Computational approaches to understand the adverse drug effect on potassium, sodium and calcium channels for predicting TdP cardiac arrhythmias.

J Mol Graph Model. 2017 Sep;76:152-160

Authors: Sharifi M

Abstract
Ion channels play a crucial role in the cardiovascular system. Our understanding of cardiac ion channel function has improved since their first discoveries. The flow of potassium, sodium and calcium ions across cardiomyocytes is vital for regular cardiac rhythm. Blockage of these channels, delays cardiac repolarization or tend to shorten repolarization and may induce arrhythmia. Detection of drug risk by channel blockade is considered essential for drug regulators. Advanced computational models can be used as an early screen for torsadogenic potential in drug candidates. New drug candidates that are determined to not cause blockage are more likely to pass successfully through preclinical trials and not be withdrawn later from the marketplace by manufacturer. Several different approved drugs, however, can cause a distinctive polymorphic ventricular arrhythmia known as torsade de pointes (TdP), which may lead to sudden death. The objective of the present study is to review the mechanisms and computational models used to assess the risk that a drug may TdP.
KEY POINTS: There is strong evidence from multiple studies that blockage of the L-type calcium current reduces risk of TdP. Blockage of sodium channels slows cardiac action potential conduction, however, not all sodium channel blocking antiarrhythmic drugs produce a significant effect, while late sodium channel block reduces TdP. Interestingly, there are some drugs that block the hERG potassium channel and therefore cause QT prolongation, but they are not associated with TdP. Recent studies confirmed the necessity of studying multiple distinctionic ion channels which are responsible for cardiac related diseases or TdP, to obtain an improved clinical TdP risk prediction of compound interactions and also for designing drugs.

PMID: 28756335 [PubMed - indexed for MEDLINE]

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

Eur J Haematol. 2017 Sep;99(3):199-206

Authors: Moreau P, Dimopoulos MA, Richardson PG, Siegel DS, Cavo M, Corradini P, Weisel K, Delforge M, O'Gorman P, Song K, Chen C, Bahlis N, Oriol A, Hansson M, Kaiser M, Anttila P, Raymakers R, Joao C, Cook G, Sternas L, Biyukov T, Slaughter A, Hong K, Herring J, Yu X, Zaki M, San-Miguel J

Abstract
OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management.
METHODS: This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required.
RESULTS: The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care.
CONCLUSIONS: Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines.

PMID: 28504846 [PubMed - indexed for MEDLINE]

Compact Magnetic Resonance Imaging Systems-Novel Cost-Effective Tools for Preclinical Drug Safety and Efficacy Evaluation.

Toxicol Sci. 2017 05 01;157(1):3-7

Authors: Ramot Y, Schiffenbauer YS, Maronpot R, Nyska A

Abstract
Practical magnetic resonance imaging for use in investigative and preclinical toxicology studies is now feasible. Newly developed, self-containing imaging systems provide an efficient and cost-effective means to rapidly obtain in vivo and ex vivo magnetic resonance imaging images to improve how we perform toxicology and toxicologic pathology.

PMID: 28329801 [PubMed - indexed for MEDLINE]

NMDA receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects.

J Neurosci. 2018 Apr 30;:

Authors: Sequerra EB, Goyal R, Castro PA, Levin JB, Borodinsky LN

Abstract
Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that N-methyl-D-aspartate (NMDA) receptors are important for the formation of the neural tube and loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation.SIGNIFICANCE STATEMENTNeural tube defects are one of the most common birth defects. Clinical investigations have determined that use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that are the side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy.

PMID: 29712790 [PubMed - as supplied by publisher]

Pharmacokinetics, pharmacodynamics, and tolerability of single-dose oral LCB01-0371, a novel oxazolidinone with broad-spectrum activity, in healthy volunteers.

Antimicrob Agents Chemother. 2018 Apr 30;:

Authors: Cho YS, Lim HS, Lee SH, Cho YL, Nam HS, Bae KS

Abstract
LCB01-0371 is a novel oxazolidinone with broad-spectrum activity against Gram-positive pathogens in both in vitro studies and animal infection models. The objectives of this study were to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics following single ascending doses (NCT01554995). Single oral doses of 600 mg Linezolid, a placebo, or LCB01-0371 between 50 mg and 3200 mg were tested in 69 healthy male subjects. Blood and urine were sampled, and LCB01-0371 concentrations were measured, and the serum inhibitory and bactericidal titers of LCB01-0371 and Linezolid were determined. LCB01-0371 was well tolerated up to 2400 mg. The most common drug-related clinical and laboratory adverse events were nausea with or without vomiting, decreased neutrophil count, and increased total bilirubin. The frequency of adverse events and drug-related adverse events was similar among the treatment groups. The systemic exposure was approximately dose-proportional over the range of 50mg--800 mg, which includes the anticipated clinical dose. The mean clearance, renal clearance, and volume of distribution were significantly decreased at higher doses (above 800 mg). LCB01-0371 exhibited early bacteriostatic activity against all tested strains except for S. pneumonia, and the potency of LCB01-0371 at 800 mg was similar to that of Linezolid at the therapeutic dose (600 mg). However, LCB01-0371 had less bactericidal activity than Linezolid. Taken together, LCB01-0371 was well tolerated and exhibited approximate dose proportionality within the anticipated clinically relevant dose range, and showed bacteriostatic and bactericidal activity comparable to that of Linezolid. These results support the further clinical development of LCB01-0371.

PMID: 29712654 [PubMed - as supplied by publisher]

Centaurea albonitens extract enhances the therapeutic effects of Vincristine in leukemic cells by inducing apoptosis.

Biomed Pharmacother. 2018 Mar;99:598-607

Authors: Bahmani F, Esmaeili S, Bashash D, Dehghan-Nayeri N, Mashati P, Gharehbaghian A

Abstract
Drug-induced toxicities and dose-related side effects are the major challenges in the conventional cancer therapy by the chemo drugs. On the other hand, herbal derivatives have obtained a great research interest in the field of therapeutic applications because of their more favorable specifications including less toxicity, cost-effective and more physiologically compatible than the chemical drugs. For this purpose, we evaluated methanolic extract prepared from Centaurea albonitens Turrill alone and in combination with Vincristine (VCR) for its potential cytotoxic effects in NALM-6, REH, NB4 and KMM-1 cell lines by using the various approaches. Centaurea genus is one of the current medicinal plants, which has used in traditional medicine, However, there are rare studies to examine its anticancer properties against hematologic malignant cells. In this study, we demonstrated Centaurea albonitens extract (CAE) induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose- and time- dependent manner, although with varying efficiency. Interestingly, normal cells didn't exhibit significant cytotoxicity after CAE treatment. Moreover, we found that low dose of CAE enhances anti-cancer effects of VCR in pre-B ALL cell lines (NALM-6 and REH). Further investigations validated synergistic anticancer activities of VCR and CAE through inducing apoptosis without significant cell cycle arrest. Taken together, our results demonstrated for the first time that the methanolic extract of Centaurea albonitens can be considered as a potential anticancer agent and/or an enhancer of chemotherapeutic sensitivity of VCR.

PMID: 29710458 [PubMed - in process]

PhID: An Open-Access Integrated Pharmacology Interactions Database for Drugs, Targets, Diseases, Genes, Side-Effects, and Pathways.

J Chem Inf Model. 2017 Oct 23;57(10):2395-2400

Authors: Deng Z, Tu W, Deng Z, Hu QN

Abstract
The current network pharmacology study encountered a bottleneck with a lot of public data scattered in different databases. There is a lack of an open-access and consolidated platform that integrates this information for systemic research. To address this issue, we have developed PhID, an integrated pharmacology database which integrates >400 000 pharmacology elements (drug, target, disease, gene, side-effect, and pathway) and >200 000 element interactions in branches of public databases. PhID has three major applications: (1) assisting scientists searching through the overwhelming amount of pharmacology element interaction data by names, public IDs, molecule structures, or molecular substructures; (2) helping visualizing pharmacology elements and their interactions with a web-based network graph; and (3) providing prediction of drug-target interactions through two modules: PreDPI-ki and FIM, by which users can predict drug-target interactions of PhID entities or some drug-target pairs of their own interest. To get a systems-level understanding of drug action and disease complexity, PhID as a network pharmacology tool was established from the perspective of data layer, visualization layer, and prediction model layer to present information untapped by current databases.

PMID: 28906116 [PubMed - indexed for MEDLINE]

Influence of knowledge and beliefs on consumption of performance enhancing agents in north-western Saudi Arabia.

Ann Saudi Med. 2017 Jul-Aug;37(4):317-325

Authors: Al OM, Elshatarat RA

Abstract
BACKGROUND: Consumption of performance enhancing agents (PEAs) has a wide range of negative health consequences, but knowledge of these consequences among gym users of PEAs in Saudi Arabia is not well understood.
OBJECTIVES: Identify the knowledge, awareness, beliefs and attitudes of gym users about negative health consequences of using PEAs, and the relationship between these factors and use of these agents.
DESIGN: Cross-sectional study.
SETTING: Five gyms in Madinah city, Saudi Arabia.
SUBJECTS AND METHODS: Convenience sampling was used to recruit gym users. An electronic self-administered questionnaire was used to collect data.
MAIN OUTCOME MEASURE(S): Level of knowledge about the negative health consequences of PEAs among gym users.
RESULTS: About 70% of 316 participants had used one or more of PEAs over the last six months. Of those, about 68.4% used protein powder supplements and 48.1% used energy drinks. Participants who believed that protein powder supplements (c2=52.3, P < .01) and energy drinks (c2=35.2, P < .01) had health hazards used these agents less often than others during the six months preceding data collection. Participants who had less knowledge about the negative health consequences were more likely to use protein powder supplement (t=2.38, P=.018). On the other hand, those who were more knowledgeable about the negative health consequences of insulin, were more likely to use insulin (t=2.45, P=.015).
CONCLUSION: Misuse of PEAs is widespread among gym users in Saudi Arabia. Improving the level of knowledge and awareness of possible serious health consequences would hopefully lead to reduced PEA consumption.
LIMITATIONS: The temporal sequence of cause and effect could not be determined in a cross sectional study. Convenience sampling in a single city limited the generalizability of the findings to all regions of Saudi Arabia.

PMID: 28761032 [PubMed - indexed for MEDLINE]

Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials.

Int Immunopharmacol. 2017 Aug;49:85-94

Authors: Peng TR, Tsai FP, Wu TW

Abstract
OBJECTIVE: The purpose of this study is to evaluate the efficacy and adverse effects of nivolumab and pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC) by meta-analysis.
MATERIALS AND METHODS: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, and American Society of Clinical Oncology meeting abstracts, clinicaltrial gov, and Cochrane library databases. Two reviewers independently assessed the quality of the trials. Outcomes analysis was overall response rates (ORR), overall survival (OS), progression- free survival (PFS) and major adverse effects with odds ratio (OR) or hazard ratio (HR) and 95% confidence intervals (CI).
RESULTS: Results reported from three RCTs involving 1,887 patients are included in this analysis. Indirect comparison between pembrolizumab and nivolumab in advanced NSCLC shows no statistically significant difference in ORR (OR: 1.14, 95% CI, 0.60-2.01), OS (HR: 0.98, 95% CI, 0.35-2.74) and PFS (HR: 1.12, 95% CI, 0.70-1.77). The incidence of grades≥3 adverse effects is higher with pembrolizumab as compared with nivolumab (OR: 3.44, 95% CI, 1.87-6.32). There are no significant statistical differences between severe adverse effects, such as pneumonitis and hypothyroidism, of the two drugs.
CONCLUSIONS: This study has demonstrated that pembrolizumab and nivolumab have similar survival outcomes in patients with advanced NSCLC, but pembrolizumab has a higher incidence of grades≥3 adverse effects than nivolumab.

PMID: 28554108 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/05/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Hypersensitivity reactions to intravenous antibiotics in cystic fibrosis.

Paediatr Respir Rev. 2018 Apr 05;:

Authors: Wright MFA, Bush A, Carr SB

Abstract
Hypersensitivity reactions to intravenous antibiotics are common in cystic fibrosis (CF). As well as causing immediate morbidity, the need for future avoidance of the causative antibiotic can have a long-term negative impact on CF management. This paper reviews the epidemiology and clinical presentation of hypersensitivity reactions in CF patients, and using an illustrative case describes a rare but severe form of delayed drug reaction for which a high index of suspicion is required.

PMID: 29703693 [PubMed - as supplied by publisher]

Adverse events of fluoroquinolones vs. other antimicrobials prescribed in primary care: A systematic review and meta-analysis of randomized controlled trials.

Int J Antimicrob Agents. 2018 Apr 24;:

Authors: Tandan M, Cormican M, Vellinga A

Abstract
BACKGROUND: Fluoroquinolones (FQs) are second line antimicrobial agents. Once the decision to prescribe an antimicrobial is made, its choice should be based on both the benefits and harms. This systematic review quantifies the occurrence of common adverse events (AEs) related to FQs in relation to any other antimicrobial for any indication in primary care.
METHODS: We searched randomized controlled trials from Embase, PubMed, Cochrane Central Register of Controlled Trials and CINHAL. FQs had to be administered orally, for any indication, to adults and in primary care. Data were extracted independently in standard forms in "Covidence". Pooled estimates of the intervention effects for AEs were determined by the Peto odds ratios (ORs) and 95% confidence intervals in Revman.
RESULTS: Of the 39 studies selected, the most commonly reported AEs were nausea, vomiting, diarrhoea, headache, dizziness, and rash. A meta-analysis of 28 studies reporting AEs showed central nervous system (CNS) (OR 1.40 (1.12-1.75) p=0.003, heterogeneity (I2) = 0%) and gastrointestinal (GI) related AEs (OR 1.20 (1.06-1.36) p=0.005, I2=80%) were significantly associated with FQs use compared to other antimicrobials. Compared to FQs, co-amoxiclav showed significantly more total AEs (OR 0.70 (0.54-0.90) p=0.006, I2=78%) and GI-related AEs (OR 0.69(0.52-0.91) p=0.008, I2=94%). Withdrawal and/or discontinuation due to drug-related AEs were higher for FQs (OR 1.19 (1.00-1.42) p=0.05, I2=5%). Sensitivity analyses did not change these results.
CONCLUSION: FQs are associated with more CNS and GI-related AEs compared to other types of antimicrobial. This information is relevant to support decision making in relation to antimicrobial prescribing.

PMID: 29702230 [PubMed - as supplied by publisher]

Calcium channel blockers for antipsychotic-induced tardive dyskinesia.

Cochrane Database Syst Rev. 2018 03 26;3:CD000206

Authors: Essali A, Soares-Weiser K, Bergman H, Adams CE

Abstract
BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments.
OBJECTIVES: To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.
SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA: We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication.
DATA COLLECTION AND ANALYSIS: We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE.
MAIN RESULTS: Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients.
AUTHORS' CONCLUSIONS: Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.

PMID: 29578611 [PubMed - indexed for MEDLINE]

Evaluating quality of life in epilepsy: The role of screening for adverse drug effects, depression, and anxiety.

Epilepsy Behav. 2017 Oct;75:18-24

Authors: Micoulaud-Franchi JA, Bartolomei F, Duncan R, McGonigal A

Abstract
OBJECTIVE: The objective of this study was to evaluate the contribution of validated screening tools for antiepileptic drug (AED) adverse effects, depression, and anxiety to measure the quality of life (QoL) in people with epilepsy (PWE).
METHODS: Patients in a tertiary epilepsy service were screened for quality of life (using QOLIE-31), major depressive disorder (MDD) (NDDI-E), generalized anxiety disorder (GAD) (GAD-7), and AED effects (AEP). Mini International Neuropsychiatric Interview (MINI) generalized anxiety disorder module was also performed. For AEP validation in French, the internal structural validity was analyzed. Dimensional (NDDI-E and GAD-7 scores) and categorical (MDD and GAD) analyses were performed to investigate interactions between QoL and AEP.
RESULTS: A total of 132 (87 females) subjects were included. The French version of the AEP demonstrated satisfactory psychometric properties (Cronbach's α 0.87). Correlations between NDDI-E, GAD-7, AEP, and QOLIE-31 scores were high, and significant for all subscales of QOLIE-31; no effect of seizure-related variables was seen. Some sex differences in QOLIE-31 subscales were found, and mean AEP score was higher in females. Age, sex, NDDI-E, GAD-7, and AEP scores accounted for 61% of variance of QOLIE-31 scores. Differential effects were seen on QOLIE-31 subscales: AEP strongly correlated with all subscales; GAD-7 scores more strongly correlated with "Seizure Worry"; NDDI-E with "Energy-Fatigue"; and both NDDI-E and GAD-7 scores strongly correlated with "Emotional Well-Being". Categorical analysis of groups with MDD alone, GAD alone, MDD+GAD, and neither MDD nor GAD showed significant differences in AEP and QOLIE-31 scores, with MDD+GAD showing the most AED effects and the poorest QoL.
SIGNIFICANCE: The combination of screening tools for depression (NDDI-E), anxiety (GAD-7), and AED effects (AEP) has a strong power for evaluating QoL in PWE. Coexisting MMD and GAD were associated with the poorest quality of life and the highest AEP scores.

PMID: 28818810 [PubMed - indexed for MEDLINE]

Safety of Cancer Therapies: At What Cost?

Popul Health Manag. 2017 Aug;20(4):318-328

Authors: Fitzner K, Oteng-Mensah F, Donley P, Heckinger EAF

Abstract
The cost of cancer drugs has increased concurrently with drug safety resulting in both increased survivorship and increased out-of-pocket costs and co-payments for patients. This article evaluates the interplay between patient safety and cancer drug costs to determine how cancer drug costs affect patient safety and well-being. A literature review was performed that identified the main drivers of drug safety costs: drug-drug interactions, adverse drug events, medication errors, and nonadherence. Three main types of costs were identified: out-of-pocket spending, drug cost growth, and safety-related costs. Insured patients receiving chemotherapy pay an average of $10,000/month on out-of-pocket expenses. Annual drug cost growth has been as much as 21% in recent years. Over a span of 13 years, 1999-2013, insurance premiums and out-of-pocket payments have increased by 182% and 200%, respectively. Safety-related concerns include the high cost of developing a new drug, estimated at $5 billion. The cost of development is reflected in the cost of the 12 new cancer drugs that received Food and Drug Administration approval in 2012; 11 were priced at 6 figures. Although advances in pharmaceutical technology and research have yielded effective cancer therapies that reduce physical or treatment-related toxicity, patients have had to face worsening financial uncertainty both during and after treatment. Actions are needed to achieve financial safety, as well as therapeutic and clinical safety, for cancer patients.

PMID: 28112578 [PubMed - indexed for MEDLINE]

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children: 20 years study in a tertiary care hospital.

World J Pediatr. 2017 Jun;13(3):255-260

Authors: Techasatian L, Panombualert S, Uppala R, Jetsrisuparb C

Abstract
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe lifethreatening skin conditions. The most common cause of these manifestations is medications. Beside discontinued of the culprit drug, systemic corticosteroids were used as a primary treatment option among pediatric population. This study aimed to explore causative drugs (drug group/ latent period), treaments, complications, and treatment outcome (morbidity, mortality, length of hospital stay) of SJS and TEN in children.
METHODS: A retrospective chart was reviewed during the period of 1992 to 2012 at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. SJS and TEN were clinically diagnosed and confirmed by pediatric dermatologists. Other possible causes other than druginduced SJS and TEN were excluded.
RESULTS: A total of 30 patients was recorded, including 24 (80%) SJS patients and 6 (20%) TEN patients. The mean age was 6.9 years (SD 4.4). Male to female ratio was 1.5:1. Antiepileptic drug group was the most common causative drug (n=18, 60%), followed by antibiotic drug group (n=8, 26.6%), and others (n=4, 13.3%) which included nonsteroidal antiinflammtory drugs (NSAIDs) and chemotherapy drugs. Systemic corticosteroids were used in 29 patients (96.6%). Intravenous immunoglobulin was used in one TEN patient (3.3%). There was a medium correlation between time to treatment (systemic corticosteroids) and the length of hospital stay (Spearman correlation coefficient=0.63, P=0.005). Two TEN patients (6.6%) died.
CONCLUSIONS: Carbamazepine was the most common causative drug of SJS and TEN in our study. The severity of skin detachment is not correlated to severity of ocular findings. However, the persistent of ocular complications up to one year is suggested for promptly appropriate ocular treatment in all SJS and TEN patients. Our data suggested that early administration of systemic corticosteroid may reduce the length of hospital stay and should be considered for the treatment of pediatric druginduced SJS and TEN.

PMID: 27650525 [PubMed - indexed for MEDLINE]

Meaningful Use IT reduces hospital-caused adverse drug events even at challenged hospitals.

Healthc (Amst). 2015 Mar;3(1):12-7

Authors: Encinosa WE, Bae J

Abstract
BACKGROUND: many Meaningful Use (MU) requirements involve medication management. Little is known about what impact these will have on adverse drug events (ADEs) at challenged hospitals.
METHODS: we use the Florida State Inpatient Database (HCUP, AHRQ), the AHA IT Supplement, and Hospital Compare. Controlling for non-response selection bias, we use multi-level GLLAMM regression analysis to examine the impact of the 5 core MU medication elements on hospital-caused ADEs.
RESULTS: adopting all 5 core MU elements was associated with a reduction in ADEs. Hospitals reporting costs as the main barrier to MU reduced their ADE rates by 35%; low quality hospitals reduced ADEs by 29%, compared to 27% at high quality hospitals. Among hospitals reporting these medication elements among their top MU challenges, ADEs were reduced by 69%, compared to 45% for hospitals with no drug functions as their top MU challenges. However, ADEs increased by 14% at hospitals with physician resistance to MU, compared to a 52% ADE reduction without physician resistance.
CONCLUSIONS: the bundling all five medication functions in MU is associated with large reductions in ADEs.
IMPLICATIONS: without physician buy-in at the hospital, MU will have no impact on ADEs.

PMID: 26179584 [PubMed - indexed for MEDLINE]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/04/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/04/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

In response to: "Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning".

Eur J Clin Pharmacol. 2018 02;74(2):251

Authors: Harmouche E, Howland MA, K Su M

PMID: 29159489 [PubMed - indexed for MEDLINE]