Expanding biological space coverage enhances the prediction of drug adverse effects in human using in vitro activity profiles.

Sci Rep. 2018 02 28;8(1):3783

Authors: Huang R, Xia M, Sakamuru S, Zhao J, Lynch C, Zhao T, Zhu H, Austin CP, Simeonov A

Abstract
In vitro assay data have recently emerged as a potential alternative to traditional animal toxicity studies to aid in the prediction of adverse effects of chemicals on humans. Here we evaluate the data generated from a battery of quantitative high-throughput screening (qHTS) assays applied to a large and diverse collection of chemicals, including approved drugs, for their capacity in predicting human toxicity. Models were built with animal in vivo toxicity data, in vitro human cell-based assay data, as well as in combination with chemical structure and/or drug-target information to predict adverse effects observed for drugs in humans. Interestingly, we found that the models built with the human cell-based assay data performed close to those of the models based on animal in vivo toxicity data. Furthermore, expanding the biological space coverage of assays by including additional drug-target annotations was shown to significantly improve model performance. We identified a small set of targets, which, when added to the current suite of in vitro human cell-based assay data, result in models that greatly outperform those built with the existing animal toxicity data. Assays can be developed for this set of targets to screen compounds for construction of robust models for human toxicity prediction.

PMID: 29491351 [PubMed - indexed for MEDLINE]

[New recommendations in oncocardiology].

Magy Onkol. 2017 Sep 20;61(3):219-227

Authors: Nagy CA, Lódi M, Balogh I, Czuriga D, Kocsis J

Abstract
It is well-known that modern oncotherapy significantly reduced the mortality of malignant diseases. However, serious side effects of the applied cancer therapies have evolved, which may adversely affect the cardiovascular system. Early side effects often limit therapeutic success of oncotherapy and may require treatment interruption, while late-onset side effects can adversely influence the long-term survival of patients recovering from cancer. Oncocardiology is a new medical field gaining more and more attention. It aims at the optimisation of the efficacy of cancer therapy and clinical outcome of patients. In the current review we present such important recommendations that may help the management of cardiovascular toxicity of cancer therapy in the everyday clinical practice.

PMID: 28931095 [PubMed - indexed for MEDLINE]

24 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 2019/10/01

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.

16 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 2019/09/29

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.

15 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 2019/09/28

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.

[Epidemiology and prevention of heat-related adverse health effects on elderly people].

Z Gerontol Geriatr. 2019 Aug;52(5):487-502

Authors: Herrmann A, Haefeli WE, Lindemann U, Rapp K, Roigk P, Becker C

Abstract
Heat waves increase the morbidity and mortality in Germany, particularly of older patients in need of care. Due to climate change the number of heat waves in Germany will increase threefold by the end of the century. In addition, the proportion of patients at risk will grow due to demographic change. Therefore, the Government and the Federal States have developed recommendations for heat action plans, in which the medical profession should also participate in the prevention of heat-related damage to health. Physicians and their team should first become acquainted with the topic. In addition, they should inform patients at risk and their relatives of the risks and preventive measures. In the summer a critical check of drugs is also needed because medications impair cooling mechanisms in heat waves, the pharmacokinetics can change and unwanted side effects of drugs occur more frequently. Lastly, due to their central position in the healthcare system, physicians should participate in the coordination of a good nursing care and intensification of social contacts during heat waves.

PMID: 31346679 [PubMed - indexed for MEDLINE]

Topiramate Induced Serious Ocular Side Effects.

J Assoc Physicians India. 2018 Jun;66(6):111

Authors: Patel DM, Patel MV, Garg AV

PMID: 31331158 [PubMed - indexed for MEDLINE]

Evaluation of Correlation Between the Pharmacogenetic Profiles of Risperidone Treated Psychiatry Patients with Plasma and Urine Concentration of Risperidone and its Active Moiety 9-OH Risperidone Determined with Optimized Bioanalytical LC Method.

Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2018 Dec 01;39(2-3):97-106

Authors: Filipce A, Naumovska Z, Nestorovska AK, Sterjev Z, Brezovska K, Tonic-Ribarska J, Grozdanova A, Suturkova L, Raleva M

Abstract
Atypical antipsychotic risperidone is widely used first-line monotherapy in schizophrenia and combined therapy in bipolar disorders. Therapeutic plasma concentrations of risperidone and its active moiety are directly influenced by genetic variations in metabolic CYP450 enzymes (CYP2D6 and CYP3A4/5) and transporter (ABCB1) protein and additional environmental factors. Since active metabolite 9-OH risperidone has a greater percentage of the pharmacologically active fraction and is equipotent to the parent drug risperidone, it is assumed that it contributes significantly to therapeutic and adverse effects. Unpredictable dose/concentration ratio, narrow therapeutic index, number of interactions, along with serious adverse reactions (ADR), raises the need for individualization of risperidone treatment and establishing of good therapeutic regime using TDM. A simple and reliable validated bioanalytical liquide-liquide extraction HPLC/UV method was applied for the simultaneous determination of risperidone and its active metabolite, 9-OH risperidone, in human plasma and urine of 52 hospitalized schizophrenia/bipolar disorder patients treated with risperidone as monotherapy and in polytherapy. All the patients were previously genotyped for CYP2D6 (EM=30, EM/IM=14, IM=4 IM/PM=1 and PM=3) and ABCB1 using Real-Time PCR methods with TaqMan SNP genotyping suitable assays according to the guidelines of the manufacturer (Life Technologies, USA).The influence of CYP2D6 phenotype on metabolic ratio MR (Ris/9-OHRis) in plasma (p=0.012) and in urine (p=0.048) was confirmed. Statistically significant correlation (R2=55.53%, Rho=0.844, p<0,0001) for MR in both plasma and urine indicates that urine may be utilized as appropriate media for initial CYP2D6 phenotype identification and selection of patients on risperidone treatment with high risk for ADR.

PMID: 30864366 [PubMed - indexed for MEDLINE]

[Single-center retrospective analysis of extracorporal photopheresis in clinical practice : Peripheral venous compared to central venous access].

Hautarzt. 2019 Mar;70(3):193-203

Authors: Hambsch J, Büttner S, Heck M, Nicolay JP, Felcht M, Booken N, Klemke CD

Abstract
BACKGROUND: Extracorporal photopheresis (ECP) was shown to be effective without severe side effects in the treatment of cutaneous T cell lymphoma (CTCL) and graft versus host disease (GvHD). However, only few studies investigated the practical aspects of ECP.
METHODS: Treatment protocols of 2038 ECP procedures in 52 patients (CTCL, n = 29; GvHD, n = 15; other, n = 8) were evaluated. The patients were treated with the UVAR® XTS™ ECP system (Therakos, Inc. Johnson & Johnson, Raritan, NJ, USA) between 2001 and 2010. All patients started with a peripheral venous access. During the course of treatment 7 patients were treated via a port and 4 via a central venous catheter.
RESULTS: In all, 1765 (86.6%) treatments were performed with a peripheral venous access; 239 (11.7%) ECPs were done via a port and 34 (1.7%) via a central venous catheter. The peripheral venous access showed a higher flow rate and longer photoactivation time. ECPs via port lead to higher UV-irradiated volumes, longer treatment times and higher differences in systolic blood pressure. The following side effects were observed: being unwell (n = 13), hypo- (n = 13) and hypertension (n = 7), vertigo (n = 4), headache (n = 4), shortness of breath (n = 4), fever (n = 3) and metallic taste (n = 3). Technical complications such as problems with venous access (9.6%) occurred in 385 (18.9%) treatments.
CONCLUSIONS: Peripheral venous access should be preferred for ECP treatments.

PMID: 30627743 [PubMed - indexed for MEDLINE]

Druggability of Coronary Artery Disease Risk Loci.

Circ Genom Precis Med. 2018 08;11(8):e001977

Authors: Tragante V, Hemerich D, Alshabeeb M, Brænne I, Lempiäinen H, Patel RS, den Ruijter HM, Barnes MR, Moore JH, Schunkert H, Erdmann J, Asselbergs FW

Abstract
BACKGROUND: Genome-wide association studies have identified multiple loci associated with coronary artery disease and myocardial infarction, but only a few of these loci are current targets for on-market medications. To identify drugs suitable for repurposing and their targets, we created 2 unique pipelines integrating public data on 49 coronary artery disease/myocardial infarction-genome-wide association studies loci, drug-gene interactions, side effects, and chemical interactions.
METHODS: We first used publicly available genome-wide association studies results on all phenotypes to predict relevant side effects, identified drug-gene interactions, and prioritized candidates for repurposing among existing drugs. Second, we prioritized gene product targets by calculating a druggability score to estimate how accessible pockets of coronary artery disease/myocardial infarction-associated gene products are, then used again the genome-wide association studies results to predict side effects, excluded loci with widespread cross-tissue expression to avoid housekeeping and genes involved in vital processes and accordingly ranked the remaining gene products.
RESULTS: These pipelines ultimately led to 3 suggestions for drug repurposing: pentolinium, adenosine triphosphate, and riociguat (to target CHRNB4, ACSS2, and GUCY1A3, respectively); and 3 proteins for drug development: LMOD1 (leiomodin 1), HIP1 (huntingtin-interacting protein 1), and PPP2R3A (protein phosphatase 2, regulatory subunit b-double prime, α). Most current therapies for coronary artery disease/myocardial infarction treatment were also rediscovered.
CONCLUSIONS: Integration of genomic and pharmacological data may prove beneficial for drug repurposing and development, as evidence from our pipelines suggests.

PMID: 30354342 [PubMed - indexed for MEDLINE]

Strategies to Enhance the Intravenous Treatment Satisfaction and Drug Safety Awareness Among Patients with Multiple Sclerosis in Macedonia.

Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2018 Jul 01;39(1):115-121

Authors: Barbov I, Korunoska J, Bonevska V, Smokovski A

PMID: 30110255 [PubMed - indexed for MEDLINE]

Bias-Corrected Estimates of Time-Varying Adverse Drug Event Rates for Patients on Outpatient Parenteral Antimicrobial Therapy.

Clin Infect Dis. 2018 07 02;67(2):316-318

Authors: Kinlaw AC, Marx AH, Farel CE

PMID: 29481658 [PubMed - indexed for MEDLINE]

Reply to Kinlaw et al.

Clin Infect Dis. 2018 07 02;67(2):318-319

Authors: Keller SC, Hsu YJ, Cosgrove SE

PMID: 29481607 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy.

Clin Gastroenterol Hepatol. 2018 02;16(2):268-277

Authors: Roberts SK, Lim R, Strasser S, Nicoll A, Gazzola A, Mitchell J, Siow W, Khoo T, Hamarneh Z, Weltman M, Gow P, Janko N, Tse E, Mishra G, Cheng EH, Levy M, Cheng W, Sood S, Skoien R, Mitchell J, Zekry A, George J, MacQuillan G, Wigg A, Stuart K, Sievert W, McCaughan G, ALA Clinical Research Network

Abstract
BACKGROUND & AIMS: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine.
METHODS: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment.
RESULTS: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events.
CONCLUSION: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

PMID: 29050991 [PubMed - indexed for MEDLINE]

Safety and Efficacy of 6-thioguanine as a Second-line Treatment for Autoimmune Hepatitis.

Clin Gastroenterol Hepatol. 2018 02;16(2):290-291

Authors: Legué C, Legros L, Kammerer-Jacquet S, Jézequel C, Houssel-Debry P, Uguen T, Le Lan C, Guillygomarc'h A, Moirand R, Turlin B, Guyader D, Bardou-Jacquet E

PMID: 28782666 [PubMed - indexed for MEDLINE]

16 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 2019/09/26

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.

16 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 2019/09/26

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.

19 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 2019/09/24

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.

Comparative analysis of sublingual immunotherapy medicines for adherence and clinical outcomes.

Eur Arch Otorhinolaryngol. 2019 Sep 21;:

Authors: Kim JA, Lee YM, Yi KI, Kim SD, Mun SJ, Cho KS

Abstract
OBJECTIVE: Sublingual immunotherapy (SLIT) has been considered as an effective and safe alternative to the subcutaneous route. However, different modalities and administration methods may lead to significant changes in their adherence and clinical outcomes. The purpose of this study was to compare the adherence, efficacy, and side effects of SLIT medicines: SLITone®, Lais®, and Staloral®.
SUBJECTS AND METHODS: Eighty-two patients suffering from AR symptoms and sensitized only to house dust mite allergens were included. The patients were treated with SLITone®, Lais®, or Staloral®. Treatment outcomes related to efficacy, dropout rate, and adverse events were evaluated. The visual analogue scale (VAS) including sneezing, rhinorrhea, nasal obstruction, and itching was scored from 0 (normal) to 10 (severe), before and after SLIT. Dropout rate was defined as the number of patients who discontinue SLIT of oneself compared to the number of patients who receive SLIT.
RESULTS: All of the nasal symptoms and total symptom scores were significantly decreased in SLITone®, Lais®, and Staloral®. Furthermore, there were significant difference in the improvement of rhinorrhea and TNSS between SLITone® and Staloral® group (p = 0.011 and p = 0.001, respectively). Four patients out of 26 in SLITone® group, 4 patients out of 30 in Lais® group, and 11 patients out of 26 in Staloral® group have stopped SLIT of themselves. The dropout rate was significantly higher in the Staloral® group than other two groups (p = 0.024). Only one patient complained adverse reaction such as swelling of mouth floor in the Staloral® group.
CONCLUSION: Although all three SLIT medicines are effective in improving AR symptoms, the adherence to SLIT assessed in accordance with dropout rate was the lowest in the Staloral®.

PMID: 31542829 [PubMed - as supplied by publisher]

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 2019/09/21

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.