S D Med. 2023 Mar;76(3):124-127.

ABSTRACT

Polypharmacy is defined as concurrent use of multiple drugs for one or more conditions. The occurrence of polypharmacy in vulnerable populations, particularly the elderly, is frequent. Increased incidents of adverse drug reactions and drug-drug interactions plus high costs are not offset by a noticeable improvement in outcome. The practice of polypharmacy persists despite frequent adverse outcomes and reduced effectiveness. We present a case in which an elderly woman presented with falls and delirium. She was taking multiple medications for anxiety and depression in addition to several psychoactive medications for pain, restless leg syndrome, muscle spasms, blood pressure and many nonpsychoactive medications for other conditions. In total, she was taking 24 medications, many of which were likely contributing to her presenting problems.

PMID:36898199

Obstet Gynecol. 2023 Mar 9. doi: 10.1097/AOG.0000000000005114. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the safety, tolerability, and effect of fezolinetant on endometrial health over 52 weeks.

METHODS: We conducted a phase 3, randomized, double-blind, 52-week safety study (SKYLIGHT 4 [Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause]) of placebo, fezolinetant 30 mg, and fezolinetant 45 mg once daily (1:1:1). Participants were postmenopausal and seeking treatment for vasomotor symptoms associated with menopause. Primary endpoints were treatment-emergent adverse events, percentage of participants with endometrial hyperplasia, and percentage with endometrial malignancy. Endometrial hyperplasia or malignancy was evaluated according to U.S. Food and Drug Administration guidance (point estimate of 1% or less with an upper bound of one-sided 95% CI of 4% or less). Secondary endpoints included change in bone mineral density (BMD) and trabecular bone score. A sample size of 1,740 was calculated to enable observation of one or more events (≈80% probability for events with background rate of less than 1%).

RESULTS: A total of 1,830 participants were randomized and took one or more medication dose (July 2019-January 2022). Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo group, 67.9% (415/611) of the fezolinetant 30-mg group, and 63.9% (389/609) of the fezolinetant 45-mg group. Treatment-emergent adverse events leading to discontinuation were similar across groups (placebo, 26/610 [4.3%]; fezolinetant 30 mg, 34/611 [5.6%]; fezolinetant 45 mg, 28/609 [4.6%]). Endometrial safety was assessed in 599 participants. In the fezolinetant 45-mg group, 1 of 203 participants had endometrial hyperplasia (0.5%; upper limit of one-sided 95% CI 2.3%); there were no cases in the placebo (0/186) or fezolinetant 30 mg (0/210) group. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI 2.2%) with no cases in the other groups. Liver enzyme elevations more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of 590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants; no Hy's law cases were reported (ie, no severe drug-induced liver injury with alanine aminotransferase or aspartate aminotransferase more than three times the upper limit of normal and total bilirubin more than two times the upper limit of normal, with no elevation of alkaline phosphatase and no other reason to explain the combination). Changes in BMD and trabecular bone score were similar across groups.

CONCLUSION: Results from SKYLIGHT 4 confirm the 52-week safety and tolerability of fezolinetant and support its continued development.

FUNDING SOURCE: Astellas Pharma Inc.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04003389.

PMID:36897180 | DOI:10.1097/AOG.0000000000005114

Expert Opin Drug Saf. 2023 Mar 10. doi: 10.1080/14740338.2023.2189235. Online ahead of print.

ABSTRACT

BACKGROUND: BRAF and MEK inhibitor combination therapy have significantly improved the outcome of several BRAF-mutation tumors, but it also confers the risk of drug-induced ocular adverse events (oAEs). However, very few studies focused on this risk.

METHODS: The United States Food and Drug Administration Adverse Event Reporting System (FAERS) data from Quarter 1-2011 to Quarter 2-2022 were searched to detect signs of oAEs of three marketed BRAF and MEK inhibitor combination therapies: vemurafenib plus cobimetinib (V+C), dabrafenib plus trametinib (D+T), and encorafenib plus binimetinib (E+B). Disproportionality analyses were performed by calculating the proportional reporting ratio (PRR), χ2 (chi-square), and reporting odds ratios (RORs) with a 95% confidence interval (CI).

RESULTS: A series of oAEs were identified, including 42 preferred terms, which could be classified into 8 aspects. In addition to previously reported oAEs, several unexpected oAE signals were detected. Moreover, differences in oAE profiles were found among three combination therapies (V+C, D+T, and E+B).

CONCLUSIONS: Our findings support an association between several oAEs and BRAF and MEK inhibitor combination therapies, including several new oAEs. In addition, oAEs profiles may vary across the treatment regimens. Further studies are needed to better quantify these oAEs.

PMID:36896641 | DOI:10.1080/14740338.2023.2189235

Front Toxicol. 2023 Feb 21;5:1113032. doi: 10.3389/ftox.2023.1113032. eCollection 2023.

ABSTRACT

More than fifteen million women with the human immunodeficiency virus type-1 (HIV-1) infection are of childbearing age world-wide. Due to improved and affordable access to antiretroviral therapy (ART), the number of in utero antiretroviral drug (ARV)-exposed children has exceeded a million and continues to grow. While most recommended ART taken during pregnancy suppresses mother to child viral transmission, the knowledge of drug safety linked to fetal neurodevelopment remains an area of active investigation. For example, few studies have suggested that ARV use can be associated with neural tube defects (NTDs) and most notably with the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG). After risk benefit assessments, the World Health Organization (WHO) made recommendations for DTG usage as a first and second-line preferred treatment for infected populations including pregnant women and those of childbearing age. Nonetheless, long-term safety concerns remain for fetal health. This has led to a number of recent studies underscoring the need for biomarkers to elucidate potential mechanisms underlying long-term neurodevelopmental adverse events. With this goal in mind, we now report the inhibition of matrix metalloproteinases (MMPs) activities by INSTIs as an ARV class effect. Balanced MMPs activities play a crucial role in fetal neurodevelopment. Inhibition of MMPs activities by INSTIs during neurodevelopment could be a potential mechanism for adverse events. Thus, comprehensive molecular docking testing of the INSTIs, DTG, bictegravir (BIC), and cabotegravir (CAB), against twenty-three human MMPs showed broad-spectrum inhibition. With a metal chelating chemical property, each of the INSTI were shown to bind Zn++ at the MMP's catalytic domain leading to MMP inhibition but to variable binding energies. These results were validated in myeloid cell culture experiments demonstrating MMP-2 and 9 inhibitions by DTG, BIC and CAB and even at higher degree than doxycycline (DOX). Altogether, these data provide a potential mechanism for how INSTIs could affect fetal neurodevelopment.

PMID:36896351 | PMC:PMC9988942 | DOI:10.3389/ftox.2023.1113032

J Dtsch Dermatol Ges. 2023 Mar;21(3):239-243. doi: 10.1111/ddg.14961. Epub 2023 Mar 9.

ABSTRACT

Colchicine, which was already used by the ancient Egyptians, has recently experienced a renaissance in various medical disciplines, including dermatology. However, due to the potentially significant side effects of systemic use, many clinicians are cautious in their use of colchicine. This review provides a practical overview of the data on the established and emerging use of systemic and topical colchicine in dermatologic diseases.

PMID:36892188 | DOI:10.1111/ddg.14961

S D Med. 2022 Nov;75(11):500-502.

ABSTRACT

Within most electronic medical records, automated decision support helps health care providers reduce the frequency of adverse drug reactions. Historically, this decision support has been used to prevent drug-drug interactions (DDIs). More recently, the clinical and scientific communities have been moving toward the use of this approach to predict and prevent drug-gene interactions (DGIs). Genetic variation in cytochrome P450 2D6 (CYP2D6) is known to impact clinical outcome for many drugs, including opioids. Randomized trials have been initiated to assess the utility of CYP2D6 gene-based dosing versus usual care. We review the use of this approach to guide opioid prescribing in the post-operative setting.

PMID:36893027

Nat Commun. 2023 Mar 9;14(1):1299. doi: 10.1038/s41467-023-36686-8.

ABSTRACT

mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

PMID:36894554 | PMC:PMC9996559 | DOI:10.1038/s41467-023-36686-8

J Clin Pharmacol. 2023 Mar 9. doi: 10.1002/jcph.2233. Online ahead of print.

ABSTRACT

This article discusses the rare but serious occurrence of sedative hypnotic drug induced sexual thoughts. We searched PubMed from the earliest date to 2/7/2023. Articles were selected if they provided data on sexual assault hallucinations or sexual fantasies associated with the use of sedative hypnotic drugs including benzodiazepines, propofol, nitric oxide, ether, chloroform, ketamine, or esketamine. Twenty-two citations provided useful information, including 87 cases of hallucinations about sexual assault or sexual fantasy. In several of the cases, the environment and monitoring made the actual occurrence of sexual assault unlikely but there was still significant anguish for the patients and the accused clinicians. In many of the cases, the places of the body where procedures were conducted coincided the area of the body where the patients perceived the sexual assault or fantasy occurred. The higher the dose of sedative hypnotic administered, the greater the risk of experiencing a hallucination about sexual assault or sexual fantasy. The FDA Adverse Events Reporting System has numerous occurrences where "excessive sexual fantasies" and "abnormal dreams" were associated with the use of sedative hypnotic medication but also occurrences of "sexual abuse" as well. While sexual assault hallucinations or fantasies associated with sedative hypnotics are rare, it is imperative that healthcare providers take the necessary precautions and follow recommendations to provide safety for themselves and their patients. This article is protected by copyright. All rights reserved.

PMID:36895011 | DOI:10.1002/jcph.2233

Lancet Infect Dis. 2023 Mar 6:S1473-3099(23)00048-8. doi: 10.1016/S1473-3099(23)00048-8. Online ahead of print.

ABSTRACT

BACKGROUND: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children.

METHODS: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140.

FINDINGS: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]).

INTERPRETATION: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis.

FUNDING: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

PMID:36893784 | DOI:10.1016/S1473-3099(23)00048-8

Front Oncol. 2023 Feb 20;13:1003565. doi: 10.3389/fonc.2023.1003565. eCollection 2023.

ABSTRACT

INTRODUCTION: Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear which pharmacological treatment option is the most beneficial.

METHODS: We searched databases, such as PubMed, Embase, and Cochrane Library, and conference abstracts according to keywords. We extracted progression-free survival (PFS), overall survival (OS) data, and overall response rate (ORR) from randomized controlled trials and single-arm studies of HER2-positive breast cancer brain metastasis treatment for meta-analysis and analyzed different drug-related adverse events (AEs).

RESULTS: Three randomized controlled trials and seven single-arm clinical studies with 731 patients with HER2-positive brain metastases from breast cancer involving at least seven drugs were included. In randomized controlled trials, our results showed that trastuzumab deruxtecan significantly improved PFS and OS in patients and was superior to other drug regimens. In the single-arm study, the ORR was more pronounced for the trastuzumab deruxtecan and pyrotinib plus capecitabine regimens (ORR, 73.33%; 95% confidence intervals [CI], 44.90%-92.21%; ORR, 74.58%; 95% CI, 61.56%-85.02%, respectively). We found that the main AEs of antibody-drug conjugate (ADC) were nausea and fatigue, while the main AE of small-molecule tyrosine kinase inhibitor (TKI) drugs and large monoclonal antibodies was diarrhea.

CONCLUSIONS: Trastuzumab deruxtecan was shown to be the most significant in improving survival in patients with HER2-positive breast cancer brain metastases in network meta-analysis, and in single-arm study, patients with HER2-positive breast cancer brain metastases treated with trastuzumab deruxtecan and pyrotinib plus capecitabine regimen had the highest ORR. The main AEs associated with ADC, large monoclonal antibodies, and TKI drugs were nausea, fatigue, and diarrhea, respectively.

PMID:36890831 | PMC:PMC9986525 | DOI:10.3389/fonc.2023.1003565

BMC Pulm Med. 2023 Mar 8;23(1):79. doi: 10.1186/s12890-023-02367-x.

ABSTRACT

BACKGROUND: With the use of targeted drugs in lung cancer patients, targeted drug-induced interstitial lung disease (ILD) has attracted more and more attention. The incidence, time, and severity of different targeted drug-induced ILD vary. Almonertinib/HS-10296 is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Post-marketing safety and effectiveness of almonertinib have been confirmed. The reported adverse events of almonertinib were mainly an increase in creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase, and onset of rash. Almonertinib-induced ILD is rare.

CASE REPORT: This paper reported the case of a patient with lung adenocarcinoma complicated with interstitial lung abnormality (ILA). Gene detection showed L858R mutation in exon 21 of the EGFR gene. After operation, almonertinib (110 mg per day) was prescribed. 3 months later, ILD was found by chest CT due to dyspnea.

MANAGEMENT AND OUTCOME: Subsequently, almonertinib was stopped. With the administration of intravenous glucocorticoid and oxygen inhalation, the patient's dyspnea was significantly regressed and lung lesions regressed on follow-up chest CT done after discharge.

DISCUSSION: This case suggested that we should pay attention to the existence of ILD/ILA before using targeted drugs. The use of targeted drugs should be more strictly controlled and monitored in patients with previous ILA or ILD. This paper also reviewed the relevant literature on the drug characteristics and summarized the risk factors of ILD caused by EGFR-TKI.

PMID:36890493 | DOI:10.1186/s12890-023-02367-x

Ther Apher Dial. 2023 Mar 8. doi: 10.1111/1744-9987.13980. Online ahead of print.

ABSTRACT

OBJECTIVE: To observe the effect of ticagrelor on the function of tunneled cuffed catheter (TCC) in maintenance hemodialysis (MHD) patients.

METHODS: Eighty MHD patients (control group: 39 cases, observation group: 41 cases) using TCC as vascular access were enrolled from January 2019 to October 2020 in the prospective study. Patients in the control group were routinely treated with aspirin for antiplatelet therapy, while patients in the observation group were treated with ticagrelor. The catheter life time, catheter dysfunction, coagulation function and antiplatelet drug-related adverse events of the two groups were recorded.

RESULTS: The median life time of TCC in the control group was significantly higher than that in the observation group. And the log rank test showed that the difference was statistically significant (P<0.001).

CONCLUSION: Ticagrelor may reduce the incidence of catheter dysfunction and prolong the life time of the catheter by preventing and reducing the thrombosis of TCC in MHD patients, without obvious side effects.

PMID:36889934 | DOI:10.1111/1744-9987.13980

J Med Internet Res. 2023 Mar 8;25:e41100. doi: 10.2196/41100.

ABSTRACT

BACKGROUND: Drug-induced suicide has been debated as a crucial issue in both clinical and public health research. Published research articles contain valuable data on the drugs associated with suicidal adverse events. An automated process that extracts such information and rapidly detects drugs related to suicide risk is essential but has not been well established. Moreover, few data sets are available for training and validating classification models on drug-induced suicide.

OBJECTIVE: This study aimed to build a corpus of drug-suicide relations containing annotated entities for drugs, suicidal adverse events, and their relations. To confirm the effectiveness of the drug-suicide relation corpus, we evaluated the performance of a relation classification model using the corpus in conjunction with various embeddings.

METHODS: We collected the abstracts and titles of research articles associated with drugs and suicide from PubMed and manually annotated them along with their relations at the sentence level (adverse drug events, treatment, suicide means, or miscellaneous). To reduce the manual annotation effort, we preliminarily selected sentences with a pretrained zero-shot classifier or sentences containing only drug and suicide keywords. We trained a relation classification model using various Bidirectional Encoder Representations from Transformer embeddings with the proposed corpus. We then compared the performances of the model with different Bidirectional Encoder Representations from Transformer-based embeddings and selected the most suitable embedding for our corpus.

RESULTS: Our corpus comprised 11,894 sentences extracted from the titles and abstracts of the PubMed research articles. Each sentence was annotated with drug and suicide entities and the relationship between these 2 entities (adverse drug events, treatment, means, and miscellaneous). All of the tested relation classification models that were fine-tuned on the corpus accurately detected sentences of suicidal adverse events regardless of their pretrained type and data set properties.

CONCLUSIONS: To our knowledge, this is the first and most extensive corpus of drug-suicide relations.

PMID:36884281 | DOI:10.2196/41100

Curr Drug Saf. 2023;18(2):138-142. doi: 10.2174/1574886317666220428125943.

ABSTRACT

There is a growing awareness of a disease at many levels, its treatment, and treatment outcomes including side effects. Alternative therapy techniques, herbal medicines and formulations are extensively acknowledged and practiced in India and around the world. Herbal medicine is usually considered being safe regardless of the absence of scientific evidence to support its claims. Several issues concerning the methods in which herbal medications are labelled, evaluated, sourced, and used are connected to herbal medicine. Herbal therapeutics in the management and treatment of diabetes, rheumatism, hepatic disorders and other mild to chronic diseases and disorders are widely accepted. However, the adversities are difficult to recognize. The idea that the nature is safe and may be taken without the prescription of a physician has resulted in widespread self-medication across the world, sometimes with disappointing results, side effects, or unpleasant after-effects. The existing pharmacovigilance paradigm and its accompanying tools were created in connection with synthetic medicines. Nevertheless, adopting these approaches to keep records of herbal medications' safety poses a distinct challenge. This might be due to the variations in the usage of non-traditional medicines, which can offer unique toxicological issues whether taken alone or in conjunction with other medications. The goal of pharmacovigilance is to identify, analyse, explain, and minimize the adverse reactions and other drug-related complications associated with herbal, traditional, and complementary medications. Systematic pharmacovigilance is required to collect accurate data on the safety of herbal medications to create adequate guidelines for effective and safe usage.

PMID:36883268 | DOI:10.2174/1574886317666220428125943

Expert Opin Drug Saf. 2023 Feb;22(2):111-114. doi: 10.1080/14740338.2023.2188189. Epub 2023 Mar 9.

NO ABSTRACT

PMID:36881668 | DOI:10.1080/14740338.2023.2188189

Sci Rep. 2023 Mar 7;13(1):3779. doi: 10.1038/s41598-023-28912-6.

ABSTRACT

As society continues to age, it is becoming increasingly important to monitor drug use in the elderly. Social media data have been used for monitoring adverse drug reactions. The aim of this study was to determine whether social network studies (SNS) are useful sources of drug side effects information. We propose a method for utilizing SNS data to plot the known side effects of geriatric drugs in a dosing map. We developed a lexicon of drug terms associated with side effects and mapped patterns from social media data. We confirmed that well-known side effects may be obtained by utilizing SNS data. Based on these results, we propose a pharmacovigilance pipeline that can be extended to unknown side effects. We propose the standard analysis pipeline Drug_SNSMiner for monitoring side effects using SNS data and evaluated it as a drug prescription platform for the elderly. We confirmed that side effects may be monitored from the consumer's perspective based on SNS data using only drug information. SNS data were deemed good sources of information to determine ADRs and obtain other complementary data. We established that these learning data are invaluable for AI requiring the acquisition of ADR posts on efficacious drugs.

PMID:36882478 | DOI:10.1038/s41598-023-28912-6

PLoS One. 2023 Mar 7;18(3):e0281983. doi: 10.1371/journal.pone.0281983. eCollection 2023.

ABSTRACT

Adverse events(AEs) related to hepatotoxicity have been reported in patients treated with immune checkpoint inhibitors (ICIs). As the number of adverse events increases, it is necessary to assess the differences in each immune checkpoint inhibitor regimen. The purpose of this study was to examine the relationship between ICIs and hepatotoxicity in a scientific and systematic manner. Data were obtained from the FDA Adverse Event Reporting System database (FAERS) and included data from the first quarter of 2014 to the fourth quarter of 2021. Disproportionality analysis assessed the association between drugs and adverse reactions based on the reporting odds ratio (ROR) and information components (IC). 9,806 liver adverse events were reported in the FAERS database. A strong signal was detected in older patients (≥65 years) associated with ICIs. hepatic adverse events were most frequently reported with Nivolumab (36.17%). Abnormal liver function, hepatitis, and autoimmune hepatitis were most frequently reported, and hepatitis and immune-mediated hepatitis signals were generated in all regimens. In clinical use, patients should be alert to these adverse effects, especially in elderly patients, who may be aggravated by the use of ICI.

PMID:36881599 | PMC:PMC9990950 | DOI:10.1371/journal.pone.0281983

In Vivo. 2023 Mar-Apr;37(2):955-961. doi: 10.21873/invivo.13168.

ABSTRACT

BACKGROUND/AIM: Pomalidomide is an immunomodulatory drug that is used to treat multiple myeloma. We examined the time-to-onset and outcome of lung adverse events (LAEs) related to pomalidomide in Japanese patients based on information obtained from the spontaneous reporting system of the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency.

PATIENTS AND METHODS: We analyzed adverse events (AEs) reports recorded between April 2004 and March 2021 from JADER. Data on LAEs were extracted, and the relative risk of AEs was estimated using the reporting odds ratio and 95% confidence interval. We analyzed 1,772,494 reports and identified 2,918 reports of AEs caused by pomalidomide. Of these, 253 LAEs were reportedly associated with pomalidomide.

RESULTS: Signals were detected for five LAEs: pneumonia, pneumocystis jirovecii pneumonia, bronchitis, pneumonia bacterial, and pneumonia pneumococcal. Pneumonia was the most frequently mentioned condition (68.8%). The median time-to-onset of pneumonia was 66 days, but some cases of pneumonia occurred as late as 20 months after the start of administration. Fatal outcomes were observed in two of the five AEs wherein signals were detected and were due to pneumonia and bacterial pneumonia.

CONCLUSION: Serious outcomes can occur after pomalidomide administration. It has been suggested that these LAEs occur relatively early after pomalidomide administration. Since some situations can result in fatal consequences, patients should be monitored for the emergence of these AEs over a prolonged period of time, especially for pneumonia.

PMID:36881059 | DOI:10.21873/invivo.13168

JAMA. 2023 Mar 7;329(9):713-715. doi: 10.1001/jama.2023.1002.

NO ABSTRACT

PMID:36881043 | DOI:10.1001/jama.2023.1002

Eur J Hosp Pharm. 2023 Mar 7:ejhpharm-2022-003645. doi: 10.1136/ejhpharm-2022-003645. Online ahead of print.

ABSTRACT

INTRODUCTION: Few if any studies have been conducted to date on the association between polypharmacy and cognitive impairment among older trauma patients. Therefore, we investigated whether polypharmacy is associated with cognitive impairment in trauma patients aged ≥70 years.

METHODS: This is a cross-sectional study of patients aged ≥70 years hospitalised due to a trauma-related injury. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score ≤24 points. Medications were coded according to the Anatomical Therapeutic Chemical classification. Three exposures were examined: polypharmacy (≥5 medications), excessive polypharmacy (≥10 medications), and number of medications. Separate logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking, independent living, frailty, multimorbidity, depression, and type of trauma were used to test the association between the three exposures and cognitive impairment.

RESULTS: A total of 198 patients were included (mean age 80.2; 64.7% women and 35.4% men), of which 148 (74.8%) had polypharmacy and 63 (31.8%) had excessive polypharmacy. The prevalence of cognitive impairment was 34.3% overall, 37.2% in the polypharmacy group and 50.8% in the excessive polypharmacy group. More than 80% of participants were taking at least one analgesic. Overall, polypharmacy was not statistically significantly associated with cognitive impairment (odds ratio (OR) 1.20 [95% confidence interval (CI) 0.46 to 3.11]). However, patients in the excessive polypharmacy group were more than two times more likely to have cognitive impairment (OR 2.88 [95% CI 1.31 to 6.37]) even after adjustments for relevant confounders. Similarly, the number of medications was associated with greater odds of cognitive impairment (OR 1.15 [95% CI 1.04 to 1.28]) after adjustments for the same relevant confounders.

CONCLUSION: Cognitive impairment is common among older trauma patients, particularly among those in the excessive polypharmacy group. Polypharmacy was not associated with cognitive impairment. Excessive polypharmacy and number of medications, on the other hand, were associated with greater odds of cognitive impairment in older trauma patients.

PMID:36882299 | DOI:10.1136/ejhpharm-2022-003645