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Hepatotoxic Medication

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141. Itraconazole Dosing and Drug Monitoring at a Tertiary Children's Hospital. (Abstract)

retrospective review of medical records of children at the Royal Children's Hospital Melbourne who received oral itraconazole and had therapeutic drug monitoring (TDM).Overall, 81 children received 92 courses of oral itraconazole and had TDM. Of 222 TDM samples, 183 (82.4%) were taken at the appropriate time (trough level at steady state). Patients ≤12 and >12 years of age required median doses of 6.2 and 3.9 mg/kg/d, respectively, to attain target trough levels (P < 0.001). Of children ≤12 years of age (...) Itraconazole Dosing and Drug Monitoring at a Tertiary Children's Hospital. Itraconazole is a broad-spectrum antifungal agent used for prophylaxis and treatment of fungal infections in immunocompromised children. Achieving the recommended target serum itraconazole trough concentration of ≥0.5 mg/L is challenging in children because of variation in itraconazole pharmacokinetics with age. We studied itraconazole use and treatment outcomes in a tertiary children's hospital.We did a 10-year

2018 Pediatric Infectious Dsease Journal

142. Has doxycycline, in combination with anti-malarial drugs, a role to play in intermittent preventive treatment of Plasmodium falciparum malaria infection in pregnant women in Africa? Full Text available with Trip Pro

 consecutive days seems to be a good option to retard the emergence and the spread of resistance to artemisinin-based combination therapy (ACT) in Africa and improve the effectiveness of ACT in term of preterm births, neonatal morbidity and mortality. Contrary to preconceived ideas, scientific and medical data suggest that the risk of congenital malformations in the fetus or of tooth staining in infants whose mothers take doxycycline and hepatotoxicity during pregnancy is very low or non-existent (...) Has doxycycline, in combination with anti-malarial drugs, a role to play in intermittent preventive treatment of Plasmodium falciparum malaria infection in pregnant women in Africa? According to the World Health Organization (WHO), Plasmodium falciparum malaria during pregnancy is responsible for deleterious consequences for the mother and her child. The administration of intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) at each antenatal care visit as early as 13

2018 Malaria journal

143. Liver transplantation for acute liver failure due to antitubercular drugs – a single-center experience Full Text available with Trip Pro

Liver transplantation for acute liver failure due to antitubercular drugs – a single-center experience Patients receiving treatment for tuberculosis are at risk of developing acute liver failure due to the hepatotoxicity of antitubercular drugs. We aimed to describe our experience with liver transplantation from deceased donors in this situation.We identified patients undergoing transplantation for acute liver failure due to antitubercular drugs in our prospectively maintained database.Of 81 (...) patients undergoing transplantation for acute liver failure, 8 cases were attributed to antitubercular drugs during the period of 2006-2016. Regarding the time of tuberculosis treatment until the onset of jaundice, patients were on antitubercular drugs for a mean of 64.7 days (21-155 days). The model for end-stage liver disease (MELD) score of patients ranged from 32 to 47 (median 38), and seven patients underwent transplantation under vasopressors. The 1-year survival was 50%. Three patients died

2018 Clinics

144. Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury. Full Text available with Trip Pro

Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury. Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic (...) EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific

2017 PLoS ONE

145. Using subcutaneous methotrexate to prolong duration of methotrexate therapy in rheumatoid arthritis Full Text available with Trip Pro

Using subcutaneous methotrexate to prolong duration of methotrexate therapy in rheumatoid arthritis Our study aims to determine whether the use of subcutaneous methotrexate (SC MTX) is associated with prolonged MTX use and lower incidence of hepatotoxicity in rheumatoid arthritis (RA) patients on MTX monotherapy and multiple drug therapy.We conducted a retrospective cohort study using national databases of a large hospital system. Subjects had been diagnosed with RA and treated with MTX between (...) September 30, 1999, and October 1, 2009. Outcomes of interest were the amount of time on MTX monotherapy or multiple disease-modifying anti-rheumatic drug (DMARD) therapy before addition of additional DMARDs or biologic agents, respectively. We conducted Cox regressions and Kaplan-Meier curves for association between SC MTX use and length of time before therapeutic change. We conducted chi-square tests for association between SC MTX use and elevated liver function tests (LFT).MTX monotherapy: SC MTX

2018 European journal of rheumatology

146. Treatment of HIV-1-positive adults with antiretroviral therapy (interim update)

frequency 63 6.1.4 Fixed-dose combinations 64 6.1.5 Single-tablet regimens 65 6.2 Pharmacology 67 6.2.1 Drug interactions 67 6.2.2 Therapeutic drug monitoring 68 6.2.3 Stopping therapy: pharmacological considerations 70 6.2.4 Switching therapy: pharmacological considerations 71 6.3 Switching antiretroviral therapy in virological suppression 74 6.3.1 Introduction 74 6.3.2 Switching antiretrovirals in combination antiretroviral therapy 74 6.3.3 Protease inhibitor monotherapy 78 6.3.4 Treatment with one (...) boosted protease inhibitor and one NRTI 80 6.4 Stopping therapy 81 6.4.1 Recommendation 81 6.4.2 Auditable outcomes 81 6.4.3 Rationale 81 6.4.4 References 81 7.0 Managing virological failure 82 7.1 Introduction 82 7.1.1 Summary of auditable measures 82 7.2 Blips, low-level viraemia and virological failure 83 7.2.1 Recommendations 83 7.2.2 Rationale 83 7.3 Individuals with no or limited drug resistance 86 7.3.1 Recommendations 86 7.3.2 Rationale 86 7.4 Individuals with multiple class virological

2017 British HIV Association

147. A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Liver Cirrhosis

infection, chronic hepatitis C virus infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, alpha-1-antitrypsin deficiency, iron overload, and hemochromatosis) Current or past history of hepatocellular carcinoma (HCC) Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation Other protocol defined inclusion/exclusion criteria could apply Contacts and Locations Go (...) A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Liver Cirrhosis A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Liver Cirrhosis - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number

2018 Clinical Trials

148. A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis

hepatitis C virus infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, alpha-1-antitrypsin deficiency, iron overload, and hemochromatosis) Current or past history of hepatocellular carcinoma (HCC) Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation Other protocol defined inclusion/exclusion criteria could apply Contacts and Locations Go to Information from (...) A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached

2018 Clinical Trials

149. A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C

of screening (SVR is defined as a negative hepatitis C RNA greater than or equal to 12 weeks from the end of therapy) Participants must have METAVIR Stage 3 or 4 (or equivalent if using other classification; eg, Ishak) Exclusion Criteria: Other causes of liver disease (eg, alcoholic liver disease, HBV [serologically positive as determined using United States Centers for Disease Control and Prevention guidance for interpretation of hepatitis B serologic test results], autoimmune hepatitis, drug-induced (...) A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved

2018 Clinical Trials

150. Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy. Full Text available with Trip Pro

Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy. Previous studies have suggested that heterozygous variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma (POLG1) increase the risk for liver injury for patients on valproate (VPA) therapy. We assessed the prevalence of these common variants and seven (...) other pathogenic mutations in POLG1 and determined the occurrence of VPA-induced hepatotoxicity (VHT) or pancreatic toxicity in a cohort of patients with epilepsy.Patients with epilepsy (N = 367) were retrospectively identified from medical record files and screened for mutations in POLG1. Patients who had received VPA monotherapy and carried either of the two variants, p.Q1236H or p.E1143G, without other pathogenic mutations in POLG1 (n = 33, variant group) and patients without these variants (n

2018 Epilepsia

151. Functional Liver Imaging and Dosimetry to Predict Hepatotoxicity Risk in Cirrhotic Patients with Primary Liver Cancer. (Abstract)

Functional Liver Imaging and Dosimetry to Predict Hepatotoxicity Risk in Cirrhotic Patients with Primary Liver Cancer. Mitigating radiation-induced liver disease (RILD) is an ongoing need in patients with hepatocellular carcinoma. We hypothesize that [99mTc]-sulfur colloid (SC) single photon emission computed tomography (SPECT)/computed tomography (CT) scans can provide global functional liver metrics and functional liver dosimetric parameters that are predictive of hepatotoxicity risk (...) in patients with primary liver cancer with cirrhosis.We retrospectively reviewed 47 patients (n = 26 proton, n = 21 stereotactic body radiation therapy) with Child-Pugh (CP)-A (62%) or CP-B (38%) cirrhosis who underwent SC SPECT/CT scans for radiation therapy planning. SC SPECT scans were mined for image intensity threshold-based functional liver volumes (FLV), mean liver-spleen uptake ratio (L/Smean), and total liver function (TLF = FLV*L/Smean). Radiation therapy doses were voxel-wise converted

2018 Biology and Physics

152. Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication. Full Text available with Trip Pro

Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication. To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults.This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT (...) or comorbidities were: critical care admissions: 75.3% versus 52.6 and 48.6%; and organ failures: 69.4% versus 46.7 and 51.5%. Adjusted IRRs of severe hepatotoxicity for anidulafungin versus caspofungin and micafungin were 1.43 (p = 0.002) and 1.19 (p = 0.183) overall, and 0.88 (P = 0.773) and 0.97 (P = 0.945) for normal baseline LFT, respectively.Accounting for confounders, severe hepatotoxicity risk was not significantly different across echinocandins in this real-world head-to-head study. Anidulafungin

2018 BMC Infectious Diseases

153. A Suspected Case of Hydralazine-Induced Hepatotoxicity: A Case Report and Review of Literature Full Text available with Trip Pro

, which all resolved after discontinuation of hydralazine, and liver function test results also dramatically improved. CONCLUSIONS It is imperative that clinicians be aware of the possible hepatotoxicity of hydralazine and its clinical features so that the medication can be promptly discontinued to help promote liver recovery. This case report will add to the current literature about such infrequent cases of hydralazine-induced hepatotoxicity. (...) A Suspected Case of Hydralazine-Induced Hepatotoxicity: A Case Report and Review of Literature BACKGROUND Hydralazine is an effective antihypertensive agent but may rarely have devastating hepatotoxic effects that are extremely variable, thus making the diagnosis difficult. CASE REPORT We report the case of a 74-year-old male patient who had transaminitis after being started on hydralazine by his cardiologist for poorly controlled hypertension. He had extreme dizziness, nausea, and weakness

2018 The American journal of case reports

154. Antidepressants and Hepatotoxicity: A Cohort Study among 5 Million Individuals Registered in the French National Health Insurance Database Full Text available with Trip Pro

Antidepressants and Hepatotoxicity: A Cohort Study among 5 Million Individuals Registered in the French National Health Insurance Database Hepatotoxicity may be a concern when prescribing antidepressants. Nevertheless, this risk remains poorly understood for serotonin and noradrenaline reuptake inhibitors (SNRIs: venlafaxine, milnacipran, duloxetine) and 'other antidepressants' (mianserin, mirtazapine, tianeptine and agomelatine), particularly in comparison with selective serotonin reuptake (...) 1.07 (0.51-2.23)]. This finding was confirmed by the results of an additional study using a case-time-control design.These results do not provide evidence of an increased risk of serious liver injury following initiation of SNRIs or 'other antidepressants' compared with SSRIs in real-life practice. This could reflect an inherent lack of difference in risk between the drug classes, or the fact that individuals with higher susceptibility to drug-induced liver injury are not prescribed drugs

2018 CNS drugs

155. Effects of Olive Oil supplementation on Sodium Arsenate-induced Hepatotoxicity in Mice Full Text available with Trip Pro

Effects of Olive Oil supplementation on Sodium Arsenate-induced Hepatotoxicity in Mice Sodium arsenate (As), a toxic substance with induced oxidative stress, lead to hepatotoxicity. Olive oil (OO) with antioxidant property has protective effect on toxicity. The aim of this study was to investigate protective effect of OO on sodium As-induced hepatotoxicity in mice.In this experimental study, 32 adult male BALB/c mice were divided randomly into four groups: control group (received only normal (...) saline, the same volume as other groups), OO (0.4 mL/day, gavage), sodium As (15 mg/kg, gavage), and OO + sodium As (received OO 1 h before sodium As). Drugs were given for 30 consecutive days. After the last receipt of the drugs, oxidative stress parameters [malondialdehyde (MDA), glutathione (GSH)] in tissue, liver function parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)] in serum, ferric reducing ability of plasma (FRAP) in plasma

2018 International journal of preventive medicine

156. Polygonum multiflorum Thunb.: A Review on Chemical Analysis, Processing Mechanism, Quality Evaluation, and Hepatotoxicity Full Text available with Trip Pro

Polygonum multiflorum Thunb.: A Review on Chemical Analysis, Processing Mechanism, Quality Evaluation, and Hepatotoxicity Polygonum multiflorum Thunb. and its processed products have been used in China for centuries due to their multiple beneficial effects to human body. Currently, liver injuries caused by taking P. multiflorum have been reported worldwide, but the potential toxic components and possible mechanism that caused hepatotoxicity remain unclear. It is worth noting that the processing (...) and qualitative analysis of P. multiflorum as well as its related species. In addition, the processing mechanism and quality evaluation of processed P. multiflorum are discussed. Moreover, the toxicity of P. multiflorum is analyzed from the perspectives of exploration of the proposed toxic ingredients, metabolite identification, metabolomics studies, and exogenous contaminant determination. Furthermore, trends and perspectives for future research of this medicine are discussed.

2018 Frontiers in pharmacology

157. Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers Full Text available with Trip Pro

Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) analyses and multivariate statistics was implemented (...) to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC) curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury

2018 Disease markers

158. Hepatotoxicity in Advanced Lung Adenocarcinoma: A Retrospective Study of 2108 Cases Full Text available with Trip Pro

no differences were found concerning grade ¾ hepatotoxicity between 844 pemetrexed and 844 non-pemetrexed regimen matched cases (P<0.0001 and P=0.4220, respectively). After first-line treatment, the presence of hepatitis virus (OR 2.905, 95% CI 1.487-5.675; P=0.002) and TKI therapy (OR 2.621, 95% CI 1.809-3.798; P<0.001) were additionally associated with increased hepatotoxicity. Patients with advanced lung adenocarcinoma with younger age, pretreatment liver injury, and presence of hepatitis virus were (...) Hepatotoxicity in Advanced Lung Adenocarcinoma: A Retrospective Study of 2108 Cases The study aimed to identify the risk factors and frequency of hepatotoxicity in patients with advanced lung adenocarcinoma. Liver function tests were documented in 2108 patients with advanced (IIIB/IV) lung adenocarcinoma at a single institution who received first line platinum-based doublet chemotherapy. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version

2018 Journal of Cancer

159. Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity Full Text available with Trip Pro

Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure and remains a critical problem in medicine. PARP1-dependent poly(ADPribosyl)ation is a key mediator of cellular stress responses and functions in multiple physiological and pathological processes. However, whether it is involved in the process of APAP metabolism remains elusive. In this study, we find that PARP1 is activated (...) transcription, thus resulting in increases of APAP pro-toxic metabolism. Additionally, PXR silence antagonizes the effects of PARP1 on APAP-induced hepatotoxicity. These results identifies poly(ADP-ribosyl)ation of PXR by PARP1 as a key step in APAP-induced liver injury. We propose that inhibition of PARP1-dependent poly(ADP-ribosyl)ation might represent a novel approach for the treatment of drug-induced hepatotoxicity.

2018 Cell death & disease

160. Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity Full Text available with Trip Pro

Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity CKA, a chemokine receptor antagonist intended for treating inflammatory conditions, produced dose-dependent hepatotoxicity in rats but advanced into the clinic where single doses of CKA up to 600 mg appeared safe in humans. Because existing toxicological platforms used during drug development are not perfectly predictive, a quantitative systems toxicology model investigated (...) in the rat also contributed. We conclude that mechanistic modeling can elucidate species differences in the hepatotoxic potential of drug candidates.

2018 Toxicological Sciences

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