Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study.

Lancet Haematol. 2018 Oct;5(10):e450-e461

Authors: Locatelli F, Mauz-Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Suri A, Gore L

Abstract
BACKGROUND: Despite remarkable progress in the treatment of newly-diagnosed classical Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, treatment of relapsed or refractory disease remains challenging. The aims of this study were to assess the safety, tolerability, recommended phase 2 dose, and efficacy of brentuximab vedotin in paediatric patients with relapsed or refractory Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma.
METHODS: This open-label, dose-escalation phase 1/2 study was done at 12 centres across eight countries (France, Germany, Italy, Mexico, The Netherlands, Spain, UK, and USA). We recruited paediatric patients aged 7-18 years with relapsed or refractory classical Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, for whom standard treatment was unavailable or no longer effective. Participants were allocated to receive brentuximab vedotin at 1·4 mg/kg (phase 1) or 1·8 mg/kg (phases 1 and 2) via intravenous infusion once every 3 weeks for up to 16 cycles. Dose escalation was done via a 3+3 design. Key exclusion criteria were stem-cell transplantation less than 3 months before administration of the first dose of study drug, presence of cytomegalovirus infection after allogeneic stem-cell transplantation, previous treatment with an anti-CD30 antibody, and concurrent immunosuppressive or systemic therapy for chronic graft-versus-host disease. Primary outcomes were safety profile in the safety-evaluable population and maximum tolerated dose, recommended phase 2 dose, pharmacokinetics (phase 1), and proportion of patients who achieved best overall response (phase 2; evaluated by an independent review facility) in the response-evaluable population. This trial is registered with ClinicalTrials.gov, number NCT01492088.
FINDINGS: Between April 16, 2012, and April 4, 2016, we screened 41 paediatric patients and enrolled 36 (aged 7-18 years), of whom 19 had relapsed or refractory classical Hodgkin's lymphoma and 17 had relapsed or refractory systemic anaplastic large-cell lymphoma. At the data cutoff (Oct 12, 2016), all 36 patients had discontinued study drug treatment; the most common reason was progressive disease (15 patients). The maximum tolerated dose was not reached. The recommended phase 2 dose was 1·8 mg/kg. The proportion of patients who achieved overall response was 47% (95% CI 21-73) for classical Hodgkin's lymphoma and 53% (28-77) for systemic anaplastic large-cell lymphoma. All 36 patients had a treatment-emergent adverse event and 16 patients (44%) had at least one grade 3 or worse treatment-emergent adverse event. The most common treatment-emergent adverse events were pyrexia (16 [44%] of 36) and nausea (13 [36%]). The most common grade 3 or worse treatment-emergent adverse events were neutropenia (four [11%]), increased γ-glutamyl transpeptidase (two [6%]), and pyrexia (two [6%]). 12 (33%) patients had transient, limited-severity peripheral neuropathy. Eight patients (22%) had a serious adverse event; three (8%) had a drug-related serious adverse event. One patient died of cardiac arrest (disease progression of a large huge mediastinal mass, unrelated to the study drug). Paediatric pharmacokinetic profiles were consistent with those from studies of adult patients.
INTERPRETATION: Brentuximab vedotin has manageable toxicity and is associated with clinically meaningful responses in paediatric patients with relapsed or refractory Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, and could allow subsequent stem-cell transplantation in some patients who were initially ineligible for stem-cell transplantation.
FUNDING: Millennium Pharmaceuticals Inc.

PMID: 30290902 [PubMed - in process]

Impact of novel antifibrotic therapy on patient outcomes in idiopathic pulmonary fibrosis: patient selection and perspectives.

Patient Relat Outcome Meas. 2018;9:321-328

Authors: Graney BA, Lee JS

Abstract
Patients with idiopathic pulmonary fibrosis, an incurable, progressive fibrotic interstitial lung disease, suffer an impaired quality of life due to symptoms, resultant functional limitations, and the constraints of supplemental oxygen. Two antifibrotic medications, nintedanib and pirfenidone, are approved for the treatment of idiopathic pulmonary fibrosis. Both medications slow the rate of decline of lung function, but their effect on patient-reported outcomes is not yet fully understood. Nintedanib may slow the decline in health-related quality of life for treated patients. Pirfenidone may slow the progression of dyspnea and improve cough. Patients and providers should participate in shared decision-making when starting antifibrotic therapy, taking into consideration the benefits of treatment in addition to drug-related side effects and dosing schedules. Although antifibrotic therapy may have an impact on health-related quality of life, providers should also focus on comprehensive care of the patient to improve health-related outcomes. This includes a multidisciplinary evaluation, diagnosis and treatment of comorbid medical conditions, and referral to and participation in a pulmonary rehabilitation program.

PMID: 30288134 [PubMed]

Applications of Machine Learning Methods in Drug Toxicity Prediction.

Curr Top Med Chem. 2018;18(12):987-997

Authors: Zhang L, Zhang H, Ai H, Hu H, Li S, Zhao J, Liu H

Abstract
Toxicity evaluation is an important part of the preclinical safety assessment of new drugs, which is directly related to human health and the fate of drugs. It is of importance to study how to evaluate drug toxicity accurately and economically. The traditional in vitro and in vivo toxicity tests are laborious, time-consuming, highly expensive, and even involve animal welfare issues. Computational methods developed for drug toxicity prediction can compensate for the shortcomings of traditional methods and have been considered useful in the early stages of drug development. Numerous drug toxicity prediction models have been developed using a variety of computational methods. With the advance of the theory of machine learning and molecular representation, more and more drug toxicity prediction models are developed using a variety of machine learning methods, such as support vector machine, random forest, naive Bayesian, back propagation neural network. And significant advances have been made in many toxicity endpoints, such as carcinogenicity, mutagenicity, and hepatotoxicity. In this review, we aimed to provide a comprehensive overview of the machine learning based drug toxicity prediction studies conducted in recent years. In addition, we compared the performance of the models proposed in these studies in terms of accuracy, sensitivity, and specificity, providing a view of the current state-of-the-art in this field and highlighting the issues in the current studies.

PMID: 30051792 [PubMed - indexed for MEDLINE]

Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm.

Biomed Res Int. 2018;2018:1245616

Authors: Chen W, Yang J, Wang HL, Shi YF, Tang H, Li GH

Abstract
Aim: To explore the associations between adverse events and pharmacotherapy in patients with non-small cell lung cancer.
Methods: 16,527 patients with non-small cell lung cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences, between January 1, 2010, and December 31, 2016, were included in the study. Their medication and laboratory examinations data were extracted from the medical records. Common Terminology Criteria for Adverse Events Version 4.03 were utilized for adverse events reporting. A new association algorithm was developed based on Apriori algorithm and used to investigate the associations between drugs and adverse events. In addition, a statistical comparison was conducted to compare the modified Apriori algorithm with the conventional Apriori algorithm.
Results: Different types and levels of adverse events were identified from the abnormal laboratory findings. The three most common adverse events were hypocalcemia, elevated creatine phosphokinase, and hypertriglyceridemia. In addition, using the modified Apriori algorithm, 380 association rules were found between adverse events and chemotherapy. Moreover, the statistical comparison of the two methods demonstrated that the modified Apriori algorithm was more advantageous in analyzing the correlation between drugs and adverse events than the conventional Apriori algorithm.
Conclusions: The modified Apriori algorithm can be used to more efficiently associate pharmacotherapy with adverse events. Based on the modified Apriori algorithm, meaningful association rules between drugs and adverse events were found, demonstrating a promising way to reveal the risk factors of adverse events during cancer treatment.

PMID: 29850483 [PubMed - indexed for MEDLINE]

Oral administration of liquid iron preparation containing excess iron induces intestine and liver injury, impairs intestinal barrier function and alters the gut microbiota in rats.

J Trace Elem Med Biol. 2018 May;47:12-20

Authors: Fang S, Zhuo Z, Yu X, Wang H, Feng J

Abstract
The aim of this study was to determine the toxicological effects of excess iron in a liquid iron preparation (especially on intestinal barrier function) and the possible etiology of side effects or diseases caused by the excess iron. In study 1, forty male Sprague-Dawley rats (4-5 wk old) were subjected to oral gavage with 1 ml vehicle (0.01 mol/L HCl) or 1 ml liquid iron preparation containing 8 mg, 16 mg or 24 mg of iron for 30 d. Iron status, oxidative stress, histology (H&E staining), ultrastructure (electron microscopy) and apoptosis (TUNEL assay) in the intestines and liver were assessed. The cecal microbiota was evaluated by 16S rRNA sequencing. In study 2, twenty rats with the same profile as above were subjected to oral gavage with 1 ml vehicle or 24 mg Fe for 30 d. The intestinal barrier function was determined by in vivo studies and an Ussing chamber assay; tight junction proteins and serum pro-inflammatory cytokines were observed by enzyme-linked immunosorbent assay. In study 1, the intestinal mucosa and liver showed apparent oxidative stress. In addition, iron concentration-dependent ultrastructural alterations to duodenal enterocytes and hepatocytes and histological damage to the colonic mucosa were detected. Notably, apoptosis was increased in duodenal enterocytes and hepatocytes. Impaired intestinal barrier function and lower expression of intestinal tight junction proteins were observed, and the phenotype was more severe in the colon than in the duodenum. A trend toward higher expression of serum pro-inflammatory cytokines might indicate systemic inflammation. Furthermore, the caecal microbiota showed a significant change, with increased Defluviitaleaceae, Ruminococcaceae, and Coprococcus and reduced Lachnospiraceae and Allobaculum, which could mediate the detrimental effects of excess iron on gut health. We concluded that excessive iron exposure from liquid iron preparation induces oxidative stress and histopathological alterations in the intestine and liver. Impaired intestinal barrier function could increase iron transportation, and inflammation along with oxidative stress-enhanced liver iron deposition may cause further liver injury in a vicious circle. These effects were accompanied by lower intestinal segment damage and altered gut microbial composition of rats toward a profile with an increased risk of gut disease.

PMID: 29544798 [PubMed - indexed for MEDLINE]

Adverse drug reactions of analgesic medicines: analysis of the Romanian pharmacovigilance database.

Fundam Clin Pharmacol. 2018 Jun;32(3):330-336

Authors: Cazacu I, Stroe R, Dondera R, Mogosan C, Haramburu F, Fourrier-Réglat A, Loghin F

Abstract
The results of national safety studies are essential for decision-making at the regulatory level and have also educational implications for prescribing patterns. The aim of this study was to analyze the adverse drug reactions (ADRs) of analgesic medicines spontaneously reported to Pharmacovigilance and Risk Management Service of the Romanian National Agency for Medicines and Medical Devices between 2011 and 2015. For the 71 reports, patients had a mean age of 39.8 years; 60.6% of patients were female, and 38% male and 1.4% were unknown. Reporters were mainly physicians (74.7%), and 52.1% of ADR reports were transmitted through marketing authorization holders. Of the serious ADRs (32.4%), 34.7% led to hospitalization or prolonged hospitalization. The most frequent ADRs reported were skin and subcutaneous tissue disorders (25.8%) and general disorders and administration site conditions (19.2%). Metamizole, alone or in combination, was the main analgesic suspected in almost 15.5% of the cases and remains one of the most popular analgesics in Romania. Ten cases were assessed as preventable or potentially preventable (14%), of which two cases were serious. Even if the level of reporting is still low, this study conducted on ADRs of analgesics reported to the national pharmacovigilance center represents an essential step toward promoting the rational use of analgesics in Romania.

PMID: 29314262 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis: A Network Meta-analysis.

JAMA Dermatol. 2018 Oct 03;:

Authors: Torbahn G, Hofmann H, Rücker G, Bischoff K, Freitag MH, Dersch R, Fingerle V, Motschall E, Meerpohl JJ, Schmucker C

Abstract
Importance: Controversies about the choice of antibiotic agent and treatment modality exist in the management of erythema migrans in early cutaneous Lyme borreliosis (LB).
Objective: To conduct a network meta-analysis (NMA) of all randomized clinical trials on various antibiotic agents and treatment modalities in early cutaneous LB.
Data Sources: Electronic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception until July 2017. The reference lists of the included studies were hand searched, authors were contacted, and ongoing trials were searched at ClinicalTrials.gov.
Study Selection: One reviewer screened the titles and abstracts of the 9975 reports identified by the electronic searches. Full-text copies of 161 potentially relevant articles were obtained, and 2 reviewers independently assessed those articles for inclusion. Adults with a physician-confirmed early localized skin infection who were treated with antibiotics of any dose or duration were included.
Data Extraction and Synthesis: Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analyses on treatment effects and adverse outcomes were calculated with a frequentist approach using the R package netmeta. The Grading of Recommendations Assessment, Development and Evaluation guidance for NMA was used to assess the certainty of evidence.
Main Outcomes and Measures: Treatment effects for response to treatment (resolution of symptoms) and treatment-related adverse events.
Results: Overall, 19 studies (2532 patients) were included. The mean patient age ranged between 37 and 56 years, and the percentage of female patients ranged from 36% to 60%. The antibiotics investigated were doxycycline, cefuroxime axetil, ceftriaxone, amoxicillin, azithromycin, penicillin V, and minocycline. Pooled effect sizes from NMAs did not suggest any significant differences in treatment response by antibiotic agent (eg, amoxicillin vs doxycycline odds ratio, 1.26; 95% CI, 0.41-3.87), dose, or duration (eg, doxycycline, 200 mg/d for 3 weeks, vs doxycycline, 200 mg/d for 2 weeks, odds ratio, 1.28; 95% CI, 0.49-3.34). Treatment failures were rare at both 2 months (4%; 95% CI, 2%-5%) and 12 months (2%, 95% CI, 1%-3%) after treatment initiation. There were also no differences in the effect sizes among antibiotic agents and treatment modalities for treatment-related adverse outcomes, which were generally mild to moderate. Certainty of evidence was categorized as low and very low mostly because of imprecision, indirectness, and study limitations (high risk of bias) of the included studies.
Conclusions and Relevance: This NMA suggests that neither the antibiotic agent nor treatment modality contributed to comparative effectiveness or drug-related adverse outcomes. This finding is relevant for physicians treating patients with LB and for patient decision making.

PMID: 30285069 [PubMed - as supplied by publisher]

Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size.

Laryngoscope. 2018 Oct 04;:

Authors: Laidlaw TM, Prussin C, Panettieri RA, Lee S, Ferguson BJ, Adappa ND, Lane AP, Palumbo ML, Sullivan M, Archibald D, Dworetzky SI, Hebrank GT, Bozik ME

Abstract
OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia is a disease of the upper respiratory tract for which few therapies are available. Because the oral investigational drug dexpramipexole serendipitously decreased blood eosinophils in amyotrophic lateral sclerosis studies, we assessed its safety, eosinophil-lowering activity, and preliminary clinical efficacy in patients with CRSwNP and eosinophilia.
METHODS: Sixteen subjects with CRSwNP, absolute eosinophil count (AEC) ≥ 0.300 × 109 /L, and polyp tissue eosinophils were evaluable for efficacy in a 6-month open-label, multi-center study of dexpramipexole 150 mg twice daily. The coprimary endpoints were change in AEC and change in total polyp score (TPS) from baseline to month 6, with additional clinical and histologic endpoints assessed.
RESULTS: Thirteen of 16 subjects completed 6 months of dexpramipexole treatment. Geometric mean baseline AEC was 0.525 ± 0.465 eosinophils × 109 /L and decreased to 0.031 ± 0.019 after 6 months of dexpramipexole treatment, a 94% reduction (P < 0.001). Ten of 16 subjects had eosinophil counts reduced to ≤ 0.020 × 109 /L at month 6. In 12 subjects with nasal polyp biopsies at baseline and month 6, tissue eosinophils were reduced from a mean of 168 ± 134 to 5 ± 2 per high-power field (HPF) (P = 0.001), a 97% reduction from baseline. There was no significant reduction in TPS or improvement in other clinical endpoints. Dexpramipexole was well tolerated, with no drug-related serious adverse events.
CONCLUSION: Dexpramipexole treatment produced profound eosinophil-lowering in peripheral blood and nasal polyp tissue. Despite the near-elimination of polyp eosinophils, decreased TPS and nasal symptom improvement were not observed.
LEVEL OF EVIDENCE: 2. Laryngoscope, 2018.

PMID: 30284267 [PubMed - as supplied by publisher]

Hepatic toxicity following actinomycin D chemotherapy in treatment of familial gestational trophoblastic neoplasia: A case report.

Medicine (Baltimore). 2018 Sep;97(38):e12424

Authors: Mu X, Yin R, Wang D, Song L, Ma Y, Zhao X, Li Q

Abstract
RATIONALE: Familial hydatidiform mole is extremely rare while familial gestational trophoblastic neoplasia (GTN) has never been reported. Inspired by 2 biological sisters with postmolar GTN and liver toxicity, we reviewed susceptible maternal-effect genes and explored the role of possible drug transporter genes in the development of GTN.
PATIENT CONCERNS: We reported one Chinese family where the two sisters developed postmolar GTN while experiencing fast remission and significant hepatic toxicity from actinomycin D chemotherapy.
DIAGNOSES: The index pregnancy was diagnosed with curettage. The following GTN was confirmed when there was a rise in beta-hCG for three consecutive weekly measurements over at least a period of 2 weeks. Computed tomography was used to identify lung metastasis. The elder sister was diagnosed with gestational trophoblastic neoplasia (III: 2) while the younger sister was diagnosed as III: 3 according to WHO scoring system.
INTERVENTIONS: Patients were treated with actinomycin D of 10 μg/kg intravenously for 5 days every 2 weeks. When hepatic toxicity was indicated, polyene phosphatidyl choline and magnesium isoglycyrrhizinate were prescribed.
OUTCOMES: Both patients responded extremely well to the 5-day actinomycin D regimen. Beta-hCG remained less than 2 mIU/ml after 5 cycles while computed tomography scan showed downsized pulmonary nodules. Both experienced significant rise in ALT and AST levels that could be ameliorated with corresponding medication. Monthly followed-up showed negative beta-hCG levels and normal liver enzyme levels.
LESSONS: We speculated that the known or unknown NLRP7 and KHDC3L mutations might be correlated with drug disposition in liver while liver drug transporters such as P-glycoprotein family that are also expressed in trophoblasts might be correlated to GTN susceptibility. Future genomic profiles of large samples alike using next generation sequencing are needed to confirm our hypothesis and discover yet unknown genes.

PMID: 30235719 [PubMed - indexed for MEDLINE]

Signal Detection for Recently Approved Products: Adapting and Evaluating Self-Controlled Case Series Method Using a US Claims and UK Electronic Medical Records Database.

Drug Saf. 2018 05;41(5):523-536

Authors: Zhou X, Douglas IJ, Shen R, Bate A

Abstract
INTRODUCTION: The Self-Controlled Case Series (SCCS) method has been widely used for hypothesis testing, but there is limited evidence of its performance for safety signal detection.
OBJECTIVE: The objective of this study was to evaluate SCCS for signal detection on recently approved products.
METHODS: A retrospective study covered the period after three recently marketed drugs were launched through to 31 December 2010 using The Health Improvement Network, a UK primary care database, and Optum, a US claims database. The SCCS method was applied to examine five heterogenous outcomes with desvenlafaxine and escitalopram and six outcomes with adalimumab for Signals of Disproportional Recording (SDRs); a positive finding was determined to be when the lower bound of 95% Confidence Interval of the incidence rate ratio (IRR) estimate was >  1. Multiple design choices were tested and the trend in IRR estimates over calendar time for one drug event pair was examined.
RESULTS: All six outcomes with adalimumab, three of five outcomes with desvenlafaxine, and four of five outcomes with escitalopram had SDRs. SCCS highlighted all acute events in the primary analysis but was less successful with slower-onset outcomes. Performance varied by risk period definition. Changes in IRR estimates over quarterly intervals for adalimumab with herpes zoster showed marked higher SDR within 9 months of drug launch.
CONCLUSION: SCCS shows promise for signal detection: it may highlight known associations for recent marketed products and has potential for early signal identification. SCCS performance varied by design choice and the nature of both exposure and event pair. Future work is needed to determine how effective the approach is in prospective testing and determining the performance characteristics of the approach.

PMID: 29327136 [PubMed - indexed for MEDLINE]

A Review of Methods for Monitoring Adverse Events in Pediatric Psychopharmacology Clinical Trials.

Drug Saf. 2018 May;41(5):465-471

Authors: Coates M, Spanos M, Parmar P, Chandrasekhar T, Sikich L

Abstract
Pediatric psychotropic prescription rates are rising, emphasizing the need for careful monitoring of drug safety in this population. Currently, no standardized assessments are used in clinical trials for adverse event (AE) elicitation focused on long-term drug treatment in pediatric patients. Despite a lack of standardized AE elicitation methods in psychiatric clinical trials, it is clear that psychiatric medications have developmentally dependent AEs that differ from those observed in adults. In this review, we discuss the use of general inquiry elicitation, drug-specific checklists, and systematic elicitation scales for AE reporting in pediatric psychopharmacology trials. The checklists evaluated include the Barkley Side Effect Rating Scales (SERS), the Pittsburg side effect rating scale, and the Systematic Monitoring of Adverse events Related to TreatmentS (SMARTS) checklist. The systematic assessment scales discussed include the Systematic Assessment for Treatment of Emergent Events (SAFTEE) and the Safety Monitoring Uniform Report Form (SMURF). We review the advantages and disadvantages of each method and discuss the need for optimal assessment of AEs. AE instruments that are created and utilized for pediatric psychiatric trials must begin to incorporate symptoms that are relevant to this population and account for the nature of the disorders to better characterize treatment-emergent AEs and monitor long-term safety.

PMID: 29318515 [PubMed - indexed for MEDLINE]

Adverse Drug Reaction Reports Received Through the Mobile App, VigiBIP®: A Comparison with Classical Methods of Reporting.

Drug Saf. 2018 05;41(5):511-514

Authors: Montastruc F, Bagheri H, Lacroix I, Damase-Michel C, Chebane L, Rousseau V, Jouanjus E, Lapeyre-Mestre M, Durrieu G, Montastruc JL

Abstract
INTRODUCTION: The use of mobile apps is increasing in medicine. In pharmacovigilance, mobile apps may help to increase adverse drug reaction reporting and improve the communication of safety issues. The Toulouse University Pharmacovigilance Center has developed VigiBIP®, a free smartphone app available on Android and Apple stores, for reporting adverse drug reactions and requesting drug safety information.
OBJECTIVE: The present study was performed to compare the main characteristics of spontaneous adverse drug reaction reports received through VigiBIP® with classical methods of reporting (phone, e-mail, fax, letter, website) during 25 months (2015-17).
METHODS: Using the Chi squared test, we compared the type of reporter, adverse drug reaction seriousness, drugs involved and reported ADRs using VigiBIP® and classical methods of reporting RESULTS: A total of 4102 reports were received by the Toulouse University Pharmacovigilance Center, including 4.7% through VigiBip®. Patients' reports were significantly more frequent with VigiBip® (6.7%) than with classical methods (3.4%) [p = 0.01]. Reported adverse drug reactions and involved drugs differed according to the method of reporting used.
CONCLUSION: Our study shows that a mobile app is an additional tool used in pharmacovigilance. Types of reporters and adverse drug reactions in VigiBIP were different to those seen in classical methods of reporting.

PMID: 29270770 [PubMed - indexed for MEDLINE]

Reported Adverse Events with Painkillers: Data Mining of the US Food and Drug Administration Adverse Events Reporting System.

Drug Saf. 2018 Mar;41(3):313-320

Authors: Min J, Osborne V, Kowalski A, Prosperi M

Abstract
INTRODUCTION: One-third of adults in the USA experience chronic pain and use a variety of painkillers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. However, some serious adverse events (AEs), such as cardiovascular incidents, overdose, and death, have been found to be related to painkillers.
METHODS: We used 2015 and 2016 AE reports from the US FDA's Adverse Events Reporting System (FAERS) to conduct exploratory analysis on the demographics of those who reported painkiller-related AEs, examine the AEs most commonly associated with different types of painkillers, and identify potential safety signals. Summary descriptive statistics and proportional reporting ratios (PRRs) were performed.
RESULTS: Out of over 2 million reports submitted to FAERS in 2015 and 2016, a total of 64,354 AE reports were associated with painkillers. Reports of opioid-associated AEs were more likely to be from males or younger patients (mean age 47.6 years). The highest numbers of AEs were reported for NSAID and opioid use, and the most commonly found AEs were related to drug ineffectiveness, administration issues, abuse, and overdose. Death was reported in 20.0% of the reports, and serious adverse reactions, including death, were reported in 67.0%; both adverse outcomes were highest among patients using opioids or combinations of painkillers and were associated with PRRs of 2.12 and 1.87, respectively.
CONCLUSIONS: This study examined the AEs most commonly associated with varying classes of painkillers by mining the FAERS database. Our results and methods are relevant for future secondary analyses of big data and for understanding adverse outcomes related to painkillers.

PMID: 29098610 [PubMed - indexed for MEDLINE]

Emergency department visits caused by adverse drug reactions: results of aTurkish university hospital.

Turk J Med Sci. 2016 Jun 23;46(4):945-52

Authors: Girgin MC, Yanturali S, Arici MA, Çolak Oray N, Doylan Ö, Demiral Y, Tunçok Y

Abstract
BACKGROUND/AIM: We aimed to evaluate adverse drug reaction (ADR)-related emergency department (ED) visits in the ED of the Dokuz Eylül University Hospital prospectively.
MATERIALS AND METHODS: Patients who were admitted to the ED during 1-week periods of four different seasons between July 2010 and April 2011 were enrolled. Demographics of patients, previous ADR history, clinical progress, and outcomes were recorded. Causality assessment was done according to World Health Organization Uppsala Monitoring Centre categories. ADRs were categorized as certain, probable, or possible.
RESULTS: Patients who were on medications (26.5%, n = 1838) were evaluated for ADR-related ED admissions. ADRs accounted for 5.9% of cases (n = 108). The most frequently affected systems were the gastrointestinal (35.2%, n = 38), dermatological (23.1%, n = 25), and hematological (10.2%, n = 11) systems (7.4%, n = 8). The most common causes of ADRs were antiinfectives (31.6%, n = 33). Amoxicillin, Coumadin, and paracetamol were the most common medications that caused ADRs.
CONCLUSION: Nearly 6% of the admissions were ADR-related. ADRs should always be considered when patients who are on medication are admitted to the ED. Multicenter epidemiologic studies are required to know the real rates of ADR cases in EDs in Turkey.

PMID: 27513388 [PubMed - indexed for MEDLINE]

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

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

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

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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.

Stop Chasing One's Tail: Resist the Practice of Treating Serial Side-Effects.

Asian J Psychiatr. 2018 Jan;31:A1-A2

Authors: Bruijnzeel DM, Tandon R

PMID: 29631713 [PubMed - indexed for MEDLINE]