Retrospective evaluation of statin prescription in the elderly.

Intern Med J. 2018 Dec;48(12):1463-1471

Authors: Chee WJ, Abdullahi H, Chan Y, Rattle A, Snedden S, Junckerstorff R

Abstract
BACKGROUND: Statins are one of the most commonly prescribed medications in Australia. Although the cardioprotective effects of statins are well documented, questions remain regarding their risk-benefit profile in elderly adults, especially those with limited life expectancies.
AIM: To describe the prevalence and pattern of statin use in elderly patients admitted to a General Medicine Unit.
METHODS: We retrospectively reviewed medical records of patients aged ≥80 years who were admitted to the General Medical Unit at Monash Medical Centre between 1 January 2015 and 30 June 2015. Patients receiving statin therapy prior to admission were identified and included. Data including patient demographics, indication for statin, comorbidities, co-prescription of interacting medications, presence of muscle-related toxicity and any change to statin prescription were collected and described.
RESULTS: Of 852 patients admitted to hospital, 359 (42%) were taking statins prior to admission. Statins were used for the secondary prevention of cardiovascular disease in 63% of patients and for primary prevention in 24%. Most patients were taking high- (16%) or medium-intensity statins (78%); 46% of patients were co-prescribed medications with the potential to increase the risk of statin toxicity. Statins were discontinued in 16% of patients; however, the majority of patients had no change to their statin prescription. Muscle-related toxicity was documented in 4% of patients.
CONCLUSION: Statin use and the co-prescription of potentially interacting medications are common in elderly adults admitted to hospital. Statin prescription in elderly patients with multiple comorbidities is rarely reviewed unless directly relevant to their admission diagnosis.

PMID: 29869449 [PubMed - indexed for MEDLINE]

The adverse effects of interferon-free regimens in 149 816 chronic hepatitis C treated Egyptian patients.

Aliment Pharmacol Ther. 2018 May;47(9):1296-1305

Authors: Attia D, El Saeed K, Elakel W, El Baz T, Omar A, Yosry A, Elsayed MH, Said M, El Raziky M, Anees M, Doss W, El Shazly Y, Wedemeyer H, Esmat G

Abstract
BACKGROUND: Interferon-free regimens are associated with high sustained virological response; however, associated adverse effects have yet to be fully reported.
AIM: To evaluate the adverse effects associated with the different direct-acting antiviral drug (DAA) regimens in Egyptian patients.
METHODS: This multicenter retrospective study included all adverse effects during and after treatment with DAA regimens of 149 816 chronic hepatitis C treated Egyptian patients. Patients received sofosbuvir (SOF)/ribavirin (RBV) (n = 21 835), SOF/simeprevir (n = 24 215) SOF/daclatasvir (DCV) (n = 58 477), SOF/DCV/RBV (n = 45 188) and paritaprevir/ombitasvir/ritonavir/RBV (n = 101). The duration of treatment varied between 12 and 24 weeks. All changes in the treatment regimens, discontinuation, mortality, and serious side effects were reported.
RESULTS: Adverse effects developed in 2475 (1.7%) (mean age [54 ± 9], male gender [53%]) patients. Serious side effects developed in 68% of these patients, and SOF/RBV was the most common causing regimen (73%, P < 0.001). Anaemia and hyperbilirubinemia were the most common side effects (731/149816, 0.5% and 463/149816, 0.3%, respectively) and SOF/RBV (588/21835, 3% and 353/21835, 1.6%, respectively) showed the highest incidence in the treated patients. Hepatocellular carcinoma and mortality were reported in 0.02% and 0.06% of all treated patients, respectively. Patients with liver cirrhosis showed higher incidence of serious side effects (Log rank P = 0.045) and mortality (Log rank P = 0.025) than patients without liver cirrhosis. Male gender (P = 0.012), lower haemoglobin (P < 0.001), platelets (P < 0.001) and albumin (P = 0.001), higher bilirubin (P = 0.002) and cirrhosis (P < 0.001) were factors associated with serious side effects development.
CONCLUSION: Adverse effects associated with DAAs are few, anaemia being the most common. SOF/RBV regimen showed the highest rate of side effects while SOF/DCV showed the least.

PMID: 29504152 [PubMed - indexed for MEDLINE]

Predictors of vasomotor symptoms among breast cancer survivors.

J Cancer Surviv. 2018 06;12(3):379-387

Authors: Reeves KW, Pennell M, Foraker RE, Crandall CJ, Stefanick M, Paskett ED

Abstract
PURPOSE: Vasomotor symptoms (VMS) are a common side effect of breast cancer treatment, yet modifiable factors that may predict VMS among breast cancer survivors are unknown.
METHODS: We estimated multivariable-adjusted odds ratios and 95% confidence intervals (aOR, 95% CI) for predictors of VMS among 3595 breast cancer survivors enrolled in the Life and Longevity after Cancer (LILAC) study, an ancillary study of the Women's Health Initiative (WHI).
RESULTS: VMS post-diagnosis were reported by 790 (22.0%) participants. Risk of VMS after diagnosis was positively associated with prior chemotherapy (aOR 1.80, 95% CI 1.21-2.68) and adjuvant hormone therapy (aOR 2.73, 95% CI 2.08-3.58), postmenopausal hormone therapy use (aOR 1.67, 95% CI 1.30-2.13), prior VMS (aOR 2.20, 95% CI 1.73-2.80), bilateral oophorectomy (aOR 1.77, 95% CI 1.37-2.27), and baseline antidepressant use (aOR 1.49, 1.06-2.09). VMS post-diagnosis were less likely among younger women (aOR 0.94, 95% CI 0.93-0.96), women younger at menopause (aOR 0.98, 95% CI 0.97-1.00), women with more time since diagnosis (aOR 0.92, 95% CI 0.90-0.94), and diabetics (aOR 0.45, 95% CI 0.21-0.95). Metabolic syndrome was not associated with post-diagnosis VMS (aOR 0.76, 95% CI 0.45-1.28).
CONCLUSIONS: VMS following breast cancer diagnosis was related to a number of modifiable factors, but was unrelated to metabolic syndrome.
IMPLICATIONS FOR CANCER SURVIVORS: Identification of factors that predispose women to VMS following a breast cancer diagnosis may allow clinicians to recognize and address VMS in the subset of women who are most likely to experience such symptoms.

PMID: 29427202 [PubMed - indexed for MEDLINE]

History and Future of KALIS: Towards Computer-assisted Decision Making in Prescriptive Medicine.

J Integr Bioinform. 2019 May 30;:

Authors: Friedrichs M, Shoshi A

Abstract
With an increasing older population in Germany and the need for polypharmacy to treat multimorbid patients computer-assisted decision making on an individual level is increasingly important to reduce prescription errors and adverse drug reactions. While current systems focus on guidelines and prescribing information, molecular information is equally important for explanation and discovery of drug-related problems. Based on the existing KALIS system and newer projects like PIMBase, a new concept for the KALIS-2 system is presented. Improvements to the modularisation of components enable future extension and greater maintainability. Interoperability with available electronic health records standards and protocols allows the integration and communication with existing workflows for healthcare professionals. Finally, new visualisation modes empower the user to explore and analyze the patient situation in an individual patient subgraph. For offline use and dialogue between patient and general practitioner, the results can be printed out using a new reporting tool. The adherence to findings from previous decision support systems and reasons for their failed adoption is an important task in the development of KALIS-2.

PMID: 31145693 [PubMed - as supplied by publisher]

IL-15 by continuous i.v. infusion to adult patients with solid tumors in a Phase I trial induced dramatic NK cell subset expansion.

Clin Cancer Res. 2019 May 29;:

Authors: Conlon KC, Potter EL, Pittaluga S, Lee CR, Miljkovic MD, Fleisher TA, Dubois S, Bryant BR, Petrus M, Perera LP, Hsu J, Figg WD, Peer CJ, Shih JH, Yovandich JL, Creekmore SP, Roederer M, Waldmann TA

Abstract
PURPOSE: The first-in-human clinical trial with human bolus i.v. infusion IL-15 (rhIL-15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL-15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial.
EXPERIMENTAL DESIGN: Patients received treatment for 10 days with CIV rhIL-15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 mcg/kg/day. Correlative laboratory tests included IL-15 pharmacokinetic (PK) analyses, and assessment of changes in lymphocyte subset numbers.
RESULTS: Twenty-seven patients were treated with rhIL-15; 2 mcg/kg/day was identified as the maximum tolerated dose (MTD). There were 8 serious adverse events including 2 bleeding events, papilledema, uveitis, pneumonitis, duodenal erosions and 2 deaths (one due to likely drug-related gastrointestinal ischemia). Evidence of antitumor effects were observed in several patients, but stable disease was the best response noted. Patients in 2 mcg/kg/day group had a 5.8-fold increase in number of circulating CD8+ T cells, 38-fold increase in total NK cells, and 358-fold increase in CD56bright NK cells. Serum IL-15 concentrations were markedly lower during the last 3 days of infusion.
CONCLUSIONS: This phase I trial identified the MTD for CIV rhIL-15 and defined a treatment regimen that produced significant expansions of CD8+ T and NK effector cells in circulation and tumor deposits. This regimen has identified several biological features, including dramatic increases in numbers of NK cells, supporting trials of IL-15 with anticancer monoclonal antibodies to increase antibody-dependent cell-mediated cytotoxicity (ADCC) and anticancer efficacy.

PMID: 31142503 [PubMed - as supplied by publisher]

Cyclosporine A and amlodipine induced gingival overgrowth in a kidney transplant recipient: case presentation with literature review.

BMJ Case Rep. 2019 May 28;12(5):

Authors: Nanda T, Singh B, Sharma P, Arora KS

Abstract
Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.

PMID: 31142490 [PubMed - in process]

Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

CNS Drugs. 2018 04;32(4):387-398

Authors: Elmer LW, Juncos JL, Singer C, Truong DD, Criswell SR, Parashos S, Felt L, Johnson R, Patni R

Abstract
BACKGROUND: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRITM) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day.
OBJECTIVE: In this study, we present pooled results from two randomized, double-blind, placebo-controlled, phase III ADS-5102 trials.
PATIENTS AND METHODS: The two studies in PD patients with dyskinesia shared design and eligibility criteria, differing only in treatment duration. Results from common assessment time points were pooled.
RESULTS: At 12 weeks, the least squares (LS) mean change in total score on the Unified Dyskinesia Rating Scale among 100 patients randomized to ADS-5102 and 96 patients randomized to placebo was - 17.7 (standard error [SE] 1.3) vs. - 7.6 (1.3) points, respectively (- 10.1 points, 95% confidence interval [CI] - 13.8, - 6.5; p < 0.0001). The relative treatment difference between groups was 27.3% (p < 0.0001). At 12 weeks, the LS mean change in OFF time was - 0.59 (0.21) vs. +0.41 (0.20) h/day, a difference of - 1.00 h/day (95% CI - 1.57, - 0.44; p = 0.0006). For both efficacy measures, a significant difference from placebo was attained by two weeks, the first post-baseline assessment, and was maintained throughout 12 weeks. In the pooled ADS-5102 group, the most common adverse events were hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension.
CONCLUSIONS: These analyses provide further evidence supporting ADS-5102 as an adjunct to levodopa for treating both dyskinesia and OFF time in PD patients with dyskinesia. Clinicaltrials.gov identifier: NCT02136914 and NCT02274766.

PMID: 29532440 [PubMed - indexed for MEDLINE]

Experts To Address Rare, Toxic Downside of Immunotherapy.

J Natl Cancer Inst. 2017 04 01;109(4):

Authors: Jenks S

PMID: 30053210 [PubMed - indexed for MEDLINE]

Respiratory Fluoroquinolones Monotherapy vs. β-Lactams With or Without Macrolides for Hospitalized Community-Acquired Pneumonia Patients: A Meta-Analysis.

Front Pharmacol. 2019;10:489

Authors: Liu S, Tong X, Ma Y, Wang D, Huang J, Zhang L, Wu M, Wang L, Liu T, Fan H

Abstract
Background: The choice of empirical antibiotic treatment for patients with community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We systematically reviewed the efficacy and safety of strategies of empirical treatment with respiratory fluoroquinolone monotherapy and β-lactam with or without macrolide for non-ICU hospitalized CAP patients. Methods: We searched databases including PubMed, the Cochrane Library (Issue11, 2018), EMbase, China National Knowledge Internet (CNKI), WanFang Data, VIP, and China Biology Medicine disc (CBMdisc) to identify randomized controlled trials (RCTs) involving the comparison of respiratory fluoroquinolone monotherapy and β-lactam with or without macrolide for the non-ICU hospitalized patients with CAP up to November 2018. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was performed with the outcomes. Results: A total of 22 studies involving 6,235 patients were included. The results of the meta-analysis showed a non-significant trend toward an advantage to the respiratory fluoroquinolone in overall mortality (RR 0.82, 95% CI 0.65-1.02). No significant difference was found between the two strategies in clinical success (the intention-to-treat population: RR 1.03, 95% CI 0.99-1.08; the clinically evaluable population: RR 1.03, 95% CI 0.999-1.055; the population in which it was unclear whether intention-to-treat or per-protocol analysis was used: RR 1.04, 95% CI 0.99-1.09), microbiological treatment success (RR 1.04, 95% CI 0.997-1.092), and length of stay (SMD -0.06, 95% CI -0.16 to 0.04). The advantage of respiratory fluoroquinolone was statistically significant on the drug-related adverse events (RR 0.87, 95% CI 0.77-0.97). Conclusions: Current evidence shows that fluoroquinolone monotherapy has similar efficacy and favorable safety compared with β-lactam with or without macrolide for non-ICU hospitalized CAP patients. Since the limitation of region, quantity and quality of included studies, more RCTs with large scale and high quality are needed to verify the above conclusion.

PMID: 31139081 [PubMed]

Similar efficacy and safety of dolutegravir between age groups of HIV-1-infected paediatric and young adult patients aged 5 years and older.

HIV Med. 2019 May 29;:

Authors: Frange P, Avettand-Fenoel V, Veber F, Blanche S

Abstract
OBJECTIVES: The aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir-based regimens among age groups of HIV-1-infected paediatric and young adult patients.
PATIENTS AND METHODS: This retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5-11, 12-17 and 18-25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV-1 RNA copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline), and maintaining virological suppression (PVL < 50 copies/mL) until the last follow-up visit (for all patients).
RESULTS: Most of the subjects were antiretroviral-experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5-11, 12-17 and 18-25 year age groups, respectively). Median follow-up was 24 months (range 6-54 months). Sustained virological success throughout follow-up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; P = 0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug-related side effects.
CONCLUSIONS: The virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.

PMID: 31140725 [PubMed - as supplied by publisher]

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials.

Medicine (Baltimore). 2019 May;98(20):e15731

Authors: Yang W, Li S, Yang Q

Abstract
BACKGROUND: Programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are promising cancer immunotherapy. Their dermatologic safety profiles are still poorly understood. The purpose of this article is to evaluate the incidence of selected dermatologic and mucosal adverse effects (AEs) and determine the risk of developing these adverse events associated with PD-1/PD-L1 inhibitors, compared with chemotherapy or ipilimumab.
METHODS: PubMed was searched for eligible studies (up to February 21, 2019). Only phase II and phase III randomized controlled trials (RCTs) compared with chemotherapy or ipilimumab monotherapy were included in this meta-analysis.
RESULTS: A total 11,465 patients from 18 clinical trials were included in this meta-analysis. Rash and pruritus were the most frequently reported dermatologic AE, with incidence 11.8% and 12.2% respectively. Compared with patients receiving chemotherapy, PD-1/PD-L1 inhibitor treated patients had higher risk of developing rash (RR = 1.84), pruritus (RR = 3.74) and vitiligo (RR = 9.54), and also lower risk in developing mucosal inflammation (RR = 0.26), stomatitis (RR = 0.26), and alopecia (RR = 0.03). Additionally, anti-PD1/PD-L1 drugs had similar risk of developing rash and lower risk of inducing pruritus compared to ipilimumab. In the subgroup analysis, PD-L1 inhibitor demonstrated better safety than PD-1 inhibitor in developing rash, with RR = 1.38 and RR = 2.11, respectively.
CONCLUSION: Our meta-analysis concluded that anti PD-1/PD-L1 drugs have different dermatological and mucosal safety profile compared to conventional therapy, and differences of dermatological toxicity between PD-1 and PD-L1 inhibitor warrant further investigation.

PMID: 31096532 [PubMed - indexed for MEDLINE]

Incidence and predictors of major adverse drug events among drug-resistant tuberculosis patients on second-line anti-tuberculosis treatment in Amhara regional state public hospitals; Ethiopia: a retrospective cohort study.

BMC Infect Dis. 2019 Mar 27;19(1):286

Authors: Merid MW, Gezie LD, Kassa GM, Muluneh AG, Akalu TY, Yenit MK

Abstract
BACKGROUND: Second line anti-tuberculosis drugs are substantially complex, long term, more costly, and more toxic than first line anti-tuberculosis drugs. In Ethiopia, evidence on the incidence and predictors of adverse drug events has been limited. Thus, this study aimed at assessing incidence and predictors of major adverse drug events among drug resistant tuberculosis patients on second line tuberculosis treatment in Amhara Regional State public hospitals, Ethiopia.
METHODS: A multi-center retrospective cohort study was conducted on 570 drug resistant tuberculosis Patients. Data were entered in to EPI-Data version 4.2.0.0 and exported to Stata version 14 for analysis. Proportional hazard assumption was checked. The univariate Weibull regression gamma frailty model was fitted. Cox-Snell residual was used to test goodness of fit and Akaike Information Criteria (AIC) for model selection. Hazard ratio with 95% CI was computed and variables with P-value < 0.05 in the multivariable analysis were taken as significant predictors for adverse drug event.
RESULTS: A total of 570 patients were followed for 5045.09 person-month (PM) observation with a median follow-uptime of 8.23 months (Inter Quartile Range (IQR) =2.66-23.33). The overall incidence rate of major adverse drug events was 5.79 per 100 PM (95% CI: 5.16, 6.49). Incidence rate at the end of 2nd, 4th, and 6th months was 13.73, 9.25, 5.97 events per 100 PM observations, respectively. Age at 25-49 (Adjusted Hazard Ratio (AHR) = 3.36, 95% CI: 1.36, 8.28), and above 50 years (AHR = 5.60, 95% CI: 1.65, 19.05), co-morbid conditions (AHR = 2.74 CI: 1.12, 6.68), and anemia (AHR = 3.25 CI: 1.40, 7.53) were significant predictors of major adverse drug events.
CONCLUSION: The incidence rate of major adverse drug events in the early 6 months of treatment was higher than that of the subsequent months. Age above 25 years, base line anemia, and co-morbid conditions were independent predictors of adverse drug events. Thus, addressing significant predictors and strengthening continuous follow-ups are highly recommended in the study setting.

PMID: 30917788 [PubMed - indexed for MEDLINE]

Adverse events and concurrent medications associated with parenteral nutrition use.

Basic Clin Pharmacol Toxicol. 2019 Feb;124(2):154-162

Authors: Eum S, Ock M, Lee S, Kim H

Abstract
In this study, clinical manifestations of adverse events and frequently used medications in patients receiving parenteral nutrition (PN) in Korea were evaluated using Korea Adverse Event Reporting System (KAERS) database records between 2011 and 2015. Amino acids, fat emulsions, carbohydrates, combinations and solutions for PN were identified as causative agents. Adverse events classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Centre criteria were analysed. In total, 6439 adverse events from 4260 patients were included for analysis. Mean patient age was 54.4 ± 18.1 years and the mean number of adverse events per patient was 1.5 ± 1.1. Frequent adverse events were gastrointestinal (2159 events, 33.5%), skin/appendage (1344 events, 20.9%), general (846 events, 13.1%) and central/peripheral nervous system (716 events, 11.1%) disorders. Common clinical symptoms were nausea (1248 events, 19.4%), vomiting (558, 8.7%), pruritus (456 events, 7.1%), rash (386 events, 6.0%) and dizziness (329 events, 5.1%). The frequently reported concomitant agents were tramadol (n = 475, 3.1%), fentanyl (n = 405, 2.7%), paracetamol (n = 329, 2.2%), ketorolac (n = 322, 2.1%) and metoclopramide (n = 289 cases, 1.9%). The frequent adverse events remained consistent after accounting for concurrent medications. Our findings from a nationwide reporting system database found that gastrointestinal disorders (nausea and vomiting) were the leading adverse events, requiring further studies on their prevalence, mechanisms and therapeutic options.

PMID: 30133153 [PubMed - indexed for MEDLINE]

Cytochrome P450 Structure, Function and Clinical Significance: A Review.

Curr Drug Targets. 2018;19(1):38-54

Authors: Manikandan P, Nagini S

Abstract
BACKGROUND: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism- based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system. Predictions based on in silico analyses followed by validation have identified several microRNAs that regulate CYPs. Genetic polymorphisms and epigenetic changes in CYP genes may be responsible for inter-individual and interethnic variations in disease susceptibility and the therapeutic efficacy of drugs.
OBJECTIVE: The present review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, pharmacoepigenetics and clinical significance.
CONCLUSION: Knowledge about the substrates, inducers, and inhibitors of CYP isoforms, as well as the polymorphisms of CYP enzymes may be used as an aid by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products.

PMID: 28124606 [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")

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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 2019/05/29

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.

An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection.

Clin Mol Hepatol. 2019 May 28;:

Authors: Lee YJ, Heo J, Kim DY, Chung WJ, Tak WY, Kim YJ, Paik SW, Sim E, Kulasingam S, Talwani R, Haber B, Hwang P

Abstract
Background/Aims: In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies.
Methods: This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or ChildPugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA <15 IU/mL).
Results: SVR12 was achieved by 73 of 74 (98.6%) patients. No patients had virologic failure and one discontinued from the study after withdrawing consent. SVR12 rates were uniformly high across all patient subgroups. A total of 16 patients had nonstructural protein 5A resistance-associated substitutions at baseline (16/73, 22%), all of whom achieved SVR12. Adverse events (AEs) reported in >5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs.
Conclusions: In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.

PMID: 31132846 [PubMed - as supplied by publisher]

Phase-1 clinical study of tadalafil administered for selective fetal growth restriction in twin pregnancy.

J Matern Fetal Neonatal Med. 2019 May 26;:1-211

Authors: Magawa S, Nii M, Tanaka H, Furuhashi F, Maki S, Kubo M, Eiji Kondo KT, Ikeda T

Abstract
Background: Selective fetal growth restriction (sFGR) is a condition of twin pregnancy in which the development of one fetus is restricted, despite normal growth of the other fetus. A method of intrauterine therapy for sFGR does not currently exist. The only treatment for sFGR is to terminate the pregnancy before the FGR worsens. In twin pregnancies, maternal and intrauterine environments are common in both fetuses, thus a placental factor is considered the cause of FGR in fetuses. Tadalafil is a phosphodiesterase (PDE)-5 inhibitor that induces an increase in uterine blood flow by dilatation of blood vessels in cases of FGR with placental dysfunction, which improves FGR. Purpose: The aim of this study was to investigate the safety and maximum tolerated dose (MTD) of tadalafil administered for twin pregnancy (diamniotic-monochorionic twin or diamniotic-dichorionic twin). Methods: In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) for twin pregnancy received tadalafil (20 or 40 mg/day) as a single dose by oral administration from the day they were diagnosed with sFGR, defined as estimated fetal weight (EFW) < 3% tiles, that is, -1.8 SD the mean EFW for gestational age (GA) to unacceptable toxicity or the day of delivery. This study evaluated the safety of maternally administered tadalafil for sFGR, examining maternal, fetal, and neonatal adverse events. Maternal adverse events were graded on the basis of the Common Terminology Criteria for Adverse Events v4.0. Results: Six women with sFGR who were pregnant with twins were treated with tadalafil. There were no severe adverse events in either cohort, although the most common (≥ 3 patients) drug-related adverse events were headache and heart failure. The MTD of tadalafil among Japanese patients was 40 mg. Conclusions: Tadalafil has a manageable safety profile up to an MTD of 40 mg/day.

PMID: 31131648 [PubMed - as supplied by publisher]

Complementary medicine use and costs in patients with breast cancer who experienced treatment-related side effects: A cross-sectional survey in Korea.

Complement Ther Med. 2019 Jun;44:210-217

Authors: Han S, Jang BH, Suh HS, Hwang DS

Abstract
OBJECTIVES: Population-based information on the costs of complementary medicine for treatment-related side effects in patients with breast cancer is scarce. We aimed to investigate the prevalence and expenditure on complementary medicine in patients with breast cancer who experienced treatment-related side effects.
DESIGN AND SETTING: Two datasets were analyzed: 1) a 2017 survey on direct and indirect costs for treatment-related side effects, which was completed by 100 patients with stage 0-IV breast cancer, and 2) a Korean representative cross-sectional survey (Patient Survey 2014) that examined the prevalence of integrative medicine in 41 patients with breast cancer.
MAIN OUTCOME MEASURES: The direct and indirect costs for treatment-related side effects.
RESULTS: In the first dataset, the mean total direct medical cost for complementary medicine was US$1,584 and the mean indirect cost was US$6,988 per patient per year. Some patients (6%) visited non-medical institutions to utilize complementary medicine and additionally spent US$460 per patient per year. Approximately one-third of participants reported a substantial-to-heavy financial burden for using complementary medicine. However, only 17% of patients got information about complementary medicine through their physician. In the second dataset, 49% of patients with breast cancer who were discharged from Korean Medicine hospitals in Patient Survey 2014 data indicated that integrative medicine had been used.
CONCLUSIONS: Despite some complementary medicine could be reimbursed by National Health Insurance in Korea, a considerable number of patients reported an economic burden associated with their use of complementary medicine. Strategies for guiding patients to receive evidence-based and cost-effective complementary medicine are needed.

PMID: 31126558 [PubMed - in process]

Melatonin and non-small cell lung cancer: new insights into signaling pathways.

Cancer Cell Int. 2019;19:131

Authors: Pourhanifeh MH, Sharifi M, Reiter RJ, Davoodabadi A, Asemi Z

Abstract
Non-small-cell lung cancer (NSCLC) is a type of malignancy with progressive metastasis having poor prognosis and lowered survival resulting from late diagnosis. The therapeutic approaches for the treatment of this incurable cancer are chemo- and radiotherapy. Since current treatments are insufficient and because of drug-induced undesirable side effects and toxicities, alternate treatments are necessary and critical. The role of melatonin, produced in and released from the pineal gland, has been documented as a potential therapy for NSCLC. Melatonin prevents tumor metastasis via inducing apoptosis processes and restraining the autonomous cell proliferation. Moreover, melatonin inhibits the progression of tumors due to its oncostatic, pro-oxidant and anti-inflammatory effects. As a result, the combined treatment with melatonin and chemotherapy may have a synergistic effect, as with some other tumors, leading to a prolonged survival and improved quality of life in patients with NSCLC. This review summarizes the available data, based on the molecular mechanisms and related signaling pathways, to show how melatonin and its supplementation function in NSCLC.

PMID: 31123430 [PubMed]