IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial.

Gastroenterology. 2020 Feb 21;:

Authors: Vaezi MF, Fass R, Vakil N, Reasner DS, Mittleman RS, Hall M, Shao JZ, Chen Y, Lane L, Gates AM, Currie MG

Abstract
BACKGROUND AIMS: Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the healthcare system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy.
METHODS: We performed a multicenter, double-blind, placebo-controlled trial from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary end point was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score.
RESULTS: Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 groups (dose-response P=.02). The treatment difference was 11.9% between the 1500-mg IW-3718 and placebo groups (P=.04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500-mg IW-3718 vs placebo groups was a reduction of 17.5% (95% CI, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events.
CONCLUSIONS: In a randomized trial of patients with refractory GERD, adding 1500-mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ClinicalTrials.gov no: NCT02637557.

PMID: 32092310 [PubMed - as supplied by publisher]

A model for an institutional response to the opioid crisis.

J Opioid Manag. 2019 Jan/Feb;16(1):73-83

Authors: Hanna MN, Chambers C, Punyala A, Iqbal A, Singh B, Oruc C, Prakash P, Prajapati Y, Wang Y, Amery Ai Z, Shechter R, Speed TJ, Koch CG, Williams K

Abstract
The use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. Physicians, policymakers, and researchers are focused on finding ways to decrease opioid use and overdose. This crisis calls for a coordinated response that includes the entire healthcare sector. In this work, the authors lay out a blueprint for such a response at the level of the academic medical center. The proposed model is a comprehensive opioid overdose prevention, response, and education program to evaluate, monitor, and address prescription opioid-related adverse events and addiction among all patients within a healthcare system. The approach includes three inter-related elements: (1) creation of an organizational structure that is subdivided into subcommittees to facilitate cross-functional collaboration and implementation. These subcommittees will focus on Research and Design, Implementation, Advisory, and Compliance with the recommendation. (2) Development of an effective communication plan throughout the institution to enable the organization to function seamlessly and efficiently as a single unit, (3) development of a data tracking and reporting system that intended to have a 360° view of all aspects of opioid prescription and downstream patient outcomes. The most effective response system will require an organizational structure that facilitates the ad hoc constitution of cross-functional teams with members drawn from all levels of the organizational hierarchy (executive leadership to frontline staff). Such a structure provides the teams with immediate solutions as developed by the frontline staff and authority to remove institutional barriers that may delay or limit the successful implementation. The model described was developed in our institution by a cross-functional team that included members from the Johns Hopkins School of Medicine and Johns Hopkins University Carey Business School, Department of Operations Management. The multidisciplinary nature of collaboration allowed us to develop a model for an immediate institution-wide response to the opioid crisis, and one that other healthcare organizations could adopt with local modification as a template for execution. The model also meant to serve as a template for an institutional rapid-response that can be seamlessly implemented during any future drug-related crisis or epidemic.

PMID: 32091620 [PubMed - as supplied by publisher]

Preoperative albumin-to-fibrinogen ratio predicts chemotherapy resistance and prognosis in patients with advanced epithelial ovarian cancer.

J Ovarian Res. 2019 Sep 18;12(1):88

Authors: Yu W, Ye Z, Fang X, Jiang X, Jiang Y

Abstract
BACKGROUND: Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery.
METHODS: A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan-Meier method using log-rank test.
RESULTS: The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan-Meier method by log-rank test (P < 0.001).
CONCLUSIONS: A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery.

PMID: 31533857 [PubMed - indexed for MEDLINE]

Assessment of Drugs Toxicity and Associated Biomarker Genes Using Hierarchical Clustering.

Medicina (Kaunas). 2019 Aug 08;55(8):

Authors: Hasan MN, Malek MB, Begum AA, Rahman M, Mollah MNH

Abstract
Background and objectives: Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (expectation-maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. Methods and materials: There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. Results: We observed that Word's HC method with each of Euclidean, Manhattan, and Minkowski distance measures produces better clustering/co-clustering results. For an example, in the case of the glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the peroxisome proliferator-activated receptor signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. Conclusions: Overall, the methods proposed in this article, co-cluster the genes and DDs as well as detect biomarker genes and their regulatory DDs simultaneously consuming less time compared to other mentioned methods. The results produced by the proposed methods have been validated by the available literature and functional annotation.

PMID: 31398888 [PubMed - indexed for MEDLINE]

Adverse events during testosterone replacement therapy in 95 young hypogonadal thalassemic men.

Acta Biomed. 2019 05 23;90(2):228-232

Authors: De Sanctis V, Soliman AT, Daar S, Di Maio S

Abstract
BACKGROUND: Hormonal treatment of hypogonadism in thalassaemia major (TM) is a complex issue due to the co-existence of other contributing factors such as severity of iron overload, associated chronic liver disease and other endocrine complications.
OBJECTIVES: Data about adverse events (AEs) of testosterone replacement therapy (TRT) in hypogonadal males with TM is scarce.We report the adverse events registered during TRT in 95 young patients with TM.
RESULTS: These AEs included gynecomastia, documented in 41/95 (43.1%) TM patients of mild to moderate severity (90%). Persistent pain in the injection site and local reactions to testosterone (T) skin patch occurred in a third of patients. Priapism was reported in 2 patients on treatment with intramuscular T enanthate. In both patients, substitution with T gel was successful, and no recurrence during the following 24 months was observed.
CONCLUSIONS: Clinicians should exercise caution when considering TRT for hypogonadal men with TM. (www.actabiomedica.it).

PMID: 31125000 [PubMed - indexed for MEDLINE]

Causality Assessment of Adverse Drug Reaction: Controlling Confounding Induced by Polypharmacy.

Curr Pharm Des. 2019;25(10):1134-1143

Authors: Dang TT, Nguyen TH, Ho TB

Abstract
BACKGROUND: Post-marketing pharmaceutical surveillance, a.k.a. pragmatic clinical trials (i.e., PCT), plays a vital role in preventing accidents in practical treatment. The most important and difficult task in PCT is to assess which drug causes adverse reactions (i.e., ADRs) from clinical texts. The confounding (i.e., factors cause confusions in causality assessment) is generated by the polypharmacy (i.e., multiple drugs use), which makes most of existing methods poor for detecting drugs that capably cause observed ADRs.
OBJECTIVE: We aim to improve the performance of detecting drug-ADR causal relations from clinical texts. To this end, a mechanism for reducing the impact of confounding on the detecting process is needful.
METHODS: We proposed a novel model which is called the analogy-based active voting (i.e., AAV) for improving the ability of detecting causal drug-ADR pairs, in case multiple drugs are prescribed for treating the comorbidity. This model is inspired by the analogy principle which was proposed by Bradford Hill.
RESULTS: The experimental results show the improvement of recognizing causal relations between drugs and ADRs that are confirmed by the SIDER. In addition, the proposed model is promising to detect infrequently observed causal drug-ADR pairs when the drug is not commonly used.
CONCLUSION: The proposed model demonstrates its ability for controlling the polypharmacy-induced confounding, to improve the quality of causality assessment of ADRs. Additionally, this also shows that the analogy principle is applicable for the assessment.

PMID: 31038058 [PubMed - indexed for MEDLINE]

Computational Drug Designing and Prediction Of Important Parameters Using in silico Methods- A Review.

Curr Comput Aided Drug Des. 2019;15(5):384-397

Authors: Khan T, Lawrence AJ, Azad I, Raza S, Joshi S, Khan AR

Abstract
BACKGROUND: Computational or in silico studies are undertaken to assess the drug like properties of lead compounds. These studies help in fast prediction of relevant properties.
OBJECTIVE: Through this review, an effort is made to encapsulate some of the important parameters which should be met by a compound for it to be considered as a potential drug candidate along with an overview of automated softwares which can be used for making various predictions.
METHODS: Drug uptake, its absorption, evacuation and associated hazardous effects are important factors for consideration in drug designing and should be known in early stages of drug development. Several important physicochemical properties like molecular weight, polar surface area (PSA), molecular flexibility etc. have to be taken into consideration in drug designing. Toxicological assessment is another important aspect of drug discovery which predicts the safety and adverse effects of a drug.
RESULTS: Additionally, bioactivity scores of probable drug leads against various human receptors can also be predicted to evaluate the probability of them to act as a potential drug candidate. The in vivo biological targets of a molecule can also be efficiently predicted by molecular docking studies.
CONCLUSION: Some important software like iGEMDOCK, AutoDock, OSIRIS property explorer, Molinspiration, MetaPrint2D, admetSAR and their working methodology and principle of working have been summarized in this review.

PMID: 30914032 [PubMed - indexed for MEDLINE]

Evaluation of Drugs for Use in Infants and Children: Where Are We Now, and Where Must We Go?

Anesth Analg. 2019 10;129(4):1170-1174

Authors: Brown RE

PMID: 30882517 [PubMed - indexed for MEDLINE]

Efficient methods for signal detection from correlated adverse events in clinical trials.

Biometrics. 2019 09;75(3):1000-1008

Authors: Diao G, Liu GF, Zeng D, Wang W, Tan X, Heyse JF, Ibrahim JG

Abstract
It is an important and yet challenging task to identify true signals from many adverse events that may be reported during the course of a clinical trial. One unique feature of drug safety data from clinical trials, unlike data from post-marketing spontaneous reporting, is that many types of adverse events are reported by only very few patients leading to rare events. Due to the limited study size, the p-values of testing whether the rate is higher in the treatment group across all types of adverse events are in general not uniformly distributed under the null hypothesis that there is no difference between the treatment group and the placebo group. A consequence is that typically fewer than 100 α percent of the hypotheses are rejected under the null at the nominal significance level of α . The other challenge is multiplicity control. Adverse events from the same body system may be correlated. There may also be correlations between adverse events from different body systems. To tackle these challenging issues, we develop Monte-Carlo-based methods for the signal identification from patient-reported adverse events in clinical trials. The proposed methodologies account for the rare events and arbitrary correlation structures among adverse events within and/or between body systems. Extensive simulation studies demonstrate that the proposed method can accurately control the family-wise error rate and is more powerful than existing methods under many practical situations. Application to two real examples is provided.

PMID: 30690717 [PubMed - indexed for MEDLINE]

2019 Taiwan Society of Lipids and Atherosclerosis expert consensus statement on statin intolerance.

J Formos Med Assoc. 2019 Oct;118(10):1385-1392

Authors: Chien SC, Chen PS, Huang YH, Tang SC, Li YH, Yeh HI

Abstract
Statin reduces low-density lipoprotein cholesterol and improves clinical outcomes in high risk patients. In general, statin is a safe and well-tolerated medication. However, varieties of adverse effects are reported in some patients and may interfere long-term drug compliance. Statin-associated muscle events and liver function change account for most of these adverse effects. Patients are regarded as statin intolerance if they need to discontinue statin therapy due to these adverse effects. To date, there is no universal standard definition of statin intolerance. But a pragmatic definition of statin intolerance is essential and helpful for clinicians in daily practice. In this article, after expert consensus meetings and literature review, criteria were recommended to identify patients with statin intolerance in Taiwan. The purpose of this statement is to help health care professionals in Taiwan to diagnose and manage individuals who develop muscular and hepatic side effects after statin therapy.

PMID: 30584005 [PubMed - indexed for MEDLINE]

Clinical Effectiveness of Levetiracetam Compared to Fosphenytoin in the Treatment of Benzodiazepine Refractory Convulsive Status Epilepticus.

Indian J Pediatr. 2020 Feb 22;:

Authors: Nalisetty S, Kandasamy S, Sridharan B, Vijayakumar V, Sangaralingam T, Krishnamoorthi N

Abstract
OBJECTIVES: To determine whether levetiracetam is an alternative to fosphenytoin to control Benzodiazepine Refractory Status Epilepticus (BRSE) in pediatric population and also to compare the acute drug related side-effects and ventilation requirement among the both arms of anti-epileptic drug therapy.
METHODS: All consecutive children admitted with BRSE were randomized to group A, who received fosphenytoin at 20 mg/kg phenytoin equivalents (PE) dose and group B who received levetiracetam at 40 mg/kg over 10 min. Time to terminate seizure (response latency) was measured. If seizure remained refractory after 20 min of test drug administration, appropriate drug escalation was made according to pediatrician's discretion. All primary and secondary outcome measures were compared between the two therapeutic groups.
RESULTS: Of 61 children enrolled over 18 mo period, 29 (47.5%) were randomized to group A and 32 (52.5%) were randomized to Group B. Baseline characteristics were comparable between the two groups. Among 61 children, 58(98%) required Pediatric Intensive Care Unit (PICU) admission and among those 5(8.2%) children required mechanical ventilation. Duration of PICU stay, hospital stay, the response latency and seizure recurrence were compared between both groups. Significant number of children received additional anti-epileptic drugs (AEDs) in fosphenytoin group [9/29(31%)] compared to levetiracetam group [2/32(7%)] to control seizure.
CONCLUSIONS: Levetiracetam may be an effective alternative to fosphenytoin in management of BRSE in children but multicentric trials with large sample size are needed to substantiate this observation.

PMID: 32088913 [PubMed - as supplied by publisher]

Prospective evaluation of fexapotide triflutate injection treatment of Grade Group 1 prostate cancer: 4-year results.

World J Urol. 2020 Feb 22;:

Authors: Shore N, Kaplan SA, Tutrone R, Levin R, Bailen J, Hay A, Kalota S, Bidair M, Freedman S, Goldberg K, Snoy F, Epstein JI

Abstract
PURPOSE: This study was undertaken to determine the safety and efficacy of fexapotide triflutate (FT) 2.5 mg and 15 mg for the treatment of Grade Group 1 prostate cancer.
METHODS: Prospective randomized transrectal intraprostatic single injection FT 2.5 mg (n = 49), FT 15 mg (n = 48) and control active surveillance (AS) (n = 49) groups were compared in 146 patients at 28 U.S. sites, with elective AS crossover (n = 18) to FT after first follow-up biopsy at 45 days. Patients were followed for 5 years including biopsies (baseline, 45 days, and 18, 36, and 54 months thereafter), and urological evaluations with PSA every 6 months. Patients with Gleason grade increase or who elected surgical or radiotherapeutic intervention exited the study and were cumulatively included in the data analysis. Percentage of normal biopsies in baseline focus quadrant, tumor grades, and volumes; and outcomes including Gleason grade in entire prostate as well as treated prostate lobe, interventions associated with Gleason grade increase and total incidence of interventions were assessed.
RESULTS: Significantly improved long-term clinical outcomes were found after 4-year follow-up, with percentages of patients progressing to interventions with and without Gleason grade increase significantly reduced by FT single treatment. Results in the FT 15-mg group were superior to the FT 2.5-mg dose group. There were no drug-related serious adverse events (SAEs).
CONCLUSIONS: FT showed statistically significant long-term efficacy in the treatment of Grade Group 1 patients regarding clinical and pathological progression. FT 15 mg showed superior results to FT 2.5 mg. There were no drug-related SAEs; FT injection was well tolerated.

PMID: 32088746 [PubMed - as supplied by publisher]

22 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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21 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 2020/02/22

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.

Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial.

Lancet Oncol. 2020 Feb 17;:

Authors: Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, Chevreau C, Duffaud F, Entz-Werlé N, Saada E, Ray-Coquard I, Lervat C, Gaspar N, Marec-Berard P, Pacquement H, Wright J, Toulmonde M, Bessede A, Crombe A, Kind M, Bellera C, Blay JY

Abstract
BACKGROUND: Patients with Ewing sarcoma or osteosarcoma have a median overall survival of less than 12 months after diagnosis, and a standard treatment strategy has not yet been established. Pharmacological inhibition of MET signalling and aberrant angiogenesis has shown promising results in several preclinical models of Ewing sarcoma and osteosarcoma. We aimed to investigate the activity of cabozantinib, an inhibitor of MET and VEGFR2, in patients with advanced Ewing sarcoma and osteosarcoma.
METHODS: We did a multicentre, single-arm, two-stage, phase 2 trial in patients with advanced Ewing sarcoma or osteosarcoma recruited from ten centres in the French Sarcoma Group. Key eligibility criteria were aged 12 years or older, Eastern Cooperative Oncology Group performance status of 0-1, and documented disease progression (according to Response Evaluation Criteria in Solid Tumors version 1.1) before study entry. The number of previous lines of treatment was not limited. Patients received cabozantinib (adults 60 mg, children [<16 years] 40 mg/m2) orally once daily in 28-day cycles until disease progression, unacceptable toxicity, the investigator's decision to discontinue, or participant withdrawal. The primary endpoint for Ewing sarcoma was best objective response within 6 months of treatment onset; for osteosarcoma, a dual primary endpoint of 6-month objective response and 6-month non-progression was assessed. All enrolled patients who received at least one dose of cabozantinib were included in the safety analysis, and all participants who received at least one complete or two incomplete treatment cycles were included in the efficacy population. This study was registered with ClinicalTrials.gov, number NCT02243605.
FINDINGS: Between April 16, 2015, and July 12, 2018, 90 patients (45 with Ewing sarcoma 45 with osteosarcoma) were recruited to the study. Median follow-up was 31·3 months (95% CI 12·4-35·4) for patients with Ewing sarcoma and 31·1 months (24·4-31·7) for patients with osteosarcoma. 39 (87%) patients with Ewing sarcoma and 42 (93%) patients with osteosarcoma were assessable for efficacy after histological and radiological review. In patients with Ewing sarcoma, ten (26%; 95% CI 13-42) of 39 patients had an objective response (all partial responses) by 6 months; in patients with osteosarcoma, five (12%; 4-26) of 42 patients had an objective response (all partial responses) and 14 (33%; 20-50) had 6-month non-progression. The most common grade 3 or 4 adverse events were hypophosphataemia (five [11%] for Ewing sarcoma, three [7%] for osteosarcoma), aspartate aminotransferase increase (two [4%] for Ewing sarcoma, three [7%] for osteosarcoma), palmar-plantar syndrome (three [7%] for Ewing sarcoma, two [4%] for osteosarcoma), pneumothorax (one [2%] for Ewing sarcoma, four [9%] for osteosarcoma), and neutropenia (two [4%] for Ewing sarcoma, four [9%] for osteosarcoma). At least one serious adverse event was reported in 61 (68%) of 90 patients. No patients died from drug-related toxic effects.
INTERPRETATION: Cabozantinib has antitumor activity in patients with advanced Ewing sarcoma and osteosarcoma and was generally well tolerated. Cabozantinib could represent a new therapeutic option in this setting, and deserves further investigation.
FUNDING: Institut Bergonié; French National Cancer Institute; Association pour la Recherche contre le Cancer.

PMID: 32078813 [PubMed - as supplied by publisher]

Twenty years of metabonomics: so what has metabonomics done for toxicology?

Xenobiotica. 2020 Jan;50(1):110-114

Authors: Griffin JL

Abstract
In 1999 the journal Xenobiotica published a perspective article detailing the new concept of metabonomics and its application to toxicology. The approach was to apply analytical chemistry techniques, and in particular 1 H NMR spectroscopy, to profile biofluids and tissues to assess the metabolic effects of xenobiotics. Metabonomics has been shown to be sensitive not only to organ specific toxicity but also provides information on the cells, tissues and mechanisms involved, as well as their interactions with the host's sex, age, diet and environment. This review assesses the impact of metabonomics on drug toxicology over the past twenty years and its future prospects. These applications include:Pharmacometabonomics - the prediction of drug effects through the analysis of predose, biofluid metabolite profiles, which reflect both genetic and environmental influences on physiology.The microbiomes role in toxicology - understanding how xenobiotics can be modified by the microbiome dramatically changing their impact on the host.Development of expert systems for toxicity prediction.Data fusion of different omics to better understand the underlying mechanisms of drug toxicity.Metabonomics and exposome - understanding how multiple environmental toxicants might interact with the host organism to produce their overall phenotype. While there has been huge growth in the use of metabonomics within toxicology these applications are set to increase as the tools become more sensitive and robust, as well as the increased use of both experimental and in silico databases to aid prediction of toxicology.

PMID: 31826699 [PubMed - indexed for MEDLINE]

[Attitude Survey Data on Interaction between Dietary Supplements and Medicines].

Yakugaku Zasshi. 2019;139(11):1463-1470

Authors: Ikuta T, Miura T, Shinozuka K

Abstract
Since "Foods with Function Claims" system was established in 2015, the percentage of people taking health foods and supplements is gradually increasing. The number of people taking both dietary supplements and medicines is also increasing. Therefore, providing information on interaction between dietary supplements and medicines has become increasingly important. We have conducted a study for understanding the awareness of the consumers on the interaction of health foods and supplements with medicines. The ratio of those who do not consult with an informed opinion on the interaction between health foods and supplements with medicines was 76% and 55.2% admitted that they did not experience any side effects as a result of this interaction. In conclusion, the understanding of the interaction between health foods and medication among consumers is still limited and most of them do not consult with specialized physicians. It has been revealed that efforts to expanding the consumers understanding on the risk of interaction between supplements and medicines are necessary. It was suggested that the "Database for guiding the interaction between medicines and health foods" could be a useful tool for providing this type of information.

PMID: 31685743 [PubMed - indexed for MEDLINE]

Is hypothyroidism rare in multidrug resistance tuberculosis patients on treatment? A systematic review and meta-analysis.

PLoS One. 2019;14(6):e0218487

Authors: Tola HH, Holakouie-Naieni K, Lejisa T, Mansournia MA, Yaseri M, Tesfaye E, Mola M

Abstract
BACKGROUND: Hypothyroidism is one of the adverse drug reactions that associated with Multidrug Resistant Tuberculosis (MDR-TB) medications. Extremely variable magnitude of hypothyroidism in MDR-TB patients has been reported from different parts of the world. However, there is no evidence that tried to estimate the pooled prevalence of hypothyroidism to confirm the rareness of hypothyroidism in MDR-TB patients on treatment. Therefore, we did a systematic review and meta-analysis to estimate the prevalence of hypothyroidism in MDR-TB patients on treatment, and to summarize the demographic and clinical characteristics of the patients.
METHODS: We conducted a systematic review and meta-analysis on studies reported around the world on the prevalence of hypothyroidism in MDR-TB patients on treatment. We searched electronic databases: PubMed/Medline, EMBASE, CINAHL, Science Direct, Academic Search Complete and Google scholar for English language articles without limiting publication year. We also reviewed the bibliographies of relevant studies and conducted an electronic search for relevant conference abstracts. Eligible studies were cross-sectional and cohort studies that included at least five participants. We used a random-effects model to estimate the pooled prevalence of hypothyroidism. The registration number of this review study protocol is CRD42018109237.
RESULTS: We included 30 studies and pooled data on a total of 6,241 MDR-TB patients. The crude prevalence of hypothyroidism was extremely heterogeneous. The pooled prevalence of hypothyroidism in MDR-TB patients on treatment was 17.0% (95% CI: 13.0-20.0). Ethionamide and para-aminosalicylic acid (PAS) were the most frequently reported drugs that associated with the occurrence of hypothyroidism.
CONCLUSION: This review revealed that hypothyroidism is not a rare adverse drug reaction in MDR-TB patients on treatment. Ethionamide and PAS were the most frequently reported drugs that associated with the occurrence of hypothyroidism. Screening of hypothyroidism in MDR-TB patients on treatment is important while targeting patients on Ethionamide and PAS based treatment regimen.

PMID: 31211809 [PubMed - indexed for MEDLINE]

Comment on: "Quality of electronic records documenting adverse drug reactions…".

N Z Med J. 2019 03 08;132(1491):99-100

Authors: Fountain JS, Kenyon SH

Abstract

PMID: 30845135 [PubMed - indexed for MEDLINE]

Analysis of comprehensive pharmacogenomic profiling to impact in-hospital prescribing.

Pharmacogenet Genomics. 2019 02;29(2):23-30

Authors: Lee YM, Danahey K, Knoebel RW, Ratain MJ, Meltzer DO, O'Donnell PH

Abstract
INTRODUCTION: In-hospital adverse medication events result in increased morbidity and mortality. Many implicated drugs carry pharmacogenomic information. We hypothesized that comprehensive pre-emptive pharmacogenomic profiling could have high relevance for in-hospital prescribing.
PATIENTS AND METHODS: We retrospectively analyzed the in-hospital medications of a genotyped outpatient cohort admitted at our institution from 2012 to 2015. The endpoints were medication changes (new medications initiated, dose adjustments, or medications discontinued) involving drugs with pharmacogenomic annotations from three sources: Clinical Pharmacogenetics Implementation Consortium guidance, Food and Drug Administration label information, and drugs with clinical decision supports in our institutional pharmacogenomic Genomic Prescribing System.
RESULTS: Of 867 genotyped outpatients, 20 were hospitalized (mean: 78.2 years, 65% male). This hospitalized cohort was significantly older (78.2 vs. 61.3 years, P<0.0001) and took more medications (8.9 vs. 5.0 medications, P<0.0001). Out of 159 medication changes made, most (67.9%) were new medications (average: 2.5/hospitalization) with one-third of these having clinically annotated pharmacogenomic information. Half of all hospitalizations involved at least one pharmacogenomic medication. Over half (55%) of the hospitalized cohort was newly prescribed at least one of eight key pharmacogenomic medications, including high-risk drugs such as clopidogrel, codeine, and warfarin.
CONCLUSION: Our study suggested that older patients and those with polypharmacy were at increased risk for hospitalizations, where many new prescriptions included frequently used pharmacogenomic drugs. Targeting this group for pre-emptive genotyping would facilitate the delivery of highly relevant information to inform inpatient prescribing.

PMID: 30531378 [PubMed - indexed for MEDLINE]