chang, Tiffany; Albright, Karen C.; Burns, Christopher; Beasley, T. Mark; Martin-Schild, Sheryl

    2015-01-01

    Objectives Extended time in the emergency department (ED) has been related to adverse outcomes among stroke patients. We examined the associations of ED nursing shift change (SC) and length of stay in the ED with outcomes in patients with intracerebral hemorrhage (ICH). Methods Data were collected on all spontaneous ICH patients admitted to our stroke center from 7/1/08–6/30/12. Outcomes (frequency of pneumonia, modified Rankin Scale (mRS) score at discharge, NIHSS score at discharge, and mortality rate) were compared based on shift change experience and length of stay (LOS) dichotomized at 5 hours after arrival. Results Of the 162 patients included, 60 (37.0%) were present in the ED during a SC. The frequency of pneumonia was similar in the two groups. Exposure to an ED SC was not a significant independent predictor of any outcome. LOS in the ED ?5 hours was a significant independent predictor of discharge mRS 4–6 (OR 3.638, 95% CI 1.531–8.645, and P = 0.0034) and discharge NIHSS (OR 3.049, 95% CI 1.491–6.236, and P = 0.0023) but not death. Conclusions Our study found no association between nursing SC and adverse outcome in patients with ICH but confirms the prior finding of worsened outcome after prolonged length of stay in the ED. PMID:26473167

  19. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Park, Jae-Hyeong; Park, Margaret M.; Farha, Samar; Sharp, Jacqueline; Lundgrin, Erika; Comhair, Suzy; Tang, Wai Hong; Erzurum, Serpil C.

    2015-01-01

    Background New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. Methods Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). Results GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (? -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). Conclusion GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (? -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients. PMID:26140151

  20. Drug-induced blood consumption: the impact of adverse drug reactions on demand for blood components in German departments of internal medicine.

    PubMed

    Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Thuermann, Petra A; Hasford, Joerg

    2012-10-01

    Therapy for adverse drug reactions (ADRs) often results in the application of blood components. This study aims to assess the demand for blood components and the resulting economic burden (hospital perspective) in German hospitals induced by ADRs leading to admissions to departments of internal medicine. In this prospective study, ADRs leading to hospitalization were surveyed in four regional pharmacovigilance centres in Germany during the years 2000-2007. ADRs assessed as 'possible', 'likely' or 'very likely' were included. Market prices for blood components and hospitalization data were determined by desktop research. A probabilistic sensitivity analysis was performed. A total of 6099 patients were admitted to internal medicine departments because of an outpatient ADR of whom 1165 patients (19.1%; mean age, 73.0 ± 13.0 years) required treatment with blood components owing to major bleeding events. Overall consumption was 4185 erythrocyte concentrates (EC), 426 fresh frozen plasma (FFP) and 48 thrombocyte (TC) units. On the basis of statistical hospital data, we estimated a nationwide demand of approximately 132,020 EC, 13,440 FFP and 1515 TC units, resulting in total costs of €12.66 million per year for all German hospitals. Some 19.2% of all ADR cases were assessed as preventable. Theoretically, a nationwide decreased demand for blood components and a savings potential of €2.43 million per year could be achieved by preventing ADRs in Germany. Blood components are used in one-fifth (mainly gastrointestinal bleeding) of all ADRs, leading to hospitalizations in internal medicine departments. Both blood demand and hospital procurement costs can be significantly lowered by preventing ADRs. PMID:22487717

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

    PubMed

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

    2015-03-01

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

  2. Sarcoma-associated sarcoid reaction: Report of cutaneous sarcoid reaction in a patient with liposarcoma

    PubMed Central

    Beutler, Bryce D; Cohen, Philip R

    2015-01-01

    Sarcoidosis is a systemic inflammatory condition in which noncaseating epithelioid cell granulomas appear within one or several body sites. Sarcoid reaction (also referred to as sarcoidal or sarcoid-like reaction) occurs in patients who do not fulfill the diagnostic criteria for systemic sarcoidosis but present with similar clinical and histological features. As sarcoma-associated sarcoid reactions are rare, we describe the features of sarcoid reaction that developed in a man with liposarcoma and summarize reports of other oncology patients with sarcoma-associated sarcoid reactions. A 68-year-old man with retroperitoneal liposarcoma presented for evaluation of erythematous dermal plaques on his left leg. Microscopic examination of a tissue specimen revealed multiple epithelioid granulomas in the superficial and mid-reticular dermis. Correlation of the clinical presentation and histopathologic findings established a diagnosis of liposarcoma-associated cutaneous sarcoid reaction. Sarcoid reactions have been described in only seven individuals with sarcoma, including two patients with leiomyosarcoma and one patient with either carcinosarcoma, Kaposi sarcoma, liposarcoma, malignant peripheral nerve sheath tumor, rhabdosarcoma, or synovial sarcoma. Sarcoidal granulomas most commonly develop within the locoregional draining lymph nodes. Sarcoid reactions may also affect other organs, such as the lungs, skin, and spleen. PMID:26677448

  3. Sarcoma-associated sarcoid reaction: Report of cutaneous sarcoid reaction in a patient with liposarcoma.

    PubMed

    Beutler, Bryce D; Cohen, Philip R

    2015-12-16

    Sarcoidosis is a systemic inflammatory condition in which noncaseating epithelioid cell granulomas appear within one or several body sites. Sarcoid reaction (also referred to as sarcoidal or sarcoid-like reaction) occurs in patients who do not fulfill the diagnostic criteria for systemic sarcoidosis but present with similar clinical and histological features. As sarcoma-associated sarcoid reactions are rare, we describe the features of sarcoid reaction that developed in a man with liposarcoma and summarize reports of other oncology patients with sarcoma-associated sarcoid reactions. A 68-year-old man with retroperitoneal liposarcoma presented for evaluation of erythematous dermal plaques on his left leg. Microscopic examination of a tissue specimen revealed multiple epithelioid granulomas in the superficial and mid-reticular dermis. Correlation of the clinical presentation and histopathologic findings established a diagnosis of liposarcoma-associated cutaneous sarcoid reaction. Sarcoid reactions have been described in only seven individuals with sarcoma, including two patients with leiomyosarcoma and one patient with either carcinosarcoma, Kaposi sarcoma, liposarcoma, malignant peripheral nerve sheath tumor, rhabdosarcoma, or synovial sarcoma. Sarcoidal granulomas most commonly develop within the locoregional draining lymph nodes. Sarcoid reactions may also affect other organs, such as the lungs, skin, and spleen. PMID:26677448

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

    PubMed

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

    2015-01-01

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

  5. Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy

    PubMed Central

    Yoshihara, Ai; Noh, Jaeduk Yoshimura; Watanabe, Natsuko; Iwaku, Kenji; Kobayashi, Sakiko; Suzuki, Miho; Ohye, Hidemi; Matsumoto, Masako; Kunii, Yo; Mukasa, Koji; Sugino, Kiminori; Ito, Koichi

    2014-01-01

    The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves' disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low. PMID:24523983

  6. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

    PubMed

    Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

    2015-12-01

    Ibrutinib is associated with bleeding-related adverse events of grade ?2 in severity, and infrequently with grade ?3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ?2 bleeding-related adverse events in 55% of 85 patients. No grade ?3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ?2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733. PMID:26430171

  7. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    PubMed Central

    Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ?2 in severity, and infrequently with grade ?3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ?2 bleeding-related adverse events in 55% of 85 patients. No grade ?3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ?2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID:26430171

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

    PubMed

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

    2013-11-01

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

  9. The Comparison of Intrathecal Morphine and IV Morphine PCA on Pain Control, Patient Satisfaction, Morphine Consumption, and Adverse Effects in Patients Undergoing Reduction Mammoplasty

    PubMed Central

    Akda?, Osman; Kara, ?nci; Y?ld?ran, Gokce Unal; Tosun, Zekeriya

    2015-01-01

    Background: Following breast reduction procedures, the level of postoperative pain can be severe, and sufficient pain control influences a patient's physiological, immunological, and psychological status. Objective: The aim of this study was to examine the use of intrathecal morphine (ITM) in breast reduction surgery with patient-controlled analgesia (PCA). Methods: Sixty-two female patients who underwent breast reductions with the same technique participated in this study. The study group (ITM + PCA) included 32 patients; a single shot (0.2 mg) of ITM and intravenous morphine with PCA were administered. In the control group, morphine PCA alone was intravenously administered to 30 patients. Comparisons between the groups of cumulative morphine consumption, visual analog scale scores, and patient satisfaction scores, which were the primary outcome measures, and adverse effects, which were the secondary outcome measures, were conducted. Results: The patients in the 2 groups had similar degrees of pain and satisfaction scores. The study group had lower cumulative morphine consumption (P = .001) than the PCA-only control group; there was no statistically significant difference in adverse effects between the 2 groups. Conclusion: Intrathecal morphine may effectively control pain with lower total morphine consumption following breast reduction surgery. PMID:25987940

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  13. Fatal anaphylactic sting reaction in a patient with mastocytosis.

    PubMed

    Wagner, N; Fritze, D; Przybilla, B; Hagedorn, M; Ruëff, F

    2008-01-01

    We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a 'prophylactic' VIT. PMID:18204283

  14. Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries

    PubMed Central

    Pratt, Nicole; Chan, Esther W; Choi, Nam-Kyong; Kimura, Michio; Kimura, Tomomi; Kubota, Kiyoshi; Lai, Edward Chia-Cheng; Man, Kenneth K C; Ooba, Nobuhiro; Park, Byung-Joo; Sato, Tsugumichi; Shin, Ju-Young; Wong, Ian C K; Kao Yang, Yea-Huei; Roughead, Elizabeth E

    2015-01-01

    Background Prescription sequence symmetry analysis (PSSA) is a signal detection method for adverse drug events. Its capacity to consistently detect adverse drug events across different settings has not been tested. We aimed to determine the consistency of PSSA results for detecting positive and negative control adverse drug events across different settings. Methods Using a distributed network model, we analyzed prescription dispensing data using PSSA in Australia, Hong Kong, Japan, Korea, and Taiwan. Positive control was amiodarone and thyroxine, as a marker of amiodarone-induced hypothyroidism, a known adverse event with a clear temporal relationship to amiodarone initiation. Negative controls were amiodarone and allopurinol, as a marker of amiodarone-induced gout and thyroxine and allopurinol, as a marker of thyroxine-induced gout. Gout is not recorded as an adverse event in product information for either medicine. Adjusted sequence ratios (ASR) were calculated for each country. Pooled estimates were obtained by using the generic inverse variance method. Results A positive association was identified between amiodarone and thyroxine in all settings with a pooled ASR 2.63 (95% confidence interval (CI) 1.47–4.72). Temporal analysis showed the effect occurred within the first few weeks of treatment. No significant associations were found for the negative controls in any setting; pooled ASR were 0.76 (95%CI 0.62–0.93) and 0.98 (95%CI 0.85–1.12) for amiodarone-allopurinol and thyroxine-allopurinol, respectively. Conclusion Despite different health settings, different populations, and different patterns of medicine utilization, PSSA gave consistent estimates across countries for a well-known positive association and two negative control adverse events. © 2015 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID:25907076

  15. Questionnaire about the Adverse Events and Side Effects Following Botulinum Toxin A Treatment in Patients with Cerebral Palsy

    PubMed Central

    Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael

    2015-01-01

    Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP. PMID:26561833

  16. Questionnaire about the Adverse Events and Side Effects Following Botulinum Toxin A Treatment in Patients with Cerebral Palsy.

    PubMed

    Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael

    2015-01-01

    Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP. PMID:26561833

  17. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ? 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  18. Effectiveness of Prior Use of Beta-Blockers for Preventing Adverse Influences of Severe Hypoglycemia in Patients With Diabetes

    PubMed Central

    Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Kajio, Hiroshi; Kishimoto, Miyako; Noto, Hiroshi; Hachiya, Remi; Kimura, Akio; Kakei, Masafumi; Noda, Mitsuhiko

    2015-01-01

    Abstract The study aimed to identify predictors of severe acute hypertension (?180/110?mmHg) during severe hypoglycemia and to assess the efficacy of prior use of catecholamine-blocking agents for preventing adverse influences in diabetic patients with severe hypoglycemia. We performed a retrospective study between January 2006 and March 2012 to assess diabetic patients with severe hypoglycemia at a single center in Japan. Severe hypoglycemia was defined as the presence of any hypoglycemic symptoms that required the medical assistance of another person after visiting the emergency room by ambulance. Multivariate logistic regression analysis was performed to identify possible predictors of severe hypertension due to severe hypoglycemia and to assess whether prior use of alpha- or beta-blockers is beneficial for the prevention of severe hypertension in diabetic patients with severe hypoglycemia. Multivariate adjustments were made for age, sex, preexisting hypertension, history of ischemic heart disease, blood glucose level upon arrival, estimated GFR, and prior use of alpha- or beta-blockers. A total of 59,602 patients who visited the emergency room were screened and 352 diabetic patients with severe hypoglycemia were enrolled. Incidences of severe hypertension before and at 3 and 6?hours after the initiation of antihypoglycemic treatment were 21.3%, 6.7%, and 0% in patients with type 1 diabetes (n?=?61) and 38.8%, 18.2%, and 8.2% in patients with type 2 diabetes (n?=?291), respectively. Aging was positively (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00?1.03; P?=?0.02) and female sex was negatively (OR, 0.50; 95% CI, 0.29?0.86; P?=?0.01) associated with occurrence of severe hypertension during severe hypoglycemia. In addition, prior use of beta-blockers was negatively associated with occurrence of severe hypertension during severe hypoglycemia using multivariate logistic regression analysis (OR, 0.31; 95% CI, 0.11?0.83; P?=?0.02). None of the patients with prior use of beta-blockers had hypokalemia (<3.0?mEq/L). Prior use of beta-blockers may prevent adverse influences such as severe hypertension and hypokalemia during severe hypoglycemia in diabetic patients. PMID:26426649

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

    PubMed Central

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

    2014-01-01

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

  20. Urinary Catheterization May Not Adversely Impact Quality of Life in Multiple Sclerosis Patients

    PubMed Central

    Frasure, Heidi E.; Mahajan, Sangeeta T.

    2014-01-01

    Background. Multiple sclerosis (MS) healthcare providers (HCP) have undergone considerable educational efforts regarding the importance of evaluating and treating pelvic floor disorders, specifically, urinary dysfunction. However, limited data are available to determine the impact of catheterization on patient quality of life (QoL). Objectives. To describe the use of urinary catheterization among MS patients and determine the differences between those who report positive versus negative impact of this treatment on QoL. Methods. Patients were queried as part of the 2010 North American Research Committee On Multiple Sclerosis survey; topics included 1) urinary/bladder, bowel, or sexual problems; 2) current urine leakage; 3) current catheter use; 4) catheterizing and QoL. Results. Respondents with current urine leakage were 5143 (54.7%), of which 1201 reported current catheter use (12.8%). The types of catheters (intermittent self-catheterization and Foley catheter (indwelling and suprapubic)) did not differ significantly. Of the current catheter users, 304 (25.35%) respondents reported catheterization negatively impacting QoL, 629 (52.4%) reported a positive impact on QoL, and 223 (18.6%) reported neutral QoL. Conclusions. A large proportion of catheterized MS patients report negative or positive changes in QoL associated with urinary catheterization. Urinary catheterization does not appear to have a universally negative impact on patient QoL. PMID:25006498

  1. Acute pancreatitis as an adverse event in patients with the duodenal-jejunal bypass liner.

    PubMed

    Betzel, Bark; Homan, Jens; Aarts, Edo; Janssen, Ignace; Spanier, Marcel; Wahab, Peter; Groenen, Marcel; Berends, Frits

    2015-11-01

    Placement of the duodenal-jejunal bypass liner (DJBL) is a minimally invasive technique for the management of patients with type 2 diabetes mellitus and obesity. Acute pancreatitis was seen in 5 of 167 patients (3?%) in our series. It is suggested that acute pancreatitis in patients with the DJBL results from either direct blockage or edema of the major duodenal papilla, which may be caused by the following: migration of the anchor of the DJBL, accumulation of food debris between the liner and the duodenal wall, or reflux of duodenal contents into the pancreatic duct due to intraluminal hypertension caused by the liner. Early removal of the DJBL resulted in fast and complete recovery, whereas delayed diagnosis and removal led to severe, necrotizing acute pancreatitis. PMID:26021308

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    A retrospective cohort study was conducted on 1541 HIV-infected patients to determine variables associated with the incidence of herpes zoster. A single failure Cox model showed that herpes zoster incidence increased following the first 6 months of antiretroviral treatment adjusted hazard ratio (AHR)=5 (95%CI=2.6-9.2), P<0.001; in the >60 years age group AHR=2 (95%CI=1-4), P=0.04; in patients in the top CD8 quartile AHR=2.1 (95%CI=1.3-3.6), P<0.001; and in patients previously reported to use crack cocaine AHR=5.9, (95%CI=1.4-25), P=0.02. Herpes zoster incidence increased in patients with CD4 counts<500 per mm3 and gradually declined since 1992-1996, with AHR=0.3 (95%CI=0.2-0.5), P<0.001 for the 1997-2002 period and AHR=0.24 (95%CI=0.14-0.4), P<0.001 for the 2002-2008 period. Contrary to what has been described elsewhere, there was no specific effect of protease inhibitors on herpes zoster incidence. The present study is the first to suggest that crack cocaine is associated with an increased incidence of herpes zoster. The neurological or immunological effects of crack are discussed. PMID:24244647

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

    PubMed

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

    2010-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Cesaretti, Jamie A.; Atencio, David P.; Peters, Sheila B.A.; Burri, Ryan J.; Stone, Nelson N.; Ostrer, Harry; Rosenstein, Barry S.

    2008-03-01

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

  8. Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience.

    PubMed

    Gao, J; He, Q; Subudhi, S; Aparicio, A; Zurita-Saavedra, A; Lee, D H; Jimenez, C; Suarez-Almazor, M; Sharma, P

    2015-10-01

    Targeting a T-cell inhibitory checkpoint with the anti-CTLA-4 monoclonal antibody, ipilimumab, represents a scientific breakthrough in immunotherapy for the treatment of cancer. However, ipilimumab therapy is also associated with unique side effects, known as immune-related adverse events (irAEs), which need to be recognized and managed with immunosuppressive agents. To date, the majority of our knowledge regarding ipilimumab-associated side effects is based upon clinical studies in melanoma. Here we provide a review of ipilimumab-induced irAEs and our experience in a cohort of 44 patients with prostate cancer who were treated at the MD Anderson Cancer Center on two different clinical trial protocols. PMID:25659583

  9. Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France

    PubMed Central

    Le Saux, Olivia; Taylor, Aliki; Chia, Victoria; Pillas, Demetris; Kaur, Moninder; Freyer, Gilles

    2015-01-01

    Purpose The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB–IV) or recurrent epithelial ovarian cancer (EOC). Methods A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB–IV) or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists) participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. Results Of the 127 patients included, 92 (72.4%) had advanced EOC and 35 (27.6%) had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%). Vascular (10.2%), metabolic (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%). Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression). Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy), eleven were partially platinum sensitive (recurrence 6–12 months after stopping platinum-based therapy), seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy), and one was platinum refractory (recurrence within 6 months from the start of first-line platinum-based therapy). Conclusion In this cross-sectional study of advanced and metastatic ovarian cancer patients, approximately one-third of patients were diagnosed with comorbidities, and approximately three-quarters were diagnosed with AEs (12.6% with severe AEs). PMID:26604823

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2011-01-01

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

  12. Adverse reaction to ceftriaxone in a 28-day-old infant undergoing urgent craniotomy due to epidural hematoma: review of neonatal biliary pseudolithiasis

    PubMed Central

    Bartkowska-?niatkowska, Alicja; Jo?czyk-Potoczna, Katarzyna; Zieli?ska, Marzena; Rosada-Kurasi?ska, Jowita

    2015-01-01

    The debate as to whether to administer ceftriaxone to neonates is likely to continue. Ceftriaxone has numerous advantages for critically ill pediatric patients. However, it is also known to contribute substantially to the development of biliary pseudolithiasis. Although pediatric patients rarely develop gallbladder disorders, this complication may lead to adverse events in high-risk patients with predisposing factors, particularly in neonates and infants treated with ceftriaxone. In this paper we present an interesting case report of a 28-day-old neonate with spontaneous severe epidural hematoma who developed biliary pseudolithiasis related to the use of ceftriaxone. We also discuss the efficacy of ceftriaxone in neonates and infants. Neonatologists and pediatric intensivists should be aware of the higher risk of co-existence of hyperbilirubinemia and gallbladder disorders while using ceftriaxone in pediatric settings. PMID:26170682

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

    SciTech Connect

    Paravati, Anthony J.; Russo, Andrea L.; Aitken, Candice

    2011-10-01

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

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

    PubMed

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

    2011-03-01

    The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials. PMID:24073038

  15. Does repeated Ramadan fasting adversely affect kidney function in renal transplant patients?

    PubMed

    Ghalib, Mohamed; Qureshi, Junaid; Tamim, Hani; Ghamdi, Ghormullah; Flaiw, Ahmed; Hejaili, Fayez; Taher, Saadi; Katheri, Abculmalik; Shaheen, Faissal; Al-Khader, Abdulla A

    2008-01-15

    This is a prospective cohort study in renal transplant patients who fasted or who did not fast for three consecutive Ramadans. The baseline estimated glomerular filtration rate (GFR), mean arterial pressure (MAP), and urinary protein excretion before the first Ramadan were compared to those after the third Ramadan in 35 fasters and 33 nonfasters. The effect of age, time after transplantation, presence of diabetes mellitus (DM), and proteinuria on changes in the GFR were studied. The two groups were comparable in gender, age, donor source, time posttransplantation, presence of DM, hypertension, proteinuria, serum creatinine, and MAP. Among the fasters, there was no change in estimated GFR after fasting for three Ramadans (56.4 mL/min versus 55.4 mL/min, P=0.8) even after adjusting for age, DM, baseline GFR, proteinuria, or time after transplantation. There were no significant differences between the fasters and the nonfasters in the changes in GFR, MAP, and urinary protein excretion between baseline and the third Ramadan. PMID:18192924

  16. Local and regional adverse reactions to BCG-SSI vaccination: a 12-month cohort follow-up study.

    PubMed

    Dommergues, M A; de La Rocque, F; Guy, C; Lécuyer, A; Jacquet, A; Guérin, N; Fagot, J P; Boucherat, M; d'Athis, Ph; Cohen, R

    2009-11-23

    In a 12-month cohort follow-up study of 2435 children vaccinated in 2007 by Statens Serum Institute BCG strain (BCG SSI, 17.8% had an adverse event (AE): erythema 12.4%, induration 12.2%, abscesses 2.5%, ulceration 0.9%, lymphadenitis 0.1%. The factors associated with a lower risk of AE were: age at vaccination <1 year compared to age >1 year (OR=0.35 [0.2-0.6] for age <28 days, 0.29 [0.2-0.42] for age 29 days to 2 months, and 0.53 [0.37-0.74] for age 3-11 months), a visible papule (OR=0.48 [0.36-0.63]), and a low vaccine dose (OR=0.42 [0.31-0.58]). AE to BCG SSI vaccination were frequent but rarely severe. PMID:19800440

  17. Adverse Drug Reaction Labeling for Atomoxetine, Methylphenidate and Modafinil: Comparison of Product Information for oral Formulations in Australia, Denmark and the United States.

    PubMed

    Aagaard, Lise; Hansen, Ebba Holme

    2013-08-01

    Objective Hyponatraemia is a serious adverse event commonly reported in elderly people treated with serotonergic antidepressants. The mechanism, incidence and risk factors for antidepressant induced hyponatraemia are not fully understood. Method In a retrospective chart analysis, depressed patients aged >63 years were investigated for change in serum sodium levels between two time points, separated by a median period of 45.5 days, with the first specimen taken prior to treatment. Patients were grouped into three cohorts; treated with an SSRI or SNRI (n=77), treated with an antidepressant other than an SSRI or SNRI (n=54) and not treated with an antidepressant (n=128). Results For change in sodium level between measurements and total number of patients with hyponatraemia, there was no significant difference between cohorts. However, the rate of reduction of serum sodium levels between time points was significantly greater for SSRI and SNRI treated patients (p<0.001) and patients treated with other antidepressants (p=0.03) compared to patients not treated with antidepressants. Moreover, the distribution of values of change in serum sodium was skewed towards reduced serum sodium in patients treated with SSRI or SNRIs (skew -0.43) and patients treated with other antidepressants (skew -0.09) but not for patients without antidepressants (skew 0.25). Conclusions These data suggest that antidepressant treatment is associated with hyponatraemia affecting a subgroup of individuals only. Generalised linear modelling showed that the risk of hyponatraemia increases with increased age, female gender, and particularly the antidepressant agents sertraline and escitalopram. The findings are of clinical significance as they demonstrate that hyponatraemia can occur rapidly with antidepressants, and SSRI/SNRI medications induce more rapid changes. They support the use of electrolyte monitoring early in antidepressant treatment in patients receiving antidepressants. PMID:23909708

  18. Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register

    PubMed Central

    Jackson, Richard George; Ball, Michael; Ibrahim, Zina M.; Broadbent, Matthew; Dzahini, Olubanke; Stewart, Robert; Johnston, Caroline; Dobson, Richard J. B.

    2015-01-01

    Objectives Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim of this study was to develop an application to identify instances of Adverse Drug Events (ADEs) from free text psychiatric EHRs. Methods We used the GATE Natural Language Processing (NLP) software to mine instances of ADEs from free text content within the Clinical Record Interactive Search (CRIS) system, a de-identified psychiatric case register developed at the South London and Maudsley NHS Foundation Trust, UK. The tool was built around a set of four movement disorders (extrapyramidal side effects [EPSEs]) related to antipsychotic therapy and rules were then generalised such that the tool could be applied to additional ADEs. We report the frequencies of recorded EPSEs in patients diagnosed with a Severe Mental Illness (SMI) and then report performance in identifying eight other unrelated ADEs. Results The tool identified EPSEs with >0.85 precision and >0.86 recall during testing. Akathisia was found to be the most prevalent EPSE overall and occurred in the Asian ethnic group with a frequency of 8.13%. The tool performed well when applied to most of the non-EPSEs but least well when applied to rare conditions such as myocarditis, a condition that appears frequently in the text as a side effect warning to patients. Conclusions The developed tool allows us to accurately identify instances of a potential ADE from psychiatric EHRs. As such, we were able to study the prevalence of ADEs within subgroups of patients stratified by SMI diagnosis, gender, age and ethnicity. In addition we demonstrated the generalisability of the application to other ADE types by producing a high precision rate on a non-EPSE related set of ADE containing documents. Availability The application can be found at http://git.brc.iop.kcl.ac.uk/rmallah/dystoniaml. PMID:26273830

  19. Metal on metal total hip arthroplasty and a large groin mass: Not always adverse reaction to metallic debris

    PubMed Central

    Krishnan, Harry; Magnussen, Alex; Sharma, Aadhar; Skinner, John

    2014-01-01

    Due to their improved wear rates, Metal-on-metal bearings have been increasingly used in the past decade by orthopaedic surgeons carrying out total hip arthroplasty. However there is increasing evidence that there are significant complications associated with such implants. One well documented complication is that of metallic debris leading to pseudotumour formation, however there is less known about associations with other tumours within the pelvis. We present two cases where an intra-pelvic mass in patients with metal-on-metal implants were diagnosed as being of a different aetiology. This highlights the need for careful assessment of such patients in order to guide appropriate management. PMID:25560054

  20. Symptomatic reactions, clinical outcomes and patient satisfaction associated with upper cervical chiropractic care: A prospective, multicenter, cohort study

    PubMed Central

    2011-01-01

    Background Observational studies have previously shown that adverse events following manipulation to the neck and/or back are relatively common, although these reactions tend to be mild in intensity and self-limiting. However, no prospective study has examined the incidence of adverse reactions following spinal adjustments using upper cervical techniques, and the impact of this care on clinical outcomes. Methods Consecutive new patients from the offices of 83 chiropractors were recruited for this practice-based study. Clinical outcome measures included 1) Neck pain disability index (100-point scale), 2) Oswestry back pain index (100-point scale), 3) 11-point numerical rating scale (NRS) for neck, headache, midback, and low back pain, 4) treatment satisfaction, and 5) Symptomatic Reactions (SR). Data were collected at baseline, and after approximately 2 weeks of care. A patient reaching sub-clinical status for pain and disability was defined as a follow-up score <3 NRS and <10%, respectively. A SR is defined as a new complaint not present at baseline or a worsening of the presenting complaint by >30% based on an 11-point numeric rating scale occurring <24 hours after any upper cervical procedure. Results A total of 1,090 patients completed the study having 4,920 (4.5 per patient) office visits requiring 2,653 (2.4 per patient) upper cervical adjustments over 17 days. Three hundred thirty- eight (31.0%) patients had SRs meeting the accepted definition. Intense SR (NRS ?8) occurred in 56 patients (5.1%). Outcome assessments were significantly improved for neck pain and disability, headache, mid-back pain, as well as lower back pain and disability (p <0.001) following care with a high level (mean = 9.1/10) of patient satisfaction. The 83 chiropractors administered >5 million career upper cervical adjustments without a reported incidence of serious adverse event. Conclusions Upper cervical chiropractic care may have a fairly common occurrence of mild intensity SRs short in duration (<24 hours), and rarely severe in intensity; however, outcome assessments were significantly improved with less than 3 weeks of care with a high level of patient satisfaction. Although our findings need to be confirmed in subsequent randomized studies for definitive risk-benefit assessment, the preliminary data shows that the benefits of upper cervical chiropractic care may outweigh the potential risks. PMID:21974915

  1. RANKL and OPG Polymorphisms Are Associated with Aromatase Inhibitor-Related Musculoskeletal Adverse Events in Chinese Han Breast Cancer Patients

    PubMed Central

    Wang, Jingxuan; Lu, Kangping; Song, Ying; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Tang, Dabei; Zhao, Hong; Liu, Lei; Zhang, Qingyuan

    2015-01-01

    Background Breast cancer patients treated with aromatase inhibitors (AIs) may experience musculoskeletal adverse events (MS-AEs). Several studies have confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone health. Therefore, this study aimed to analyze the relationship between the serum levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI-related MS-AEs. Methodology and Principal Findings Patients with early stage, hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We included 208 cases with AI-related MS-AEs and 212 without (controls). The levels of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG and lumbar spine BMD were measured, and questionnaires were completed. We analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR-based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS-AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870 CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05). Conclusions and Significance In conclusion, the RANKL and OPG risk genotypes synergize to negatively impact bone health and predispose breast cancer patients to AI-related MS-AEs. PMID:26218592

  2. Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end stage renal disease

    PubMed Central

    Walker, Joy; Hiramoto, Jade; Gasper, Warren; Auyang, Philip; Conte, Michael S.; Rapp, Joseph; Lovett, David; Owens, Christopher D.

    2014-01-01

    Background Plasma 25 hydroxycholecalciferol (vit D) deficiency has been associated with adverse cardiovascular outcomes in epidemiological studies. Chronic kidney disease is associated with loss of 1-?-hydroxylase and consequently vit D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end stage renal disease. Methods This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 who also had concurrent plasma vit D levels. Levels were considered deficient at <20 ng/mL. Multivariable analysis was used to determine the association between vit D and mortality and vascular access outcomes. Results The mean age was 66.7; 96.8% were male and 32.0% African American; 60.9% had diabetes mellitus. In the entire cohort 55.5% were vitamin D (vit D) deficient, despite similar rates of repletion among the vit D deficient and non-deficient groups. During median follow up of 2.73 years there were 40 (31%) deaths. Vit D deficient patients tended to be younger (P=.01), have higher total cholesterol (P=.001), lower albumin levels (P=.017), and lower calcium levels (P=.007). Despite their younger age, mortality was significantly higher (P=.026) and vascular access failure was increased (P=.008) in the vit D deficient group. In multivariate logistic regression analysis vit D deficiency OR=3.64; (CI 1.12-11.79) P=.031, hemodialysis via central catheter OR=3.08; (CI 1.04-9.12) P=.042, coronary artery disease OR=3.08; (CI 1.06-8.94) P=.039, increased age OR=1.09; (CI 1.03-1.15) P=.001 and albumin OR=0.27 (CI 0.09-0.83) P=.023 remained independent predictors of mortality. Vit D deficiency HR=2.34 (CI 1.17-4.71) P=.02, synthetic graft HR=3.50 (CI 1.38-8.89) P=.009, , and hyperlipidemia HR=0.42 (CI .22-.81) P=.01 were independent predictors of vascular access failure in a Cox proportional harzardmodel. Conclusion Vit D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population. PMID:24582700

  3. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

    PubMed

    Hoban, Claire L; Byard, Roger W; Musgrave, Ian F

    2015-07-01

    Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications. PMID:25988866

  4. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  5. The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

    PubMed

    Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

    2015-03-15

    There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (<1%) patients, respectively. The decision aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. PMID:25633190

  6. [News in severe clinical adverse drug reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)].

    PubMed

    Martínez-Cabriales, Sylvia Aide; Gómez-Flores, Minerva; Ocampo-Candiani, Jorge

    2015-01-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening conditions associated with significant morbidity and mortality. They are considered to be part of a spectrum of cutaneous drug reactions, differing only by their extent of skin detachment due to keratinocyte apoptosis. Drugs are assumed as the main cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in most cases. The pathophysiology is incompletely understood; however, current pathogenic models involve Fas ligand, granulysin, and cytokines. Diagnosis relies mainly on clinical signs together with the histological analysis, and treatment requires early cessation of the causative drug and supportive care. Of these conditions, herein we will review the advances in clinical, pathogenesis, and management. PMID:26581536

  7. Systemic glucocorticoid therapy: risk factors for reported adverse events and beliefs about the drug. A cross-sectional online survey of 820 patients.

    PubMed

    Morin, Clément; Fardet, Laurence

    2015-12-01

    Despite systemic glucocorticoids are widely used, risk factors for most of their adverse events and patients' beliefs about the drug are poorly known. An online survey was conducted between February and July 2013 through the website www.cortisone-info.fr . Demographic (e.g., age, gender) and therapeutic (e.g., type of prescribed glucocorticoid, duration of prescription) data were collected. Patients were further asked to answer questions about glucocorticoid-induced adverse events and their beliefs about efficacy and safety of the drug. Risk factors for adverse events and efficacy/safety beliefs were assessed using multivariate logistic regression models. Eight hundred twenty questionnaires were analyzed (women 74.3 %; median age 49 [34-62] years, median equivalent prednisone dosage 20 [10-48] mg/day). The most frequently reported adverse events were insomnia (n?=?477, 58.2 %), mood disturbances (n?=?411, 50.1 %), hyperphagia (n?=?402, 49.0 %), and lipodystrophy (n?=?387, 47.2 %). The risk of some adverse events (e.g., weight gain, easy bruising) increased with the duration of exposure while other adverse events (e.g., insomnia, mood disorders, epigastric pain) were present since the first days of exposure. The risk of hirsutism, altered wound healing, mood disturbances, weight gain, lipodystrophy, hyperphagia, and epigastric pain decreased with age. Cutaneous disorders, morphological changes, and epigastric pain were more frequently reported by women. Interestingly, patients prescribed prednisolone reported less adverse events than those prescribed prednisone. No adverse event, demographical or prescribing characteristics were associated with beliefs about efficacy while factors associated with safety concerns were age (OR: 1.2 [1.1-1.3] per 10-year increase), osteoporosis (OR: 3.3 [1.4-7.9]), easy bruising (OR: 1.6 [1.1-2.3]), insomnia (OR: 1.7 [1.2-2.4]), and weight gain (OR: 1.6 [1.1-2.2]). These results may help clinicians to adapt information speech, therapeutic education, and clinical and laboratory monitoring of patients prescribed glucocorticoid therapy. PMID:25956956

  8. Risk of Adverse Vascular Events in Newly Diagnosed Glioblastoma Multiforme Patients Treated with Bevacizumab: a Systematic Review and Meta-Analysis

    PubMed Central

    Li, Xiaoqing; Huang, Rongzhong; Xu, Zhongye

    2015-01-01

    Previous evidence suggests that the humanized anti-VEGF antibody bevacizumab increases thrombosis risk in glioma patients. Here, we comprehensively assessed the risk of adverse vascular events in adult glioma patients receiving bevacizumab therapy. Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted to find prospective phase II/III clinical trials on adult bevacizumab-treated glioma patients and non-bevacizumab-treated controls that reported data on adverse vascular events. Four high-quality trials were finally included in the systematic review, scoring greater than or equal to 7/8 on the Newcastle-Ottawa Scale. Three trials provided sufficient data for four meta-analytical comparisons between bevacizumab-treated and control groups of newly diagnosed glioblastoma multiforme (GBM) patients: all-cause discontinuation, thrombocytopenia, deep vein thrombosis (DVT), and pulmonary embolism. None of these adverse outcomes were found to be significantly different between bevacizumab-treated and control groups (P?>?0.05); however, there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism (P?=?0.07). As there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism, anticoagulation may be advisable in certain newly diagnosed adult GBM patients who display a history of thromboembolism and/or more serious risk factors for thromboembolic events. PMID:26423913

  9. Adverse drug reactions for medicine newly approved in Japan from 1999 to 2013: Syncope/loss of consciousness and seizures/convulsions.

    PubMed

    Nagayama, Takashi

    2015-08-01

    Many approved medicines are used with their adverse drug reactions (ADRs) appropriately managed in the clinical setting based on their risks and benefits. In this survey, the correlation between human ADR (specifically syncope/loss of consciousness and seizures/convulsions) and safety signals reported in animal studies has been investigated for 393 Japanese medicines which were approved between September 1999 and March 2013. Clinically important drug-induced ADR, syncope/loss of consciousness and seizures/convulsions are reported in this paper. Of 393 medicines, 101 (25.7%) showed syncope/loss of consciousness and 105 (26.7%) showed seizures/convulsions. Syncope/loss of consciousness and seizures/convulsions were reported for many medicines affecting the central nervous system. The animal toxicity concordance ratio with syncope/loss of consciousness and seizures/convulsions was 4.0% (4/101) and 23.8% (25/105), respectively. The underlying cases of syncope/loss of consciousness attributed to hypotension, arrhythmia, hypoglycemia or acute toxic reaction was 16.8%, 5.0%, 4.0% or 4.0%, respectively. Mechanism of seizures/convulsions for the remaining 101 medicines was not identified except for four local anesthetics. This survey suggested that the careful attention to and understanding of medicine profiles is necessary for the appropriate use of recently approved medicines in Japan. PMID:26056066

  10. Interplay between Genetic and Clinical Variables Affecting Platelet Reactivity and Cardiac Adverse Events in Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Siller-Matula, Jolanta M.; Lang, Irene M.; Neunteufl, Thomas; Kozinski, Marek; Maurer, Gerald; Linkowska, Katarzyna; Grzybowski, Tomasz; Kubica, Jacek; Jilma, Bernd

    2014-01-01

    Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1–6.8, p<0.001) for a score level of ?1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ?75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ?75 years and HTPR were the strongest predictors of MACE. PMID:25051347

  11. Continuous reaction time in patients with hepatic encephalopathy. A quantitative measure of changes in consciousness.

    PubMed

    Elsass, P; Christensen, S E; Ranek, L; Theilgaard, A; Tygstrup, N

    1981-04-01

    In 14 patients with encephalopathy due to cirrhosis of the liver levels of consciousness were assessed by clinical ratings and continuous reaction time measurements. The observations were compared with similar measurements made in patients with chronic brain syndrome, patients sedated with diazepam, and hospitalized controls. Patients with hepatic encephalopathy were characterized by having slower reaction times than patients from the other groups. Furthermore, the performance of several liver patients was decreasing during the test. This phenomenon was not seen in the other groups. The continuous reaction times in the liver patients were correlated with the clinical ratings, but the reaction times appeared to be more sensitive, since on several occasions this test became abnormal before the clinical rating. Patients dying within 3 months after the test had more abnormal reaction times than patients surviving this period, indicating a relation between this test and the severity of the liver disease. PMID:16435490

  12. Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances.

    PubMed

    Zheng, Zhuanzhen; Qiao, Zhenhua; Gong, Rong; Wang, Yalin; Zhang, Yiqun; Ma, Yanping; Zhang, Li; Lu, Yujin; Jiang, Bo; Li, Guoxia; Dong, Chunxia; Chen, Wenliang

    2016-02-01

    This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway. PMID:26717974

  13. Adverse drug reactions associated with the use of NSAIDs: a case/noncase analysis of spontaneous reports from the French pharmacovigilance database 2002-2006.

    PubMed

    Lapeyre-Mestre, Maryse; Grolleau, Sabrina; Montastruc, Jean-Louis

    2013-04-01

    To evaluate the safety profile of eight oral nonsteroidal anti-inflammatory drugs (NSAIDs) available in France, using data reported through the French pharmacovigilance system. Data (from 2002 to 2006) were analysed for aceclofenac, diclofenac, ketoprofen, meloxicam, naproxen, nimesulide, piroxicam and tenoxicam, focusing on the reported rates of serious adverse drug reactions (ADRs) in the following system organ classes: gastrointestinal, hepatic, cutaneous, renal and cardiovascular. A total of 42 389 serious ADR reports were identified, and 38 506 were included in a case/noncase analysis. Ketoprofen was associated with the highest cumulative reported rate of serious ADRs (0.78 cases per million defined daily doses), followed by diclofenac (0.58), nimesulide (0.52), naproxen (0.50), piroxicam (0.47), tenoxicam (0.42), meloxicam (0.41) and aceclofenac (0.30). The most frequently reported serious ADRs were cutaneous, followed by gastrointestinal, hepatic, renal and rarely, cardiovascular events. In the case/noncase analysis, ketoprofen, piroxicam and naproxen were associated with the highest risk of serious gastrointestinal ADRs (odds ratios [ORs] of 6.87, 6.54 and 5.07, respectively). Nimesulide and aceclofenac were associated with the highest risk of liver ADRs (adjusted ORs of 4.53 and 3.67, respectively), as was meloxicam for cutaneous ADRs (adjusted OR of 3.15) and tenoxicam for renal ADRs (adjusted OR of 3.17). The most frequent serious ADRs reported with the selected oral NSAIDs are cutaneous, followed by gastrointestinal, hepatic and renal events. The highest risks for serious gastrointestinal, hepatic, cutaneous and renal adverse events were linked, respectively, with ketoprofen, nimesulide, meloxicam and tenoxicam compared with the other NSAIDs. PMID:21929527

  14. Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

    PubMed Central

    Crowley, James J.; Kim, Yunjung; Lenarcic, Alan B.; Quackenbush, Corey R.; Barrick, Cordelia J.; Adkins, Daniel E.; Shaw, Ginger S.; Miller, Darla R.; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F.; Valdar, William

    2014-01-01

    Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug. PMID:24240528

  15. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study

    PubMed Central

    Ko, Tai-Ming; Tsai, Chang-Youh; Chen, Shih-Yang; Chen, Kuo-Shu; Yu, Kuang-Hui; Chu, Chih-Sheng; Huang, Chung-Ming; Wang, Chrong-Reen; Weng, Chia-Tse; Yu, Chia-Li; Hsieh, Song-Chou; Tsai, Jer-Chia; Lai, Wen-Ter; Tsai, Wen-Chan; Yin, Guang-Dar; Ou, Tsan-Teng; Cheng, Kai-Hung; Yen, Jeng-Hsien; Liou, Teh-Ling; Lin, Tsung-Hsien; Chen, Der-Yuan; Hsiao, Pi-Jung; Weng, Meng-Yu; Chen, Yi-Ming; Chen, Chen-Hung; Liu, Ming-Fei; Yen, Hsueh-Wei; Lee, Jia-Jung; Kuo, Mei-Chuan; Wu, Chen-Ching; Hung, Shih-Yuan; Luo, Shue-Fen; Yang, Ya-Hui; Chuang, Hui-Ping; Chou, Yi-Chun; Liao, Hung-Ting; Wang, Chia-Wen; Huang, Chun-Lin; Chang, Chia-Shuo; Lee, Ming-Ta Michael; Chen, Pei; Wong, Chih-Shung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Chen, Yuan-Tsong

    2015-01-01

    Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres. PMID:26399967

  16. Cognitive interviewing of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Hay, Jennifer L.; Atkinson, Thomas M.; Reeve, Bryce B.; Mitchell, Sandra A.; Mendoza, Tito R.; Willis, Gordon; Minasian, Lori M.; Clauser, Steven B.; Denicoff, Andrea; O’Mara, Ann; Chen, Alice; Bennett, Antonia V.; Paul, Diane B.; Gagne, Joshua; Rogak, Lauren; Sit, Laura; Viswanath, Vish; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Methods Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea); attribute terms (regarding frequency, severity, or interference); response options; and recall period. Three interview rounds were conducted with ?20 patients completing each item per round. Items were modified and retested if ?3 patients exhibited cognitive difficulties or if experienced by ?25% patients. Results 127 patients participated (35% ?high school; 28% non-white; 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7-days) was improved when the reference period was incorporated. Conclusions This study provides evidence confirming comprehension of the U.S. English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment. PMID:23868457

  17. Cadec: A corpus of adverse drug event annotations.

    PubMed

    Karimi, Sarvnaz; Metke-Jimenez, Alejandro; Kemp, Madonna; Wang, Chen

    2015-06-01

    CSIRO Adverse Drug Event Corpus (Cadec) is a new rich annotated corpus of medical forum posts on patient-reported Adverse Drug Events (ADEs). The corpus is sourced from posts on social media, and contains text that is largely written in colloquial language and often deviates from formal English grammar and punctuation rules. Annotations contain mentions of concepts such as drugs, adverse effects, symptoms, and diseases linked to their corresponding concepts in controlled vocabularies, i.e., SNOMED Clinical Terms and MedDRA. The quality of the annotations is ensured by annotation guidelines, multi-stage annotations, measuring inter-annotator agreement, and final review of the annotations by a clinical terminologist. This corpus is useful for studies in the area of information extraction, or more generally text mining, from social media to detect possible adverse drug reactions from direct patient reports. The corpus is publicly available at https://data.csiro.au.(1). PMID:25817970

  18. A Nodular Foreign Body Reaction in a Dialysis Patient Receiving Long-term Treatment With Lanthanum Carbonate.

    PubMed

    Valika, Aziz K; Jain, Dhanpat; Jaffe, Phillip E; Moeckel, Gilbert; Brewster, Ursula C

    2016-01-01

    A 63-year-old man with HIV (human immunodeficiency virus) infection and end-stage renal disease, treated with lanthanum carbonate phosphate binder for 4 years, presented with anemia and an upper gastrointestinal bleed. Upper endoscopy revealed a nodular hyperplastic epithelium, with an endoscopic ultrasound confirming hyperechoic material within the nodules. Light microscopy showed collections of histiocytes and multinucleated giant cells containing brown granular cytoplasmic material and extracellular crystalline material, a finding confirmed by electron microscopy. Similar pathologic findings associated with lanthanum exposure have been described recently. In our patient, lanthanum carbonate treatment was withdrawn and gastrointestinal bleeding has since ceased. The patient was exposed to a high amount of lanthanum over a long period, which may explain his adverse reaction. However, other contributing factors, such as competing medications or comorbid conditions, also may have increased his sensitivity to the drug. PMID:26385816

  19. Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

    PubMed

    Grohmann, R; Engel, R R; Möller, H-J; Rüther, E; van der Velden, J W; Stübner, S

    2014-03-01

    This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice. PMID:23835526

  20. Comparison of the knowledge, attitudes, and perception of barriers regarding adverse drug reaction reporting between pharmacy and medical students in Pakistan

    PubMed Central

    Umair Khan, Muhammad; Ahmad, Akram; Ejaz, Areeba; Ata Rizvi, Syed; Sardar, Ayesha; Hussain, Kazim; Zaffar, Tayyaba; Q. Jamshed, Shazia

    2015-01-01

    Purpose: The goal of this study was to compare the knowledge and attitudes of pharmacy and medical students regarding adverse drug reactions (ADRs), as well as their perceptions of barriers to ADR reporting, in a Higher Education Commission-recognised Pakistani university. Methods: A cross-sectional study was conducted among final-year pharmacy (n=91) and medical (n=108) students in Pakistan from June 1 to July 31, 2014. A self-administered questionnaire was used to collect the data. The responses of pharmacy students were compared to those of medical students. Results: Pharmacy students had a significantly better knowledge of ADRs than medical students (mean±SD, 5.61±1.78 vs. 3.23±1.60; P<0.001). Gender showed a significant relationship to knowledge about ADRs, and male participants were apparently more knowledgeable than their female counterparts (P<0.001). The attitudes of pharmacy students regarding their capability to handle and report ADRs were significantly more positive than those of medical students (P<0.05). In comparison to pharmacy students, a lack of knowledge of where and how to report ADRs was the main barrier that medical students perceived to ADR reporting (P=0.001). Conclusion: Final-year pharmacy students exhibited more knowledge about ADRs and showed more positive attitudes regarding their capacity to handle and report ADRs than final-year medical students. PMID:26072906

  1. Audiovestibular disorders as autoimmune reaction in patients with melanoma.

    PubMed

    Barozzi, S; Ginocchio, D; Socci, M; Alpini, D; Cesarani, A

    2015-09-01

    Melanoma is an aggressive form of cancer derived from neuroectodermal melanocytes. Melanocytes are present in the skin and hair follicles, as well as in the eye (iris and choroids), the leptomeninges, the anal canal and the inner ear. In the inner ear melanocytes are found both in the intermediate layer of the stria vascularis of the cochlea and in the dark cells of the vestibular organs. They are believed to play an important role in the production of endolymphatic potentials and in the maintenance of normal volumes of the inner ear fluids. Recently, audiovestibular dysfunctions have been demonstrated in patients treated with immunotherapy for metastatic melanoma and have been related to an autoimmune attack on the normal melanocytes of the inner ear. Melanoma is an immunogenic tumor type frequently associated with spontaneous autoimmune manifestations which seem to be associated with better prognosis. The melanoma-associated antigens are also expressed in normal melanocytes in the skin, eye and ear. We hypothesize that inner ear melanocytes could be a target of an autoimmune process in patients affected by melanoma. The immune system could produce antibodies that cross-react with both the melanoma cells and the labyrinth melanocytes causing an altered homeostasis of endolymphatic liquids and provoking some labyrinthic disorders such as vertigo, hearing loss, aural fullness and tinnitus resembling or influencing Ménière's disease. In this perspective, audiovestibular disorders could be interpreted as an attempt by the individual immune system to develop anti-tumor response. In patients affected by melanoma an autoimmune genesis has already been advocated for ocular symptoms in melanoma-associated retinopathy, where the cross-reaction happens against retinal cells. A possible role of inner ear melanocytes should be considered as a potential cause of audiovestibular disorders. Further research is needed to demonstrate a connection between melanoma and labyrinth dysfunctions such as in melanoma-associated retinopathy. PMID:26115944

  2. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Reeve, Bryce B.; Mitchell, Sandra A.; Clauser, Steven B.; Minasian, Lori M.; Dueck, Amylou C.; Mendoza, Tito R.; Hay, Jennifer; Atkinson, Thomas M.; Abernethy, Amy P.; Bruner, Deborah W.; Cleeland, Charles S.; Sloan, Jeff A.; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St. Germain, Diane; O’Mara, Ann M.; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V.; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B.; Schrag, Deborah

    2014-01-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  3. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

    PubMed

    Basch, Ethan; Reeve, Bryce B; Mitchell, Sandra A; Clauser, Steven B; Minasian, Lori M; Dueck, Amylou C; Mendoza, Tito R; Hay, Jennifer; Atkinson, Thomas M; Abernethy, Amy P; Bruner, Deborah W; Cleeland, Charles S; Sloan, Jeff A; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St Germain, Diane; O'Mara, Ann M; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B; Schrag, Deborah

    2014-09-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  4. Ethnic minority patients not at increased risk of adverse events during hospitalisation in urban hospitals in the Netherlands: results of a prospective observational study

    PubMed Central

    van Rosse, Floor; Essink-Bot, Marie-Louise; Stronks, Karien; de Bruijne, Martine; Wagner, Cordula

    2014-01-01

    Objectives We analysed potential differences in incidence, type, nature, impact and preventability of adverse events (AEs) during hospitalisation between ethnic Dutch and ethnic minority patients, and the role of patient-related determinants. We hypothesised an increased AE incidence for ethnic minority patients. Setting We conducted a prospective cohort study in four urban hospitals. Participants 763 Dutch patients and 576 ethnic minority patients aged between 45 and 75, admitted for at least one night, were included in the study. All patients completed a questionnaire on patient-related determinants (eg, language proficiency). Outcome measures Incidence, type (eg, diagnostic AEs), impact and nature of AEs were assessed with a two-stage medical record review. Logistic regression analysis was used to adjust for patient and admission characteristics, and to investigate the contribution of patient-related determinants to AE risk. Results There was no significant difference in the incidence of AEs: 11% (95% CI 9% to 14%) in Dutch patients and 10% (95% CI 7% to 12%) in ethnic minority patients. Also, there was no significant difference in the incidence of preventable AEs: 3% (95% CI 1% to 4%) in Dutch patients and 1% (95% CI 0% to 2%) in ethnic minority patients. Low language proficiency, inadequate health literacy and low educational level did not increase the risk of an AE. Conclusions Compared with Dutch patients, ethnic minority patients were not at increased risk of AEs while receiving care in Dutch hospitals. Healthcare providers seem to have responded effectively to specific patient care needs, but we do not know whether this occurred in an ad hoc or in a systematic way. PMID:25550290

  5. Are nilotinib-associated vascular adverse events an under-estimated problem?

    PubMed

    Stève-Dumont, Marie; Baldin, Bernadette; Legros, Laurence; Thyss, Antoine; Re, Daniel; Rocher, Fanny; Ajmia, Florian; Spreux, Anne; Drici, Milou-Daniel

    2015-04-01

    Vascular adverse events have been reported with nilotinib, a tyrosine kinase inhibitor prescribed for chronic myeloid leukaemia. However, few data specify their incidence, or whether they occur in predisposed patients. Hence, we prospectively studied 30 consecutive patients to assess the frequency of such adverse reactions and determine whether the patients presenting with these adverse events bear predisposing factors. From 3 to 73 months after nilotinib initiation, 10 of the 30 patients experienced vascular events. Three patients of these 10 were devoid of any patent cardiovascular risk factor, except for age. This study points out an occurrence more frequent than expected of vascular adverse events associated with nilotinib (> 30% vs. < 1% in summary of product characteristics), and particularly of vascular events of late onset in patients with no pre-existing risk factors. PMID:25619238

  6. When Can Patients with Potentially Life-Threatening Adverse Effects Be Rechallenged with Clozapine? A Systematic Review of the Published Literature

    PubMed Central

    Manu, Peter; Sarpal, Deepak; Muir, Owen; Kane, John M.; Correll, Christoph U.

    2012-01-01

    Background Clozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms. Objective To review the outcome of clozapine rechallenge after potentially life threatening adverse effects. Methods Electronic, all-language, literature search (1972–2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%. Results Altogether, 138 patients (mean age: 36.3 years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI:60.6–77.4) after neutropenia, 3/15 (20%, CI:7.1–45.2) after agranulocytosis, 5/5 (100%, CI:56–100) after NMS, 3/4 (75%, CI:30–95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16–96 weeks. None of the rechallenged patients died. Conclusions Although controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis. PMID:22113154

  7. Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

    PubMed Central

    Masrani Mehta, Shriti; Depta, Jeremiah P; Novak, Eric; Patel, Jayendrakumar S; Patel, Yogesh; Raymer, David; Facey, Gabrielle; Zajarias, Alan; Lasala, John M; Singh, Jasvindar; Bach, Richard G; Kurz, Howard I

    2015-01-01

    Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients. PMID:26289346

  8. What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? Experiences from reports to a consumer association

    PubMed Central

    2011-01-01

    Background According to the World Health Organization (WHO) the cost of adverse drug reactions (ADRs) in the general population is high and under-reporting by health professionals is a well-recognized problem. Another way to increase ADR reporting is to let the consumers themselves report directly to the authorities. In Sweden it is mandatory for prescribers to report serious ADRs to the Medical Products Agency (MPA), but there are no such regulations for consumers. The non-profit and independent organization Consumer Association for Medicines and Health, KILEN has launched the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. This study aimed to analyze these consumer reports. Methods All reports submitted from January 2002 to April 2009 to an open web site in Sweden where anyone could report their experience with the use of pharmaceuticals were analyzed with focus on common psychiatric side effects related to antidepressant usage. More than one ADR for a specific drug could be reported. Results In total 665 reports were made during the period. 442 reports concerned antidepressant medications and the individual antidepressant reports represented 2392 ADRs and 878 (37%) of these were psychiatric ADRs. 75% of the individual reports concerned serotonin-reuptake inhibitor (SSRI) and the rest serotonin-norepinephrine reuptake inhibitor (SNRI). Women reported more antidepressant psychiatric ADRs (71%) compared to men (24%). More potentially serious psychiatric ADRs were frequently reported to KILEN and withdrawal symptoms during discontinuation were also reported as a common issue. Conclusions The present study indicates that consumer reports may contribute with important information regarding more serious psychiatric ADRs following antidepressant treatment. Consumer reporting may be considered a complement to traditional ADR reporting. PMID:22026961

  9. Low health-related quality of life is a predictor of major adverse cardiovascular events in patients with chronic nonischemic heart failure

    PubMed Central

    Zakliczy?ski, Micha?; Owczarek, Aleksander; Partyka, Robert; Mo?ci?ski, Mateusz; Pudlo, Robert; Kaczmarczyk, Marcin; Zembala, Marian; Polo?ski, Lech

    2014-01-01

    Introduction The need to indentify patients with chronic heart failure (CHF) at a higher risk of major adverse cardiovascular events (MACEs) has become increasingly important; therefore, new parameters, such as health-related quality of life (HRQoL), are gaining ground. The aim of this study The aim of this study was to determine the risk factors for MACEs, with a special emphasis on HRQoL in chronic non-ischemic heart failure (NIHF) patients. Material and methods This prospective study enrolled 271 hospitalized patients with heart failure symptoms (NYHA II and III), without neoplastic disease, diabetes, hepatic cirrhosis or chronic kidney disease, who had been receiving optimal medical treatment. In all the patients, laboratory examinations, electrocardiography, echocardiography, a 6-minute walking test, invasive right heart pressure measurements and coronary angiography were performed. HRQoL assessment was conducted with the Short-Form Health Survey (SF-36). Clinical observation commenced on admission to the hospital and lasted 3 years. Data concerning MACE incidence (death, transplantation, circulatory support, hospitalization) were obtained during outpatient visits. Results The final analysis enrolled 202 patients, while 17 patients were lost to follow up. The MACE incidence was 42.1%. Major adverse cardiovascular events risk factors in multiple factor analysis were: alkaline phosphatase (hazard ratio [HR] = 1.01; p < 0.05); right ventricular end-diastolic diameter (HR = 1.08; p < 0.001); hsCRP (HR = 1.04; p < 0.05); and the following HRQoL indices: Bodily Pain (HR = 0.98; p < 0.05) and Mental Health (HR = 0.97; p < 0.01). Conclusions Low values for HRQoL parameters (Bodily Pain and Mental Health), right ventricular end-diastolic diameter, serum concentration of hsCRP and alkaline phosphatase are prognostic factors in NIHF patients. PMID:26336436

  10. Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

    SciTech Connect

    Chiang, Andrew; Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON ; Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward; Sahgal, Arjun; Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON

    2013-07-15

    Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

  11. Reactions to thimerosal in hepatitis B vaccines.

    PubMed

    Rietschel, R L; Adams, R M

    1990-01-01

    Hypersensitivity to thimerosal in vaccines has been reported to induce persistent local reactions, urticarial and generalized exanthematic eruptions, and, in the case of the hepatitis B vaccine, urticaria with asthma. The authors describe two cases of extensive reactions, one in a patient who did not form antibodies to the principal vaccine antigen. Although not all thimerosal-sensitive patients develop adverse reactions to vaccines containing this material, there is a potential risk, and the reactions can be very long lasting. PMID:2137393

  12. Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

    PubMed Central

    de la Hera, Belén; Urcelay, Elena; Brassat, David; Chan, Andrew; Vidal-Jordana, Angela; Salmen, Anke; Villar, Luisa Maria; Álvarez-Cermeño, José Carlos; Izquierdo, Guillermo; Fernández, Oscar; Oliver, Begoña; Saiz, Albert; Ara, Jose Ramón; Vigo, Ana G.; Arroyo, Rafael; Meca, Virginia; Malhotra, Sunny; Fissolo, Nicolás; Horga, Alejandro; Montalban, Xavier

    2014-01-01

    Objectives: We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. Methods: HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. Results: A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (pM-H = 3 × 10?7; odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40–23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (pM-H = 6 × 10?4; ORM-H = 0.2, 95% CI = 0.08–0.50), with a PPV of 81%. Conclusions: HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration. PMID:25520955

  13. Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation

    PubMed Central

    Trepte, Ulrike; Seeger, Julia; Gonska, Birgid; Koenig, Wolfgang; Rottbauer, Wolfgang

    2015-01-01

    Background It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE) in these patients. Methods Thirty-four patients with symptomatic severe mitral valve insufficiency with a mean STS-Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP), Cystatin C, high-sensitive C-reactive protein (hsCRP), high-sensitive troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1) were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF). Results During a median follow-up of 211 days (interquartile range 133 to 333 days), 9 patients (26.5%) experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients). Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF). Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L), NT-proBNP (Median 11251 vs 1974 pg/mL) and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001) were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT-proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT-proBNP, and 0.822 for hsTnT. Conclusions MR-proANP and hsTnT strongly predict cardiovascular death and rehospitalization for HF in patients undergoing percutaneous repair of mitral valve insufficiency. Both markers might be useful components in new scoring systems to better predict short- and potentially long-term mortality and morbidity after MitraClip procedure. PMID:26368980

  14. Reversible Ototoxicity: A Rare Adverse Reaction of Liposomal Amphotericin-B Used for the Treatment of Antimony-Resistant Visceral Leishmaniasis in an Elderly Male

    PubMed Central

    Das, PC; Kandel, Ramesh; Sikka, Kapil; Dey, AB

    2014-01-01

    Amphotericin-B, a broad spectrum antifungal agent, has been known to cause adverse effects such as nephrotoxicity and infusion-related side effects such as fever, chills, rigor, and arthralgias. However, ototoxicity as an adverse effect of Amphotericin-B has not yet been reported in medical literature. We here report a case of a reversible form of ototoxicity induced by liposomal Amphotericin-B (L-AmB). PMID:25093006

  15. Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

    PubMed

    LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C

    2014-01-01

    Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number of CPUs to tens of thousands of protein targets and millions of potential drug candidates. PMID:25191698

  16. The relationship between childhood adversity and dysphoric inner states among borderline patients followed prospectively for 10 years.

    PubMed

    Reed, Lawrence Ian; Fitzmaurice, Garrett; Zanarini, Mary C

    2015-06-01

    Childhood experiences of abuse and neglect were assessed in relation to dysphoric states among patients with borderline personality disorder (BPD) over a 10-year course of prospective follow-up. The Revised Childhood Experiences Questionnaire was administered at baseline to 290 patients meeting DIB-R and DSM-III-R criteria for BPD. The Dysphoric Affect Scale--a 50-item self-report measure of affective and cognitive states thought to be common among and specific to borderline patients--was administered at fives waves of prospective follow-up. Significant predictors of dysphoric states included emotional abuse, verbal abuse, physical abuse, sexual abuse, emotional withdrawal, inconsistent treatment, denial of patient's feelings, lack of a real relationship, placing patient in parental role, and failure to protect patient. This suggests that abusive and neglectful childhood experiences are significant risk factors for severe affective and cognitive difficulties reported by borderline patients and that sexual abuse is neither necessary nor sufficient for the development of these troubling inner states. PMID:23445475

  17. Efficacies and adverse reactions of modified vitamin supplement programs before pemetrexed chemotherapy as a second-line treatment against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma

    PubMed Central

    Zhou, Chengzhi; Qin, Yinyin; Ming, Ouyang; Xie, Zhanghong; Zhang, Jiexia; Li, Shiyue; Chen, Rongchang; Zhong, Nanshan

    2015-01-01

    Objective: This study aims to observe the efficacies and adverse reactions of modified vitamin programs before pemetrexed chemotherapy (second-line treatment) against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma. Methods: 477 patients with IIIB, phase IV glomerular filtration rate (GFR) mutant-negative lung adenocarcinomas and performed pemetrexed chemotherapy were collected and divided into group A (167 cases, with modified program) and group B (310 cases, with traditional program). The modified program was: orally administrated 400 ?g folic acid once per day and 1 day before the first-round pemetrexed chemotherapy, until the 21st day of the final administration of pemetrexed, and intramuscularly injected 500 ?g vitamin B12 1 day before the first-round pemetrexed chemotherapy, and injected once 1 day before every round pemetrexed treatment. Results: Comparison between group A and group B: mean chemotherapy cycles (4.08 vs 3.98); effectiveness rate (22.16% vs 22.90%); disease control rate (56.51% vs 55.00%); without significant difference (P > 0.05). Two groups currently all reached the median overall survival (OS). The median progression-free survival (PFS): 4.2 vs 4.1 months; OS: 12.9 vs 13.2 months, without statistical difference (P > 0.05). Such side effects between the two groups as leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, fatigue, creatinine increasing, alanine transaminase (ALT) increasing, stomatitis, peripheral neuropathy, alopecia and rash had no significant difference (P > 0.05). Conclusions: The modified vitamin supportive treatment could ensure the efficacy, significantly simplify, facilitate the clinical application, and increase the associated toxicities, indicating that the pemetrexed-based chemotherapy did not need to be delayed because applying the vitamin supportive treatment. PMID:26550317

  18. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    SciTech Connect

    Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

    1987-09-01

    The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

  19. Chronic Kidney Disease Is an Independent Predictor of Adverse Clinical Outcomes in Patients with Recent Small Subcortical Infarcts

    PubMed Central

    Saji, Naoki; Sato, Takahiro; Sakuta, Kenichi; Aoki, Junya; Kobayashi, Kazuto; Matsumoto, Noriko; Uemura, Junichi; Shibazaki, Kensaku; Kimura, Kazumi

    2014-01-01

    Background Chronic kidney disease (CKD) is associated with cerebral small vessel diseases (SVD) and predicts stroke, cardiovascular events and mortality. However, its association with recent small subcortical infarcts (RSSI), a novel subtype of cerebral SVD, has not yet been established in stroke patients. The aim of this longitudinal study was to clarify whether CKD can predict clinical outcome in patients with RSSI. Methods We enrolled patients with first-ever RSSI (formerly categorized as acute lacunar stroke). CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 on admission. The patients were divided into two groups according to the presence or absence of CKD. The endpoints were recurrent stroke, cardiovascular events or all-cause mortality. The patients were followed up at 3, 6 and 12 months after stroke onset and yearly thereafter. Event-free survival analysis was undertaken using Kaplan-Meier plots and the log-rank test. Cox's proportional-hazards analysis was conducted regarding age, sex and the presence of any cerebral SVD. Results A total of 152 patients (66% males; mean age: 67.6 years) were consecutively enrolled, and 44 (29%) had CKD. During the follow-up period (median: 3 years; interquartile range: 1-4), 27 patients (18%) reached endpoints. The numbers of patients per endpoint were as follows: all-cause mortality 14, ischemic stroke 9, hemorrhagic stroke 2 and aortic dissection 2. Patients with CKD were significantly older (77 vs. 64 years; p < 0.001), had higher serum creatinine (0.96 vs. 0.65 mg/dl; p < 0.001), higher brain natriuretic peptide (51.1 vs. 18.5 pg/ml; p < 0.001) and a higher National Institutes of Health Stroke Scale score on admission (3 vs. 2; p < 0.001), and were less likely to have modified Rankin Scale scores of 0-2 after stroke onset (52 vs. 77%; p = 0.003). Patients with white matter hyperintensity [odds ratio (OR) 3.0; 95% confidence interval (CI): 1.5-6.2; p = 0.003] and those with microbleeds (OR 2.5; 95% CI: 1.2-5.1; p = 0.015) had more pronounced CKD than the remaining patients. A Kaplan-Meier curve analysis showed that patients with CKD had a less favorable outcome than those without CKD (p < 0.001). The multivariate Cox proportional-hazards analysis revealed that CKD was associated with recurrent stroke, cardiovascular events or all-cause mortality (hazard ratio 2.22; 95% CI: 1.12-4.25; p = 0.02). Conclusions CKD was found to be independently associated with recurrent stroke, cardiovascular events or all-cause mortality in patients with RSSI. PMID:25276119

  20. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    PubMed

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. PMID:26056325

  1. Coexistence of Low Vitamin D and High Fibroblast Growth Factor-23 Plasma Levels Predicts an Adverse Outcome in Patients with Coronary Artery Disease

    PubMed Central

    Tuñón, José; Cristóbal, Carmen; Tarín, Nieves; Aceña, Álvaro; González-Casaus, María Luisa; Huelmos, Ana; Alonso, Joaquín; Lorenzo, Óscar; González-Parra, Emilio; Mahíllo-Fernández, Ignacio; Pello, Ana María; Carda, Rocío; Farré, Jerónimo; Rodríguez-Artalejo, Fernando

    2014-01-01

    Objective Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. Methods Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. Results Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR]?=?0.67; 95% confidence interval [CI]?=?0.48–0.94; p?=?0.021) and FGF-23 (HR?=?1.13; 95% CI?=?1.04–1.23; p?=?0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p?=?0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR?=?0.50; 95% CI?=?0.31–0.80; p?=?0.003) but not in those with FGF-23 levels below this value (HR?=?1.03; 95% CI?=?0.62–1.71; p?=?0.904). Conclusions Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels. PMID:24748388

  2. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 2: Echinacea purpurea-Lavandula angustifolia.

    PubMed

    Gangemi, Sebastiano; Minciullo, Paola L; Miroddi, Marco; Chinou, Ioanna; Calapai, Gioacchino; Schmidt, Richard J

    2015-04-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench-Lavandula angustifolia Mill. PMID:25600644

  3. Angiotensin Receptor Blockers Decrease the Risk of Major Adverse Cardiovascular Events in Patients with End-Stage Renal Disease on Maintenance Dialysis: A Nationwide Matched-Cohort Study

    PubMed Central

    Yin, Yun-Ju; Li, Chien-Hsun; Chen, Hung-An; Chiu, Shih-Hsiang; Ho, Shinn-Ying; Huang, Hui-Ling

    2015-01-01

    Background Major adverse cardiovascular events (MACE) cause the leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on maintenance Hemodialysis (HD) or peritoneal dialysis (PD). Many randomized-controlled trials (RCTs) have proved that angiotensin receptor blockers (ARBs) can reduce the risk of MACE in the people with normal or impaired kidney function without dialysis. This study seeks to clarify whether ARBs therapy could also attenuate this risk in patients with ESRD on maintenance dialysis. Materials and Methods The National Health Research Institute provided a database of one million random subjects for the study. A random sample was taken of 1800 patients ?18 years y/o with ESRD on dialysis without a history of MACE and use of ARBs within 6-months prior to enrollment. Cox proportional hazard regression analysis was used to identify the risk factors and compute the hazard ratios accompanying 95% confidence intervals. Results In these 1800 patients, 1061 had never used ARBs, while 224 had used them for 1–90 days, and 515 had used them for more than 90 days. We found that ARBs significantly decrease the incidences of acute myocardial infarctions (AMI), coronary artery diseases (CAD) requiring coronary stent or percutaneous transluminal coronary angioplasty (PTCA), peripheral artery disease (PAD) requiring percutaneous transluminal angioplasty (PTA), and acute stroke. Cumulative prescription days of ARBs beyond 365–760 days or more were found to be negatively correlated with incidence of MACEs. For patients with dual comorbidity (i.e., mellitus and hyperlipidemia), 91–365 cumulative prescription days might also attenuate the risk. Conclusions For patients on maintenance dialysis, the use of ARBs could significantly attenuate the risk of major cardiovascular events: AMI, acute stroke, and PAD requiring PTA. PMID:26488749

  4. Application of a human factors classification framework for patient safety to identify precursor and contributing factors to adverse clinical incidents in hospital.

    PubMed

    Mitchell, Rebecca J; Williamson, Ann; Molesworth, Brett

    2016-01-01

    This study aimed to identify temporal precursor and associated contributing factors for adverse clinical incidents in a hospital setting using the Human Factors Classification Framework (HFCF) for patient safety. A random sample of 498 clinical incidents were reviewed. The framework identified key precursor events (PE), contributing factors (CF) and the prime causes of incidents. Descriptive statistics and correspondence analysis were used to examine incident characteristics. Staff action was the most common type of PE identified. Correspondence analysis for all PEs that involved staff action by error type showed that rule-based errors were strongly related to performing medical or monitoring tasks or the administration of medication. Skill-based errors were strongly related to misdiagnoses. Factors relating to the organisation (66.9%) or the patient (53.2%) were the most commonly identified CFs. The HFCF for patient safety was able to identify patterns of causation for the clinical incidents, highlighting the need for targeted preventive approaches, based on an understanding of how and why incidents occur. PMID:26360210

  5. Snoring, Trouble Breathing, Un-Refreshed (STBUR) Screening Questionnaire to Reduce Perioperative Respiratory Adverse Events in Pediatric Surgical Patients: A Quality Improvement Project.

    PubMed

    Terry, Karrey L; Disabato, Jennifer; Krajicek, Marilyn

    2015-08-01

    Children who present for surgery with undiagnosed sleep-disordered breathing are particularly vulnerable to perioperative respiratory adverse events (PRA Es). Preoperative screening can identify children at increased risk who would benefit from evidence-based perioperative management, reducing serious preventable harm or death. The purpose of this quality improvement study was 2-fold: (1) increase identification of pediatric surgical patients who may be at increased risk of PRAE through the introduction of a validated pediatric screening questionnaire (Snoring, Trouble Breathing, Un-Refreshed [STBUR]), and (2) reduce preventable harm by introducing evidence-based perioperative management guidelines. A pre-post intervention design was conducted in 6,216 patients aged 1 to 18 years. The STBUR questionnaire embedded in the electronic medical record was the primary intervention. Data for the primary outcome measure and 3 secondary process measures were analyzed using Yates?2 and Fisher exact test to compare proportional change. After STBUR implementation, PRAE risk identification increased from 10.5% to 15% (?2 (1, N = 12,975) = 57.19, z = -7.59, P < .001, odds ratio =1.49). Results of the secondary process measures were mixed. The STBUR screening questions embedded in the medical record significantly improved identification of patients at risk, allowing modification of perioperative management toward safer practices. PMID:26390743

  6. Combined Usefulness of the Platelet-to-Lymphocyte Ratio and the Neutrophil-to-Lymphocyte Ratio in Predicting the Long-Term Adverse Events in Patients Who Have Undergone Percutaneous Coronary Intervention with a Drug-Eluting Stent

    PubMed Central

    Cho, Kyoung Im; Ann, Soe Hee; Singh, Gillian Balbir; Her, Ae-Young; Shin, Eun-Seok

    2015-01-01

    Objectives The aim of this study was to investigate the combined usefulness of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in predicting the long-term adverse events in patients who have undergone percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods 798 patients with stable angina, unstable angina and non-ST elevated myocardial infarction (NSTEMI) who underwent elective successful PCI with DES were consecutively enrolled. The value of PLR and NLR in predicting adverse coronary artery disease (CAD) events and the correlations between these markers and adverse events (all-cause mortality, cardiac death, and nonfatal myocardial infarction) were analyzed. Results The follow-up period was 62.8 ± 28.8 months. When patients were classified into four groups according to the optimal cut-off values for the PLR and NLR on receiver operating characteristic analysis, patients with a high PLR (>128) and high NLR (>2.6) had the highest occurrence of adverse events among the groups. On Cox multivariate analysis, the NLR >2.6 [hazard ratio (HR) 2.352, 95% confidence interval (CI) 1.286 to 4.339, p = 0.006] and the PLR >128 (HR 2.372, 95% CI 1.305 to 3.191, p = 0.005) were independent predictors of long-term adverse events after adjusting for cardiovascular risk factors. Moreover, both a PLR >128 and a NLR >2.6 were the strongest predictors of adverse events (HR 2.686, 95% CI 1.452 to 4.970, p = 0.002). Conclusion High pre-intervention PLR and NLR, especially when combined, are independent predictors of long-term adverse clinical outcomes such as all-cause mortality, cardiac death, and myocardial infarction in patients with unstable angina and NSTEMI who have undergone successful PCI with DES. PMID:26207383

  7. [Clinical assessment of immune parameters at surgical patients with syndrome of systemic inflammatory reaction].

    PubMed

    Abakumov, M M; Bulava, G V; Borovkova, N V; Khvatov, V B

    2007-01-01

    Results of immunological examination of 423 patients with syndrome of systemic inflammatory reaction of different ethiology (mediastinitis--78 patients, peritonitis--85, severe acute pancreatitis--91, trauma of thorax and abdomen complicated with massive hemorrhage--111, severe burn trauma--40 patients) are analyzed. For complex and objective assessment of immune reaction the system of scores has been developed. This scale permitted to detect the immune disorders, to diagnose the degree of immune insufficiency at early stages of disease, to predict the purulent complications and to start timely immune therapy. PMID:17828122

  8. Incidence and Timing of Taper/Posttherapy–Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder

    PubMed Central

    Musgnung, Jeff; Messig, Michael; Buckley, Gina; Guico-Pabia, Christine J.; Ramey, Tanya S.

    2015-01-01

    Objective: The purpose of this post hoc analysis was to evaluate the incidence and timing of taper/posttherapy–emergent adverse events (TPAEs) following discontinuation of long-term treatment with desvenlafaxine (administered as desvenlafaxine succinate). Method: This was a phase 4, randomized, double-blind, placebo-controlled study conducted at 38 research centers within the United States between March 2010 and February 2011. Adult outpatients with major depressive disorder (MDD; DSM-IV-TR criteria) who completed 24 weeks of open-label treatment with desvenlafaxine 50 mg/d were randomly assigned to 1 of 3 groups for the double-blind taper phase: desvenlafaxine 50 mg/d for 4 weeks (no discontinuation), desvenlafaxine 25 mg/d for 1 week followed by placebo for 3 weeks (taper), or placebo for 4 weeks (abrupt discontinuation). The primary endpoint, Discontinuation-Emergent Signs and Symptoms Scale (DESS) score over the first 2 weeks of the taper phase, was described previously. Secondary assessments included incidence and timing of TPAEs (any adverse event that started or increased in severity during the double-blind phase) and the percentage of patients who could not continue the taper phase due to discontinuation symptoms. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) assessed MDD status. Results: A total of 480 patients enrolled in the open-label phase; the full analysis set included 357 patients (taper, n = 139; abrupt discontinuation, n = 146; no discontinuation, n = 72). TPAEs occurred in all groups through week 4. The incidence of any TPAE was lower for taper versus abrupt discontinuation at week 1 (P < .001), similar at week 2, and lower for taper versus abrupt discontinuation at weeks 3 and 4 (P ? .034). The most common TPAEs (incidence ? 3%) in the taper group were nausea and headache (3% each) at week 1 and dizziness (5%) and headache (4%) at week 2. The most common TPAEs in the abrupt discontinuation group were dizziness (8%), headache (8%), nausea (4%), irritability (3%), and diarrhea (3%) at week 1 and headache (3%) at weeks 2 and 3. The most common TPAE in the no discontinuation group was nausea (6%) at week 2. Conclusion: The overall incidence of any TPAE was lower in the taper versus abrupt discontinuation groups. Trial Registration: ClinicalTrials.gov identifier: NCT01056289 PMID:26137358

  9. Complex Type 2 Reactions in Three Patients with Hansen's Disease from a Southern United States Clinic.

    PubMed

    Leon, Kristoffer E; Salinas, Jorge L; McDonald, Robert W; Sheth, Anandi N; Fairley, Jessica K

    2015-11-01

    In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature is currently lacking in clinical descriptions of leprosy complications in the United States. Immune-mediated inflammatory states known as reactions are common complications of HD. Type 1 reactions are typical of borderline cases and occur in 30% of patients and present as swelling and inflammation of existing skin lesions, neuritis, and nerve dysfunction. Type 2 reactions are systemic events that occur at the lepromatous end of the disease spectrum, and typical symptoms include fever, arthralgias, neuritis, and classic painful erythematous skin nodules known as erythema nodosum leprosum. We report three patients with lepromatous leprosy seen at a U.S. HD clinic with complicated type 2 reactions. The differences in presentations and clinical courses highlight the complexity of the disease and the need for increased awareness of unique manifestations of lepromatous leprosy in non-endemic areas. PMID:26304919

  10. Are Dermatophytid Reactions in Patients with Kerion Celsi Much More Common Than Previously Thought? A Prospective Study.

    PubMed

    Topalo?lu Demir, Filiz; Karadag, Ayse Serap

    2015-01-01

    Dermatophytid reactions are secondary eruptions in response to dermatophytosis. Only a few cases demonstrating an association between dermatophytid reactions and tinea capitis have been reported. Dermatophytid reactions were evaluated in patients diagnosed with kerion celsi. Patients admitted to the dermatology clinic of Van Regional Training and Research Hospital between November 22, 2012, and July 1, 2013, diagnosed with kerion celsi were evaluated for dermatophytid reactions. Six girls (32%) and 13 boys (68%) were included in this study. Dermatophytid reactions were detected in 13 of the 19 patients (68%). Seven patients (36.84%) had eczematous patches or plaques and three (15.8%) had papules. Eczematous lesions, papules, and pustules were noted in two patients (10.5%) and one (5.3%) had signs of an angioedema-like reaction. Dermatophytid reactions in all patients were observed before the initiation of therapy. According to our clinical experiences, dermatophytid reactions in patients with kerion celsi were more common than reported. Eczematous scaly patches or plaques were the most frequently seen forms of dermatophytid in patients with kerion celsi. Dermatophytid reactions may occur before or after initiation of systemic antifungal therapy. Recognition of this reaction is important so that dermatophytids can be distinguished from drug reactions and the decision can be made whether to continue or to stop the systemic antifungal treatment. PMID:25677472

  11. Ethnographic interviews to elicit patients' reactions to an intelligent interactive telephone health behavior advisor system.

    PubMed Central

    Kaplan, B.; Farzanfar, R.; Friedman, R. H.

    1999-01-01

    Information technology is being used to collect data directly from patients and to provide educational information to them. Concern over patient reactions to this use of information technology is especially important in light of the debate over whether computers dehumanize patients. This study reports reactions that patient users expressed in ethnographic interviews about using a computer-based telecommunications system. The interviews were conducted as part of a larger evaluation of Telephone-Linked Care (TLC)-HealthCall, an intelligent interactive telephone advisor, that advised individuals about how to improve their health through changes in diet or exercise. Interview findings suggest that people formed personal relationships with the TLC system. These relationships ranged from feeling guilty about their diet or exercise behavior to feeling love for the voice. The findings raise system design and user interface issues as well as research and ethical questions. PMID:10566420

  12. Rare adverse events due to house dust mite sublingual immunotherapy in pediatric practice: two case reports.

    PubMed

    Galip, Nilufer; Bahceciler, Nerin

    2015-12-01

    Sublingual route, a noninjective way of allergen administration appears to be associated with a lower incidence of severe systemic reactions compared with the subcutaneous route. Local adverse reactions are reported which resolve spontaneously within a few days without need for discontinuation of treatment. Hereby, we report two pediatric cases, one with persistent asthma and the other one with persistent allergic rhinitis. Both were treated by house dust mite sublingual immunotherapy, one of whom developed severe wheezing (grade 2 systemic reaction based on World Allergy Organization subcutaneous systemic reaction grading system) and the other intractable vomiting (grade 3 local reaction based on World Allergy Organization sublingual immunotherapy local adverse events grading system) at the end of the build-up phase which repeated on re-administration of the same dose. Both of those two cases completed their 3-year immunotherapy successfully by patient-based adjustment of the highest tolerated dose of the maintenance. PMID:26427747

  13. Adverse Effects of Common Drugs: Adults.

    PubMed

    Lewis, Peter R; Karpa, Kelly Dowhower; Felix, Todd Matthew

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  14. Adverse Effects of Common Drugs: General Concepts.

    PubMed

    Karpa, Kelly Dowhower; Lewis, Peter R; Felix, Todd Matthew

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  15. FUNGAL SPECIATION USING QUANTITATIVE POLYMERASE CHAIN REACTION (QPCR) IN PATIENTS WITH AND WITHOUT CHRONIC RHINOSINUSITIS

    EPA Science Inventory

    Objectives/Hypothesis: 1. to determine the mycology of the middle meatus using an endoscopically guided brush sampling technique and polymerase chain reaction laboratory processing of nasal mucous. 2. To compare the mycology of the middle meatus in patients with sinus disease to...

  16. UNDERSTANDING OR NURSES' REACTIONS TO ERRORS AND USING THIS UNDERSTANDING TO IMPROVE PATIENT SAFETY.

    PubMed

    Taifoori, Ladan; Valiee, Sina

    2015-09-01

    The operating room can be home to many different types of nursing errors due to the invasiveness of OR procedures. The nurses' reactions towards errors can be a key factor in patient safety. This article is based on a study, with the aim of investigating nurses' reactions toward nursing errors and the various contributing and resulting factors, conducted at Kurdistan University of Medical Sciences in Sanandaj, Iran in 2014. The goal of the study was to determine how OR nurses' reacted to nursing errors with the goal of having this information used to improve patient safety. Research was conducted as a cross-sectional descriptive study. The participants were all nurses employed in the operating rooms of the teaching hospitals of Kurdistan University of Medical Sciences, which was selected by a consensus method (170 persons). The information was gathered through questionnaires that focused on demographic information, error definition, reasons for error occurrence, and emotional reactions for error occurrence, and emotional reactions toward the errors. 153 questionnaires were completed and analyzed by SPSS software version 16.0. "Not following sterile technique" (82.4 percent) was the most reported nursing error, "tiredness" (92.8 percent) was the most reported reason for the error occurrence, "being upset at having harmed the patient" (85.6 percent) was the most reported emotional reaction after error occurrence", with "decision making for a better approach to tasks the next time" (97.7 percent) as the most common goal and "paying more attention to details" (98 percent) was the most reported planned strategy for future improved outcomes. While healthcare facilities are focused on planning for the prevention and elimination of errors it was shown that nurses can also benefit from support after error occurrence. Their reactions, and coping strategies, need guidance and, with both individual and organizational support, can be a factor in improving patient safety. PMID:26529885

  17. Prevalence and relevance of allergic reactions in patients patch tested in North America--1984 to 1985.

    PubMed

    Storrs, F J; Rosenthal, L E; Adams, R M; Clendenning, W; Emmett, E A; Fisher, A A; Larsen, W G; Maibach, H I; Rietschel, R L; Schorr, W F

    1989-06-01

    Between Jan. 1, 1984, and May 1, 1985, 1199 patients with suspected allergic contact dermatitis were patch tested with 32 "standard" allergens, 707 patients with 19 "vehicle and preservative" allergens, and 613 patients with 10 "special study" allergens. Ten dermatologists representing nine geographic centers collected and analyzed data with the use of the American Academy of Dermatology's mainframe computer in Evanston, Illinois. The most common sensitizers identified were nickel, p-phenylenediamine, quaternium-15, neomycin, thimerosal, formaldehyde, cinnamic aldehyde, ethylenediamine, potassium dichromate, and thiuram mix. Each positive reaction was assessed for its clinical relevance. PMID:2754054

  18. Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

    PubMed Central

    Martins, M Â; Silva, M L; Marciano, A P V; Peruhype-Magalhães, V; Eloi-Santos, S M; Ribeiro, J G L; Correa-Oliveira, R; Homma, A; Kroon, E G; Teixeira-Carvalho, A; Martins-Filho, O A

    2007-01-01

    Over past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature. PMID:17309541

  19. Clinical Significance of Fecal Lactoferrin and Multiplex Polymerase Chain Reaction in Patients with Acute Diarrhea

    PubMed Central

    Lee, Hae Mi; Lee, Seungok; Lee, Bo-In; Jekarl, Dong Wook; Song, Joo-Yong; Choi, Hye-Jung; Kang, Bong Koo; Im, Eun Joo; Kim, Joon Sung; Kim, Jong In; Kim, Byung-Wook; Choi, Hwang

    2015-01-01

    Background/Aims The diagnostic yield of fecal leukocyte and stool cultures is unsatisfactory in patients with acute diarrhea. This study was performed to evaluate the clinical significance of the fecal lactoferrin test and fecal multiplex polymerase chain reaction (PCR) in patients with acute diarrhea. Methods Clinical parameters and laboratory findings, including fecal leukocytes, fecal lactoferrin, stool cultures and stool multiplex PCR for bacteria and viruses, were evaluated prospectively for patients who were hospitalized due to acute diarrhea. Results A total of 54 patients were included (male, 23; median age, 42.5 years). Fecal leukocytes and fecal lactoferrin were positive in 33 (61.1%) and 14 (25.4%) patients, respectively. Among the 31 patients who were available for fecal pathogen evaluation, fecal multiplex PCR detected bacterial pathogens in 21 patients, whereas conventional stool cultures were positive in only one patient (67.7% vs 3.2%, p=0.000). Positive fecal lactoferrin was associated with presence of moderate to severe dehydration and detection of bacterial pathogens by multiplex PCR (21.4% vs 2.5%, p=0.049; 100% vs 56.5%, p=0.032, respectively). Conclusions Fecal lactoferrin is a useful marker for more severe dehydration and bacterial etiology in patients with acute diarrhea. Fecal multiplex PCR can detect more causative organisms than conventional stool cultures in patients with acute diarrhea. PMID:25473075

  20. Incidence and pattern of 12 years of reported transfusion adverse events in Zimbabwe: a retrospective analysis

    PubMed Central

    Mafirakureva, Nyashadzaishe; Khoza, Star; Mvere, David A.; Chitiyo, McLeod E.; Postma, Maarten J.; van Hulst, Marinus

    2014-01-01

    Background Haemovigilance hinges on a systematically structured reporting system, which unfortunately does not always exist in resource-limited settings. We determined the incidence and pattern of transfusion-related adverse events reported to the National Blood Service Zimbabwe. Materials and methods A retrospective review of the transfusion-event records of the National Blood Service Zimbabwe was conducted covering the period from 1 January 1999 to 31 December 2011. All transfusion-related event reports received during the period were analysed. Results A total of 308 transfusion adverse events (0.046%) were reported for 670,625 blood components distributed. The majority (61.6%) of the patients who experienced an adverse event were female. The median age was 36 years (range, 1–89 years). The majority (68.8%) of the adverse events were acute transfusion reactions consisting of febrile non-haemolytic transfusion reactions (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%) of the adverse events occurred following administration of whole blood, although only 10.6% of the blood was distributed as whole blood. Packed cells, which accounted for 75% of blood components distributed, were associated with 20.1% of the events. Discussion The incidence of suspected transfusion adverse events was generally lower than the incidences reported globally in countries with well-established haemovigilance systems. The administration of whole blood was disproportionately associated with transfusion adverse events. The pattern of the transfusion adverse events reported here highlights the probable differences in practice between different settings. Under-reporting of transfusion events is rife in passive reporting systems. PMID:24887217

  1. Reactions of psychiatric patients to the Three Mile Island nuclear accident.

    PubMed

    Bromet, E; Schulberg, H C; Dunn, L

    1982-06-01

    The reaction of patients in the community mental health system to the nuclear accident at Three Mile Island (TMI), Middletown, Pa, were assessed. The sample was composed of 151 patients from the TMI area and 64 patients from a comparison site where a similar nuclear plant is located. Mental health status was determined for the period immediately after the accident, nine to ten months later, and one year later. No significant differences were found between the TMI group and the comparison group. To isolate risk factors within the TMI group, patients who were most distressed were compared with patients with the least distress. The results showed that quality of network support and viewing TMI as dangerous were significantly associated with mental health. PMID:7092506

  2. Assessment of an Oral Mycobacterium bovis BCG Vaccine and an Inactivated M. bovis Preparation for Wild Boar in Terms of Adverse Reactions, Vaccine Strain Survival, and Uptake by Nontarget Species

    PubMed Central

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A.; Barasona, Jose A.; Garrido, Joseba M.; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment. PMID:24173022

  3. Opposite effects of sleep deprivation on the continuous reaction times in patients with liver cirrhosis and normal persons.

    PubMed

    Lauridsen, Mette Munk; Frøjk, Jesper; de Muckadell, Ove B Schaffalitzky; Vilstrup, Hendrik

    2014-09-01

    The continuous reaction times (CRT) method describes arousal functions. Reaction time instability in a patient with liver disease indicates covert hepatic encephalopathy (cHE). The effects of sleep deprivation are unknown although cirrhosis patients frequently suffer from sleep disorders. The aim of this study was to determine if sleep deprivation influences the CRT test. Eighteen cirrhosis patients and 27 healthy persons were tested when rested and after one night's sleep deprivation. The patients filled out validated sleep quality questionnaires. Seven patients (38%) had unstable reaction times (a CRTindex?patients, the wakefulness improved or normalized their reaction speed and CRTindex (p?=?0.01). There was no change in the other patients' reaction speed or stability. Seven patients (38%) reported poor sleep that was not related to their CRT tests before or after the sleep deprivation. In the healthy participants, the sleep deprivation slowed their reaction times by 11% (p?reaction time stability of the patients with a CRTindex below 1.9 and had no effect in the patients with a CRTindex above 1.9. There was no relation between reported sleep quality and reaction time results. Thus, in cirrhosis patients, sleep disturbances do not lead to 'falsely' slowed and unstable reaction times. In contrast, the acute sleep deprivation slowed and destabilized the reaction times of the healthy participants. This may have negative consequences for decision-making. PMID:25008562

  4. Vaccine Adverse Events

    MedlinePLUS

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  5. Type I allergic hypersensitivity reactions due to ethylene oxide sterilised leucocyte filters in patients with thalassaemia: report of four cases.

    PubMed

    Belen, Burcu; Polat, Meltem

    2015-01-01

    Ethylene oxide (EO) is a highly reactive gas used in sterilisation of heat sensitive medical devices, such as infusion sets, cannulae, intubation materials, ventriculoperitoneal shunts, dialysis catheters and stents. Allergic reactions due to EO have been reported in haemodialysis patients, patients undergoing extracorporeal photopheresis and donors of plasmapheresis. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions. We report four patients with thalassaemia who experienced anaphylaxis during transfusion due to ethylene oxide sterilised leucocyte filters. The aim of this report is to highlight the fact that frequently transfused patients can have allergic reactions due to EO particles left in leucocyte filters. PMID:25725028

  6. Anaphylactic reactions after cisatracurium administration in two patients -a report of two cases-

    PubMed Central

    Yoon, Yangin; Lee, Byungdoo; Seo, Hyung-Seok; Bang, Jiyoun; Song, Jun-Gol

    2013-01-01

    Cisatracurium was initially characterized to have no evident histamine-releasing potential with excellent cardiovascular stability. However, severe anaphylactic reactions to cisatracurium that resulted in bronchospasms and cardiovascular collapse have been reported worldwide. Two cases of severe anaphylactic reactions after the administration of cisatracurium are presented. The anesthetics used in both cases were lidocaine, midazolam, propofol (microemulsion propofol in the second case), remifentanil and cisatracurium. After the administration of these drugs, bronchospasm and hypotension manifested, leading to the diagnosis of anaphylaxis and appropriate treatment. Skin intradermal testing confirmed that both cases were due to immune-mediated anaphylaxis to cisatracurium, despite the fact that neither of the patients had been exposed to the allergen previously. The anaphylaxis may be due to cross-reactivity between neuromuscular blocking agents and substances with quaternary ammonium ions. Anesthesiologists should be aware that cisatracurium has the potential to trigger severe anaphylactic reactions via an immune-mediated mechanism. PMID:24023998

  7. Reduced Adverse Symptoms Once BP is Controlled

    PubMed Central

    Weber, Cynthia A.; Leloux, Megan R.; Carter, Barry L.; Farris, Karen B.; Xu, Yinghui

    2008-01-01

    Study Objectives To describe trends in adverse drug reaction (ADR) scores as blood pressure (BP) came under control during a study of physician-pharmacist collaboration in the management of hypertension. Design Secondary analysis from a randomized controlled clinical trial. Setting Five primary care clinics affiliated with the University of Iowa, Iowa City, IA, USA. Subjects One hundred seventy-nine patients with uncontrolled primary hypertension aged 21-85 years taking 0-3 antihypertensive medications at baseline. Intervention Patient-reported symptoms suggestive of ADRs were recorded at each study visit using a structured ADR questionnaire. Social support (SS) and self-efficacy (SE) questionnaires were also administered at each study visit. Measurements and Main Results ADR scores decreased significantly from baseline to the end of the study (p<0.0001) in both the control (26.5 to 18.4) and intervention (29.9 to 22.7) groups although there were no differences between groups. Antihypertensive medication use increased for both intervention (1.5±1.0 to 2.4±0.9) and control (1.4±1.0 to 1.9±1.0) groups. We performed additional analyses on SE and SS to determine a potential reason for the reduction in adverse symptom scores despite an increase in medication use. Improvements in SE and SS scores were significantly and independently associated with improvement in ADR score (p<0.05). Conclusions ADR scores improved despite an increase in antihypertensive medication use. Improvements in SS and, to a lesser extent, SE are associated with improvements in ADR scores. Patients should not expect an increase in distressful symptoms as their BP becomes controlled with antihypertensive medications, especially when adequate social support is available. PMID:18752381

  8. [Systemic inflammatory reaction and indices of the organ hepatic dysfunction in patients with abdominal sepsis].

    PubMed

    Veliev, N A; Ismailov, V F

    2011-03-01

    In 26 patients in complex of treatment of abdominal sepsis there was applied a 1.5% solution of reamberin intravenously in 400 ml dose during 5 days. The results of treatment were estimated, studying indices of systemic inflammatory reaction (SIR) and hepatic tests. Reamberin application have promoted rapid normalization of the parameters studied. The authors consider, that efficacy of reamberin is caused not only by positive impact on the SIR course, but by hepatoprotective action of the preparation as well. PMID:21695970

  9. Methylchloroisothiazolinone-methylisothiazolinone reactions in patients screened for vehicle and preservative hypersensitivity.

    PubMed

    Rietschel, R L; Nethercott, J R; Emmett, E A; Maibach, H I; Storrs, F J; Larsen, W G; Adams, R M; Taylor, J S; Marks, J G; Mitchell, J C

    1990-05-01

    More than 1100 patients were tested with methylchloroisothiazolinone-methylisothiazolinone, 100 ppm, in aqueous and petrolatum-based patch test materials from 1985 to 1987 by members of the North American Contact Dermatitis Group. Thirteen reactions to the aqueous materials and 10 to the petrolatum-based materials were observed. Irritant reactions were infrequent, and about half the reactions were deemed relevant. From 1984 to 1985, patch tests with this substance at a concentration of 250 ppm in petrolatum were conducted. Thirteen persons were identified as allergic, but three others were sensitized by the patch test procedure. Sensitization as not observed in tests with aqueous or petrolatum-based substance at a concentration of 100 ppm, and this concentration appears to be the best compromise between safety and sensitive detection of allergy. Use tests are helpful but not infallible as a guide in establishing relevance with methylchloroisothiazolinone-methylisothiazolinone. Wash-off products are frequently well tolerated by patients with positive reactions to this substance. PMID:2347960

  10. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection

    PubMed Central

    Breen, R; Smith, C; Bettinson, H; Dart, S; Bannister, B; Johnson, M; Lipman, M

    2004-01-01

    Background: It has been suggested that deterioration of tuberculosis (TB) during appropriate treatment, termed a paradoxical reaction (PR), is more common and severe in HIV positive individuals on highly active antiretroviral therapy (HAART). Method: A study was undertaken to determine the frequency of PR and its associated features in a population of HIV+TB+ patients and a similar sized group of HIV–TB+ individuals. Results: PR occurred in 28% of 50 HIV+TB+ patients and 10% of 50 HIV–TB+ patients. Disseminated TB was present in eight of 13 HIV+TB+ patients and four of five HIV–TB+ patients with PR. In 28 HIV+TB+ patients starting HAART, PR was significantly associated with commencing HAART within 6 weeks of starting antituberculosis treatment (p = 0.03) and was more common in those with disseminated TB (p = 0.09). No association was found between development of PR and baseline CD4 count or CD4 response to HAART. Conclusions: PR is common in HIV infected and uninfected individuals with TB. Early introduction of HAART and the presence of disseminated TB appear to be important in co-infected patients. PMID:15282393

  11. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented. PMID:26482404

  12. Pharmacotherapeutics for the AIDS Patient.

    ERIC Educational Resources Information Center

    Fife, Kenneth H.

    1991-01-01

    Anticipated shifts in the demographics of the Acquired Immune Deficiency Syndrome (AIDS) epidemic are examined, current state-of-the-art AIDS patient management is summarized, and some unique facets of drug therapy in the AIDS patient are discussed, including adverse reactions, complex drug interactions, use of investigational drugs, and…

  13. Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

    PubMed

    Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia

    2015-12-01

    Background Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. Objective The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. Methods We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Main outcome measures Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. Results A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Conclusion Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics. PMID:26267215

  14. DNA Double-Strand Break Analysis by {gamma}-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

    SciTech Connect

    Goutham, Hassan Venkatesh; Mumbrekar, Kamalesh Dattaram; Vadhiraja, Bejadi Manjunath; Fernandes, Donald Jerard; Sharan, Krishna; Kanive Parashiva, Guruprasad; Kapaettu, Satyamoorthy; Bola Sadashiva, Satish Rao

    2012-12-01

    Purpose: Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. Methods and Materials: DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting {gamma}-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: The correlation between residual DSBs and the severity of acute reactions demonstrated that residual {gamma}-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. Conclusions: Our results suggest that {gamma}-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

  15. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  16. Orofacial adverse effects of biological agents.

    PubMed

    Georgakopoulou, Eleni A; Scully, Crispian

    2015-11-01

    Biological agents (BA) are increasingly used effectively in the treatment of a range of disorders, but to date, their application in diseases affecting the orofacial region has been fairly limited. Several orofacial adverse effects related to BA have been recently reported. However, the evidence for such adverse reactions is not always strong, and some of the adverse effects of BA have only been reported in case reports or case series. Most reactions to BA reported thus far have been in association with antitumor necrosis factor-? agents, which is not surprising, as these are the most widely-used BA. In the present study, the orofacial adverse effects are reported with various BA in order to sensitize clinicians to the possibilities. In addition, we briefly summarize the mode of action and indications of these BA. As the use and range of BA increases, the number and diversity of adverse effects might well increase. Despite the adverse effects of biological agents, these may often be less serious than the adverse effects of the more traditional immunosuppressive agents. PMID:24850782

  17. Drug-induced skin reactions: a 2-year study

    PubMed Central

    Farshchian, Mahmood; Ansar, Akram; Zamanian, Abbas; Rahmatpour-Rokni, Ghasem; Kimyai-Asadi, Arash; Farshchian, Mehdi

    2015-01-01

    Background The aim of this study was to analyze the clinical characteristics of patients with adverse cutaneous drug reactions, which occur when a medicinal product results in cutaneous morbidity. Methods The study included 308 patients who were diagnosed as having an adverse cutaneous drug reaction during the study period (2007–2009). In 84 cases, histopathologic examination of skin biopsies were also performed. Results Patients with drug reactions were found to be more commonly female (63%) than male (37%). Beta-lactam antibiotics were found to be the most frequent cause of adverse cutaneous drug reactions (42.7%), followed by non-steroidal anti-inflammatory drugs (16.5%). Acute urticaria was the most common clinical presentation (59.2%) followed by fixed drug eruptions (18.5%), and maculopapular eruptions (14.9%). Conclusion Adverse cutaneous drug reactions in our study population were mainly induced by beta-lactam antibiotics and non-steroidal anti-inflammatory drugs. The most common forms of cutaneous adverse drug reactions were found to be acute urticaria, fixed drug eruptions, and maculopapular rashes. PMID:25709487

  18. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  19. An analysis of skin prick test reactions in 656 asthmatic patients.

    PubMed Central

    Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

    1975-01-01

    Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied. Images PMID:1168378

  20. Polymerase chain reaction in the detection of circulating tumour cells in peripheral blood of melanoma patients.

    PubMed

    Schittek, B; Blaheta, H J; Ellwanger, U; Garbe, C

    2001-01-01

    Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique. PMID:11092036

  1. Heart-type fatty acid binding protein and high-sensitivity troponin T are myocardial damage markers that could predict adverse clinical outcomes in patients with peripheral artery disease

    PubMed Central

    Otaki, Yoichiro; Takahashi, Hiroki; Watanabe, Tetsu; Yamaura, Gensai; Funayama, Akira; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Kubota, Isao

    2015-01-01

    Background Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators of future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD. Methods and results We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow-up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H-FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan–Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors. Conclusion The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients. PMID:26673681

  2. Tracing of Helicobacter Pylori in Patients of Otitis Media with Effusion by Polymerase Chain Reaction

    PubMed Central

    Shishegar, Mahmood; Motamedi-Far, Mohammad; Hashemi, Seyed Basir; Bigham-Sadegh, Abbas; Emami, Amir

    2015-01-01

    Otitis media with effusion (OME) is one of the most common causes of hearing loss (HL) in children. It has been reported that several factors such as eustachian tube dysfunction, insufficiencies in the aeration of the mastoid cells, allergies, immunity, and infections play an important role in the etiology of the disease. Little is known about the role of Helicobacter pylori (H. pylori) in extragastric diseases. Because of the near location of the nose, sinuses, tonsils, and adenoids to the eustachian tube and middle ear, we believe it is possible to have H. pylori in the middle ear. The present study was designed to investigate the presence of H. pylori by polymerase chain reaction (PCR) in the middle ear effusion of patients with OME. The study was performed on 21 patients, 19 patients were affected bilaterally, and 2 patients were affected unilaterally, from which 40 specimens were collected. OME was diagnosed through findings by otoscopic examination and tympanogram. The middle ear fluid samples were collected under sterile conditions. A total of 40 samples was stored at -80°C until analyzed by PCR assay. From 40 specimens, 2 specimens were serosal and 38 specimens were mucoid. PCR results of the study in assays for Helicobacter pylori were not positive in all collected specimens. Overall, probably there was no H. pylori organism in free-floating form and thus could not be detected by PCR. PMID:25999629

  3. How we treat delayed haemolytic transfusion reactions in patients with sickle cell disease.

    PubMed

    Gardner, Kate; Hoppe, Carolyn; Mijovic, Aleksandar; Thein, Swee L

    2015-09-01

    Transfusion therapy is effective in the prevention and treatment of many complications of sickle cell disease (SCD). However, its benefits must be balanced against its risks, including delayed haemolytic transfusion reactions (DHTR). Not only is the relative rate of alloimmunization higher in patients with SCD than in other patient populations, but attendant risks associated with DHTR are even greater in SCD. Clinicians' awareness of DHTR events is poor because symptoms of DHTR mimic acute vaso-occlusive pain and immunohaematology findings are often negative. Transfusions delivered in the acute rather than elective setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends on the clinical severity, ranging from supportive care to immunosuppression, and optimization of erythropoiesis. DHTR must be considered in any recently transfused patient presenting with acute sickle cell pain. Meticulous documentation of transfusion and immunohaematology history is key. We anticipate an increase in DHTR events in SCD patients with the increasing use of red blood cell transfusion therapy. PMID:25967919

  4. Identifying Adverse Drug Events

    PubMed Central

    Jha, Ashish K.; Kuperman, Gilad J.; Teich, Jonathan M.; Leape, Lucian; Shea, Brian; Rittenberg, Eve; Burdick, Elisabeth; Seger, Diane Lew; Vliet, Martha Vander; Bates, David W.

    1998-01-01

    Abstract Background: Adverse drug events (ADEs) are both common and costly. Most hospitals identify ADEs using spontaneous reporting, but this approach lacks sensitivity; chart review identifies more events but is expensive. Computer-based approaches to ADE identification appear promising, but they have not been directly compared with chart review and they are not widely used. Objectives: To develop a computer-based ADE monitor, and to compare the rate and type of ADEs found with the monitor with those discovered by chart review and by stimulated voluntary report. Design: Prospective cohort study in one tertiary-care hospital. Participants: All patients admitted to nine medical and surgical units in a tertiary-care hospital over an eight-month period. Main Outcome Measure: Adverse drug events identified by the computer-based monitor, by chart review, and by stimulated voluntary report. Methods: A computer-based monitoring program identified alerts, which were situations suggesting that an ADE might be present (e.g., an order for an antidote such as naloxone). A trained reviewer then examined patients' hospital records to determine whether an ADE had occurred. The results of the computer-based monitoring strategy were compared with two other ADE detection strategies: intensive chart review and stimulated voluntary report by nurses and pharmacists. The monitor and the chart review strategies were independent, and the reviewers were blinded. Results: The computer monitoring strategy identified 2,620 alerts, of which 275 were determined to be ADEs. The chart review found 398 ADEs, whereas voluntary report detected 23. Of the 617 ADEs detected by at least one method, 76 ADEs were detected by both computer monitor and chart review. The computer monitor identified 45 percent; chart review, 65 percent; and voluntary report, 4 percent. The ADEs identified by computer monitor were more likely to be classified as “severe” than were those identified by chart review (51 versus 42 percent, p =.04). The positive predictive value of computer-generated alerts was 16 percent during the first eight weeks of the study; rule modifications increased this to 23 percent in the final eight weeks. The computer strategy required 11 person-hours per week to execute, whereas chart review required 55 person-hours per week and voluntary report strategy required 5. Conclusions: The computer-based monitor identified fewer ADEs than did chart review but many more ADEs than did stimulated voluntary report. The overlap among the ADEs identified using different methods was small, suggesting that the incidence of ADEs may be higher than previously reported and that different detection methods capture different events. The computer-based monitoring system represents an efficient approach for measuring ADE frequency and gauging the effectiveness of ADE prevention programs. PMID:9609500

  5. Stress and psoriasis: psychoendocrine and metabolic reactions in psoriatic patients during standardized stressor exposure.

    PubMed

    Arnetz, B B; Fjellner, B; Eneroth, P; Kallner, A

    1985-01-01

    Psychoendocrine and metabolic reactions during standardized stressor exposure (color-word conflict test and forced mental arithmetics) were studied in ten psoriatic and ten matched healthy subjects. During resting conditions, the groups were similar with regard to psychologic and biochemical variables, except for plasma glucose, which was slightly elevated in the psoriatic group. During stressor exposure, the psoriatic group reported significantly higher strain levels. Blood pressure, pulse rate, plasma glucose, and urinary adrenaline excretion increased in both groups during exposure, with more pronounced increases of the latter two in the psoriatic group. Serum cortisol, prolactin, progesterone and urinary cortisol decreased in both groups during stressor exposure. The decrease in serum cortisol was more pronounced in the psoriatic group. Thus, no psychoendocrine differences were found between the healthy and psoriatic subjects during resting conditions. In contrast, during a standardized stressor exposure, psoriatic subjects reported higher levels of strain, which was accompanied by higher levels of urinary adrenaline and lower levels of plasma cortisol. These results fit the hypothesis that psoriatic patients perceive certain challenging situations as more stressful than do nonpsoriatic controls, and react accordingly in their differential psychoendocrine reaction pattern. Possible pathophysiologic implications of the different pituitary-adrenocortical and sympatho-adrenomedullary reactions in psoriatics submitted to stressor exposure are discussed. PMID:4070523

  6. Relaxation training during chemotherapy for breast cancer improves mental health and lessens adverse events

    PubMed Central

    Song, Qing-Hua; Xu, Rong-Mei; Zhang, Quan-Hai; Ma, Ming; Zhao, Xin-Ping

    2013-01-01

    Objective: Mental health issues like anxiety and depression and other adverse events often accompany chemotherapy for breast cancer and can result in reduced quality of life for patients. The present study was aimed to determine whether relaxation training intervention reduces anxiety and other adverse reactions during chemotherapy in patients with breast cancer. Methods: Using a prospective, randomized study design, patients with breast cancer were divided into a control group (n=50) and an experimental group (n=50). Patients in the control group received routine nursing care; those in the experimental group received routine nursing care plus relaxation training, which comprised controlled abdominal breathing and progressive muscle relaxation. Anxiety Inventory and Rotterdam Symptom checklists were administered to patients in both groups before and after chemotherapy to assess mental and physical health status. Mean scores were compared by ANOVA. Results: Mean baseline scores were similar between control and experimental groups before chemotherapy began. Following chemotherapy, all measures in the control group significantly increased from baseline while all measures in the experimental group were similar to baseline. After chemotherapy, mental and physical health scores in the experimental group were significantly lower than those in the control group (P<0.05). Conclusion: Relaxation training during chemotherapy can reduce anxiety and other adverse events in postoperative breast cancer patients. This should be considered a valuable complementary approach in improving patient care. PMID:24260607

  7. Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions.

    PubMed

    Hermann, K; Rittweger, R; Ring, J

    1992-09-01

    Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions. PMID:1422942

  8. Factors influencing polymerase chain reaction outcomes in patients with clinically suspected ocular tuberculosis

    PubMed Central

    2014-01-01

    Background Polymerase chain reaction (PCR) assay can be a useful method for definitive diagnosis in paucibacillary infections such as ocular tuberculosis (TB). In this study, we have evaluated factors affecting PCR outcomes in patients with clinically suspected ocular TB. Patients with clinically suspected ocular TB were investigated by PCR of aqueous or vitreous samples. Three control groups were also tested: group 1 included culture-proven non-tuberculous endophthalmitis, group 2 culture-negative non-tuberculous endophthalmitis, and group 3 patients undergoing surgery for uncomplicated cataract. PCR targeted one or more of following targets: IS6110, MPB64, and protein b genes of Mycobacterium tuberculosis complex. Multiple regression analysis (5% level of significance) was done to evaluate the associations between positive PCR outcome and laterality of disease, tuberculin skin test (TST)/interferon-gamma release assay (IGRA), chest radiography, and type of sample (aqueous or vitreous). The main outcome measures were positive PCR by one or more gene targets, and factors influencing positive PCR outcomes. Results All 114 samples were tested for MPB64, 110 for protein b, and 88 for IS6110. MPB64 was positive in 70.2% (n?=?80) of tested samples, protein b in 40.0% (n?=?44), and IS6110 in only 9.1% (n?=?8). DNA sequencing of amplicons from four randomly chosen PCR reactions showed homology for M. tuberculosis complex. Of the 80 PCR-positive patients, 71 completed a full course of antitubercular therapy, of which 65 patients (91.5%) had complete resolution of inflammation at final follow-up. Among controls, 12.5% (3 out of 24) in group 1 and 18.7% (6 out of 32) in group 2 also tested positive by PCR. No PCR-positive outcome was observed in control group 3 (n?=?25). Multiple regression analysis revealed significant association of positive PCR outcome with bilateral presentation, but not with a positive TST/IGRA, chest radiography, or type of sample (aqueous/vitreous) used. Conclusions Careful selection of gene targets can yield high PCR positivity in clinically suspected ocular TB. Bilateral disease presentation but not any evidence of latent systemic TB influences PCR outcomes. False-positive results may be seen in ocular inflammation unrelated to ocular TB. PMID:24661354

  9. Platelet/lymphocyte ratio was associated with impaired myocardial perfusion and both in-hospital and long-term adverse outcome in patients with ST-segment elevation acute myocardial infarction undergoing primary coronary intervention

    PubMed Central

    Tabakci, Mehmet M.; Simsek, Zeki; Arslantas, Ugur; Durmus, Halil I.; Ocal, Lutfi; Demirel, Muhittin; Ozturkeri, Burak; Ozal, Ender; Kargin, Ramazan

    2015-01-01

    Introduction Platelet/lymphocyte ratio (PLR) has been shown to be an inflammatory and thrombotic biomarker for coronary heart disease, but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. Aim To investigate the relationship between PLR and no-reflow, along with the in-hospital and long-term outcomes in patients with STEMI. Material and methods In the present study, we included 304 consecutive patients suffering from STEMI who underwent primary percutaneous coronary intervention (p-PCI). Patients were stratified according to PLR tertiles based on the blood samples obtained in the emergency room upon admission. No-reflow after p-PCI was defined as a coronary thrombolysis in myocardial infarction (TIMI) flow grade ? 2 after vessel recanalization, or TIMI flow grade 3 together with a final myocardial blush grade (MBG) < 2. Results The mean follow-up period was 24 months (range: 22–26 months). The number of patients characterized with no-reflow was counted to depict increments throughout successive PLR tertiles (14% vs. 20% vs. 45%, p < 0.001). In-hospital major adverse cardiovascular events and death increased as the PLR increased (p < 0.001, p < 0.001). Long-term MACE and death also increased as the PLR increased (p < 0.001, p < 0.001). Multivariable logistic regression analysis revealed that PLR remained an independent predictor for both in-hospital (OR = 1.01, 95% CI: 1.00–1.01; p = 0.002) and major long-term (OR = 1.01, 95% CI: 1.00–1.01; p < 0.001) adverse cardiac events. Conclusions Platelet/lymphocyte ratio on admission is a strong and independent predictor of both the no-reflow phenomenon and long-term prognosis following p-PCI in patients with STEMI. PMID:26677378

  10. [Delayed hemolytic transfusion reaction in sicle cell disease patients: a new challenge for the Hemovigilance network].

    PubMed

    Rieux, C; De Meyer, E; Boudjedir, K

    2015-03-01

    Delayed hemolytic reaction transfusion in patients with sickle cell disease (SCD) is a serious and still under diagnosed event. Clinical and biological presentation mimics an acute SCD complication. It is a life-threatening event, especially in hyperhemolysis syndrome (HS) characterized by a massive destruction of both the donor's and patient's red blood cells. The main cause is related to the presence of alloantibodies directed against red blood cell antigens, more rarely autoantibodies. In approximately a third of the cases, no new antibody is highlighted. Pathophysiological hypotheses are still under debate but most of the authors agree on the role played by the SCD inflammatory state. Several therapeutic approaches are used but the data are still insufficient to estimate their efficiency. It is admitted that a new transfusion may exacerbate the phenomenon and the benefit-risk of any transfusion must be carefully evaluated. Measures limiting alloimmunization and rigorous follow-up of SCD patients and their immunohematologic status can prevent some of these accidents. The Hemovigilance network has a role to play in the recognition and the description of this risk. A first analysis realized on the French national Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM) over the period 2000-2013, shows us interesting information but some inadequacies, described here, must be taken into account to strengthen these data and insure in the future a better reporting quality. PMID:25441454

  11. Beyond Respiratory Depression and Constipation: Adverse Effects of Opioids.

    PubMed

    Mcdonald, Jay P; Torrey, Alan J; Mehta, Mahesh P; Delima, Luiz G R

    2015-07-01

    The numbers of opioid presciptions have skyrocketed over the last two decades. Adverse effects of opioids are difficult to diagnose because the usual presenting complaints is persistence of severe pain and decreases function leading to chronic usage of medication with minimal benefit to patients. This concise review discusses the adverse effects of opioids to appropriately diagnose and treat patients on opioid therapy. We emphasize less commonly known adverse effects and the controversial use of opioids in non-cancer pain. PMID:26434168

  12. Development of Clostridium septicum gas gangrene as an adverse effect of clindamycin-induced Clostridium difficile infection in a pediatric patient.

    PubMed

    Kiser, Casey J; Urish, Kenneth L; Boateng, Henry A

    2014-09-01

    Clostridium myonecrosis or gas gangrene is a life-threatening infection characterized by either traumatic or atraumatic etiology. It has been widely described in patients with traumatic open wounds and in immunocompromised patients, including malignancy. A third source can result from natural flora in the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is even less commonly described in the pediatric population. We present a pediatric patient who developed Clostridium septicum myonecrosis as an iatrogenic complication from clindamycin-induced Clostridium difficile ischemic colitis. PMID:24590337

  13. Safety of intra-cerebrospinal fluid chemotherapy in onco-haematological patients: a retrospective analysis of 627 interventions.

    PubMed

    Pardo-Moreno, Javier; Fernández, Cristina; Arroyo, Rafael; Ruiz-Ocaña, Carlos; Aláez, Concepción; Cuadrado, María-Luz

    2015-11-01

    Intra-cerebrospinal fluid chemotherapy (ICC) is used widely to treat or prevent neoplastic meningitis (NM), although its safety has not been thoroughly assessed. We aimed to analyse the incidence, severity and cause of the adverse reactions provoked by ICC in a cohort of onco-haematological patients. We retrospectively reviewed all the adverse reactions related to ICC procedures performed by the same researcher over a 5-year period. We classified them according to their severity and cause, and examined their association with certain characteristics of the patients and interventions. A total of 627 procedures were performed on 124 patients, in which 59 adverse reactions were documented (9.4 %). Thirty-two (54 %) of these were considered severe and 30 (51 %) were due to the drug itself. NM was associated with a higher incidence of adverse reactions (p = 0.002) and severe adverse reactions (p < 0.001). Adverse reactions were more common (p = 0.028) and more often severe (p = 0.008) when an Ommaya reservoir was used, as opposed to the lumbar puncture procedure. The use of liposomal cytarabine was also associated with a higher incidence of adverse reactions (p < 0.001) and serious adverse reactions (p < 0.001) than immediate-release drugs. Liposomal cytarabine provoked more adverse reactions attributable to the drug when administered by lumbar puncture (p = 0.192), whereas the remaining drugs had higher risk when administered via Ommaya reservoir (p = 0.015). ICC seems a relatively safe procedure. Adverse reactions appear to be more frequent when NM is already present. Lumbar puncture seems to be safer than the Ommaya reservoir, except when liposomal cytarabine is administered. PMID:26342710

  14. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  15. Cytochrome P450 CYP 2C19*2 Associated with Adverse 1-Year Cardiovascular Events in Patients with Acute Coronary Syndrome

    PubMed Central

    Yang, Hao; Cao, Heng

    2015-01-01

    Background The cytochrome P450 (CYP450) 2C19 681 genotypes affect the antiplatelet activity of clopidogrel. We investigated the correlation of CYP 2C19 681G > A mutation with clopidogrel resistance (CR). Additionally, we studied the effect of CR on clinical prognosis of patients with acute coronary syndrome (ACS). Methods One hundred ten ACS patients undergoing percutaneous coronary intervention, who were followed-up for 1 year, were included in the study. The patients were co-administered aspirin 100 mg/d and clopidogrel 75mg/d following a loading dose of 300 mg. CR was assessed on the basis of polymorphism observed in the CYP2C19 subgroup. Results Patients in GG genotype group exhibited greater inhibition of platelet aggregation than patients in GA and AA genotype groups (16.2 ± 10.1%; 10.2 ± 9.9%; 8.0 ± 5.9%, respectively, p < 0.01). CYP2C19 681GG genotype group was associated with lower CR than CYP2C19 681A allele (GA + AA) group (9/59 vs. (12+5)/51; p = 0.009). Over a follow-up of 12 months, the incidence of recurrent angina, acute myocardial infarction, and intra-stent thrombosis in CYP2C19 681 GG carriers was significantly lower than that in CYP2C19 681A allele (GA + AA) group (2/59 vs. 8/51, 1/59 vs. 6/51, 0 vs. 4/51, respectively, p < 0.05). Conclusion CYP 2C19*2 is associated with reduced clopidogrel antiplatelet activity and might be an important marker for poor prognosis of ACS. PMID:26147597

  16. Gastrointestinal Adverse Events of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Sun, Feng; Chai, Sanbao; Yu, Kai; Quan, Xiaochi; Yang, Zhirong; Wu, Shanshan; Zhang, Yuan; Ji, Linong

    2015-01-01

    Abstract Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs used in the treatment of type 2 diabetes mellitus (T2DM). Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs for GLP-1 RAs. We aim to evaluate the effect of GLP-1 RAs on the incidence of GI AEs of T2DM. Materials and Methods: The overview of the GI events of GLP-1 RAs has been performed on relevant publications through the literature search, such as MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov The manufacturer was contacted regarding unpublished data. We analyzed direct and indirect comparisons of different treatments using Bayesian network meta-analysis. Results: Taspoglutide 30?mg once weekly (TAS30QW) and lixisenatide 30??g twice daily (LIX30BID) were ranked the top two drugs in terms of GI AEs versus placebo. The odds ratios of nausea and vomiting for TAS30QW were 11.8 (95% confidence interval [CI], 2.89, 46.9) and 51.7 (95% CI, 7.07, 415), respectively, and that of diarrhea was 4.93 (95% CI, 1.75, 14.7) for LIX30BID. Conclusions: Our study found all GLP-1 RA dose regimens significantly increased the incidence of GI AEs, compared with placebo or conventional treatment. The occurrence of GI AEs was different with diverse dose regimens of GLP-1 RAs. TAS30QW had the maximum probability to occur nausea and vomiting, whereas LIX30BID had the maximum probability to cause development of diarrhea versus other treatments. PMID:25375397

  17. An Investigation of Nursing Staff Attitudes and Emotional Reactions towards Patients with Intellectual Disability in a General Hospital Setting

    ERIC Educational Resources Information Center

    Lewis, Sharna; Stenfert-Kroese, Biza

    2010-01-01

    Background: It has been suggested that inequalities in health care for people with intellectual disabilities may be partly explained by negative attitudes of health professionals. This study aimed to investigate the attitudes and emotional reactions reported by nursing staff working in general hospitals towards caring for patients with…

  18. Prescription-medication sharing among family members: an unrecognized cause of a serious drug adverse event in a patient with impaired renal function.

    PubMed

    Makówka, Agnieszka; Zawiasa, Anna; Nowicki, Michal

    2015-03-01

    Many medications need to be avoided in chronic kidney disease (CKD) because of increased toxicity. Metformin - an oral hypoglycemic drug universally recommended as the first-line treatment for type 2 diabetes mellitus (T2DM) - undergoes significant accumulation in advanced CKD that may ultimately lead to lactic acidosis. Recently, it has been found that side effects of the therapy may occasionally neither be linked to improper prescription nor lack of dose adjustment by the physician, but can result from borrowing and sharing of drugs with relatives and friends. This poorly recognized problem has never been studied in renal patients. This work contains a discussion on the diagnostic problems associated with proper diagnosis of the etiology of severe acidosis in an elderly woman with advanced CKD and diabetes. The patient developed severe lactic acidosis by taking metformin that was prescribed by another doctor to her son, who was also diabetic. The diagnosis of lactic acidosis was delayed since the initial laboratory assessments had focused mostly on dehydration and substance abuse. PMID:24691009

  19. [The effect of the ecologically adverse factors of a Donets Basin industrial region on the clinico-immunological indices of patients with viral hepatitis A and B].

    PubMed

    Petrunia, A M; Frolov, V M; Peresadin, N A; Dekaliuk, I V

    1994-01-01

    Clinicoimmunological features of viral hepatitis A and B (VH A and VH B) were studied in residents of unfavorable (from the environmental standpoint) regions. 180 VH A, 86 VII B patients were examined. Clinical picture of VH was characterized by predominance of more severe forms, frequent occurrence of cholestatic variant of VH, high rate of protracted and recurrent (in VH B) course of VH, hepato- and splenomegaly of long duration. The immunologic status was characterized by more pronounced T-lymphopenia, noticeable imbalance of T-helpers and T-suppressors, decrease in the level of immunoglobulins, as well as in phagocytic activity of neutrophilic granulocytes and monocytes in peripheral blood. The use of adaptogens and antioxidants in multimodality treatment promotes rapid normalization of clinicoimmunological parameters in VH. PMID:7831925

  20. Airway pressure release ventilation: improving oxygenation: indications, rationale, and adverse events associated with airway pressure release ventilation in patients with acute respiratory distress syndrome for advance practice nurses.

    PubMed

    Ferdowsali, Kameron; Modock, Jacqueline

    2013-01-01

    Airway pressure release ventilation (APRV) is a mode of ventilation that has been around since the 1980s and was originally viewed as a type of continuous positive pressure mode of ventilation. Conceptually, APRV can be thought of as a type of inverse-ratio, pressure-controlled, intermittent mandatory ventilation during which the maintenance of spontaneous breathing and prolonged application of high mean airway pressure contribute to the clinical benefits. The aim of this review article was to familiarize the bedside clinician working in the intensive care unit with the theory and rationale behind this mode of ventilation. The potential advantages and disadvantages of APRV will also be discussed to empower the advance practice clinician and bedside nurse to advocate for their patient diagnosed with the often-high mortality disease of acute respiratory distress syndrome. PMID:23933639

  1. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    PubMed Central

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  2. Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management.

    PubMed

    Tuccori, Marco; Montagnani, Sabrina; Mantarro, Stefania; Capogrosso-Sansone, Alice; Ruggiero, Elisa; Saporiti, Alessandra; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado

    2014-03-01

    Statins, or 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, such as lovastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin and pitavastatin, are cholesterol-lowering drugs used in clinical practice to prevent coronary heart disease. These drugs are generally well tolerated and have been rarely associated with severe adverse effects (e.g. rhabdomyolysis). Over the years, case series and data from national registries of spontaneous adverse drug reaction reports have demonstrated the occurrence of neuropsychiatric reactions associated with statin treatment. They include behavioural alterations (severe irritability, homicidal impulses, threats to others, road rage, depression and violence, paranoia, alienation, antisocial behaviour); cognitive and memory impairments; sleep disturbance (frequent awakenings, shorter sleep duration, early morning awakenings, nightmares, sleepwalking, night terrors); and sexual dysfunction (impotence and decreased libido). Studies designed to investigate specific neuropsychiatric endpoints have yielded conflicting results. Several mechanisms, mainly related to inhibition of cholesterol biosynthesis, have been proposed to explain the detrimental effects of statins on the central nervous system. Approaches to prevent and manage such adverse effects may include drug discontinuation and introduction of dietary restrictions; maintenance of statin treatment for some weeks with close patient monitoring; switching to a different statin; dose reduction; use of ?-3 fatty acids or coenzyme Q10 supplements; and treatment with psychotropic drugs. The available information suggests that neuropsychiatric effects associated with statins are rare events that likely occur in sensitive patients. Additional data are required, and further clinical studies are needed. PMID:24435290

  3. Health care students' reactions towards HIV patients: examining prejudice, emotions, attribution of blame and willingness to interact with HIV/AIDS patients.

    PubMed

    Philip, Jannel; Chadee, Derek; Yearwood, Rosana Patricia

    2014-01-01

    One of the most pervasive stigmatising conditions in society today is HIV/AIDS. In Trinidad and Tobago, stigma and discrimination are still pervasive especially against persons living with HIV/AIDS (PLHIV) and at-risk groups. HIV stigmatisation takes place at all levels including health care institutions, and is a major obstacle to effective HIV/AIDS prevention and care. This study examined health care students' reactions towards HIV patients. A stratified random sample of 339 health care students from Trinidad was used. A 2 × 2 factorial design using vignettes manipulated a male patient's sexual orientation (heterosexual/homosexual) and HIV onset controllability (high/low). Multivariate analysis of variance and discriminant function analysis were used to analyse the data. There was a significant main effect of HIV onset controllability on participants' attribution of blame, emotions, prejudicial evaluation and willingness to interact with PLHIV, ? (.64) F(6, 330) = 31.44, p <.001, [Formula: see text] = .37. Attribution of blame and prejudicial evaluation discriminated between reactions to patients in low onset control and high onset control vignettes. Cognitive-affective appraisal processes are instrumental in determining health care providers' reaction towards PLHIV. PMID:24646404

  4. Adalimumab-induced psoriatic alopecia/alopecia areata-like reaction in a patient with Crohn's disease.

    PubMed

    Toda-Brito, H; Lopes, L; Soares-Almeida, L; Filipe, P

    2015-01-01

    Anti-tumor necrosis factor (anti-TNF) agents have been successfully used to treat both chronic idiopathic inflammatory bowel disease and other immune-mediated chronic diseases, but they can also induce a wide array of cutaneous reactions, including new-onset psoriasis and alopecia. We report a case of alopecia associated with psoriasiform skin lesions in a patient on adalimumab treatment for Crohn's disease. PMID:26632930

  5. Neuropsychiatric Adverse Effects of Interferon-?

    PubMed Central

    Raison, Charles L.; Demetrashvili, Marina; Capuron, Lucile; Miller, Andrew H.

    2005-01-01

    Recombinant preparations of the cytokine interferon (IFN)-? are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN? induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN?, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN?-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21–58% of patients receiving IFN?, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN? dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN?-induced depression: antidepressant pretreatment or symptomatic treatment once IFN? has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN?-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN?-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may he more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally. IFN? appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN? and antidepressants should be stopped, an emergency psychiatric consultation should he obtained, and treatment with a mood stabiliser should be initiated. PMID:15697325

  6. Adversity, attachment, and mentalizing.

    PubMed

    Fonagy, Peter; Bateman, Anthony W

    2016-01-01

    The papers in this special issue offer evidence of personality disorder as a dysfunction of higher-order cognition, which is conceptualized variously as a disorder of mentalizing, metacognition, mindfulness, social cognition and reflective function. While there may be differences in the scope of these concepts, they all imply that higher-order mental processing is at the core of personality function. In this commentary, the authors use mentalizing as an umbrella term for these concepts, and argue that it is the complex interaction of adversity, attachment and mentalizing that leads to the characteristic symptoms of borderline personality disorder and other personality disorders. Evidence is provided from the papers in this special issue, comments made on the findings and further avenues for research are recommended. PMID:26654293

  7. Quantitative Electroencephalography Reflects Inattention, Visual Error Responses, and Reaction Times in Male Patients with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Roh, Sang-Choong; Park, Eun-Jin; Park, Young-Chun; Yoon, Sun-Kyung; Kang, Joong-Gu; Kim, Do-won; Lee, Seung-Hwan

    2015-01-01

    Objective Quantitative electroencephalography (qEEG) has been increasingly used to evaluate patients with attention deficit hyperactivity disorder (ADHD). The aim of this study was to assess the correlation between qEEG data and symptom severity in patients with ADHD. Methods Fifteen patients with ADHD and 20 healthy controls (HCs) were recruited. Electroencephalography was assessed in the resting-state, and qEEG data were obtained in the eyes-closed state. The Korean version of the ADHD Rating Scale (K-ARS) and continuous performance tests (CPTs) were used to assess all participants. Results Theta-band (4–7 Hz) power across the brain was significantly positively correlated with inattention scores on the K-ARS, reaction times and commission errors on the CPTs in ADHD patients. Gamma-band (31–50 Hz) power was significantly positively correlated with the results of the auditory CPTs in ADHD patients. The theta/alpha (8–12 Hz) and theta/beta (13–30 Hz) ratios were significantly negatively correlated with commission and omission errors on auditory CPTs in ADHD patients. No significant correlations between qEEG relative power and K-ARS and CPT scores were observed in HCs. Conclusion Our results suggest that qEEG may be a useful adjunctive tool in patients with ADHD. PMID:26243846

  8. Phototoxic reactions to piroxicam, naproxen and tiaprofenic acid.

    PubMed

    Diffey, B L; Daymond, T J; Fairgreaves, H

    1983-11-01

    Photosensitivity investigations have been carried out using an irradiation monochromator on 31 patients taking one of seven different nonsteroidal anti-inflammatory agents for the treatment of rheumatoid and osteoarthritis. Six patients, who were taking either piroxicam, naproxen or tiaprofenic acid, experienced adverse immediate reactions of erythema and flaring, together with an urticarial response in four of these six patients. No phototoxic response was observed in patients taking either indomethacin, ketoprofen, benorylate or ibuprofen, although firm conclusions about the non-phototoxic nature of these four drugs cannot be drawn from this pilot study because of the small numbers of patients investigated. PMID:6652387

  9. Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

    PubMed Central

    Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

    2012-01-01

    Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. PMID:23078769

  10. Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease.

    PubMed

    Steenholdt, Casper; Svenson, Morten; Bendtzen, Klaus; Thomsen, Ole Østergaard; Brynskov, Jørn; Ainsworth, Mark Andrew

    2012-02-01

    A 61 year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8 weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4 weeks after the 8th infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion. Anti-infliximab IgG antibody concentration was high (100 U/ml) prior to the 8th infusion and up to 1 year after infliximab discontinuation (81 U/ml). Anti-infliximab IgE antibodies were not found, and the anti-infliximab antibodies did not cross react with adalimumab. One week after the anaphylactoid reaction to infliximab, adalimumab therapy was initiated. Twelve days after the first adalimumab administration (80 mg), a delayed hypersensitivity reaction occurred. This was likely caused by rapidly generated anti-adalimumab IgG antibodies (45 U/ml), as these antibodies appeared to be specific for adalimumab in that infliximab failed to compete with adalimumab/anti-adalimumab antibody binding ex vivo. In conclusion, immunogenicity to infliximab and adalimumab may be associated with both acute anaphylactoid reactions and delayed hypersensitivity reactions. Reactions may be precipitated by newly induced specific anti-drug antibodies rather than by cross-reactivity of previously generated antibodies. PMID:22261535

  11. Comparison of acute non-haemolytic transfusion reactions in female and male patients receiving female or male blood components

    PubMed Central

    Imoto, S; Araki, N; Shimada, E; Saigo, K; Nishimura, K; Nose, Y; Bouike, Y; Hashimoto, M; Mito, H; Okazaki, H

    2007-01-01

    To study the relationship between antibodies detected in patients’ and/or donors’ sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study. PMID:18067650

  12. Comparison of acute non-haemolytic transfusion reactions in female and male patients receiving female or male blood components.

    PubMed

    Imoto, S; Araki, N; Shimada, E; Saigo, K; Nishimura, K; Nose, Y; Bouike, Y; Hashimoto, M; Mito, H; Okazaki, H

    2007-12-01

    To study the relationship between antibodies detected in patients' and/or donors' sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study. PMID:18067650

  13. Pattern Analysis of Acute Mucosal Reactions in Patients With Head and Neck Cancer Treated With Conventional and Accelerated Irradiation

    SciTech Connect

    Wygoda, Andrzej Maciejewski, Boguslaw; Skladowski, Krzysztof; Hutnik, Marcin; Pilecki, Boleslaw; Golen, Maria; Rutkowski, Tomasz

    2009-02-01

    Purpose: To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials: Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results: Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4-6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20-36%. Conclusions: Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a 'wave-like' pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring.

  14. Detection of herpesvirus DNA by the polymerase chain reaction (PCR) in vitreous samples from patients with necrotising retinitis

    PubMed Central

    Nogueira, M; Siqueira, R; Freitas, N; Amorim, J; Bonjardim, C; Ferreira, P; Orefice, F; Kroon, E

    2001-01-01

    Aims—Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients. Methods—PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital São Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber. Results—Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each. Conclusion—These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach. Key Words: polymerase chain reaction • uveitis • retinitis PMID:11215276

  15. Vitamin D receptor expression levels determine the severity and complexity of disease progression among leprosy reaction patients

    PubMed Central

    Mandal, D.; Reja, A.H.H.; Biswas, N.; Bhattacharyya, P.; Patra, P.K.; Bhattacharya, B.

    2015-01-01

    We studied the roles of vitamin D and its receptor, VDR, in the progression of leprosy. The majority of individuals with leprosy from Kolkata, India, with a type 1 or type 2 reaction have low levels of vitamin D3 in serum samples. Interestingly, individuals with a type 2 reaction associated with neuritis/erythema nodosum leprosum had very low VDR mRNA expression levels, ranging from 5% to 10%, compared to that of healthy control subjects; these patients also had a high bacilli index, ranging from 3+ to 5+. This is the first report to indicate that VDR expression levels may determine the complexity and severity of the progression of leprosy. PMID:26106480

  16. Peri-operative adverse respiratory events in children.

    PubMed

    von Ungern-Sternberg, B S; Ramgolam, A; Hall, G L; Sly, P D; Habre, W

    2015-04-01

    Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse respiratory event should rely on clinical, rather than immunological, assessment. PMID:25421587

  17. Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis.

    PubMed

    Qvarnstrom, Yvonne; Xayavong, Maniphet; da Silva, Ana Cristina Aramburu; Park, Sarah Y; Whelen, A Christian; Calimlim, Precilia S; Sciulli, Rebecca H; Honda, Stacey A A; Higa, Karen; Kitsutani, Paul; Chea, Nora; Heng, Seng; Johnson, Stuart; Graeff-Teixeira, Carlos; Fox, LeAnne M; da Silva, Alexandre J

    2016-01-01

    Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis. PMID:26526920

  18. 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

    SciTech Connect

    Werbrouck, Joke Ruyck, Kim de; Duprez, Frederic; Veldeman, Liv; Claes, Kathleen; Eijkeren, Marc van; Boterberg, Tom; Willems, Petra; Vral, Anne; Neve, Wilfried de; Thierens, Hubert

    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-volume 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.

  19. Processing of Emotion Words by Patients with Autism Spectrum Disorders: Evidence from Reaction Times and EEG

    ERIC Educational Resources Information Center

    Lartseva, Alina; Dijkstra, Ton; Kan, Cornelis C.; Buitelaar, Jan K.

    2014-01-01

    This study investigated processing of emotion words in autism spectrum disorders (ASD) using reaction times and event-related potentials (ERP). Adults with (n = 21) and without (n = 20) ASD performed a lexical decision task on emotion and neutral words while their brain activity was recorded. Both groups showed faster responses to emotion words…

  20. Adverse effects of spinal manipulation: a systematic review

    PubMed Central

    Ernst, E

    2007-01-01

    Objective To identify adverse effects of spinal manipulation. Design Systematic review of papers published since 2001. Setting Six electronic databases. Main outcome measures Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports. Results The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature. Conclusions Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. PMID:17606755

  1. The sudden onset of mastocytosis in the course of venom-induced anaphylactic reaction in a patient with myelodysplastic syndrome.

    PubMed

    Rybicka, Malwina; Helbig, Grzegorz; Wo?niczka, Krzysztof; Kopera, Ma?gorzata; Paj?k, Jacek; Kyrcz-Krzemie?, S?awomira

    2015-01-01

    Mastocytosis is a disease resulting from a proliferation of clonal, abnormal mast cells in tissues and organs, defined as Philadelphia-negative myeloproliferative neoplasm. We present a male patient with clinically, morphologically and immunohistochemically confirmed mastocytosis with preceding myelodysplastic syndrome, occurred after wasp bite in the course of anaphylactic reaction. The propensity to hymenoptera venom-induced anaphylaxis and the presence of an increased population of atypical mast cells in bone marrow found after anaphylactic shock may suggest the possible relationship between hymenoptera venom allergy and anaphylaxis and the development of mastocytosis of unusual course in a predisposed person. PMID:26181160

  2. Adverse drug events in hospital: pilot study with trigger tool

    PubMed Central

    Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

    2013-01-01

    OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension. PMID:24626548

  3. Adverse Events of Monoclonal Antibodies Used for Cancer Therapy

    PubMed Central

    Guan, Mei; Zhou, Yan-Ping; Sun, Jin-Lu; Chen, Shu-Chang

    2015-01-01

    In 1997, the first monoclonal antibody (MoAb), the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug administration for use in cancer patients. Since then, the panel of MoAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has continued to expand, currently encompassing a stunning amount of 20 distinct molecules for 11 targets. We provide a brief scientific background on the use of MoAbs in cancer therapy, review all types of monoclonal antibodies-related adverse events (e.g., allergy, immune-related adverse events, cardiovascular adverse events, and pulmonary adverse events), and discuss the mechanism and treatment of adverse events. PMID:26075239

  4. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events.

    PubMed

    Lenz, Heinz-Josef

    2006-04-01

    Overexpression of the epidermal growth factor receptor (EGFR) is correlated with poor prognosis in many human cancers. Two main classes of anticancer agents affect the EGFR: those targeting the extracellular ligand-binding domain and those that block the intracellular tyrosine kinase (TK) domain. Cetuximab (Erbitux) is a mouse/human chimeric monoclonal antibody that targets the ligand-binding domain of the EGFR, whereas erlotinib (Tarceva) and gefitinib (Iressa) are small-molecule TK inhibitors. Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Given the common pathway through which these agents work, some adverse events are similar. Many patients treated with these agents develop an acne-like rash on the face and upper body, most likely related to keratinocyte alterations and hair follicle proliferation and maturation. Although clinical manifestation of this reaction closely resembles acne vulgaris, the histology is more similar to infectious folliculitis. Other adverse events appear to be related to a drug class or individual agent. For example, interstitial lung disease is a rare but potentially fatal reaction that has been reported with gefitinib. Hypomagnesemia reported in association with cetuximab may be related to EGFR blockade in the kidney. Anaphylactic or anaphylactoid infusion reactions are also seen with cetuximab, as with other monoclonal antibodies. PMID:16736978

  5. Identification of methicillin-susceptible or methicillin-resistant Staphylococcus aureus carrier status preoperatively using polymerase chain reaction in patients undergoing elective surgery with hardware implantation.

    PubMed

    Bebko, Serge P; Byers, Patricia; Green, David M; Awad, Samir S

    2015-06-01

    We compared bedside polymerase chain reaction to culture for identifying Staphylococcus aureus in patients about to undergo surgery with hardware implantation. Patients were screened for S. aureus carrier status at the preoperative clinic and on the day of surgery. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. PMID:25732409

  6. Hypersensitivity reaction with deferasirox.

    PubMed

    Sharma, Atul; Arora, Ekta; Singh, Harmanjit

    2015-01-01

    Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. PMID:25969661

  7. Hypersensitivity reaction with deferasirox

    PubMed Central

    Sharma, Atul; Arora, Ekta; Singh, Harmanjit

    2015-01-01

    Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. PMID:25969661

  8. Natural Oil-Based Emulsion Containing Allantoin Versus Aqueous Cream for Managing Radiation-Induced Skin Reactions in Patients With Cancer: A Phase 3, Double-Blind, Randomized, Controlled Trial

    SciTech Connect

    Chan, Raymond Javan; Mann, Jennifer; Tripcony, Lee; Keller, Jacqui; Cheuk, Robyn; Blades, Rae; Keogh, Samantha; Poole, Christopher; Walsh, Christopher

    2014-11-15

    Purpose: To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions. Methods and Materials: A total of 174 patients were randomized and participated in the study. Patients received either cream 1 (the natural oil-based emulsion containing allantoin) or cream 2 (aqueous cream). Skin toxicity, pain, itching, and skin-related quality of life scores were collected for up to 4 weeks after radiation treatment. Results: Patients who received cream 1 had a significantly lower average level of Common Terminology Criteria for Adverse Events at week 3 (P<.05) but had statistically higher average levels of skin toxicity at weeks 7, 8, and 9 (all P<.001). Similar results were observed when skin toxicity was analyzed by grades. With regards to pain, patients in the cream 2 group had a significantly higher average level of worst pain (P<.05) and itching (P=.046) compared with the cream 1 group at week 3; however, these differences were not observed at other weeks. In addition, there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 (P=.056). Overall, more participants in the cream 1 group were required to use another topical treatment at weeks 8 (P=.049) and 9 (P=.01). Conclusion: The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week 5; however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching, and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream seems to be a more preferred option.

  9. An analysis of skin prick test reactions in allergic rhinitis patients in Istanbul, Turkey.

    PubMed

    Aydin, Sedat; Hardal, Umit; Atli, Hakki

    2009-03-01

    This retrospective, population-based study reviewed skin prick test (SPT) results against various allergens of 1,552 patients with allergic rhinitis (AR) in the district of Kartal, Istanbul, Turkey. The skin prick tests yielded a positive result in 946 patients (60.9%). Seven hundred and forty-give (48%) patients had perennial AR, 558 (36%) perennial AR with seasonal exacerbations and 249 (16%) had seasonal AR. The prevalence of AR was highest in the age of 21-40 years with 48.7%. The allergen group with the highest SPT positivity was pollens at 44.3%, followed by molds at 38.4%, mites at 35.1%, and epithelia-insect at 30.8%. The strongest single allergen was Altemaria altemata with 33.3%, followed by Dermatophagoides farinae with 29.3%, Dermatophagoides pteronyssinus with 25.3% and a mix of four cereals (barley, maize, oat, wheat) with 25.2%. This information will help etiological research as well as the development of more efficient treatment plans for patients with allergic rhinitis in our country. PMID:19548626

  10. Adverse Events of Auricular Therapy: A Systematic Review

    PubMed Central

    Molassiotis, Alexander; Wang, Tao; Suen, Lorna K. P.

    2014-01-01

    The aim of this study was to systematically evaluate the literature on adverse events associated with auricular therapy (AT). Case reports, case series, surveys, and all types of clinical trials reporting adverse events of AT were included. Relevant articles were mainly retrieved from 13 electronic databases and seven Chinese journals on complementary medicine. AT-related adverse events were reported in 32 randomized controlled trials, five uncontrolled clinical trials, four case reports, and two controlled clinical trials. For auricular acupuncture, the most frequently reported adverse events were tenderness or pain at insertion, dizziness, local discomfort, minor bleeding and nausea, and so forth. For auricular acupressure, local skin irritation and discomfort, mild tenderness or pain, and dizziness were commonly reported. Skin irritation, local discomfort, and pain were detected in auricular electroacupuncture, and minor infection was identified in auricular bloodletting therapy. Most of these events were transient, mild, and tolerable, and no serious adverse events were identified. Our findings provide preliminary evidence that AT is a relatively safe approach. Considering the patient's safety, prospective or retrospective surveys are needed in future research to gather practitioner-reported and patient-reported adverse events on AT, and the quality of adverse events reporting in future AT trials should be improved. PMID:25435890

  11. Nursing care quality and adverse events in US hospitals

    PubMed Central

    Lucero, Robert J; Lake, Eileen T; Aiken, Linda H

    2010-01-01

    Aim To examine the association between nurses' reports of unmet nursing care needs and their reports of patients' receipt of the wrong medication or dose, nosocomial infections and patient falls with injury in hospitals. Background Because nursing activities are often difficult to measure, and data are typically not collected by health care organisations, there are few studies that have addressed the association between nursing activities and patient outcomes. Design Secondary analysis of cross-sectional data collected in 1999 from 10,184 staff nurses and 168 acute care hospitals in the US. Methods Multivariate linear regression models estimated the effect of unmet nursing care needs on adverse events given the influence of patient factors and the care environment. Results The proportion of necessary nursing care left undone ranged from 26% for preparing patients and families for discharge to as high as 74% for developing or updating nursing care plans. A majority of nurses reported that patients received the wrong medication or dose, acquired nosocomial infections, or had a fall with injury infrequently. However, nurses who reported that these adverse events occurred frequently varied considerably [i.e. medication errors (15%), patient falls with injury (20%), nosocomial infection (31%)]. After adjusting for patient factors and the care environment, there remained a significant association between unmet nursing care needs and each adverse event. Conclusion The findings suggest that attention to optimising patient care delivery could result in a reduction in the occurrence of adverse events in hospitals. Relevance to clinical practice The occurrence of adverse events may be mitigated when nurses complete care activities that require them to spend time with their patients. Hospitals should engage staff nurses in the creation of policies that influence human resources management to enhance their awareness of the care environment and patient care delivery. PMID:20659198

  12. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  13. Comparative evaluation of staining techniques and polymerase chain reaction for diagnosis of intestinal microsporidiosis in immunocompromised patients

    PubMed Central

    Ghoshal, Ujjala; Khanduja, Sonali; Agarwal, Vikas; Dhole, Tapan N; Ghoshal, Uday C

    2015-01-01

    Context: Microsporidia, which causes chronic diarrhoea in immunocompromised hosts, are often missed. The commonest diagnostic techniques include modified trichrome (MT) stain; however, it requires expertise and does not identify the species, which is important therapeutically. Other diagnostic techniques include Calcoflour white staining and polymerase chain reaction (PCR). Data on comparative utility of different diagnostic techniques are scanty. Aim: Comparison of Calcoflour white, MT staining and PCR for the diagnosis of intestinal microsporidiosis. Subjects and Methods: Fecal samples of consecutive immunocompromised patients were evaluated for Microsporidia using Calcoflour white, MT stain and PCR. Species were identified by restriction fragment length polymorphism using HindIII and HinfI. Presence of Microsporidia by two or more techniques was considered true positive. Absence of Microsporidia by all three techniques was taken as true negative. Results: Of 730 patients, Microsporidia was detected in 28 (3.8%), 250 (34.2%) and 30 (4.1%) patients by MT, Calcoflour white stains and PCR, respectively. Enterocytozoon bieneusi was identified in all 30 (4.1%) patients. 30 (4.1%) and 479 (65.6%) patients were true positive and true negative, respectively. Sensitivity and specificity of Calcoflour white, MT stains and PCR were 100%, 93.8%, 96.8% and 68.5%, 100% and 99.8%, respectively. Diagnostic accuracy of MT stain and PCR was superior to Calcoflour white (99.6% vs. 69.8%; P < 0.05). Conclusions: Though Calcoflour white stain is a highly sensitive, but it is nonspecific technique. MT stain and PCR with high sensitivity, specificity and diagnostic accuracy are useful diagnostic techniques. Furthermore, PCR is useful for species identification, which has therapeutic implications.

  14. [Reactions to infliximab infusions in dermatologic patients: consensus statement and treatment protocol. Working Group of the Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología ].

    PubMed

    Puig Sanz, Lluís; Sáez, E; Lozano, M J; Bordas, X; Carrascosa, J M; Gallardo, F; Luelmo, J; Sánchez-Regaña, M; Alsina, M; García-Patos, V

    2009-03-01

    Infliximab is a chimeric monoclonal antibody that binds to and blocks tumor necrosis factor alpha and is the most effective biologic agent approved for the treatment of moderate-to-severe psoriasis. It is administered by intravenous infusion, usually in day hospitals on an outpatient basis. The main problem with the administration of infliximab is the possibility of infusion reactions, which may be immediate or delayed; these reactions are related to the immunogenicity of this monoclonal antibody, leading to the production of anti-infliximab antibodies. Infusion reactions to infliximab are not usually anaphylactic (ie, they are not mediated by immunoglobulin E), and re-exposure of the patient using specific protocols to prevent and treat these reactions is therefore possible. The extensive experience in the use of infliximab for the treatment of rheumatic conditions and chronic inflammatory bowel disease has made it possible to develop infusion reaction management protocols; these can be applied to dermatologic patients, who constitute a growing proportion of patients treated with intravenous biological agents. The aim of this review is to draw up a consensus protocol for the treatment of infusion reactions in dermatologic patients treated with infliximab. PMID:19445874

  15. Detection of Mixed Populations of Clostridium difficile from Symptomatic Patients Using Capillary-Based Polymerase Chain Reaction Ribotyping

    PubMed Central

    Lo, Eugene S.; Ewing, Sarah A.; Waslawski, Sheila; Newton, Duane W.; Young, Vincent B.; Aronoff, David M.; Walk, Seth T.

    2014-01-01

    OBJECTIVE To investigate the simultaneous occurrence of more than 1 Clostridium difficile ribotype in patients' stool samples at the time of diagnostic testing. METHODS Stool samples submitted for diagnostic testing for the presence of toxigenic C. difficile were obtained for 102 unique patients. A total of 95 single colonies of C. difficile per stool sample were isolated on selective media, subcultured alongside negative (uninoculated) controls, and polymerase chain reaction (PCR) ribotyped using capillary gel electrophoresis. RESULTS Capillary-based PCR ribotyping was successful for 9,335 C. difficile isolates, yielding a median of 93 characterized isolates per stool sample (range, 69–95). More than 1 C. difficile ribotype was present in 16 of 102 (16%) C. difficile infection (CDI) cases; 2 of the 16 mixtures were composed of at least 3 ribotypes, while the remaining 14 were composed of at least 2. CONCLUSIONS Deep sampling of patient stool samples coupled with capillary-based PCR ribotyping identified a high rate of mixed CDI cases compared with previous estimates. Studies seeking to quantify the clinical significance of particular C. difficile ribotypes should account for mixed cases of disease. PMID:23917911

  16. Physiologic Reactions After Proton Beam Therapy in Patients With Prostate Cancer: Significance of Urinary Autoactivation

    SciTech Connect

    Shimizu, Masakazu; Sasaki, Ryohei Miyawaki, Daisuke; Nishimura, Hideki; Demizu, Yusuke; Akagi, Takashi; Suga, Daisaku; Sakamoto, Hidenobu; Murakami, Masao; Sugimura, Kazuro; Hishikawa, Yoshio

    2009-10-01

    Purpose: Proton therapy is a sophisticated treatment modality for prostate cancer. We investigated how physiologic factors affected the distribution of autoactivation as detected by positron emission tomography (PET) after proton beam therapy. Methods and Materials: Autoactivation was evaluated in 59 patients treated with a 210-MeV proton beam. Data acquisition for autoactivation by PET started 5minutes after proton irradiation to assess activation. In the first 29 patients, five regions of interest were evaluated: planning target volume (PTV) center, urinary bladder inside the PTV, urinary bladder outside the PTV, rectum (outside the PTV), and contralateral femoral bone head (outside the PTV). In the remaining 30 patients, urine activity was measured directly. In a phantom study autoactivation and its diffusion after proton beam irradiation were evaluated with water or an ice block. Results: Mean activities calculated by use of PET were 629.3Bq in the PTV center, 555.6Bq in the urinary bladder inside the PTV, 332.5Bq in the urinary bladder outside the PTV, 88.4Bq in the rectum, and 23.7Bq in the femoral bone head (p < 0.001). Mean urine activity was 679.4Bq, recorded 10minutes after therapy completion, and the half-life for urine autoactivation was 4.5minutes. Conclusions: Urine is a major diffusion mediator of autoactivation after proton beam therapy. Our results indicate that physiologic factors can influence PET images of autoactivation in the context of proton beam therapy verification.

  17. Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

    PubMed

    Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

    2012-11-01

    Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. PMID:22502948

  18. Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz

    PubMed Central

    Abah, Isaac Okoh; Akanbi, Maxwell; Abah, Mercy Enuwa; Finangwai, Amos Istifanus; Dady, Christy W; Falang, Kakjing Dadul; Ebonyi, Augustine Odoh; Okopi, Joseph Anejo; Agbaji, Oche Ochai; Sagay, Altiene Solomon; Okonkwo, Prosper; Idoko, John A; Kanki, Phyllis J

    2015-01-01

    Introduction Adverse drug reactions associated with efavirenz (EFV) therapy are poorly described beyond the first year of treatment. We aimed to describe the incidence and predictors of EFV-related adverse drug reactions (ADRs) in a cohort of adult Nigerian HIV-infected patients on antiretroviral therapy (ART). Methods This retrospective cohort study utilized clinical data of HIV-1 infected adults (aged ?15 years), commenced on efavirenz containing-regimen between January 2004 and December 2011. The time-dependent occurrence of clinical adverse events as defined by the World Health Organization was analyzed by Cox regression analysis. Results A total of 2920 patients with baseline median (IQR) age of 39 (33-46) years, largely made up of men (78%) were included in the study. During 8834 person-years of follow up, 358 adverse drug events were reported; the incidence rate was 40.3 ADRs per 1000 person-years of treatment. Lipodystrophy and neuropsychiatric disorders were the most common ADRs with incidences of 63 and 30 per 1000 patients respectively. About one-third of the neuropsychiatric adverse events were within 12 months of commencement of ART. The risk of neuropsychiatric ADRs was independently predicted for women [adjusted hazard ratio (aHR) 9.05; 95% CI: 5.18-15.82], those aged <40 years (aHR 2.59; 95% CI: 1.50-4.45), advanced HIV disease (WHO stage 3 or 4) [aHR 2.26; 95% CI: 1.37-3.72], and zidovudine [aHR 2.21; 95% CI: 1.27-3.83] or stavudine [aHR 4.22; 95% CI: 1.99-8.92] containing regimen compared to tenofovir. Conclusion Neuropsychiatric adverse drug events associated with efavirenz-based ART had both early and late onset in our clinical cohort of patients on chronic EFV therapy. Continuous neuropsychiatric assessment for improved detection and management of neuropsychiatric ADRs is recommended in resource-limited settings where the use of efavirenz-based regimens has been scaled up. PMID:26405676

  19. The Use of Patient Instructors to Teach Interviewing Skills.

    ERIC Educational Resources Information Center

    Gardner, Marie E.; And Others

    1983-01-01

    A program using patient instructors programmed with a history of hypertension, chronic pulmonary disease, or congestive heart failure to teach and evaluate pharmacy students' interviewing skills is described. Content areas included drug therapy, adverse reactions, drug interactions, etc. (Author/MSE)

  20. Leukemoid reaction after methotrexate-induced pancytopenia in a patient undergoing continuous ambulatory peritoneal dialysis.

    PubMed

    Sun, Chiao-Ying; Lin, Hou-Chang; Chen, Yung-Chih; Tsai, Chi-Ren; Wu, Mai-Szu

    2006-01-01

    Methotrexate has been used as an important alternative therapy in the treatment of various rheumatic diseases. Life threatening marrow suppression in end-stage renal disease patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis has been reported. A 33-year-old woman with systemic lupus erythematosus undergoing chronic peritoneal dialysis developed severe mucositis and pancytopenia after low-dose methotrexate treatment for arthritis. The leukocyte count recovered after methotrexate was withdrawn but a leukemoid blood picture developed during her recovery. No evidence of leukemia was found on bone marrow biopsy. The leukocyte count gradually returned to normal with conservative therapy. PMID:17214397

  1. Risk factors for developing infusion reaction after rituximab administration in patients with B-cell non-Hodgkin's lymphoma.

    PubMed

    Tachi, T; Yasuda, M; Usui, K; Umeda, M; Nagaya, K; Osawa, T; Ichihashi, A; Noguchi, Y; Goto, H; Kasahara, S; Takahashi, T; Goto, C; Teramachi, H

    2015-10-01

    Rituximab (RTX), a monoclonal antibody against CD20, is known to cause fewer side effects than conventional anti-cancer drugs; however, infusion reaction (IR), which is specific to monoclonal antibody therapy, is frequently triggered by RTX. Therefore, we designed this study to identify risk factors based on clinical test values for developing IR after RTX administration. Eighty-nine patients with B-cell non-Hodgkin's lymphoma who had received RTX for the first time between February 2010 and March 2013, at the Gifu Municipal Hospital were enrolled as subjects. Analysis of data was conducted for 87 patients, after excluding patients whose data were missing. Univariate analysis showed significant differences in the number of patients exhibiting a soluble interleukin-2 receptor (sLL-2R) level > 2,000 U/L and hemoglobin (Hb) < lower standard limit (LSL) between the IR and non-IR groups. Multivariate analysis showed significant differences with respect to slL-2R > 2,000 U/L [odds ratio (OR), 4.463; 95% confidence interval (Cl), 1.262-15.779; P = 0.020], Hb < LSL [OR, 3.568; 95% CI,