Use of over the counter products in older cardiovascular patients admitted to a tertiary care center in USA.

BMC Geriatr. 2018 12 04;18(1):301

Authors: Sheikh-Taha M, Dimassi H

Abstract
BACKGROUND: In recent years there has been a substantial increase in the use of over-the-counter (OTC) products around the world. While they are assumed to be safe by consumers, they can potentially lead to adverse effects and drug interactions particularly in older adults.
METHODS: We assessed the patterns of OTC products used by older adults admitted to the cardiology service in a tertiary care medical center in the USA over a three month period. We conducted a retrospective chart review where older adults with cardiovascular diseases (CVD) who were taking at least one OTC product at home were included.
RESULTS: Out of 404 patients who were admitted to the cardiology service, 281 (69.6%) were taking OTC products. Patients were taking a total of 659 OTC products; mean of 2.35 ± 1.57 and the range varied from 1 to 9 products. The most commonly used products were vitamins (37.3%), followed by laxatives (17%), minerals (13.6%), stomach acid reducers (9%), and analgesics (3.6%). OTC users were found to be suffering from more comorbidities and received more prescription medications as compared to non-users. Gender and age did not have an impact on the use of OTC products while patients with atrial fibrillation, sleep apnea and gastro-esophageal reflux disease were more likely to use OTC products.
CONCLUSION: Use of OTC products is quite frequent in older adults with CVD in our study. Clinicians should ask about OTC product usage and counsel patients about the risks and benefits associated with their use.

PMID: 30514238 [PubMed - indexed for MEDLINE]

Patient preferences concerning the efficacy and side-effect profile of schizophrenia medications: a survey of patients living with schizophrenia.

BMC Psychiatry. 2018 09 12;18(1):292

Authors: Achtyes E, Simmons A, Skabeev A, Levy N, Jiang Y, Marcy P, Weiden PJ

Abstract
BACKGROUND: Despite the availability of numerous antipsychotic medications, many patients with schizophrenia continue to experience side effects that contribute to the overall burden of the illness. The present survey of patients with schizophrenia and schizoaffective disorder aimed to assess patient attitudes toward antipsychotic treatment, and understand key factors about willingness to try a new medication.
METHODS: A cross-sectional survey was administered to 250 patients with a primary clinical diagnosis of a schizophrenia spectrum disorder across five outpatient clinics in the United States. The survey included self-reported gender, age, weight, and height, and questions about the importance of efficacy and side effects on the decision to take a prescribed antipsychotic medication.
RESULTS: Patients rated efficacy and side effects as important attributes of antipsychotic treatment, with 93.6% and 83.6% of patients listing these as "very" or the "most" important factors in taking prescribed medication. A total of 87.6% of respondents identified the ability to think more clearly as an important property of their medication. Patients identified weight gain, physical restlessness, and somnolence as important side effects of current treatments ("very" or "most" important by 61.6%, 60.8%, and 58.8%, respectively). When asked about willingness to change antipsychotic medication, anticipated weight gain had a negative influence on willingness to try the new treatment, with 22.0% declining to try a medication that would lead to weight gain of 2.7-4.5 kg (6-10 lb), 34.0% declining for anticipated weight gain of 5.0-9.1 kg (11-20 lb), and 52.4% declining for anticipated weight gain greater than 9 kg (20 lbs).
CONCLUSION: Patients living with schizophrenia spectrum disorders are influenced by many factors when considering whether to take their medication, including efficacy and side effects. It is important for clinicians to assess specific patient concerns to develop a comprehensive treatment plan that maximizes adherence to the prescribed therapy.

PMID: 30223804 [PubMed - indexed for MEDLINE]

A simple high-dose gentamicin regimen showed no side effects among neonates.

Dan Med J. 2017 Jun;64(6):

Authors: Blaabjerg AS, Kofoed PE, Dalegaard MC, Fenger-Gron J

Abstract
INTRODUCTION: Treatment of infections in neonates with gentamicin is a balance between optimising bactericidal effect and minimising adverse effects. Previously, at the Neonatal Intensive Care Unit (NICU) at Kolding Hospital, Denmark, neonates suspected of having infections were treated daily with gentamicin 5 mg/kg for the first three days, thus exposing the smallest neonates to double gentamicin amounts compared with those used in most Danish NICUs. We aimed to evaluate if this regimen increased the trough values and oto- and nephrotoxicity.
METHODS: Neonates admitted to the NICU between 2008 and 2012 and treated with gentamicin were included retrospectively in the study. Neonates with trough serum (S)-gentamicin level ≥ 2.0 mg/l before the third dose were reviewed in detail.
RESULTS: In total, S-gentamicin level was measured in 253 treated neonates of whom 7% displayed elevated trough values. Neonates < 32 weeks of age had a slightly higher incidence of S-gentamicin level ≥ 2.0 mg/l compared with less premature and mature infants (16%, 13%, and 2%, respectively). No oto- or nephrotoxicity was found despite the high-dose gentamicin regimen.
CONCLUSIONS: The incidence of elevated S-gentamicin trough levels was increased among very premature neonates. However, no evidence of oto- or nephrotoxicity was observed. This simple regimen of gentamicin 5 mg/kg for the first three days should be considered for all neonates as it potentially minimises the risk of dosing errors and bacterial breakthrough infection.
FUNDING: none.
TRIAL REGISTRATION: Danish Data Protection Agency (2008-58-0035).

PMID: 28566120 [PubMed - indexed for MEDLINE]

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Dasatinib can Impair Left Ventricular Mechanical Function But May Lack Proarrhythmic Effect: A Proposal of Non-clinical Guidance for Predicting Clinical Cardiovascular Adverse Events of Tyrosine Kinase Inhibitors.

Cardiovasc Toxicol. 2019 Jul 06;:

Authors: Izumi-Nakaseko H, Fujiyoshi M, Hagiwara-Nagasawa M, Goto A, Chiba K, Kambayashi R, Naito AT, Ando K, Kanda Y, Ishii I, Sugiyama A

Abstract
Tyrosine kinase inhibitors are known to clinically induce various types of cardiovascular adverse events; however, it is still difficult to predict them at preclinical stage. In order to explore how to better predict such drug-induced cardiovascular adverse events, we tried to develop a new protocol by assessing acute electrophysiological, cardiohemodynamic, and cytotoxic effects of dasatinib in vivo and in vitro. Dasatinib at 0.03 and 0.3 mg/kg was intravenously administered to the halothane-anesthetized dogs for 10 min with an interval of 20 min between the dosing (n = 4). Meanwhile, that at 0.1, 0.3, and 1 μM was cumulatively applied to the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) (n = 7). In the dogs, the low and high doses provided peak plasma concentrations of 40 ± 5 (0.08) and 615 ± 38 ng/mL (1.26 μM), respectively. The low dose decreased the heart rate, impaired the left ventricular mechanical function, and prolonged the ventricular effective refractory period. The high dose prolonged the repolarization period, induced hemorrhagic tendency, and increased plasma cardiac troponin I level in addition to enhancement of the changes observed after the low dose, whereas it neither affected the cardiac conduction nor induced ventricular arrhythmias. In the hiPSC-CMs, dasatinib prolonged the repolarization and refractory periods like in dogs, while it did not induce apoptotic or necrotic process, but that it increased the conduction speed. Clinically observed major cardiovascular adverse events of dasatinib were observed qualitatively by currently proposed assay protocol, which may become a useful guide for predicting the cardiotoxicity of new tyrosine kinase inhibitors.

PMID: 31280457 [PubMed - as supplied by publisher]

Increased infection rates associated with tetracycline therapy given for epidermal growth factor receptor inhibitor (EGFRI)-associated acneiform eruption: A retrospective study of data from two cancer centers.

J Am Acad Dermatol. 2019 Jul 04;:

Authors: Magnino MZ, Perry DJ, Subramaniam DS, DeKlotz CMC

PMID: 31279812 [PubMed - as supplied by publisher]

Recent developments in drug-induced movement disorders: a mixed picture.

Lancet Neurol. 2019 Jul 03;:

Authors: Factor SA, Burkhard PR, Caroff S, Friedman JH, Marras C, Tinazzi M, Comella CL

Abstract
A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and inappropriately managed. In particular, second generation antipsychotics, like first generation agents, are associated with potentially debilitating side-effects, most notably tardive syndromes and parkinsonism, as well as potentially fatal acute syndromes. Appropriate, evidence-based management is essential as these drugs are being prescribed to a growing population vulnerable to these side-effects, including children and elderly people. Prevention of the development of drug-induced movement disorders is an important consideration when prescribing medications that can induce movement disorders. Recent developments in diagnosis, such as the use of dopamine transporter imaging for drug-induced parkinsonism, and treatment, with the approval of valbenazine and deutetrabenazine, the first drugs indicated for tardive syndromes, have improved outcomes for many patients with drug-induced movement disorders. Future research should focus on development of safer antipsychotics and specific therapies for the different tardive syndromes and the treatment of drug-induced parkinsonism.

PMID: 31279747 [PubMed - as supplied by publisher]

Evaluation of 8-Week Glecaprevir/Pibrentasvir Treatment in Direct-acting Antiviral -naïve Non-cirrhotic Genotype 1 and 2 HCV Patients in a Real-world Setting in Japan.

J Viral Hepat. 2019 Jul 06;:

Authors: Ikeda H, Watanabe T, Atsukawa M, Toyoda H, Takaguchi K, Nakamuta M, Matsumoto N, Okuse C, Tada T, Tsutsui A, Yamashita N, Kondo C, Hayama K, Kato K, Itokawa N, Arai T, Shimada N, Asano T, Uojima H, Ogawa C, Mikami S, Ikegami T, Fukunishi S, Asai A, Iio E, Tsubota A, Hiraoka A, Nozaki A, Okubo H, Tachi Y, Moriya A, Oikawa T, Matsumoto Y, Tsuruoka S, Tani J, Kikuchi K, Iwakiri K, Tanaka Y, Kumada T, KTK49 Liver Study Group

Abstract
Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV) infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and non-cirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virological response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per protocol population. The SVR12 rates by subgroups were: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among 4 patients with virological failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA naïve non-cirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan. This article is protected by copyright. All rights reserved.

PMID: 31278795 [PubMed - as supplied by publisher]

Nutrition and Breast Cancer: A Literature Review on Prevention, Treatment and Recurrence.

Nutrients. 2019 Jul 03;11(7):

Authors: De Cicco P, Catani MV, Gasperi V, Sibilano M, Quaglietta M, Savini I

Abstract
Breast cancer (BC) is the second most common cancer worldwide and the most commonly occurring malignancy in women. There is growing evidence that lifestyle factors, including diet, body weight and physical activity, may be associated with higher BC risk. However, the effect of dietary factors on BC recurrence and mortality is not clearly understood. Here, we provide an overview of the current evidence obtained from the PubMed databases in the last decade, assessing dietary patterns, as well as the consumption of specific food-stuffs/food-nutrients, in relation to BC incidence, recurrence and survival. Data from the published literature suggest that a healthy dietary pattern characterized by high intake of unrefined cereals, vegetables, fruit, nuts and olive oil, and a moderate/low consumption of saturated fatty acids and red meat, might improve overall survival after diagnosis of BC. BC patients undergoing chemotherapy and/or radiotherapy experience a variety of symptoms that worsen patient quality of life. Studies investigating nutritional interventions during BC treatment have shown that nutritional counselling and supplementation with some dietary constituents, such as EPA and/or DHA, might be useful in limiting drug-induced side effects, as well as in enhancing therapeutic efficacy. Therefore, nutritional intervention in BC patients may be considered an integral part of the multimodal therapeutic approach. However, further research utilizing dietary interventions in large clinical trials is required to definitively establish effective interventions in these patients, to improve long-term survival and quality of life.

PMID: 31277273 [PubMed - in process]

Retrospective analysis of drug therapy problems identified with a telephonic appointment-based model of medication synchronization.

Pharm Pract (Granada). 2019 Apr-Jun;17(2):1373

Authors: Fitzpatrick RM, Witry MJ, Doucette WR, Kent K, Deninger MJ, Mcdonough RP, Veach S

Abstract
Objectives: To describe the drug therapy problems (DTPs) identified for patients enrolled in an Appointment Based Model (ABM) for medication synchronization, describe the pharmacist-delivered clinical interventions, and assess what patient characteristics are associated with the number of DTPs identified.
Methods: A cross-sectional chart review of 1 month of pharmacist notes for telephone ABM encounters at one independent community pharmacy in the Midwest U.S. was performed for a systematic random sample of patients active in the program during September 2017. Included patients were 18 years and older and took one or more synchronized medications. Data included months in the program, gender, age, insurance type, refill interval, medications (synchronized and total), DTP category, and intervention category. Descriptive statistics were calculated, and a multiple linear regression tested the association between patient characteristics and the number of DTPs identified.
Results: The study involved 209 subjects, 54% women, with a mean age of 69.5 years and. The average number of medications synchronized was 4.7, the mean total number of medications was 6.3, and mean length of time in the program was 20 months. The DTPs (n=334) identified included needs additional drug therapy (43.1%), inappropriate adherence (31.4%), unnecessary drug therapy (15.0%), and adverse drug reaction (9.6%). The regression showed age and number of medications was positively associated with number of DTPs identified, but months enrolled was not.
Conclusions: This ABM approach identified several hundred DTPs with corresponding interventions within a one-month period, suggesting that ABMs have a significant potential to improve patient care. The data also suggest that pharmacist interventions within an ABM program are valuable beyond the first few fills as patients move into maintenance use of their medications, especially for patients of advancing age and polypharmacy.

PMID: 31275491 [PubMed]

ODAE: Ontology-based systematic representation and analysis of drug adverse events and its usage in study of adverse events given different patient age and disease conditions.

BMC Bioinformatics. 2019 May 01;20(Suppl 7):199

Authors: Yu H, Nysak S, Garg N, Ong E, Ye X, Zhang X, He Y

Abstract
BACKGROUND: Drug adverse events (AEs), or called adverse drug events (ADEs), are ranked one of the leading causes of mortality. The Ontology of Adverse Events (OAE) has been widely used for adverse event AE representation, standardization, and analysis. OAE-based ADE-specific ontologies, including ODNAE for drug-associated neuropathy-inducing AEs and OCVDAE for cardiovascular drug AEs, have also been developed and used. However, these ADE-specific ontologies do not consider the effects of other factors (e.g., age and drug-treated disease) on the outcomes of ADEs. With more ontological studies of ADEs, it is also critical to develop a general purpose ontology for representing ADEs for various types of drugs.
RESULTS: Our survey of FDA drug package insert documents and other resources for 224 neuropathy-inducing drugs discovered that many drugs (e.g., sirolimus and linezolid) cause different AEs given patients' age or the diseases treated by the drugs. To logically represent the complex relations among drug, drug ingredient and mechanism of action, AE, age, disease, and other related factors, an ontology design pattern was developed and applied to generate a community-driven open-source Ontology of Drug Adverse Events (ODAE). The ODAE development follows the OBO Foundry ontology development principles (e.g., openness and collaboration). Built on a generalizable ODAE design pattern and extending the OAE and NDF-RT ontology, ODAE has represented various AEs associated with the over 200 neuropathy-inducing drugs given different age and disease conditions. ODAE is now deposited in the Ontobee for browsing and queries. As a demonstration of usage, a SPARQL query of the ODAE knowledge base was developed to identify all the drugs having the mechanisms of ion channel interactions, the diseases treated with the drugs, and AEs after the treatment in adult patients. AE-specific drug class effects were also explored using ODAE and SPARQL.
CONCLUSION: ODAE provides a general representation of ADEs given different conditions and can be used for querying scientific questions. ODAE is also a robust knowledge base and platform for semantic and logic representation and study of ADEs of more drugs in the future.

PMID: 31074377 [PubMed - indexed for MEDLINE]

[Self and hetero evaluation of cancer treatment side effects].

Rev Prat. 2019 Jan;69(1):55-57

Authors: Di Palma M

Abstract
Self and hetero evaluation of cancer treatment side effects. The accurate and continuous assessment of the side effects of cancer treatments is a major factor in the quality of patient care. The combination of self-evaluation by the patient himself and hetero-evaluation by health professionals makes it possible to optimize the follow-up of the patients and to better adapt the therapeutics. The use of connected devices and modern communication tools fits in perfectly with the need for regular monitoring of patients, which also makes the best use of professional resources.

PMID: 30983285 [PubMed - indexed for MEDLINE]

Neighborhood Greenness Attenuates the Adverse Effect of PM2.5 on Cardiovascular Mortality in Neighborhoods of Lower Socioeconomic Status.

Int J Environ Res Public Health. 2019 03 06;16(5):

Authors: Yitshak-Sade M, James P, Kloog I, Hart JE, Schwartz JD, Laden F, Lane KJ, Fabian MP, Fong KC, Zanobetti A

Abstract
Features of the environment may modify the effect of particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) on health. Therefore, we investigated how neighborhood sociodemographic and land-use characteristics may modify the association between PM2.5 and cardiovascular mortality. We obtained residence-level geocoded cardiovascular mortality cases from the Massachusetts Department of Public Health (n = 179,986), and PM2.5 predictions from a satellite-based model (2001⁻2011). We appended census block group-level information on sociodemographic factors and walkability, and calculated neighborhood greenness within a 250 m buffer surrounding each residence. We found a 2.54% (1.34%; 3.74%) increase in cardiovascular mortality associated with a 10 µg/m³ increase in two-day average PM2.5. Walkability or greenness did not modify the association. However, when stratifying by neighborhood sociodemographic characteristics, smaller PM2.5 effects were observed in greener areas only among cases who resided in neighborhoods with a higher population density and lower percentages of white residents or residents with a high school diploma. In conclusion, the PM2.5 effects on cardiovascular mortality were attenuated by higher greenness only in areas with sociodemographic features that are highly correlated with lower socioeconomic status. Previous evidence suggests health benefits linked to neighborhood greenness may be stronger among lower socioeconomic groups. Attenuation of the PM2.5⁻mortality relationship due to greenness may explain some of this evidence.

PMID: 30845676 [PubMed - indexed for MEDLINE]

Utilizing Twitter data for analysis of chemotherapy.

Int J Med Inform. 2018 12;120:92-100

Authors: Zhang L, Hall M, Bastola D

Abstract
OBJECTIVE: Twitter has become one of the most popular social media platforms that offers real-world insights to healthy behaviors. The purpose of this study was to assess and compare perceptions about chemotherapy of patients and health-care providers through analysis of chemo-related tweets.
MATERIALS AND METHODS: Cancer-related Twitter accounts and their tweets were obtained through using Tweepy (Python library). Multiple text classification algorithms were tested to identify the models with best performance in classifying the accounts into individual and organization. Chemotherapy-specific tweets were extracted from historical tweetset, and the content of these tweets was analyzed using topic model, sentiment analysis and word co-occurrence network.
RESULTS: Using the description in Twitter users' profiles, the accounts related with cancer were collected and coded as individual or organization. We employed Long Short Term Memory (LSTM) network with GloVe word embeddings to identify the user into individuals and organizations with accuracy of 85.2%. 13, 273 and 14,051 publicly available chemotherapy-related tweets were retrieved from individuals and organizations, respectively. The content of the chemo-related tweets was analyzed by text mining approaches. The tweets from individual accounts pertained to personal chemotherapy experience and emotions. In contrast with the personal users, professional accounts had a higher proportion of neutral tweets about side effects. The information about the assessment of response to chemotherapy was deficient from organizations on Twitter.
DISCUSSION: Examining chemotherapy discussions on Twitter provide new lens into content and behavioral patterns associated with treatments for cancer patients. The methodology described herein allowed us to collect relatively large number of health-related tweets over a greater time period and exploit the potential power of social media, which provide comprehensive view on patients' perceptions of chemotherapy.
CONCLUSION: This study sheds light on using Twitter data as a valuable healthcare data source for helping oncologists (organizations) in understanding patients' experiences while undergoing chemotherapy, in developing personalize therapy plans, and a supplement to the clinical electronic medical records (EMRs).

PMID: 30409350 [PubMed - indexed for MEDLINE]

Authenticity and credibility aware detection of adverse drug events from social media.

Int J Med Inform. 2018 12;120:157-171

Authors: Hoang T, Liu J, Pratt N, Zheng VW, Chang KC, Roughead E, Li J

Abstract
OBJECTIVES: Adverse drug events (ADEs) are among the top causes of hospitalization and death. Social media is a promising open data source for the timely detection of potential ADEs. In this paper, we study the problem of detecting signals of ADEs from social media.
METHODS: Detecting ADEs whose drug and AE may be reported in different posts of a user leads to major concerns regarding the content authenticity and user credibility, which have not been addressed in previous studies. Content authenticity concerns whether a post mentions drugs or adverse events that are actually consumed or experienced by the writer. User credibility indicates the degree to which chronological evidence from a user's sequence of posts should be trusted in the ADE detection. We propose AC-SPASM, a Bayesian model for the authenticity and credibility aware detection of ADEs from social media. The model exploits the interaction between content authenticity, user credibility and ADE signal quality. In particular, we argue that the credibility of a user correlates with the user's consistency in reporting authentic content.
RESULTS: We conduct experiments on a real-world Twitter dataset containing 1.2 million posts from 13,178 users. Our benchmark set contains 22 drugs and 8089 AEs. AC-SPASM recognizes authentic posts with F1 - the harmonic mean of precision and recall of 80%, and estimates user credibility with precision@10 = 90% and NDCG@10 - a measure for top-10 ranking quality of 96%. Upon validation against known ADEs, AC-SPASM achieves F1 = 91%, outperforming state-of-the-art baseline models by 32% (p < 0.05). Also, AC-SPASM obtains precision@456 = 73% and NDCG@456 = 94% in detecting and prioritizing unknown potential ADE signals for further investigation. Furthermore, the results show that AC-SPASM is scalable to large datasets.
CONCLUSIONS: Our study demonstrates that taking into account the content authenticity and user credibility improves the detection of ADEs from social media. Our work generates hypotheses to reduce experts' guesswork in identifying unknown potential ADEs.

PMID: 30409341 [PubMed - indexed for MEDLINE]

Authenticity and credibility aware detection of adverse drug events from social media.

Int J Med Inform. 2018 12;120:101-115

Authors: Hoang T, Liu J, Pratt N, Zheng VW, Chang KC, Roughead E, Li J

Abstract
OBJECTIVES: Adverse drug events (ADEs) are among the top causes of hospitalization and death. Social media is a promising open data source for the timely detection of potential ADEs. In this paper, we study the problem of detecting signals of ADEs from social media.
METHODS: Detecting ADEs whose drug and AE may be reported in different posts of a user leads to major concerns regarding the content authenticity and user credibility, which have not been addressed in previous studies. Content authenticity concerns whether a post mentions drugs or adverse events that are actually consumed or experienced by the writer. User credibility indicates the degree to which chronological evidence from a user's sequence of posts should be trusted in the ADE detection. We propose AC-SPASM, a Bayesian model for the authenticity and credibility aware detection of ADEs from social media. The model exploits the interaction between content authenticity, user credibility and ADE signal quality. In particular, we argue that the credibility of a user correlates with the user's consistency in reporting authentic content.
RESULTS: We conduct experiments on a real-world Twitter dataset containing 1.2 million posts from 13,178 users. Our benchmark set contains 22 drugs and 8089 AEs. AC-SPASM recognizes authentic posts with F1 - the harmonic mean of precision and recall of 80%, and estimates user credibility with precision@10 = 90% and NDCG@10 - a measure for top-10 ranking quality of 96%. Upon validation against known ADEs, AC-SPASM achieves F1 = 91%, outperforming state-of-the-art baseline models by 32% (p < 0.05). Also, AC-SPASM obtains precision@456 = 73% and NDCG@456 = 94% in detecting and prioritizing unknown potential ADE signals for further investigation. Furthermore, the results show that AC-SPASM is scalable to large datasets.
CONCLUSIONS: Our study demonstrates that taking into account the content authenticity and user credibility improves the detection of ADEs from social media. Our work generates hypotheses to reduce experts' guesswork in identifying unknown potential ADEs.

PMID: 30409335 [PubMed - indexed for MEDLINE]

The Application of Machine Learning Techniques in Clinical Drug Therapy.

Curr Comput Aided Drug Des. 2019;15(2):111-119

Authors: Meng HY, Jin WL, Yan CK, Yang H

Abstract
INTRODUCTION: The development of a novel drug is an extremely complicated process that includes the target identification, design and manufacture, and proper therapy of the novel drug, as well as drug dose selection, drug efficacy evaluation, and adverse drug reaction control. Due to the limited resources, high costs, long duration, and low hit-to-lead ratio in the development of pharmacogenetics and computer technology, machine learning techniques have assisted novel drug development and have gradually received more attention by researchers.
METHODS: According to current research, machine learning techniques are widely applied in the process of the discovery of new drugs and novel drug targets, the decision surrounding proper therapy and drug dose, and the prediction of drug efficacy and adverse drug reactions.
RESULTS AND CONCLUSION: In this article, we discussed the history, workflow, and advantages and disadvantages of machine learning techniques in the processes mentioned above. Although the advantages of machine learning techniques are fairly obvious, the application of machine learning techniques is currently limited. With further research, the application of machine techniques in drug development could be much more widespread and could potentially be one of the major methods used in drug development.

PMID: 29804538 [PubMed - indexed for MEDLINE]

Hepatotoxicity After Immune Checkpoint Inhibitor Therapy in Melanoma: Natural Progression and Management.

Am J Clin Oncol. 2018 08;41(8):760-765

Authors: Huffman BM, Kottschade LA, Kamath PS, Markovic SN

Abstract
OBJECTIVE: To report the clinical features, treatment, and outcomes of patients with immune checkpoint inhibitor-induced hepatotoxicity.
PATIENTS AND METHODS: In this retrospective observational study, we identified patients with metastatic malignant melanoma seen in consultation and/or treated between March 2011 and March 2016. Hepatotoxicity was assessed using the Common Terminology Criteria for Adverse Events, v4.0.
RESULTS: Seventeen patients were identified as having any degree of hepatotoxicity by history (grade 1 to 4). Twelve of 17 were diagnosed after ipilimumab, 3 of 17 were diagnosed after pembrolizumab, and 2 of 17 after ipilimumab combined with nivolumab. Median time from first dose of immune therapy to hepatotoxicity was 52 days. Clinical symptoms were variable: asymptomatic, fatigue, myalgias, headache, abdominal pain, nausea, vomiting, confusion, and/or jaundice. Eight patients had concurrent adverse events including colitis, hypophysitis, pneumonitis, and/or rash. Immune therapy was discontinued in all patients except 3. The patients were most commonly treated with systemic corticosteroids such as prednisone. Immunosuppression was discontinued by taper over a median of 42 days; in 3 patients steroids had to be reinitiated based on clinical or laboratory worsening of liver tests. Normalization of liver tests was seen within a median of 31 days of immunosuppression initiation. One patient with grade 4 hepatotoxicity had normalization with the addition of cyclosporine.
CONCLUSIONS: Melanoma patients treated with immune checkpoint inhibitors should be monitored regularly for hepatotoxicity. Treatment with discontinuation of therapy and initiation of corticosteroids is indicated with grade 3 or 4 hepatotoxicity. Cyclosporine may be beneficial in steroid-refractory hepatotoxicity.

PMID: 28749795 [PubMed - indexed for MEDLINE]

Third-line Salvage Chemotherapy for Recurrent Carcinoma of the Cervix is Associated With Minimal Response Rate and High Toxicity.

Am J Clin Oncol. 2018 08;41(8):797-801

Authors: Manders DB, Kehoe SM, Miller DS, Lea JS, Richardson DL

Abstract
BACKGROUND: Metastatic and recurrent cervical cancer is rarely a curable disease. Systemic chemotherapy is typically recommended for treatment based on clinical trials in the first-line or second-line setting. Rare patients who progress through 2 salvage regimens will have the performance status, medical ability, and desire to continue cytotoxic therapy. For these patients, there are no data to provide effective counseling regarding expected response rates (RRs) and toxicities. We sought to review our experience with this patient population.
METHODS: A single institution review was performed of all patients treated for cervical cancer between January 1, 2000 and June 30, 2013. Eligible patients were those who received at least 3 unique salvage chemotherapy regimens following primary surgery or radiation. RRs, survival statistics and toxicities were evaluated.
RESULTS: Twenty-three of 710 (3.2%) patients treated for cervical cancer met eligibility criteria. Nineteen received 2 or more cycles of a third-line regimen and were assessed for response and progression-free survival. The remainder were included in analysis of overall survival and toxicity. The RR to third-line chemotherapy was 10% (1 complete, 1 partial). An additional 27% achieved stable disease. In total, 57% suffered a grade 3 or 4 toxicity. The progression-free survival from the beginning of third-line therapy was 3.8 months, and the overall survival was 7.4 months.
CONCLUSIONS: Patients eligible to receive third-line chemotherapy for metastatic and recurrent cervical cancer can expect minimal benefit at the cost of significant toxicity. Quality of life considerations should be of paramount importance when counseling regarding the risks and benefits of further cytotoxic therapy.

PMID: 28225444 [PubMed - indexed for MEDLINE]

Safety and Effectiveness Analysis of Kivexa® (lamivudine/abacavir sulfate) in Human Immunodeficiency Virus Infected Korean Patients.

Infect Chemother. 2019 Jun;51(2):150-160

Authors: Ann H, Lee YS, Kim YS, Jung SI, Lee SH, Lee CS, Lee JS, Choi WS, Choi YH, Kim SW

Abstract
BACKGROUND: Lamivudine and abacavir sulfate are widely used nucleoside/tide reverse transcriptase inhibitors (NRTI) backbone agents, which are recommended in major international treatment guidelines. The fixed-dose combination of lamivudine and abacavir sulfate has been developed to contribute to low pill burden of antiretroviral therapy (ART) regimen and patient adherence. A mandatory post-marketing surveillance was conducted in Korea to monitor the safety of Kivexa (lamivudine 300 mg/abacavir 600 mg).
MATERIALS AND METHODS: An open label, multi-center, non-interventional post-marketing surveillance was conducted to monitor the safety of Kivexa from July 2011 to July 2017 in 23 hospitals in Korea. Subjects over 12 years old taking Kivexa per prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events during the study period. Secondary outcomes included the occurrence of adverse drug reaction, the occurrence of serious adverse events and the effectiveness of Kivexa.
RESULTS: A total of 600 patients from 23 hospitals were enrolled within the 6 years of study. The total observation period was 1,004 person-years. Three hundred and ten patients reported 674 adverse events. The incidence of upper respiratory infection (65 cases, 10.9%) was the highest, followed by diarrhea (20 cases, 3.3%), and nausea (18 cases, 3.0%). 109 subjects reported 71 events of adverse drug reactions, and the most common reaction was nausea in 2.33% of the subjects. Thirty-one subjects reported serious adverse events, none of them were considered drug related. From the total of 600 subjects, excluding 48 subjects who were 'effectiveness unassessable' by investigators, 552 patients were eligible for the subjective effectiveness analysis. 459 (83.2%) were evaluated as 'improved'. Proportion of subjects whose human immunodeficiency virus-RNA is <50 copies/ml was 61.2% (309/505) at the beginning of observation and increased to 91.9% (464/505) at the end of study period.
CONCLUSIONS: The post-marketing surveillance showed the safety of Kivexa in HIV-1 patients in Korea. Ischemic cardiovascular events and hypersensitivity associated with Kivexa were few. There was no significant new safety information. This data may be helpful in implementing Kivexa and lamivudine/abacavir sulfate containing drugs in Korea.

PMID: 31270994 [PubMed]