Quality of electronic records documenting adverse drug reactions within a hospital setting: identification of discrepancies and information completeness.

N Z Med J. 2019 01 18;132(1488):28-37

Authors: Braund R, Lawrence CK, Baum L, Kessler B, Vassart M, Coulter C

Abstract
AIM: Incomplete and incorrect documentation of adverse drug reactions (ADRs) can restrict prescribing choices resulting in suboptimal pharmaceutical care. This study aimed to examine the quality of information held within electronic systems in a hospital setting, to determine the preciseness of ADR documentation, and identify discrepancies where multiple electronic systems are utilised.
METHOD: Over a four-week period, consecutive patients admitted to the general medical ward at the study hospital had their electronic profiles reviewed. Patient demographic information (de-identified), ADR history and discrepancies between information sources (as recorded in all electronic systems utilised at initial prescribing) were recorded and analysed.
RESULTS: Over the four-week period, 332 patient profiles were reviewed, and over 1,200 alerts were identified and analysed (including duplicates of ADR reactions). Of these patients, 151 (45.5%) had at least one documented allergy or intolerance which generated 585 reactions, relating to 526 unique events. A further 151 (45.5%) were classified as having no known (drug) allergies or intolerances; however, 20 (15%) of these patients did have at least one allergy documented in at least one other electronic system. The remaining 30 (9%) patients were classified as having an unknown allergy status and of those nine had allergies documented in at least one other electronic system. Further, most systems contained information duplication, which had not been addressed during the admission process.
CONCLUSION: ADR information was both imprecise and inaccurate, as multiple discrepancies between ADR information recorded in different electronic patient management systems were found to exist. Information sharing between systems needs to be prioritised in order to allow full, accurate and complete ADR information to be collected, stored and utilised; both to reduce current inadequacies and to allow optimal pharmaceutical care.

PMID: 31851659 [PubMed - indexed for MEDLINE]

Purging with chlorambucil to prevent infusion-related reaction before obinutuzumab administration: A monocentric pilot experience.

Hematol Oncol. 2019 Dec;37(5):641-643

Authors: Autore F, Fresa A, Innocenti I, Tomasso A, Morelli F, Corbingi A, Sorà F, Laurenti L

PMID: 31604368 [PubMed - indexed for MEDLINE]

Persistent adverse effects of antidepressants.

Epidemiol Psychiatr Sci. 2019 Sep 23;29:e56

Authors: Moncrieff J

PMID: 31543093 [PubMed - indexed for MEDLINE]

Use of renal risk drugs in a nation-wide Polish older adult population: an analysis of PolSenior database.

BMC Geriatr. 2019 03 05;19(1):70

Authors: Deskur-Śmielecka E, Chudek J, Neumann-Podczaska A, Mossakowska M, Wizner B, Wieczorowska-Tobis K

Abstract
BACKGROUND: Numerous medications should be avoided, or require dose adjustment in subjects with impaired kidney function. We aimed to assess the prevalence of potentially inappropriate use of renal risk drugs in a nation-wide, community-dwelling Polish older adult population.
METHODS: We analysed regular intake of 38 medications that should be avoided, requiring dose modification, increase the risk of pre-renal kidney injury, or may cause potassium retention in subjects with moderately to severely impaired renal function in the PolSenior data base (N = 4514, mean age 76 ± 11 yrs). Kidney function was assessed with short Modification of Diet in Renal Disease formula estimated glomerular filtration rate (sMDRD) and Cockcroft-Gault creatinine clearance (CC).
RESULTS: There were 855 (19%) individuals with sMDRD < 60 ml/min/1.73m2, and 1734 (38%) with CC <  60 ml/min. Among drugs that should be avoided, spironolactone (20.4% of patients as classified by sMDRD and 17.5% by CC), non-steroidal anti-inflammatory drugs (13.4 and 11.3%), hydrochlorothiazide (11.1 and 11.0%), and metformin (6.9 and 8.2%) were most frequently used. The most frequently used drugs requiring dose modification were piracetam (13.9% by sMDRD, and 11.9% by CC), digoxin (8.3 and 8.8%), and gliclazide (6.8 and 5.9%). Classification of a drug use as 'appropriate' or 'inappropriate' was discordant depending on the method of kidney function assessment (sMDRD or CC) in up to 30%. Subgroups with sMDRD < 60 ml/min/1.73m2 and with CC <  60 ml/min were taking ≥2 drugs increasing the risk of pre-renal kidney injury more frequently than individuals with better kidney function (46.6 vs. 23.1 and 33.0% vs. 24.4%, respectively). There were 24.7% of individuals with sMDRD < 60 ml/min/1.73m2 and 18.0% with CC <  60 ml/min taking 2 or more drugs increasing serum potassium level. The proportion of subjects with hyperkalaemia increased with the number of such drugs.
CONCLUSIONS: Use of drugs that should be avoided or require dose adjustment due to renal impairment, and potentially inappropriate drug combinations is a common problem in older adults in Poland. Assessment of kidney function with sMDRD may result in overlooking of requirements for dose adjustment formulated based on creatinine clearance.
TRIAL REGISTRATION: Not applicable.

PMID: 30836952 [PubMed - indexed for MEDLINE]

When Should Iatrogenic Polypharmacy Be Considered a Disease?

AMA J Ethics. 2018 12 01;20(12):E1133-1138

Authors: Wieseler C

Abstract
This case of an elderly patient taking 17 medications, who presents with new neurological symptoms, raises multiple philosophy of medicine questions, including, What is a disease? And what would it mean to treat iatrogenic polypharmacy? Polypharmacy can obscure whether a patient like the one in this case has a neurological disease. I argue that, insofar as polypharmacy is likely to have caused, or at least contributed to, this patient's symptoms, her physician should treat it as a disease.

PMID: 30585575 [PubMed - indexed for MEDLINE]

First-in-human clinical trial to assess safety, tolerability and pharmacokinetics of P218, a novel candidate for malaria chemoprotection.

Br J Clin Pharmacol. 2020 Jan 11;:

Authors: Chughlay MF, Rossignol E, Donini C, El Gaaloul M, Lorch U, Coates S, Langdon G, Hammond T, Möhrle J, Chalon S

Abstract
AIMS: This first-in-human clinical trial of P218, a novel dihydrofolate reductase inhibitor antimalarial candidate, assessed safety, tolerability, pharmacokinetics and food effect in healthy subjects.
METHODS: The study consisted of two parts. Part A was a double-blind, randomised, placebo-controlled, parallel group, ascending dose study comprised of seven fasted cohorts. Eight subjects/cohort were randomised (3:1) to receive either a single oral dose of P218 (10, 30, 100, 250, 500, 750 and 1000 mg) or placebo. Part B was an open-label, cross-over, fed/fasted cohort (eight subjects) that received a 250 mg single dose of P218 in two treatment periods.
RESULTS: P218 was generally well tolerated across all doses; 21 treatment-emergent adverse events occurred in 15/64 subjects. Nine adverse events in five subjects, all of mild intensity, were judged drug related. No clinically relevant abnormalities in ECG, vital signs or laboratory tests changes were observed. P218 was rapidly absorbed with Cmax achieved between 0.5-2 h post-dose. Plasma concentrations declined bi-exponentially with half-life values ranging from 3.1-6.7 h (10 and 30 mg), increasing up to 8.9-19.6 h (doses up to 1000 mg). Exposure values increased dose-proportionally between 100 and 1000 mg for P218 (parent) and three primary metabolites (P218 β-acyl glucuronide, P218-OH and P218-OH β-acyl glucuronide). Co-administration of P218 with food reduced Cmax by 35% and delayed absorption by 1 h, but with no significant impact on AUC.
CONCLUSION: P218 displayed favourable safety, tolerability and pharmacokinetics. In view of its short half-life, a long-acting formulation will be needed for malaria chemoprotection.

PMID: 31925817 [PubMed - as supplied by publisher]

Occurrence of abscesses during treatment with pazopanib in metastatic renal cancer: a case report.

J Med Case Rep. 2020 Jan 11;14(1):7

Authors: Puliafito I, Russo A, Sciacca D, Puglisi C, Giuffrida D

Abstract
BACKGROUND: Pazopanib is a multitarget tyrosine kinase inhibitor used in the treatment of renal cancer and soft tissue sarcoma. Its use is commonly associated with a number of side effects, such as hemorrhagic diathesis, neutropenia, leukopenia, thrombocytopenia, nausea, vomiting, abdominal pain, increased serum aspartate aminotransferase, increased serum alanine aminotransferase, decreased serum glucose, increased serum bilirubin, decreased serum phosphate and magnesium, fatigue, hypertension, diarrhea, anorexia, proteinuria, and hypothyroidism. Abscesses of metastases caused by pazopanib administration are rarely reported in the literature.
CASE PRESENTATION: We report a case of abscesses of lung metastases related to pazopanib in a patient with metastatic renal cancer. The patient was a 53-year-old Caucasian man who developed abscesses of lung metastases during the first 3 months of treatment with pazopanib. The abscesses resolved after 1 month by stopping pazopanib and administering adequate antibiotic therapy.
CONCLUSIONS: We conclude that abscesses of metastases could be a rare side effect occurring during treatment with pazopanib in patients with renal cancer.

PMID: 31924259 [PubMed - in process]

Clinical outcomes of teicoplanin use in the OPAT setting.

Int J Antimicrob Agents. 2020 Jan 07;:105888

Authors: Dabrowski H, Wickham H, De S, Underwood J, Morris-Jones S, Logan S, Marks M, Pollara G

Abstract
Teicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. We present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens. Clinical failure with teicoplanin occurred in 5 episodes of care (4.7%), whereas clinical failure occurred in 2 episodes of ceftriaxone-based OPAT care (1.0%). Teicoplanin-associated clinical failure was observed in 2 of 6 (33%) patients with Enterococcus infections, compared to 3 of 101 (3.1%) of patient with non-Enterococcus infections. Overall there were 4 (2.9%) drug-related adverse events for teicoplanin and 4 (1.8%) for ceftriaxone, prompting a switch to teicoplanin in 3 patients. Our findings support the continued use of teicoplanin in OPAT and its consideration in centres where it is not currently being offered.

PMID: 31923571 [PubMed - as supplied by publisher]

Effective Use of the Laboratory in the Management of Patients with Inflammatory Bowel Diseases.

Gastroenterol Clin North Am. 2019 06;48(2):237-258

Authors: Ince MN, Elliott DE

Abstract
Inflammatory bowel disease (IBD) comprises a group of chronic, intestinal inflammatory disorders, including ulcerative colitis and Crohn's disease. IBD is characterized by periods of relapse and remission. Long-term progressive intestinal inflammation can result in severe and devastating complications, such as intestinal strictures and/or fistulae. Immune suppressive medications with potent side effects are often used to control inflammation and limit disease activity. Laboratory tests guide various decisions in clinical management of IBD. We discuss tests used to diagnose IBD, assess for relapse or remission, monitor the effectiveness of therapeutic regimen, screen for the maintenance of health, and diagnose or prevent complications.

PMID: 31046973 [PubMed - indexed for MEDLINE]

Implantable Pumps Require Specific Medications To Prevent Pump Failure And Risks To Patient Safety.

Am J Nurs. 2019 04;119(4):20-21

Authors: Aschenbrenner DS

PMID: 30896485 [PubMed - indexed for MEDLINE]

New Warning for Fluoroquinolone Antibiotics.

Am J Nurs. 2019 04;119(4):20

Authors: Aschenbrenner DS

PMID: 30896484 [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 2020/01/10

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.

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 2020/01/10

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.

Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Respiration. 2020 Jan 08;:1-6

Authors: Mitropoulou G, Daccord C, Sauty A, Pasche A, Egger B, Aedo Lopez V, Letovanec I, Beigelman-Aubry C, Nicod LP, Lazor R

Abstract
Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

PMID: 31914436 [PubMed - as supplied by publisher]

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial.

Lancet HIV. 2020 Jan 03;:

Authors: Schürmann D, Rudd DJ, Zhang S, De Lepeleire I, Robberechts M, Friedman E, Keicher C, Hüser A, Hofmann J, Grobler JA, Stoch SA, Iwamoto M, Matthews RP

Abstract
BACKGROUND: Islatravir (also known as ISL and MK-8591) is a unique nucleoside reverse transcriptase translocation inhibitor in clinical development for treatment of people with HIV-1 infection. In preclinical studies, intracellular islatravir-triphosphate exhibits a long half-life and prolonged virological effects. In this study, we aimed to assess islatravir safety, pharmacokinetics, and antiretroviral activity in treatment-naive adults with HIV-1 infection.
METHODS: This open-label, consecutive-panel, phase 1b trial was done at Charité Research Organisation (Berlin, Germany) and included men and women (aged 18-60 years, inclusive) with HIV-1 infection who were ART naive. Participants were required to have plasma HIV-1 RNA counts of at least 10 000 copies per mL within 30 days before the trial treatment phase, without evidence of resistance to nucleoside reverse transcriptase inhibitors. Participants were enrolled in one of five consecutive dosing panels, receiving a single oral dose of islatravir (0·5-30 mg). The primary outcomes were safety and tolerability of islatravir and change from baseline in HIV-1 plasma RNA; secondary outcomes were islatravir plasma and islatravir-triphosphate intracellular pharmacokinetics. We obtained descriptive safety and pharmacokinetics statistics, and estimated efficacy results from a longitudinal data analysis model. This study is registered with ClinicalTrials.gov, NCT02217904, and EudraCT, 2014-002192-28.
FINDINGS: Between Sept 17, 2015, and May 11, 2017, we enrolled 30 participants (six per panel). Islatravir was generally well tolerated. 27 (90%) participants had 60 adverse events after receipt of drug, of which 21 (35%) were deemed to be drug related. The most common (n>1) drug-related adverse events were headache (in nine [30%] participants) and diarrhoea (in two [7%]). No serious adverse events were reported, and no participants discontinued due to an adverse event. Plasma islatravir pharmacokinetics and intracellular islatravir-triphosphate pharmacokinetics were approximately dose proportional. The islatravir-triphosphate intracellular half-life was 78·5-128·0 h. Least-squares mean HIV-1 RNA at 7 days after dose decreased from 1·67 log10 copies per mL (95% CI 1·42-1·92) at 10 mg dose to 1·20 log10 copies per mL (0·95-1·46) at 0·5 mg dose. No genetic changes consistent with development of viral resistance were detected.
INTERPRETATION: Single doses of islatravir as low as 0·5 mg significantly suppressed HIV-1 RNA by more than 1·0 log at day 7 in treatment-naive adults with HIV-1 infection and were generally well tolerated, supporting the further development of islatravir as a flexible-dose treatment for individuals with HIV-1 infection.
FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc, Kenilworth, NJ, USA.

PMID: 31911147 [PubMed - as supplied by publisher]

Myoclonic status epilepticus induced by cefepime overdose requiring haemodialysis.

BMJ Case Rep. 2019 Jun 06;12(6):

Authors: Garin A, Bavozet F

Abstract
We report a case of cefepime neurotoxicity characterised by myoclonic status epilepticus with coma, in a context of acute renal failure and requiring one discontinuous conventional haemodialysis. Cefepime is a fourth-generation broad-spectrum cephalosporin mainly used to treat hospital-acquired Gram-negative infections. Acute neurotoxicity is an increasingly reported adverse effect which occurs predominantly in patients with renal impairment. Renal replacement therapy has been proposed to treat this condition.

PMID: 31175111 [PubMed - indexed for MEDLINE]

Safety and Immunogenicity of the Quadrivalent HPV Vaccine in Japanese Boys: a Phase 3, Open-Label Study.

Jpn J Infect Dis. 2019 Sep 19;72(5):299-305

Authors: Murata S, Takeuchi Y, Yamanaka K, Hayakawa J, Yoshida M, Yokokawa R, Wakana A, Sawata M, Tanaka Y

Abstract
Human papillomavirus (HPV)-associated disease is common among men with HPV infection. A quadrivalent HPV (qHPV) vaccine has demonstrated 85.9% efficacy against HPV6/11/16/18-related, persistent (≥ 6 month) infection in a study of Japanese men aged 16-26 years old. Here, we report the results of an open-label study of the immunogenicity and tolerability of the qHPV vaccine (NCT02576054), conducted to bridge findings from Japanese men to Japanese boys aged 9-15 years old. A total of 100 boys completed a three-vaccination regimen (Day 1, and Months 2 and 6), and 99 boys were included in the primary analysis population. The rate of seroconversion at one month after vaccine Dose 3 (Month 7) was high for each type of HPV (anti-HPV6/11/16/18 seroconversion rates [95% CI]: 94.9% [85.5%, 98.3%], 99.0% [94.4%, 100.0%], 99.0% [94.5%, 100.0%], and 99.0% [94.4%, 100.0%], respectively). Moreover, anti-HPV6/11/16/18 geometric mean titers were 482.9 mMU/mL, 1052.8 mMU/mL, 3878.3 mMU/mL, and 1114.5 mMU/mL, respectively. Immune responses to the qHPV vaccine were non-inferior among Japanese boys included in the current study and compared with young Japanese men from a separate study. Injection-site reactions were the most common adverse events, and administration of the vaccine was well tolerated in Japanese boys.

PMID: 31155600 [PubMed - indexed for MEDLINE]

Metformin administration increases the survival rate of doxorubicin-treated mice.

Pharmazie. 2019 Dec 01;74(12):737-739

Authors: Alhowail A, Almogbel Y

Abstract
Background: The chemotherapeutic agent doxorubicin (DOX), an anthracycline broadly used to treat different types of cancers, induces several side effects, including cardiotoxicity, hepatotoxicity, and nephrotoxicity, in a time- and dose-dependent manner. Metformin (MET) is an antidiabetic drug used as a first-line treatment for type-2 diabetes, and is reported to work against various various drug-induced toxicities. This study aimed to investigate whether the administration of MET prophylactically suppresses DOX-induced toxicity, and prolongs the survival following DOX treatment. Methods: Fifty mice were divided into four groups, and each group received different treatments. The animals in the control group received a single injection of saline. The animals in the DOX group received a single dose of DOX (25 mg/kg). The animals in the MET group received MET on a daily basis. The animals in the DOX+MET group received only a single dose of DOX and daily doses of MET. The animals were observed on a daily basis for determining their body weight and evaluating the survival rate of the four study groups. Results: DOX accelerated the mortality rate of the animals in the DOX-treated group. Co-administration of MET and DOX increased the survival rate of the mice. Conclusion: The results of this study demonstrated that the administration of MET can reduce DOX-induced toxicity and increase the survival rate among chemotherapy-treated mice.

PMID: 31907113 [PubMed - in process]

How to communicate evidence to patients.

Drug Ther Bull. 2019 08;57(8):119-124

Authors: Freeman ALJ

PMID: 31345957 [PubMed - indexed for MEDLINE]

An adverse drug effect mentions extraction method based on weighted online recurrent extreme learning machine.

Comput Methods Programs Biomed. 2019 Jul;176:33-41

Authors: El-Allaly ED, Sarrouti M, En-Nahnahi N, Ouatik El Alaoui S

Abstract
BACKGROUND AND OBJECTIVE: Automatic extraction of adverse drug effect (ADE) mentions from biomedical texts is a challenging research problem that has attracted significant attention from the pharmacovigilance and biomedical text mining communities. Indeed, deep learning based methods have recently been employed to solve this issue with great success. However, they fail to effectively identify the boundary of mentions. In this paper, we propose a weighted online recurrent extreme learning machine (WOR-ELM) based method to overcome this drawback.
METHODS: The proposed method for ADE mentions extraction from biomedical texts is divided into two stages: span detection and ADE mentions classification. At the first stage, we identify the boundary of the mentions irrespective of their types with a WOR-ELM in a given sentence. At the second stage, another WOR-ELM is used to classify the identified mentions to the appropriate type. Both stages use the concatenation of character-level and word-level embeddings as features. The character-level embedding is obtained using a modified online recurrent extreme learning machine, whereas the word-level embedding is obtained from a pre-trained model.
RESULTS: Several experiments were carried out on a well-known ADE corpus to evaluate the effectiveness and demonstrate the usefulness of the proposed method. The obtained results show that our method achieves an F-score of 87.5%, which outperforms the current state-of-the-art methods.
CONCLUSIONS: Our research results indicate that the proposed method for adverse drug effect mentions extraction from text can significantly improve performance over existing methods. Our experiments show the effectiveness of incorporating word-level and character level embeddings as features for WOR-ELM. They also illustrate the benefits of using IOU segment to represent ADE mentions.

PMID: 31200909 [PubMed - indexed for MEDLINE]