Cancer. 2021 Nov 2. doi: 10.1002/cncr.34005. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

METHODS: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed.

RESULTS: The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses.

CONCLUSIONS: Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development.

PMID:34726773 | DOI:10.1002/cncr.34005

J Clin Pharm Ther. 2021 Nov 2. doi: 10.1111/jcpt.13565. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Newborns, particularly preterm babies, are prone to vascular vasospasm and thromboembolism. Differences in the haemostatic system, small vessel diameter and presence of any serious diseases are predisposing causes of thromboembolic disease in newborns. The lack of randomized controlled studies on the management of vasospasm and thromboembolism exacerbates the problem. We present a case series of the successful and safe use of PTX for the treatment of vasospasm and thrombosis in neonates.

METHODS: The study was conducted in the Bezmialem Vakif University Hospital Neonatal Intensive Care Unit (NICU). A retrospective chart review was performed on consecutive patients treated for vascular spasm and thrombosis. Nine patients diagnosed with vasospasm or thrombosis were enrolled in the study.

RESULTS: Five patients had arterial injuries. Six patients were premature, and five patients were diagnosed with thrombosis by using Doppler ultrasonography (US). The drug was diluted with 5% dextrose and administered intravenously at a dose of 5 mg/kg/h over six hours, ranging from 1 to 5 days. No drug-related side effects were observed. All babies recovered, and no amputation was performed.

WHAT IS NEW AND CONCLUSION: PTX may be an alternative treatment for vascular vasospasm and thromboembolism with fewer side effects than anticoagulant and thrombolytic agents in neonates. Starting PTX in the early stages of vascular insult may prevent the development of vasospasm and thromboembolism and thus limb ischaemia.

PMID:34726284 | DOI:10.1111/jcpt.13565

Int J Clin Pract. 2021 Nov 1:e15001. doi: 10.1111/ijcp.15001. Online ahead of print.

ABSTRACT

OBJECTIVE: Warfarin-induced skin necrosis (WSN) is a rare (0.0.1-0.1%) and severe adverse reaction. The clinical characteristics of this reaction and its mortality rate have not been explored in a large population. Therefore, we present the case of a Peruvian patient who developed WSN and perform a systematic review of case reports of WSN.

METHODS: A systematic search was performed using the Pubmed / Medline, Scopus, Web of Science, and Embase databases. Patient clinical data were collected and extracted from every case report. Furthermore, we analyzed the factors associated with mortality due to WSN using the Poisson regression model with robust variations, obtaining risk ratios (RR) and their respective confidence intervals (95% CI).

RESULTS: We identified 90 case reports that included a total of 111 patients with WSN (mean age 52.5 years), 20.72% of whom died of complications due to WSN. Being male (RR: 2.87; 95% CI 1.21 - 6.83) and having three or more affected regions (RR: 6.81; 95% CI 2.62 - 17.74) were associated with an increased risk of death caused by WSN.

CONCLUSION: This systematic review identified 90 case reports of WSN with three or more affected body regions. Male sex was associated with an increased risk of death. Further studies are needed to analyze and confirm these results.

PMID:34725899 | DOI:10.1111/ijcp.15001

Reg Anesth Pain Med. 2021 Nov 1:rapm-2021-103190. doi: 10.1136/rapm-2021-103190. Online ahead of print.

NO ABSTRACT

PMID:34725258 | DOI:10.1136/rapm-2021-103190

Nihon Yakurigaku Zasshi. 2021;156(6):364-369. doi: 10.1254/fpj.21053.

ABSTRACT

In vivo cardiovascular experiments as part of safety pharmacology studies have been developed for small molecule drug candidates to maximize detection power for potential undesirable pharmacodynamic effects of a drug candidate on physiological functions, and have been established with appropriate expertise. Conscious freely-moving telemeterized non-rodents are generally used for the in vivo cardiovascular experiments. The technology and evaluation best practices for the experiments have been optimized by multiple researchers and as a result, the experiments considerably contribute to the estimation of cardiovascular risks for humans. In addition, as described in ICH E14&S7B Q&A draft, non-clinical studies are gaining importance in the integrated risk assessment for QT prolongation in humans, and high quality data obtained in non-clinical studies are being required. This manuscript introduces actual technology and evaluation for in vivo cardiovascular safety pharmacology studies based on Japan activity for Improvement of Cardiovascular Evaluation by Telemetry system (J-ICET), which is one of the working groups hosted by Japanese Safety Pharmacology Society.

PMID:34719571 | DOI:10.1254/fpj.21053

Cochrane Database Syst Rev. 2021 Nov 1;11:CD009027. doi: 10.1002/14651858.CD009027.pub4.

ABSTRACT

BACKGROUND: Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the most common clinical presentation, though people may also present with headache, symptoms of raised intracranial pressure, hydrocephalus, and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, antiepileptic drugs (AEDs), and anti-oedema drugs, such as steroids, form the mainstay of treatment. This is an updated version of the Cochrane Review previously published in 2019.

OBJECTIVES: To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis. For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in people who had neurocysticercosis but had not had a seizure. For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in people who had had at least one seizure due to neurocysticercosis. As part of primary prevention studies, we also aimed to examine which AED was beneficial in people with neurocysticercosis in terms of duration, dose, and side-effect profile.

SEARCH METHODS: For the 2021 update of this review, we searched the Cochrane Register of Studies (CRS Web), MEDLINE, and LILACS to January 2021. CRS Web includes randomised or quasi-randomised, controlled trials from CENTRAL, the Specialised Registers of Cochrane Review Groups, including Epilepsy, PubMed, Embase, ClinicalTrials.gov, and the World Health Organisation International Clinical Trials Registry Platform. We also checked the reference lists of identified studies, and contacted experts and colleagues in the field to search for additional and ongoing studies.

SELECTION CRITERIA: Randomised and quasi-randomised controlled trials. Single-blind, double-blind, or unblinded studies were eligible for inclusion.

DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion and extracted the relevant data. The primary outcomes of interest were: proportion of individuals experiencing seizures, and time to first seizure post randomisation. Secondary outcomes included: seizure freedom, number of withdrawals, side effects, number of people seizure free with short or long durations of treatment, quality of life, therapy costs, hospitalisations, and mortality. We used an intention-to-treat analysis for the primary analysis. We calculated odds ratio (OR) for dichotomous data (proportion of individuals who experienced seizures, were seizure free for a specific time period (12 or 24 months), withdrew from treatment, developed drug-related side effects or complications, were seizure-free with each treatment policy, mortality), and planned to use mean difference (MD) for continuous data, if any continuous data were identified (quality of life, cost of treatment). We intended to evaluate time to first seizure after randomisation by calculating hazard ratios (HRs). We assessed precision using 95% confidence intervals (CIs). We stratified the analysis by treatment comparison. We also considered the duration of drug usage, co-medications, and the length of follow-up.

MAIN RESULTS: We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures. We did not find any trials that directly compared individual AEDs for primary prevention in people with neurocysticercosis. We included four trials that evaluated the efficacy of short-term versus longer-term AED treatment for people with solitary neurocysticercosis (identified on computed tomography (CT) scan) who presented with seizures. In total, 466 people were enrolled. These studies compared AED treatment durations of 6, 12, and 24 months. The risk of seizure recurrence with six months of treatment compared with 12 to 24 months of treatment was inconclusive (odds ratio (OR) 1.34, 95% confidence interval (CI) 0.73 to 2.47; three studies, 360 participants; low-certainty evidence). The risk of seizure recurrence with six to 12 months of treatment compared with 24 months of treatment was inconclusive (OR 1.36, 95% CI 0.72 to 2.57; three studies, 385 participants; very low-certainty evidence). Two studies compared seizure recurrence with CT findings, and suggested that persistent and calcified lesions had a higher recurrence risk, and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of the drugs. None of the studies addressed the quality of life of the participants. These studies had methodological deficiencies, such as small sample sizes, and a possibility of bias due to lack of blinding, which affect the results of the review.

AUTHORS' CONCLUSIONS: Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as seizure prophylaxis among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. Therefore, there is a need for large scale randomised controlled trials to address these questions.

PMID:34723391 | DOI:10.1002/14651858.CD009027.pub4

Case Rep Dermatol. 2021 Sep 13;13(3):445-449. doi: 10.1159/000519029. eCollection 2021 Sep-Dec.

ABSTRACT

Raloxifene is a drug used in postmenopausal women with osteoporosis. Although hot flashes are known side effects of raloxifene, to the best of our knowledge, erythema multiforme (EM) minor has not been previously reported. Herein, we report about a 74-year-old woman who developed EM minor after the drug alfacalcidol was changed to raloxifene to treat osteoporosis. Skin biopsy revealed a suspicious eczematous drug reaction. The drug-induced lymphocyte stimulation test showed a positive result. The stimulation index was 2.2, and there were no other suspected drugs. Based on these results, we diagnosed the condition as EM minor caused by raloxifene. The patient's symptoms disappeared after the use of antihistamine drugs and topical steroids. In conclusion, raloxifene can cause EM minor in rare cases.

PMID:34720916 | PMC:PMC8460885 | DOI:10.1159/000519029

Case Rep Gastroenterol. 2021 Jul 20;15(2):662-666. doi: 10.1159/000514952. eCollection 2021 May-Aug.

ABSTRACT

We report the case of a 51-year-old male with Crohn's disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.

PMID:34720824 | PMC:PMC8458923 | DOI:10.1159/000514952

BMC Bioinformatics. 2021 Oct 30;22(1):532. doi: 10.1186/s12859-021-04406-y.

ABSTRACT

BACKGROUND: Drug repositioning has caught the attention of scholars at home and abroad due to its effective reduction of the development cost and time of new drugs. However, existing drug repositioning methods that are based on computational analysis are limited by sparse data and classic fusion methods; thus, we use autoencoders and adaptive fusion methods to calculate drug repositioning.

RESULTS: In this study, a drug repositioning algorithm based on a deep autoencoder and adaptive fusion was proposed to mitigate the problems of decreased precision and low-efficiency multisource data fusion caused by data sparseness. Specifically, a drug is repositioned by fusing drug-disease associations, drug target proteins, drug chemical structures and drug side effects. First, drug feature data integrated by drug target proteins and chemical structures were processed with dimension reduction via a deep autoencoder to characterize feature representations more densely and abstractly. Then, disease similarity was computed using drug-disease association data, while drug similarity was calculated with drug feature and drug-side effect data. Predictions of drug-disease associations were also calculated using a top-k neighbor method that is commonly used in predictive drug repositioning studies. Finally, a predicted matrix for drug-disease associations was acquired after fusing a wide variety of data via adaptive fusion. Based on experimental results, the proposed algorithm achieves a higher precision and recall rate than the DRCFFS, SLAMS and BADR algorithms with the same dataset.

CONCLUSION: The proposed algorithm contributes to investigating the novel uses of drugs, as shown in a case study of Alzheimer's disease. Therefore, the proposed algorithm can provide an auxiliary effect for clinical trials of drug repositioning.

PMID:34717542 | DOI:10.1186/s12859-021-04406-y

Asian J Psychiatr. 2021 Dec;66:102891. doi: 10.1016/j.ajp.2021.102891. Epub 2021 Oct 23.

ABSTRACT

BACKGROUND: There is still no approved mechanism of manic switch in bipolar disorder, yet many selective serotonin reuptake inhibitors were accused for this important adverse event. Therefore, we aimed to investigate to estimate SSRI's risk for reporting mania and elevated mood using FEARS database and investigate receptor mechanisms involved.

METHODS: Mania and relevant side effects approved by FDA were screened in this dataset from the first quarter of 2004 to the third quarter of 2020. Disproportionality analysis were performed to estimate reporting odds ratio (ROR) and linear regressions were conducted to investigate relationship between ROR and Ki values. Receptor occupancy ratios were calculated from in vitro receptor binding profiles. The pharmacodynamical profile was extracted from the International Union of Basic and Clinical Pharmacology and the British Pharmacology Society dataset. Child and adolescent population was also investigated separately.

RESULTS: The analysis showed that the odds of a spontaneous report of mania in the FAERS database involving an SSRI were higher than the odds that such a report involved other types of drugs (ROR: 5.324 [CI: 3.773; 7.514]). The largest effect size in this estimation was found in fluvoxamine (ROR: 13.957 [CI: 10.391; 18.747]). Significant effects were found in regression analysis for Ki values of H1 and M1 receptors on ROR. Receptor occupation was not found to have an effect on ROR.

CONCLUSION: Lower degress of Ki values on M1 and H1 may be plausible pharmacological mechanism. Further pharmacological data and clinical assessments may be important to validate this safety signal.

PMID:34717111 | DOI:10.1016/j.ajp.2021.102891

Midwifery. 2021 Oct 7;104:103166. doi: 10.1016/j.midw.2021.103166. Online ahead of print.

ABSTRACT

OBJECTIVE: the possibility of experiencing adverse reactions is an important aspect of contraceptive decision-making and information about this topic is highlighted as an essential aspect of contraceptive counseling. The aim of this study was to explore experiences of contraceptive counseling about potential adverse reactions of intrauterine contraception.

DESIGN: exploratory qualitative study of messages in discussion boards, analyzed with inductive qualitative content analysis.

SETTING: two large public Swedish web-based discussion boards about sexual and reproductive health.

PARTICIPANTS: threads related to the aim were identified through searches in the discussion boards during 2019 and 2020, resulting in in 43 included posters who had written 140 messages in total.

FINDINGS: the themes 'difficulties making an informed decision due to insufficient and untrustworthy information about adverse reactions' and 'feeling dismissed when communicating about experienced adverse reactions' illustrate the results. Posters emphasized the importance of sufficient information about adverse reactions. However, professionals were perceived as overly optimistic regarding intrauterine contraception and focusing on mild or common reactions. The importance of feeling that their adverse reactions were acknowledged was articulated, but posters felt that some professionals dismissed the reactions when being told about it, resulting in frustration and dissatisfaction with care. The discussion boards contained narratives describing a resistance among professionals to send in a formal report about the adverse reaction.

KEY CONCLUSIONS: according to statements made by posters who have experience of adverse reactions of intrauterine contraception, contraceptive counseling have room for improvement in regard to inclusion of comprehensive information about adverse reactions. The findings illustrate the importance that clients who experience adverse reactions of intrauterine contraception feel they are acknowledged and offered adequate support.

IMPLICATIONS FOR PRACTICE: echoing guidelines for high-quality contraceptive counseling, the narratives provide further weight that professionals need to have adequate training and resources to offer comprehensive information about adverse reactions of intrauterine contraception. The findings call attention to the importance of follow-up services for clients who experience adverse reactions.

PMID:34717242 | DOI:10.1016/j.midw.2021.103166

Eur J Clin Pharmacol. 2021 Oct 30. doi: 10.1007/s00228-021-03238-2. Online ahead of print.

ABSTRACT

PURPOSE: Adverse drug events are related to negative outcomes in healthcare, including hospitalization, increased duration of hospital stay and death. The aim of this study was to conduct a systematic review to evaluate hospitalizations and deaths related to adverse drug events worldwide, reported in studies with national coverage.

METHODS: The protocol was registered in PROSPERO (CRD42020157008). We performed a systematic search on Medline, Embase, CINAHL, LILACS, and the Cochrane Library (until March 2020) using pre-specified terms. We included published studies that reported data on hospitalizations and/or deaths related to adverse drug events from a national perspective and the use of secondary data as a source of information. Two reviewers independently extracted and synthesized data. The quality of the studies was assessed using an adapted version of the Joanna Briggs Institute critical appraisal checklist for prevalence studies. Narrative summaries of findings were undertaken.

RESULTS: Among 59,336 citations, 62 studies were included for data extraction and synthesis. Among these studies, 41 studies included the outcome of hospitalization, 16 included the death outcome, and five included both outcomes. Administrative databases regarding discharges and registries of vital statistics were the most common sources of information. The relative frequency of hospitalizations ranged from 0.03% to 7.3%, and from 9.7 to 383.0/100,000 population, whereas mortality rate ranged from 0.1 to 7.88/100,000 population.

CONCLUSION: Our study highlights information about adverse drug events using large administrative databases in a national scenario and provides an overview of databases and methods implemented to detect adverse drug events.

PMID:34716774 | DOI:10.1007/s00228-021-03238-2

Drug Saf. 2021 Oct 29. doi: 10.1007/s40264-021-01122-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Medication administration via intravenous push presents multiple potential advantages; however, there may be an increased risk of adverse drug reactions. In 2020, Brigham and Women's Hospital changed levetiracetam intravenous administration to intravenous push (IVP).

OBJECTIVE: The purpose of this analysis was to compare the safety profile of IVP to intravenous piggyback (IVPB) levetiracetam administration.

METHODS: This institutional review board-approved, single-center, pre-post analysis was performed between 1 November, 2019 and 30 May, 2020. The electronic health record was used to identify all administrations of intravenous levetiracetam greater than 1000 mg in patients ≥ 18 years old. The major safety outcomes included hypotension, bradycardia, drug-induced sedation, and intravenous site reactions such as phlebitis and infiltration. The major efficiency outcome was the time from pharmacy order verification to first-dose administration.

RESULTS: A total of 498 administrations in 162 patients were included in the analysis: 252 administrations in 84 patients in the IVP group and 246 administrations in 78 patients in the IVPB group. The incidence of bradycardia was 7 vs 3 (3.2% vs 1.5%, p = 0.34); hypotension 10 vs 6 (5.2% vs 3.5%, p = 0.44); sedation 21 vs 36 (19.3% vs 27.9%, p = 0.12); and peripheral IV site reactions 0 vs 1 (0% vs 0.6%, p = 0.39) in the IVP vs IVPB groups, respectively. The median time between order verification and first-dose administration was significantly reduced in the IVP vs IVPB group (23.5 vs 55 min, p < 0.001).

CONCLUSIONS: Intravenous push levetiracetam administration of doses up to 4000 mg was associated with a similar incidence of cardiovascular, sedation, and infusion site-related adverse events compared to IVPB and resulted in a significant reduction in time to first-dose administration. Intravenous push levetiracetam in doses as high as 4000 mg may be considered safe with appropriate monitoring.

PMID:34716562 | DOI:10.1007/s40264-021-01122-7

Thorax. 2021 Oct 29:thoraxjnl-2021-217429. doi: 10.1136/thoraxjnl-2021-217429. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.

METHODS: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.

RESULTS: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.

CONCLUSION: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.

PMID:34716281 | DOI:10.1136/thoraxjnl-2021-217429

Front Pediatr. 2021 Oct 12;9:716648. doi: 10.3389/fped.2021.716648. eCollection 2021.

ABSTRACT

Purpose: Biologic agent-induced cardiotoxicity is markedly concerning. Rheumatoid arthritis (RA) treated with biologic agents is known to have the potential for cardiotoxicity; however, existing clinical evidence is not adequate to explain real-world patterns of cardiotoxicity. In this study, we quantify the risk of cardiotoxicity in patients with rheumatoid arthritis treated with biological agents. Methods: Cardiotoxicity reports induced by four types of biologic agents, abatacept, adalimumab, tocilizumab, and etanercept were used to mine data from the FDA's adverse event reporting system (FAERS) database from January 1, 2004 through September 30, 2020. Reports of cardiotoxic events were analyzed using a reporting odds ratio (ROR) algorithm, the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), the multi-item gamma Poisson shrinker (MGPS), and logistic regression methods. We use the preferred term of the Medical Dictionary of Regulatory Activities to identify such events. Results: A total of 3,969 reports of cardiotoxic events were identified involving biologic agents used for RA as the suspect drugs in this study, 317 reports of abatacept, 2,137 reports of adalimumab, 273 reports of tocilizumab, and 1,242 reports of etanercept. Adalimumab was the most reported, followed by etanercept. The proportion of death and disability outcomes reported for each targeted treatment represents approximately 20-25% of the total reported severe adverse events. In addition, relatively low cardiotoxicity reporting rates were found with abatacept. Conclusion: Analysis of FAERS data offers a more precise profile on the characteristics and occurrences of cardiotoxic events. The findings are a clinical reminder to physicians that an increased vigilance concerning the cardiotoxic effects of biological agents needs to be implemented. Also, more comparative studies are required in the future to explain the mechanisms that cause these cardiac phenomena.

PMID:34712629 | PMC:PMC8546333 | DOI:10.3389/fped.2021.716648

Syst Rev. 2021 Oct 28;10(1):280. doi: 10.1186/s13643-021-01782-7.

ABSTRACT

PURPOSE: The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.

METHODS: A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.

RESULTS: A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.

CONCLUSIONS: Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42020106886.

PMID:34711264 | DOI:10.1186/s13643-021-01782-7

Expert Opin Drug Saf. 2021 Oct 28. doi: 10.1080/14740338.2022.1999409. Online ahead of print.

ABSTRACT

BACKGROUND: Safety and tolerability of glucose-lowering drugs is a key consideration for use in type 2 diabetes (T2D). We evaluated the safety and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin in Asian patients with T2D.

RESEARCH DESIGN AND METHODS: This was a post-hoc, descriptive pooled analysis of 21 randomized, double-blind, placebo-controlled clinical trials of linagliptin in T2D patients lasting ≤52 weeks. We evaluated adverse events (AEs) and laboratory parameters in Asian participants living in Asia, both overall and in the East Asian subgroup.

RESULTS: This analysis included 4457 Asian patients overall (2712 receiving linagliptin; 1745 receiving placebo) and 3057 (68.6%) East Asians. AEs were reported in 1510 (55.7%) Asian patients receiving linagliptin and 1032 (59.1%) receiving placebo but were considered drug-related in only 13.0% of each group. Serious AEs occurred in 109 (4.0%) linagliptin patients and 90 (5.2%) placebo patients. The most common AEs were nasopharyngitis (6.4% linagliptin, 7.3% placebo), upper respiratory tract infection (5.7% linagliptin, 6.5% placebo), and hypoglycemia (7.3% linagliptin, 6.3% placebo). One linagliptin patient had pancreatitis; none had bullous pemphigoid. No clinically relevant mean changes in laboratory parameters occurred. These findings were consistent in East Asians.

CONCLUSIONS: Linagliptin is well tolerated in Asian T2D patients, including East Asians, with low risk for AEs.

PMID:34711126 | DOI:10.1080/14740338.2022.1999409

WMJ. 2021 Oct;120(3):237-240.

ABSTRACT

INTRODUCTION: The electronic health record and electronic prescribing have transformed the practice of medicine. Both have led to improved efficacy and safety in medication management. However, dangers may arise when electronic prescription requests are filled by default and when electronic health record medication lists are presumed accurate. In this case, our patient underwent 2 days of inpatient evaluation before a thorough medication reconciliation revealed that his symptoms had likely resulted from a medication that had been refilled reflexively.

CASE PRESENTATION: A 69-year-old man presented with worsening weakness, weight loss, decreased appetite, and nonbloody diarrhea. Imaging revealed a large right pleural effusion and a nonspecific colitis. Lab workup revealed significant bicytopenia, hypogammaglobulinemia, and hypolipidemia. Initial evaluation and diagnoses were focused toward causes of malnutrition and malabsorption. However, on hospital day 2, a pharmacist discovered that the patient had been taking long-term oral linezolid for unclear reasons. With cessation of linezolid, the patient's myriad symptoms resolved and all lab values progressively normalized.

DISCUSSION: The side effects of linezolid have been well documented and include reversible myelosuppression and gastrointestinal symptoms. However, medication reconciliation was imperative in diagnosing and treating our patient. Further, reflexive refilling of this patient's medication likely explains why he was taking linezolid for such a long period of time, as other forms of automation bias are known to introduce errors in electronic prescribing.

CONCLUSION: This case calls attention to the importance of medication reconciliation, the danger of overreliance on electronic health record medication lists, and the pitfalls in not maintaining vigilance with electronic prescribing. It also highlights the necessity of patient and caregiver education regarding their medications.

PMID:34710309

Anasthesiol Intensivmed Notfallmed Schmerzther. 2021 Oct;56(10):652-665. doi: 10.1055/a-1226-4647. Epub 2021 Oct 26.

ABSTRACT

Analysis of preoperative medication is used to assess the benefit and risk associated with continuing or discontinuing medication before and during surgery. Identifying adverse drug reactions and assessing its risks often leads to uncertainty. Typical challenges are medication underuse, but also overuse occurs and is often more difficult to recognize, especially in the context of drug interactions and individual patient characteristics.Typical consequences of multi-medication and medical overuse may include an increased potential for drug interactions, an increased risk of adverse drug reactions and medication errors, and in particular in older adults, geriatric syndromes may occur or worsen. Adverse drug reactions may occur as a result of the dose administered and as an effect of time of exposure. Older, multi-morbid, and multi-medicated patients are often affected by adverse drug reactions. For drugs primarily metabolized via the phase I enzymes CYP2D6, CYP2C9, or CYP2C19, pharmacogenetically rapid or slow metabolism may result in altered drug exposures. Clinically relevant pharmacokinetic drug interactions frequently occur with drugs primarily metabolized via the phase I enzyme CYP3A4.

PMID:34704243 | DOI:10.1055/a-1226-4647

J Funct Biomater. 2021 Oct 8;12(4):58. doi: 10.3390/jfb12040058.

ABSTRACT

Polymers have always played a critical role in the development of novel drug delivery systems by providing the sustained, controlled and targeted release of both hydrophobic and hydrophilic drugs. Among the different polymers, polyamides or poly(amino acid)s exhibit distinct features such as good biocompatibility, slow degradability and flexible physicochemical modification. The degradation rates of poly(amino acid)s are influenced by the hydrophilicity of the amino acids that make up the polymer. Poly(amino acid)s are extensively used in the formulation of chemotherapeutics to achieve selective delivery for an appropriate duration of time in order to lessen the drug-related side effects and increase the anti-tumor efficacy. This review highlights various poly(amino acid) polymers used in drug delivery along with new developments in their utility. A thorough discussion on anticancer agents incorporated into poly(amino acid) micellar systems that are under clinical evaluation is included.

PMID:34698184 | DOI:10.3390/jfb12040058