Pulmonary toxicities of molecular targeted antineoplastic agents: a single-center 10-year experience.

Korean J Intern Med. 2021 Jan 08;:

Authors: Lee MY, Yoon SY, Kim KH, Lee N, Kim HY, Hwang JH, Won JH

Abstract
Background/Aims: A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity.
Methods: We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014.
Results: Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity.
Conclusions: During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.

PMID: 33412778 [PubMed - as supplied by publisher]

[Vaccinovigilance: Reports of adverse reactions in the year 2019].

Schweiz Arch Tierheilkd. 2020 Oct;162(10):617-624

Authors: Zaugg I, Herrmann N, Ottiger H

Abstract
INTRODUCTION: The registration of adverse events after the use of immunological veterinary medicinal products (IVMP) is the aim of the vigilance reporting system in Switzerland. Adverse events comprise suspected adverse reactions and lack of expected efficacy. Since the Institute of virology and immunology (IVI) is the competent authority for the regulation of immunological VMP in Switzerland, the reporting system is administrated by the IVI. In 2019, 137 reports concerning authorized immunological VMP were received (15% less compared to 2018). While most of the reports were submitted by the marketing authorization holders (56%), practicing veterinary surgeons contributed to the reporting system, too (40%). This corresponds to an increase of 22% of reported adverse events by the practicing veterinary surgeons compared to the previous year. Private persons (4%) submitted five reports. In comparison to 2018, in 2019 79% of the adverse events were reported by marketing authorization holders and 18% by veterinarians. Dogs (55%) and cats (20%) were mainly affected. Further reports were related to cattle (13%) and horses (5%). Recently, the numbers of reports concerning dogs (+12%) and cats (+4%) have considerably increased. Most of the reports were based on the application of vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with leptospirosis in dogs as well as cat flu and feline panleukopenia in cats. In 34% of the submitted cases, the causality assessment between the vaccination and the reaction described was evaluated as probable.

PMID: 33006556 [PubMed - indexed for MEDLINE]

Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial.

Clin Trials. 2020 08;17(4):430-436

Authors: Wise RA, Anderson JA, Amarenco P, Cowans NJ, Crim C, Denvir MA, Gomez CR, Jones MP, Morris A, Niewoehner D, Yates JC

Abstract
BACKGROUND: Adjudicated cause-specific mortality has been used in major trials of chronic obstructive pulmonary disease. However, there is less experience with adjudicated major adverse cardiovascular events as a key efficacy outcome in chronic obstructive pulmonary disease trials. The Study to Understand Mortality and Morbidity in chronic obstructive pulmonary disease trial required a Clinical Endpoint Committee to adjudicate the outcomes of modified major adverse cardiovascular events and cause-specific mortality.
METHODS AND RESULTS: A six-member Clinical Endpoint Committee reviewed adverse event and serious adverse event reports included in a list of 204 Medical Dictionary for Regulatory Activities terms. Adverse events were triaged by one Clinical Endpoint Committee member, and then reviewed by three reviewers (round 1). If these three disagreed on the adjudication, the event was discussed by the full committee to reach a consensus (round 2). Among 16,485 participants, 48,105 adverse events were reported, among which 3314 were reviewed by the Clinical Endpoint Committee. After triage, 1827 were adjudicated in round 1; 338 required committee consensus in round 2, yielding 450 myocardial infarctions, strokes, unstable anginas or transient ischaemic attacks. Only 20/1627 (1%) non-serious adverse events were adjudicated as cardiovascular events. Only 45/204 Medical Dictionary for Regulatory Activities terms reviewed yielded cardiovascular events. A total of 430 deaths were adjudicated in round 1 and 631 in round 2, yielding 459 cardiovascular deaths. Adjudication of chest pain and sudden death often required additional information from site investigators. Site assessment of cardiovascular death was moderately specific (501/602 = 83%) but not sensitive (256/459 = 56%).
CONCLUSION: A Clinical Endpoint Committee is useful for adjudication of major adverse cardiovascular events in chronic obstructive pulmonary disease trials but requires considerable resources and effort by investigators. This process can be streamlined by reviewing only serious adverse events and filtering by selected Medical Dictionary for Regulatory Activities terms.

PMID: 32441114 [PubMed - indexed for MEDLINE]

QSAR without borders.

Chem Soc Rev. 2020 06 07;49(11):3525-3564

Authors: Muratov EN, Bajorath J, Sheridan RP, Tetko IV, Filimonov D, Poroikov V, Oprea TI, Baskin II, Varnek A, Roitberg A, Isayev O, Curtarolo S, Fourches D, Cohen Y, Aspuru-Guzik A, Winkler DA, Agrafiotis D, Cherkasov A, Tropsha A

Abstract
Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in chemical sciences. This field of research, broadly known as quantitative structure-activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.

PMID: 32356548 [PubMed - indexed for MEDLINE]

[Medication management of hypertension and heart failure in older patients: What happens to therapeutic changes after hospitalization?]

Ann Cardiol Angeiol (Paris). 2020 Apr;69(2):60-66

Authors: Bouterige A, Mercier J, Makaroff Z, Krolak-Salmon P, Mouchoux C, Novais T

Abstract
PURPOSE: The objective of this study was to objectivize if the cardiovascular therapeutic changes performed during hospitalization of older patients with hypertension and/or heart failure (HF), were maintained in ambulatory 3 month after hospitalization.
METHODS: This is a longitudinal study conducted in a geriatric unit. Patients over 65 years with hypertension and/or HF, who had at least one change in cardiovascular medicaton during hospitalization, and who accepted the 3-month follow-up were included in the longitudinal study. At admission, during hospitalization and 3 months after hospitalization data concerning cardiovascular medication were collected.
RESULTS: During hospitalization, 142 (73.6%) patients had at least one change in hypertension and/or HF medication. Overall, 249 changes were performed. Forty-one patients received follow-up at 3 months. At 3 months, therapeutic changes were maintained by 48.8% of the general practitioners (n=20 patients). For the rest, 41.5% of the patients had benefited from new therapeutic changes (28 changes for 10 patients) and 9.7% of the general practitioners (n=4 patients) had restored the initial prescription before hospitalization.
CONCLUSIONS: Medication review performed by geriatricians and pharmacists during hospitalization resulted in 249 changes. These changes aimed at limiting iatrogenic disease, by reducing overtreatment and potentially inappropriate prescriptions. Difficulties in the patient care continuity between the hospital and ambulatory setting have been identified.

PMID: 32222286 [PubMed - indexed for MEDLINE]

iPS, organoids and 3D models as advanced tools for in vitro toxicology.

ALTEX. 2020;37(1):136-140

Authors: Steimberg N, Bertero A, Chiono V, Dell'Era P, Di Angelantonio S, Hartung T, Perego S, Raimondi MT, Xinaris C, Caloni F, De Angelis I, Alloisio S, Baderna D

PMID: 31960938 [PubMed - indexed for MEDLINE]

12 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 2021/01/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/07

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.

Drugs Affecting Body Weight, Body Fat Distribution, and Metabolic Function-Mechanisms and Possible Therapeutic or Preventive Measures: an Update.

Curr Obes Rep. 2021 Jan 05;:

Authors: Verhaegen AA, Van Gaal LF

Abstract
PURPOSE OF REVIEW: Weight gain and body fat redistribution are common side effects of many widely used drugs. We summarize recent literature on prevalence data and mechanisms associated with drug-induced body fat changes and mechanisms to prevent or treat metabolic side effects.
RECENT FINDINGS: The highest prevalence of metabolic complications is seen with antipsychotics and antiretroviral drugs used in the treatment of HIV and may, at least partly, be responsible for the increased risk for co-morbid diseases such as diabetes, steatosis of the liver, and cardiovascular disease. The pathogenetic mechanisms leading to weight gain from antipsychotics are increasingly known and help to unravel the complex interaction that exists between psychopathology and metabolic complications. Although the classic lipodystrophy mainly occurred with older HIV drugs, also with the newer HIV treatment, weight gain seems to be a major side effect. Early detection of the metabolic consequences of drugs can lead to an early diagnosis of the complications and their treatment. Different medications, including the newer antidiabetics, are being studied in the therapy of drug-induced obesity. Future research should focus on identifying individuals at risk for metabolic side effects and on early markers to identify individuals with side effects so that timely treatment of metabolic complications can be initiated.

PMID: 33400222 [PubMed - as supplied by publisher]

Human papillomavirus vaccine-associated premature ovarian insufficiency and related adverse events: data mining of Vaccine Adverse Event Reporting System.

Sci Rep. 2020 07 01;10(1):10762

Authors: Gong L, Ji HH, Tang XW, Pan LY, Chen X, Jia YT

Abstract
We detected disproportionate reports of premature ovarian insufficiency (POI) and related events, including amenorrhea, menstruation irregular, FSH increased, and premature menopause, following human papillomavirus (HPV) vaccine from FDA Vaccine Adverse Event Reporting System (VAERS). The signal was detected by the methods of Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS). When both methods detected a positive result, a signal was generated. Besides, time-scan map is drawn based on the IC value and 95%CI of BCPNN, if the IC curve showed a steady upward trend and the 95%CI narrowed, the signal was stable and strong association.The results showed that there were not POI reports of HPV vaccine, but VAERS received a total of 2, 389, 27 POI related events for HPV2, HPV4, HPV9 respectively from the year of marketed to 2018. No signal was detected for HPV2. HPV4-POI ralated events were all detected as signals by two methods. There was only one signal of menstruation irregular for HPV9. Time scan of HPV4-POI ralated events showed those signals were stability and strong association, but not for HPV9. Our results only represent statistical association between HPV vaccine and POI related events, causal relationship needs further investigation.

PMID: 32612121 [PubMed - indexed for MEDLINE]

Implementation and comparison of two text mining methods with a standard pharmacovigilance method for signal detection of medication errors.

BMC Med Inform Decis Mak. 2020 05 24;20(1):94

Authors: Eskildsen NK, Eriksson R, Christensen SB, Aghassipour TS, Bygsø MJ, Brunak S, Hansen SL

Abstract
BACKGROUND: Medication errors have been identified as the most common preventable cause of adverse events. The lack of granularity in medication error terminology has led pharmacovigilance experts to rely on information in individual case safety reports' (ICSRs) codes and narratives for signal detection, which is both time consuming and labour intensive. Thus, there is a need for complementary methods for the detection of medication errors from ICSRs. The aim of this study is to evaluate the utility of two natural language processing text mining methods as complementary tools to the traditional approach followed by pharmacovigilance experts for medication error signal detection.
METHODS: The safety surveillance advisor (SSA) method, I2E text mining and University of Copenhagen Center for Protein Research (CPR) text mining, were evaluated for their ability to extract cases containing a type of medication error where patients extracted insulin from a prefilled pen or cartridge by a syringe. A total of 154,209 ICSRs were retrieved from Novo Nordisk's safety database from January 1987 to February 2018. Each method was evaluated by recall (sensitivity) and precision (positive predictive value).
RESULTS: We manually annotated 2533 ICSRs to investigate whether these contained the sought medication error. All these ICSRs were then analysed using the three methods. The recall was 90.4, 88.1 and 78.5% for the CPR text mining, the SSA method and the I2E text mining, respectively. Precision was low for all three methods ranging from 3.4% for the SSA method to 1.9 and 1.6% for the CPR and I2E text mining methods, respectively.
CONCLUSIONS: Text mining methods can, with advantage, be used for the detection of complex signals relying on information found in unstructured text (e.g., ICSR narratives) as standardised and both less labour-intensive and time-consuming methods compared to traditional pharmacovigilance methods. The employment of text mining in pharmacovigilance need not be limited to the surveillance of potential medication errors but can be used for the ongoing regulatory requests, e.g., obligations in risk management plans and may thus be utilised broadly for signal detection and ongoing surveillance activities.

PMID: 32448248 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2021/01/05

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.

QTc Prolongation in COVID-19 Patients Using Chloroquine.

Cardiovasc Toxicol. 2021 Jan 02;:

Authors: Becker ML, Snijders D, van Gemeren CW, Kingma HJ, van Lelyveld SFL, Giezen TJ

Abstract
Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.

PMID: 33387252 [PubMed - as supplied by publisher]

Cancer survivorship: Reproductive health outcomes should be included in standard toxicity assessments.

Eur J Cancer. 2020 Dec 29;144:310-316

Authors: Anderson RA, Clatot F, Demeestere I, Lambertini M, Morgan A, Nelson SM, Peccatori F, Cameron D

Abstract
It is well established that cancer and its treatment, whether by chemotherapy, radiotherapy, hormone therapy, or surgery, can adversely impact reproductive function in both women and men. The effects of cancer treatment on reproductive function in both sexes may lead to loss of fertility, sexual desire and function, and hormone deficiency, which results in additional long-term morbidity in more than a third of patients. Given the importance of reproductive function to most people, and the often devastating effect of cancer treatment on it, we propose that proactive assessment of the functional and endocrinological impact of treatment be made a vital component of the assessment of modern cancer treatment, and should be a routine part of discussions with patients before and after treatment, both in trials and in routine care. Reproductive counselling should be proactive and encouraged, as implementation of such counselling has been shown to be beneficial to patient mental health, quality of life, and adherence to treatment. Similarly, efforts should be made to provide more adequate and accurate information to patients, as well as to offer appropriate fertility preservation approaches, which may potentially influence their treatment decisions.

PMID: 33385947 [PubMed - as supplied by publisher]

Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists.

Drugs. 2020 Jun;80(9):871-882

Authors: Poyurovsky M, Weizman A

Abstract
Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol's side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

PMID: 32385739 [PubMed - indexed for MEDLINE]

Update on Adverse Effects of HIV Integrase Inhibitors.

Curr Treat Options Infect Dis. 2019;11(4):372-387

Authors: Kolakowska A, Maresca AF, Collins IJ, Cailhol J

Abstract
Purpose of review: The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents.
Recent findings: Dolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution.Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Given the importance of cognitive and metabolic co-morbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Pharmacogenetics seems to be a promising tool. Safety during pregnancy is also another important issue to further clarify.
Summary: INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a higher antiviral potency compared to other classes of ARV.Clinicians and patients need however to be aware of some red flags when starting with and monitoring patients on INSTIs.All INSTIs can lead to mild increases in creatinine levels, usually without clinical significance, but caution is needed in patients with low eGFR (<30ml/min), when using other nephrotoxic drugs, such as as tenofovir disoproxil.Neuro-psychiatric (NP) effects are to be monitored with INSTIs, especially with DTG (though reports are at times contradictory); clinicians might want to avoid DTG for patients with history of severe NP symptoms, until clarity is provided.Weight gain was reported with all INSTIs, especially with DTG, with possible differential effects according to sex and ethnicity (female and non-white patients being at increased risk). This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase.Discrepancies between clinical trials - with low rates of adverse events - and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure.Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG.Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster.We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions.Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class.

PMID: 33380904 [PubMed]

Meta-analysis on outcome-worsening comorbidities of COVID-19 and related potential drug-drug interactions.

Pharmacol Res. 2020 11;161:105250

Authors: Awortwe C, Cascorbi I

Abstract
Drug-drug interactions (DDI) potentially occurring between medications used in the course of COVID-19 infection and medications prescribed for the management of underlying comorbidities may cause adverse drug reactions (ADRs) contributing to worsening of the clinical outcome in affected patients. First, we conducted a meta-analysis to determine comorbidities observed in the course of COVID-19 disease associated with an increased risk of worsened clinical outcome from 24 published studies. In addition, the potential risk of DDI between medications used in the course of COVID-19 treatment in these studies and those for the management of observed comorbidities was evaluated for possible worsening of the clinical outcome. Our meta-analysis revealed an implication cardiometabolic syndrome (e.g. cardiovascular disease, cerebrovascular disease, hypertension, and diabetes), chronic kidney disease and chronic obstructive pulmonary disease as main co-morbidities associated with worsen the clinical outcomes including mortality (risk difference RD 0.12, 95 %-CI 0.05-0.19, p = 0.001), admission to ICU (RD 0.10, 95 %-CI 0.04-0.16, p = 0.001) and severe infection (RD 0.05, 95 %-CI 0.01-0.09, p = 0.01) in COVID-19 patients. Potential DDI on pharmacokinetic level were identified between the antiviral agents atazanavir and lopinavir/ritonavir and some drugs, used in the treatment of cardiovascular diseases such as antiarrhythmics and anti-coagulants possibly affecting the clinical outcome including cardiac injury or arrest because of QTc-time prolongation or bleeding. Concluding, DDI occurring in the course of anti-Covid-19 treatment and co-morbidities could lead to ADRs, increasing the risk of hospitalization, prolonged time to recovery or death on extreme cases. COVID-19 patients with cardiometabolic diseases, chronic kidney disease and chronic obstructive pulmonary disease should be subjected to particular carefully clinical monitoring of adverse events with a possibility of dose adjustment when necessary.

PMID: 33059010 [PubMed - indexed for MEDLINE]

Medication Regimen Complexity Index Prediction of Adverse Drug Reaction-Related Hospital Admissions.

Ann Pharmacother. 2020 10;54(10):996-1000

Authors: Curtain CM, Chang JY, Cousins J, Parameswaran Nair N, Bereznicki B, Bereznicki L

Abstract
BACKGROUND: The relationship between the medication regimen complexity index (MRCI) and adverse drug reaction (ADR)-related hospital admissions has not yet specifically been investigated.
OBJECTIVE: To evaluate the MRCI and compare with medication count for prediction of ADR-related hospital admissions in older patients.
METHODS: This was a retrospective analysis of a prospectively collected convenience sample of 768 unplanned medical admissions of Australians aged 65 years old and older. The sample consisted of 115 (15.0%) ADR-related unplanned hospital admissions and 653 (85.0%) non-ADR-related unplanned medical admissions. The MRCI score was calculated from the medical records and analyzed to predict ADR-related hospital admissions.
RESULTS: The cohort had a median age of 81 years, 5 comorbidities, and 11 medications, with a slight majority of women. The MRCI score was not significantly different in patients who had ADR-related admissions compared with other medical admissions-38.5 versus 34.0, respectively; Wilcoxon Rank Sum test W = 33 522; P = 0.067. The medication count was significantly different between the ADR-related admissions compared with other medical admissions: 12 versus 10; W = 32 508; P = 0.021. However, the medication count was not a strong predictor of ADR-related admissions; unadjusted odds ratio = 1.044; 95% CI = 1.006-1.084.
CONCLUSION AND RELEVANCE: The MRCI score did not discriminate between ADR-related admissions and other medical admissions despite taking time to calculate with potential for inconsistent application. Medication count is more readily applicable with marginally greater relevance in this cohort; however, both measures do not appear to be useful when used alone for clinicians to identify patients at risk of ADRs.

PMID: 32349531 [PubMed - indexed for MEDLINE]

An investigation of single-domain and multidomain medication and adverse drug event relation extraction from electronic health record notes using advanced deep learning models.

J Am Med Inform Assoc. 2019 07 01;26(7):646-654

Authors: Li F, Yu H

Abstract
OBJECTIVE: We aim to evaluate the effectiveness of advanced deep learning models (eg, capsule network [CapNet], adversarial training [ADV]) for single-domain and multidomain relation extraction from electronic health record (EHR) notes.
MATERIALS AND METHODS: We built multiple deep learning models with increased complexity, namely a multilayer perceptron (MLP) model and a CapNet model for single-domain relation extraction and fully shared (FS), shared-private (SP), and adversarial training (ADV) modes for multidomain relation extraction. Our models were evaluated in 2 ways: first, we compared our models using our expert-annotated cancer (the MADE1.0 corpus) and cardio corpora; second, we compared our models with the systems in the MADE1.0 and i2b2 challenges.
RESULTS: Multidomain models outperform single-domain models by 0.7%-1.4% in F1 (t test P < .05), but the results of FS, SP, and ADV modes are mixed. Our results show that the MLP model generally outperforms the CapNet model by 0.1%-1.0% in F1. In the comparisons with other systems, the CapNet model achieves the state-of-the-art result (87.2% in F1) in the cancer corpus and the MLP model generally outperforms MedEx in the cancer, cardiovascular diseases, and i2b2 corpora.
CONCLUSIONS: Our MLP or CapNet model generally outperforms other state-of-the-art systems in medication and adverse drug event relation extraction. Multidomain models perform better than single-domain models. However, neither the SP nor the ADV mode can always outperform the FS mode significantly. Moreover, the CapNet model is not superior to the MLP model for our corpora.

PMID: 30938761 [PubMed - indexed for MEDLINE]