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 2021/02/20

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.

J Med Case Rep. 2021 Feb 18;15(1):86. doi: 10.1186/s13256-020-02564-w.

ABSTRACT

BACKGROUND: Myelomeningocele, which causes a neurogenic bladder, is usually treated with anticholinergics in children with neurogenic detrusor overactivity (NDO); however, anticholinergics cause side effects such as dry mouth, constipation, attention deficit, and inadequate reduction in detrusor leak point pressure. Vibegron, a novel selective beta-3 adrenoreceptor agonist, is a well-established alternative to anticholinergics in adults with an overactive bladder. It remains unknown whether this agent can be used for pediatric patients. We report the case of a girl with anticholinergic-resistant NDO due to tethered cord syndrome after myelomeningocele repair, who was treated with vibegron.

CASE PRESENTATION: A 4-year-old Filipino girl had increased frequency of daytime urinary incontinence and foul-smelling urine since the age of 3. Clinical examination revealed constipation, and urinalysis revealed bacteriuria. Voiding cystourethrography revealed an enlarged and trabeculated bladder without vesicoureteral reflux. On the urodynamic study (UDS), she was found to have detrusor overactivity (DO) and low bladder compliance. She could not void and was diagnosed with overflow incontinence. Clean intermittent catheterization (CIC) and orally administered propiverine (0.8 mg/kg/day) were initiated, and urinary incontinence was resolved. She underwent a UDS annually; the UDS at 6 years of age still revealed DO and low bladder compliance in spite of receiving propiverine. The treatment was switched from propiverine to vibegron (1.4 mg/kg/day). On the UDS after a 5-week treatment schedule of vibegron, the DO disappeared and the bladder compliance improved. CIC and orally administered vibegron have been continued for 7 months so far, and she has had no urinary tract infection with no drug-related adverse events.

CONCLUSIONS: Vibegron was effective and well tolerated in the treatment of a pediatric patient with NDO. Vibegron improved the urodynamic parameters for anticholinergic-resistant neurogenic bladder. This agent can be a beneficial and preferable alternative therapeutic agent to anticholinergics in patients with anticholinergic-resistant NDO.

PMID:33602290 | PMC:PMC7890608 | DOI:10.1186/s13256-020-02564-w

Considering patient age when treating multiple sclerosis across the adult lifespan.

Expert Rev Neurother. 2021 Feb 17;:1-12

Authors: Jakimovski D, Eckert SP, Zivadinov R, Weinstock-Guttman B

Abstract
Introduction: The successful development of anti-inflammatory disease-modifying treatments (DMT) significantly improved disease outcomes and longevity of persons with multiple sclerosis (pwMS). However, the shift toward an elderly MS population has resulted with new concerns regarding DMT efficacy and safety. Areas covered: This review summarizes the evidence of an age-based decrease in the efficacy of MS DMTs and increase in pharmacovigilance concerns. The age effects on pathophysiological MS processes, immunosenescence and its relevance to DMT selection or discontinuation are also reviewed. Lastly, the authors discuss the influence of age-associated comorbidities on DMT initiation and drug-induced events. Expert opinion: There is an age discrepancy between pwMS included in regulatory drug trials and an aging real-world MS population. Most trials demonstrate significantly diminished anti-inflammatory efficacy in patients older than 40 years old. Older age is associated with a greater risk for adverse events including serious infections. Age-associated comorbidities influence the risk-benefit analysis and sometimes cause patients to discontinue DMTs. Instead of chronological age cutoffs, therefore, studies should aim at promoting biologically-based age biomarkers.

PMID: 33595379 [PubMed - as supplied by publisher]

Etiological profile of diarrhea in solid organ transplant recipients at a tertiary care center in Southern India.

Transpl Infect Dis. 2021 Feb 16;:e13584

Authors: Vyas VD, Parameswaran SA, Paramasivan P, Sankaranarayanan K, Palaniswamy KR, Mohan AT, Srinivas U, Dhus U, Muthuswamy H, Revathy MS, Natarajan M, Karunakaran P, Venkatesh S, Mahalingam P, Patel A

Abstract
BACKGROUND: Diarrhea is one of the common gastrointestinal (GI) adverse events after solid organ transplantation. Diarrhea may be due to infectious or non-infectious etiology. The infectious etiology of diarrhea varies according to the location and duration of diarrhea. Non-infectious etiologies include drugs, inflammatory bowel disease, neoplasia. The objective of this study was to evaluate the etiological profile of diarrhea in solid organ transplant recipients presenting to a tertiary care center in Southern India.
METHODS: This was a retrospective analysis of prospectively collected data of all solid organ transplantation recipients referred to the Department of Medical Gastroenterology for evaluation of diarrhea from April 2012 till May 2014. All patients had stool evaluated by wet mount examination, modified acid fast (AFB) stain, trichrome stain, culture and Clostridium difficile toxin assay. EDTA plasma was collected for quantitative Cytomegalovirus (CMV) detection by real time PCR. If the diarrhea was acute (<2 weeks), and no etiological agent was identified, empirical antibiotic therapy was instituted and followed up. If persistent or chronic diarrhea (>2-4 weeks), endoscopic evaluation (upper GI endoscopy and/or colonoscopy with biopsies), depending on the clinical type of diarrhea was done. If no specific etiological diagnosis was established after endoscopic evaluation, breath test for SIBO, celiac serology were done. If no specific etiology was identified after the above investigations, dose of immunosuppressive drugs was reduced. If diarrhea responded to dose reduction, it was considered to be drug related.
RESULTS: Fifty-eight episodes of diarrhea occurred in 55 solid organ transplant recipients during the study period. Renal transplant recipients constituted the majority (70%). Most (79%) of patients included in the study had their transplant > 6 months ago. Infective diarrhea was the etiology in 46%, drug related diarrhea in 29.3%. No specific etiology was identified in 22.4% of patients. Parasites accounted for 69% of all infective diarrhea. Stool evaluation was the main investigation in establishing diagnosis in acute diarrhea. Endoscopic evaluation was required in two thirds of patients to establish diagnosis in chronic diarrhea.
CONCLUSION: GI infections and drug related diarrhea were the common causes of diarrhea in solid organ transplant recipients. Parasites were the most common infectious etiology of diarrhea. Step wise evaluation was able to identify the etiology in ~77% of patients. Overall, 98% of diarrheal episodes resolved.

PMID: 33594745 [PubMed - as supplied by publisher]

Pharmacol Ther. 2021 Feb 15:107820. doi: 10.1016/j.pharmthera.2021.107820. Online ahead of print.

ABSTRACT

Drug addiction is one of the leading causes of mortality worldwide. Despite great advances were achieved in understanding the neurobiology of drug addiction, the therapeutic options are severely limited, with poor effectiveness and serious side effects. The neuropeptide oxytocin (OXT) is well known for its effects on uterine contraction, sexual/maternal behaviors, social affiliation, stress and learning/memory by interacting with the OXT receptor and other neuromodulators. Emerging evidence suggests that the acute or chronic exposure to drugs can affect the OXT system. Additionally, OXT administration can ameliorate a wide range of abused drug-induced neurobehavioral changes. Overall, OXT not only suppresses drug reward in the binge stage of drug addiction, but also reduces stress responses and social impairments during the withdrawal stage and, finally, prevents drug/cue/stress-induced reinstatement. More importantly, clinical studies have also shown that OXT can exert beneficial effects on reducing substance use disorders of a series of drugs, such as heroin, cocaine, alcohol, cannabis and nicotine. Thus, the present review focuses on the role of OXT in treating drug addiction, including the preclinical and clinical therapeutic potential of OXT and its analogs on the neurobiological perspectives of drugs, to provide a better insight of the efficacy of OXT as a clinical addiction therapeutic agent.

PMID:33600854 | DOI:10.1016/j.pharmthera.2021.107820

Int J Cardiol. 2021 Feb 15:S0167-5273(21)00290-4. doi: 10.1016/j.ijcard.2021.02.037. Online ahead of print.

ABSTRACT

INTRODUCTION: Dual antiplatelet therapy (DAPT) remains the cornerstone of acute coronary syndrome (ACS) management, and ticagrelor is one of the commonly used second antiplatelet agents. There is some evidence to suggest that morphine may reduce the antiplatelet effect of ticagrelor.

METHODS AND RESULTS: In a single-center, randomized controlled trial, we compared the effect of morphine and fentanyl on platelet aggregation (PA) among patients with ACS treated with ticagrelor. Platelet aggregation was studied by automated light transmittance aggregometry (LTA) at baseline, and at 2 h after ticagrelor loading. The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related adverse events were secondary outcomes. Of 136 patients randomized, 70 received fentanyl and 66 received morphine. At baseline, the median (IQR) platelet aggregation [61.35% (54.6-to 70) Vs. 58.8% (52.7 to 72.9)] were comparable between the groups. There was no statistically significant difference between the fentanyl and the morphine groups in IPA at 2-h [85.88%(64.65-98.16) and 81.93%(44.2-98.03), p = 0.09]. However, morphine use was independently associated with a PA of >30% at 2 h (p- < 0.009). There was no difference in adverse events.

CONCLUSION: In patients with ACS, there was no significant difference between the use of fentanyl or morphine on the effect of ticagrelor on PA. (CTRI/2018/04/013423).

PMID:33600846 | DOI:10.1016/j.ijcard.2021.02.037

J Stroke. 2021 Jan;23(1):1-11. doi: 10.5853/jos.2020.02698. Epub 2021 Jan 31.

ABSTRACT

BACKGROUND AND PURPOSE: The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies.

METHODS: Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018]).

RESULTS: The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments.

CONCLUSIONS: Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.

PMID:33600699 | DOI:10.5853/jos.2020.02698

J Crohns Colitis. 2021 Feb 18:jjab023. doi: 10.1093/ecco-jcc/jjab023. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM1, induced remission in patients with moderate-to-severe ulcerative colitis (UC) in TURANDOT. We assessed long-term safety, tolerability and efficacy of ontamalimab in TURANDOT II.

METHODS: TURANDOT II was a phase 2, multicentre, open-label (OL) study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab. Patients were randomized to 75mg or 225mg ontamalimab every 4 weeks for 72 weeks (OL1). Dosage could be increased to 225mg from week 8 at the investigator's discretion. All patients then received 75mg every 4 weeks for 72 weeks (OL2), followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events (AEs), serious AEs (SAEs) and AEs leading to withdrawal. Mucosal healing (MH; centrally read endoscopy) was assessed.

RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE (10.0%) was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis (0.9%). One death and four cancers (all unrelated to ontamalimab) occurred. No PML/lymphoproliferative disorders occurred. Geometric mean hsCRP and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned placebo in TURANDOT achieving MH increased from 8.8% (6/68) at baseline to 35.3% at week 16 (24/68; non-responder imputation). The corresponding increase in the ontamalimab group was from 23.3% (61/262) to 26.7% (70/262).

CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.

PMID:33599720 | DOI:10.1093/ecco-jcc/jjab023

The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer.

Breast Cancer Res Treat. 2021 Feb 16;:

Authors: Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, Steinberg J, Sugg J, Tudor IC, Huizing M, Young R, Abramson V, Bose R, Hart L, Chan S, Cameron D, Wright GS, Graas MP, Neven P, Rocca A, Russo S, Krop IE

Abstract
PURPOSE: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.
METHODS: Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.
RESULTS: Overall, 103 women were enrolled [median age 60 years (range 34-83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0-3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.
CONCLUSIONS: Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. CLINICALTRIALS.
GOV NUMBER: NCT02091960.

PMID: 33591468 [PubMed - as supplied by publisher]

Albendazole-Induced Liver Injury.

Am J Ther. 2021 Feb 03;:

Authors: Piloiu C, Dumitrascu DL

Abstract
BACKGROUND: Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic transaminases, dizziness, neutropenia, and alopecia.
AREAS OF UNCERTAINTY: The main question of the systematic review is if albendazole administration can cause liver injury or liver failure.
DATA SOURCES: Two researchers conducted the search on PubMed and the key words used were: "albendazole," "anthelmintic," "drug-induced liver injury," and "acute hepatitis." Two new case reports were included in the systematic review.
RESULTS: Literature search concluded in 10 cases listed on PubMed. Another 2 new case reports from our experience are included in the systematic review. Most common symptoms presented are jaundice, anorexia, and vomiting after the single-use of albendazole or long-term usage. All cases presented high levels of transaminases, with remission after stopping the administration of albendazole. The treatment with albendazole was mostly given for liver hydatid cysts or empirically.
CONCLUSIONS: Albendazole is a prescription-based drug used by most patients without medical advice, without knowing the risk of side effects. The anthelmintic drug may induce liver injury, even in small doses; in result, practitioners and patients should take this information in consideration.

PMID: 33590990 [PubMed - as supplied by publisher]

Drug-induced neuropsychiatric adverse events using post-marketing surveillance.

Curr Clin Pharmacol. 2021 Feb 14;:

Authors: Wakabayashi T, Nakatsuji T, Kambara H, Niinomi I, Oyama S, Inada A, Ueno S, Uchida M, Iwanaga K, Iida T, Hosohata K

Abstract
BACKGROUND: Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs including neuraminidase inhibitors (NIs). However, information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify drugs associated with abnormal behavior using a spontaneous reporting system database.
METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed. Drug associated with abnormal behavior were estimated using disproportionality analysis with calculation of the reporting odds ratio and 95% confidence interval.
RESULTS: A total of 1,144 reports of abnormal behavior were identified. Signals were detected showing the association of 4 including neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with abnormal behavior, and these signals were stronger for oseltamivir than other neuraminidase inhibitors. Signals were also detected for acetaminophen and montelukast.
CONCLUSION: Our results should raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.

PMID: 33588740 [PubMed - as supplied by publisher]

C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab.

Am J Hematol. 2020 11;95(11):1334-1343

Authors: de Castro C, Grossi F, Weitz IC, Maciejewski J, Sharma V, Roman E, Brodsky RA, Tan L, Di Casoli C, El Mehdi D, Deschatelets P, Francois C

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hematologic disease characterized by chronic complement-mediated hemolysis and thrombosis. Despite treatment with eculizumab, a C5 inhibitor, 72% of individuals remain anemic. Pegcetacoplan (APL-2), a PEGylated C3 inhibitor, has the potential to provide more complete hemolysis control in patients with PNH. This open-label, phase Ib study was designed to assess the safety, tolerability, and pharmacokinetics of pegcetacoplan in subjects with PNH who remained anemic during treatment with eculizumab. Pharmacodynamic endpoints were also assessed as an exploratory objective of this study. Data are presented for six subjects in cohort 4 who received treatment for up to 2 years. In total, 427 treatment-emergent adverse events (TEAEs) were reported, 68 of which were possibly related to the study drug. Eight serious TEAEs occurred in two subjects; three of these events were considered possibly related to the study drug. Pegcetacoplan pharmacokinetic concentrations accumulated with repeated dosing, and steady state was reached at approximately 6-8 weeks. Lactate dehydrogenase levels were well controlled by eculizumab at baseline. Pegcetacoplan increased hemoglobin levels and decreased both reticulocyte count and total bilirubin in all six subjects. Improvements were observed in Functional Assessment of Chronic Illness Therapy Fatigue scores. Two subjects discontinued for reasons unrelated to pegcetacoplan. All four subjects who completed the study transitioned to pegcetacoplan monotherapy following eculizumab discontinuation and avoided transfusions. In this small study, pegcetacoplan therapy was generally well-tolerated, and resulted in an improved hematological response by achieving broad hemolysis control, enabling eculizumab discontinuation.

PMID: 33464651 [PubMed - indexed for MEDLINE]

Necrotising fasciitis following accidental injection of intraoral xylene: a preventable medication error.

BMJ Case Rep. 2020 Nov 23;13(11):

Authors: Eswaran S, Ayyaswamy A, Saravanam PK

Abstract
The most common cause of preventable mortality and morbidity to the patient in a healthcare system is medication error. Medication errors have got a significant impact on the patient health and healthcare system. These errors are multidisciplinary and can occur at various stages of drug therapy. Physicians, nursing staff, pharmacists, hospital administration all have an important role in preventing medication errors from recurring. The most common causes include wrong patient, wrong drug prescription, look-alike sound-alike drugs, faulty drug administration, wrong dosage, drug storage, delivery problem, lack of staff, patient and physician education and failure to monitor closely. This case illustrates the importance of incorporating protocol and cross-checking before administering a drug during the procedure. Here, we discuss a case of accidental intraoral injection of xylene instead of xylocaine (local anaesthetic agent), which was a sound-alike drug that resulted in significant morbidity to the patient.

PMID: 33229474 [PubMed - indexed for MEDLINE]

Hepatoprotection and hepatotoxicity of Chinese herb Rhubarb (Dahuang): How to properly control the "General (Jiang Jun)" in Chinese medical herb.

Biomed Pharmacother. 2020 Jul;127:110224

Authors: Zhuang T, Gu X, Zhou N, Ding L, Yang L, Zhou M

Abstract
Chinese herb Rhubarb (Dahuang), one of the most widely used traditional Chinese medicine in clinical application for over a thousand years and known as the "General (Jiang Jun)" in Chinese medical herb, currently used clinically for long-term treatment of gastrointestinal diseases and chronic liver diseases. Through previous researches, it has been identified that Rhubarb possessed a good hepatoprotective effect, which primarily protected liver from oxidation, fibrosis and cirrhosis, liver failure, hepatocellular carcinoma and various types of hepatitis. Meanwhile, it has been recently reported that long-term administration of Rhubarb preparation may undertake the risk of liver damage, which has aroused worldwide doubts about the safety of Rhubarb. Therefore, how to correctly understand the "two-way" effect of Rhubarb on liver protection and liver toxicity provides a basis for scientific evaluation of Rhubarb's efficacy on liver and side effects, as well as guiding clinical rational drug use. In this review, the mechanisms of Rhubarb how to play a role in hepatoprotection and why it causes hepatotoxic potential will be elaborated in detail and critically. In addition, some positive clinical guidances are also advised on how to reduce its hepatotoxicity in medical treatment.

PMID: 32559851 [PubMed - indexed for MEDLINE]

Evaluation of clarity of the STOPP/START criteria for clinical applicability in prescribing for older people: a quality appraisal study.

BMJ Open. 2020 02 18;10(2):e033721

Authors: Sallevelt BTGM, Huibers CJA, Knol W, Puijenbroek EV, Egberts T, Wilting I

Abstract
OBJECTIVES: Appropriate prescribing in older people continues to be challenging. Studies still report a high prevalence of inappropriate prescribing in older people. To reduce the problem of underprescribing and overprescribing in this population, explicit drug optimisation tools like Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) have been developed. The aim of this study was to evaluate the clinical applicability of STOPP/START criteria in daily patient care by assessing the clarity of singular criteria.
DESIGN: Quality appraisal study.
METHODS: For each of the 114 STOPP/START criteria V.2, elements describing the action (what/how to do), condition (when to do) and explanation (why to do) were identified. Next, the clarity of these three elements was quantified on a 7-point Likert scale using tools provided by the Appraisal of Guidelines for Research and Evaluation (AGREE) Consortium.
PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was the clarity rating per element, categorised into high (>67.7%), moderate (33.3%-67.7%) or low (<33.3%). Secondary, factors that positively or negatively affected clarity most were identified. Additionally, the nature of the conditions was further classified into five descriptive components: disease, sign, symptom, laboratory finding and medication.
RESULTS: STOPP recommendations had an average clarity rating of 64%, 60% and 69% for actions, conditions and explanations, respectively. The average clarity rating in START recommendations was 60% and 57% for actions and conditions, respectively. There were no statements present to substantiate the prescription of potential omissions for the 34 START criteria.
CONCLUSIONS: Our results show that the clarity of the STOPP/START criteria can be improved. For future development of explicit drug optimisation tools, such as STOPP/START, our findings identified facilitators (high clarity) and barriers (low clarity) that can be used to improve the clarity of clinical practice guidelines on a language level and therefore enhance clinical applicability.

PMID: 32075833 [PubMed - indexed for MEDLINE]

Broad-Spectrum Profiling of Drug Safety via Learning Complex Network.

Clin Pharmacol Ther. 2020 06;107(6):1373-1382

Authors: Liu K, Ding RF, Xu H, Qin YM, He QS, Du F, Zhang Y, Yao LX, You P, Xiang YP, Ji ZL

Abstract
Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, a reproducible method to assess drug safety systematically and quantitatively is still missing. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps reduce the attrition rate of new drug discovery by providing a reliable ADR profile in the early preclinical stage.

PMID: 31868917 [PubMed - indexed for MEDLINE]

Reducing drug prescription errors and adverse drug events by application of a probabilistic, machine-learning based clinical decision support system in an inpatient setting.

J Am Med Inform Assoc. 2019 12 01;26(12):1560-1565

Authors: Segal G, Segev A, Brom A, Lifshitz Y, Wasserstrum Y, Zimlichman E

Abstract
BACKGROUND: Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts.
OBJECTIVE: In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting.
MATERIALS AND METHODS: We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department's staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician's real-time responses to alerts generated.
RESULTS: The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients' status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders.
CONCLUSION: A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.

PMID: 31390471 [PubMed - indexed for MEDLINE]

13 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 2021/02/16

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.

13 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 2021/02/16

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.

Eur J Cancer. 2021 Feb 12;146:87-94. doi: 10.1016/j.ejca.2020.12.019. Online ahead of print.

ABSTRACT

BACKGROUND: ABTL0812 is an autophagy inducer that promotes cancer cell death by activation of cytotoxic autophagy selectively in tumour cells. ABTL0812 induces endoplasmic reticulum stress and blocks the Akt-mTOR axis; both actions converge to activate a robust and sustained autophagy leading to cancer cell death. Preclinical data supported the initiation of clinical trials in patients with cancer.

PATIENTS AND METHODS: This first-in-human trial consisted of an escalation phase (3 + 3 design), followed by an expansion phase, to assess safety and tolerability of ABTL0812. Secondary objectives were determining the recommended phase II dose (RP2D), clinical antitumour activity, pharmacokinetics (PK) and pharmacodynamics (PD).

RESULTS: A total of 29 patients were enrolled and treated; fifteen patients were treated in four escalation dosing cohorts (ranging from 500 mg once a day to 2000 mg twice a day) and fourteen in the expansion phase (dosed with 1300 mg three times a day). No maximum tolerated dose was attained, and RP2D was determined by PK/PD modelling. Most drug-related adverse events were gastrointestinal grade I-II. Correlation between drug levels and pAkt/Akt ratio was found. Two cases of long-term (>1 year) stable disease were observed.

CONCLUSIONS: ABTL0812 is safe and has an acceptable tolerability profile, allowing a long-term oral dosing. RP2D of 1300 mg three times a day was determined according to PK/PD modelling, and preliminary antitumour efficacy was observed.

CLINICAL TRIAL REGISTRATION NUMBER: NCT02201823.

PMID:33588149 | DOI:10.1016/j.ejca.2020.12.019