Eur J Case Rep Intern Med. 2023 Aug 31;10(10):004041. doi: 10.12890/2023_004041. eCollection 2023.

ABSTRACT

BACKGROUND: Linezolid is known to cause side effects, including nausea, diarrhea, and headaches of short duration. As extended use of linezolid is becoming more common, additional rare side effects should be considered.

CASE PRESENTATION: A 68-year-old man hospitalized for osteomyelitis developed severe abdominal pain and altered mental status following five weeks of linezolid therapy. Laboratory studies showed very high lipase levels, lactic acidosis not responding to resuscitation, and relative hypoglycemia. All common causes of pancreatitis were ruled out, and a trial of linezolid withdrawal was done resulting in drastic improvement in the patient's clinical status.

CONCLUSIONS: For patients on extended course of linezolid who develop abdominal pain, drug-induced pancreatitis should be considered as a side effect, and a trial of withdrawal of linezolid should be undertaken.

LEARNING POINTS: Linezolid can be associated with a rare but serious triad of adverse effects of pancreatitis, hypoglycemia, and lactic acidosis.Possible risk factors include a prolonged course of linezolid, renal dysfunction, and sepsis.

PMID:37789976 | PMC:PMC10545144 | DOI:10.12890/2023_004041

Asia Pac J Clin Nutr. 2023 Sep;32(3):308-320. doi: 10.6133/apjcn.202309_32(3).0002.

ABSTRACT

BACKGROUND AND OBJECTIVES: Emerging expert consensuses and guidelines recommend that omega-3 fatty acids may have anti-inflammatory effects in hospitalized patients with coronavirus disease (COVID-19). However, these recommendations are based on pathophysiological studies of inflammation rather than direct clinical evidence. We conducted this systematic review and meta-analysis to evaluate the efficacy of omega-3 fatty acid supplementation in hospitalized patients with COVID-19.

METHODS AND STUDY DESIGN: We retrieved literature from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), WANFANG, Chinese Biomedical Literature Database, and Cochrane Library databases up to May 1, 2023. Data from studies comparing omega-3 fatty acids with a placebo or other pharmaceutical nutrients were analyzed.

RESULTS: Of 3032 records, 42 full-text articles were reviewed, five eligible studies were identified, and one study was found in the references. In total of six studies involving 273 patients were included, pooled, and analyzed. Compared to the control group, omega-3 fatty acid intervention reduced the overall mortality of hospitalized patients with COVID-19 (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010). No serious or unexpected drug-related adverse events were observed. No statistical significance was observed in inflammatory markers such as CRP (MD=-9.69; 95% CI, [-22.52, 3.15]; p=0.14; I2=97%) and IL-6; however, the neutrophil/lymphocyte ratio was significantly lower in the omega-3 FAs group on day 7 of intervention (p < 0.001).

CONCLUSIONS: Omega-3 fatty acid administration may be associated with reduced mortality in hospitalized patients with COVID-19. Given the small sample size of enrolled studies, more rigorous and large-scale trials are urgently needed in the future to verify its efficacy.

PMID:37789651 | DOI:10.6133/apjcn.202309_32(3).0002

World J Microbiol Biotechnol. 2023 Oct 3;39(12):327. doi: 10.1007/s11274-023-03763-5.

ABSTRACT

The aim of the study was the bio-control effectiveness of the Lactiplantibacillus plantarum S61 strain, isolated from traditional fermenting green olives, against Escherichia coli B805 in ground beef. The bio-control effect of L. plantarum S61 against E. coli B805 was evaluated in ground meat during storage under refrigeration at 4 °C. The results showed that L. plantarum S61 reduced the biomass of pathogenic bacteria (E. coli) in ground meat during 10 days of storage at 4 °C. Moreover, the treatment with L. plantarum S61 has no adverse effect on the sensory properties of ground meat after 10 days of storage at 4 °C. The treatment with L. plantarum S61 and storage at 4 °C effectively decreases the growth and risk of pathogenic bacteria in ground meat and, consequently, increases the product's shelf life. Therefore, the application of L. plantarum S61 during the storage of ground meat beef may help reduce the use of chemical preservatives in meat products. Consequently, L. plantarum S61 can be applied as a bio-control agent against spoilage and pathogenic bacteria in meat and meat products.

PMID:37787857 | DOI:10.1007/s11274-023-03763-5

Iran J Med Sci. 2023 Sep;48(5):474-483. doi: 10.30476/ijms.2023.96145.2765.

ABSTRACT

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genes on serum isoniazid level and drug-induced hepatotoxicity.

METHODS: A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample t test, Chi square test, or Fisher's exact test. P<0.05 was considered statistically significant.

RESULTS: A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). NAT2*4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of NAT2*5 and NAT2*6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). NAT2*4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and CYP2E1 C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001).

CONCLUSION: Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of NAT2 SA polymorphism. Determining NAT2 and CYP2E1 genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity.

PMID:37786472 | PMC:PMC10541540 | DOI:10.30476/ijms.2023.96145.2765

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S60. doi: 10.1016/j.ijrobp.2023.06.357.

ABSTRACT

PURPOSE/OBJECTIVE(S): Liver-metastasis-directed SBRT (LM-SBRT) alone provides durable local control for liver metastases with low rates of toxicity when adhering to established dose constraints. Whether these constraints are sufficient in the context of concurrent ICI is not established. To determine whether LM-SBRT contributes to hepatotoxic adverse events (HAE) in patients receiving ICI, we analyzed potential predictors of HAE in a prospectively evaluated cohort of clinical trial patients treated with both SBRT and ICI.

MATERIALS/METHODS: Patients with metastatic solid tumors were included from three trials of multi-site SBRT with ICI given concurrently or shortly after SBRT provided they received all study treatments and were monitored for adverse events. ICI agents included pembrolizumab alone or dual agent ICI with nivolumab and either cabiralizumab, urelumab, or ipilimumab. LM-SBRT was delivered to 45 Gy in 3 fr with mean liver dose (MLD) limited to 16 Gy and <700 cc of liver receiving 17.1 Gy. HAE were defined using CTCAE 4.0 as: elevation of AST, ALT, bilirubin or alkaline phosphatase; autoimmune hepatitis; hepatic failure; or cholecystitis. HAE were included if rated at least possibly related to treatment by the trial monitoring committee. Cumulative incidence (CI) of HAE was modeled with death as a competing risk. Competing risks regression was performed using Fine-Gray modeling.

RESULTS: Two hundred thirteen patients were evaluable. Median follow-up was 10 months. Median age was 61, 90 had liver metastases at treatment, 65 received SBRT to a liver lesion, 15 had underlying liver disease (cirrhosis or hepatic steatosis) and 13 patients had a primary liver cancer. Dual agent ICI was given to 97 patients. Table 1 shows CI at 6 months of grades 1-4 HAE in all patients, LM-SBRT patients and non-liver SBRT patients (NL-SBRT). None experienced grade 5 HAE. There was no significant difference in CI of any grade of HAE between LM-SBRT and NL-SBRT patients. This was also true when comparing LM-SBRT patients to NL-SBRT patients with <0.1 Gy MLD. ICI dose reduction or cessation due to HAE occurred in 4 patients, none of whom received LM-SBRT. On univariate analysis, underlying liver disease and dual agent ICI were significantly associated with grade 2+ HAE while age, LM-SBRT, MLD, primary liver cancer and presence of liver metastases at treatment were not. On multivariate analysis, underlying liver disease and dual agent ICI remained significantly associated with grade 2+ HAE (HR: 6.7, 95% CI 2.3 - 19.1; 4.7, 95% CI 1.7 - 13.0). LM-SBRT and MLD were not significant on MVA.

CONCLUSION: LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease.

PMID:37784536 | DOI:10.1016/j.ijrobp.2023.06.357

Acta Med Port. 2023 Oct 2;36(10):689-690. doi: 10.20344/amp.20170. Epub 2023 Oct 2.

NO ABSTRACT

PMID:37788651 | DOI:10.20344/amp.20170

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e423. doi: 10.1016/j.ijrobp.2023.06.1580.

ABSTRACT

PURPOSE/OBJECTIVE(S): A majority of patients with oligometastatic prostate cancer experience relapse within 12 months of metastasis-directed therapy. Intense, triple-agent androgen annihilation therapy (AAT) with leuprolide, abiraterone acetate plus prednisone (AAP), and apalutamide may improve efficacy, but long courses of AAT have been shown to be associated with increased rates of grade≥3 toxicity. The purpose of this secondary analysis of this study is to characterize the tolerability of a short, six-month course of AAT added to metastasis-directed therapy.

MATERIALS/METHODS: All 28 patients enrolled on this phase II study were included in this analysis. All patients had oligometastatic prostate cancer after initial radical prostatectomy, defined by the presence of 1-5 extrapelvic metastases on prostate-specific membrane antigen (PSMA) PET/CT. Patients were started on six months of AAT. After the first month, patients received stereotactic body radiotherapy (SBRT) in 1, 3, or 5 fractions to metastases with or without radiotherapy to the prostate bed and pelvic lymph nodes. Physician-scored toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

RESULTS: Median follow-up time was 11.4 months. Twenty patients (71.4%) completed AAT with all three agents. Six patients (21.4%) completed six months of therapy but discontinued at least one agent [4 patients (14.3%) discontinued apalutamide, 1 patient (3.6%) discontinued AAP, and 1 patient (3.6%) discontinued both apalutamide and AAP]. Two patients (7.1%) withdrew from the trial due to adverse events and did not complete therapy. Grade 2 and grade 3 toxicity rates from AAT were each 21.4%. Of the 6 cases of grade 3 toxicity, 3 were skin rashes, 2 were hypertension, and 1 was hepatic toxicity. At the time of SBRT, 1 patient had withdrawn from the study and 1 patient declined radiation therapy. All 26 remaining patients completed SBRT. Grade 2 and grade 3 toxicity rates from SBRT were 7.7% and 0%, respectively.

CONCLUSION: A majority of patients were able to tolerate and complete AAT in combination with metastasis-directed SBRT. Some patients experienced acute grade 3 toxicities, the most common being drug-related skin rashes and hypertension. While efficacy data are needed to evaluate the oncologic benefit, these data suggest a short course of AAT is considerably better tolerated than longer courses of AAT, with grade 3 toxicity rates similar to long courses of single-agent androgen deprivation therapy alone.

PMID:37785389 | DOI:10.1016/j.ijrobp.2023.06.1580

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e412. doi: 10.1016/j.ijrobp.2023.06.1558.

ABSTRACT

PURPOSE/OBJECTIVE(S): Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for metastatic renal cell carcinoma (mRCC) but is limited by a lack of data to evaluate targeted therapy plus immunotherapy concurrently with high-dose SABR to multiple sites. We evaluated the safety and disease control for mRCC patients who concurrently received the above tri-modality treatment.

MATERIALS/METHODS: Patients were treated with SABR (40-70 Gy/5-10 fractions) for small lesions or partial-SABR (tumor center boosted with 6-8 Gy/3-5 fractions with 50-60 Gy/20-25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. When SABR/partial-SABR was not feasible, a moderate fractionated radiotherapy plan, usually 60Gy/20 fractions were applied. of Targeted therapy plus immunotherapy (PD-1 inhibitor) was not interrupted during or after radiotherapy (RT). Adverse events (AEs) were evaluated. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were calculated. The PFS1 was defined as the first progression since the start of RT. The PFS2 was defined as the second progression after the second RT course, if new metastases occurred after first RT were all re-irradiated, and the systemic therapy was not changed. The Kaplan-Meier method was used for time-to-event endpoints.

RESULTS: A total of 51 patients, with a median age of 57 yr, were enrolled. The median follow-up was 12 months. There were 75% of patients with intermediate-risk and 18% with favorable-risk disease. 61% of the patients were oligometastatic. 71% had clear cell renal cancer. There were 241 metastases while 161 (67%) were irradiated. 80% of the lesions received SABRP/partial SABR. 1 patient with 14 lesions irradiated received proton therapy. All the surviving patients are continuing using targeted therapy while 81% patients complete at least 1-year PD-1 therapy. 10 patients (20%) had grade 3 drug-related AEs: pneumonitis (n = 2), elevated alanine transaminase (n = 4), myositis (n = 1), hand-foot syndrome myositis (n = 1), enteritis (n = 1), fatigue (n = 1). There were 1 grade 4 AEs of upper gastrointestinal bleeding. No grade 3-5 RT-related AEs was found. ORR and DCR for irradiated lesion were 51% and 98%. Median OS and PFS2 was not reached. Median PFS1 was 14(6-22) months. Estimated 1- and 2-yr OS, PFS1 and PFS2 were 90% and 90%, 56% and 38%, 74% and 51% respectively. Univariate analysis showed that an PFS1 benefit was found in patients who received radiation before systemic therapy failure (p = 0.038).

CONCLUSION: We investigated the high-dose RT in combination of concurrent targeted and immunotherapy in patients with metastatic RCC. We found that this treatment regimen was well tolerated, with good cancer control. Early use of high-dose RT to multi-lesions may improve PFS. Partial-SABR for bulky lesions close to critical organs could be safely and effectively applied under certain circumstances. These encouraging findings warrant further investigation.

PMID:37785365 | DOI:10.1016/j.ijrobp.2023.06.1558

Artif Intell Med. 2023 Oct;144:102640. doi: 10.1016/j.artmed.2023.102640. Epub 2023 Aug 21.

ABSTRACT

Drug-drug interactions (DDI) may lead to unexpected side effects, which is a growing concern in both academia and industry. Many DDIs have been reported, but the underlying mechanisms are not well understood. Predicting and understanding DDIs can help researchers to improve drug safety and protect patient health. Here, we introduce DDI-GCN, a method that utilizes graph convolutional networks (GCN) to predict DDIs based on chemical structures. We demonstrate that this method achieves state-of-the-art prediction performance on the independent hold-out set. It can also provide visualization of structural features associated with DDIs, which can help us to study the underlying mechanisms. To make it easy and accessible to use, we developed a web server for DDI-GCN, which is freely available at http://wengzq-lab.cn/ddi/.

PMID:37783544 | DOI:10.1016/j.artmed.2023.102640

Artif Intell Med. 2023 Oct;144:102638. doi: 10.1016/j.artmed.2023.102638. Epub 2023 Aug 21.

ABSTRACT

In this paper, we propose a holistic AI-based pharmacovigilance optimization approach using patient's social media data. Instead of focusing on the detection and identification of Adverse Drug Events (ADE) in social media posts in single time points, we propose a holistic approach that looks at the evolution of different user behavior indicators in time. We examine various NLP-based indicators such as word frequency, semantic similarity, Adverse Drug Reactions mentions, and sentiment analysis. We introduce a classification approach to identify normal vs. abnormal time periods based on patient comments. This approach, along with user behavior indicators, can optimize the pharmacovigilance process by flagging the need for immediate attention and further investigation. We specifically focus on the Levothyrox® case in France, which sparked media attention due to changes in the medication formula and affected patient behavior on medical forums. For classification, we propose a deep learning architecture called Word Cloud Convolutional Neural Network (WC-CNN), trained on word clouds from patient comments. We evaluate different temporal resolutions and NLP pre-processing techniques, finding that monthly resolution and the proposed indicators can effectively detect new safety signals, with an accuracy of 75%. We have made the code open source, available via github.

PMID:37783543 | DOI:10.1016/j.artmed.2023.102638

JAMA Netw Open. 2023 Oct 2;6(10):e2335941. doi: 10.1001/jamanetworkopen.2023.35941.

ABSTRACT

IMPORTANCE: Patients with early breast cancer must choose between undergoing breast conservation surgery or mastectomy. This decision is often difficult as there are trade-offs between breast conservation and adverse effects, and women with higher decisional conflict have a harder time choosing the therapy that suits their preferences.

OBJECTIVE: To study the impact of a decision aid with a patient preference assessment tool for surgical decision-making on patients' decisional conflict scale (DCS) score.

DESIGN, SETTING, AND PARTICIPANTS: This 3-group randomized clinical trial was conducted between June 2017 and December 2019 at a single high-volume tertiary care cancer center in Mumbai, India. A research questionnaire comprising 16 questions answered on a Likert scale (from 1, strongly agree, to 5, strongly disagree) was used to measure DCS scores and other secondary psychological variables, with higher scores indicating more decisional conflict. The Navya Patient Preference Tool (Navya-PPT) was developed as a survey-based presentation of evidence in an adaptive, conjoint analysis-based module for and trade-offs between cosmesis, adverse effects of radiotherapy, and cost of mandatory radiation following breast-conserving surgery. Adult patients with histologically proven early breast cancer (cT1-2, N0-1) who were eligible for breast-conserving surgery as per clinicoradiological assessment were included. Those who were pregnant or unable to read the research questionnaire or who had bilateral breast cancer were excluded. Data were analyzed from January to June 2020.

INTERVENTIONS: Patients were randomized 1:1:1 to study groups: standard care including clinical explanation about surgery (control), standard care plus the Navya-PPT provided to the patient alone (solo group), and standard care plus the Navya-PPT provided to the patient and a caregiver (joint group).

MAIN OUTCOMES AND MEASURES: The primary end point of the study was DCS score. The study was 80% powered with 2-sided α = .01 to detect an effect size of 0.25 measured by Cohen d, F test analysis of variance, and fixed effects.

RESULTS: A total of 245 female patients (median [range] age, 48 [23-76] years) were randomized (82 to control, 83 to the solo group, and 80 to the joint group). The median (range) pathological tumor size was 2.5 (0-6) cm. A total of 153 participants (62.4%) had pN0 disease, 185 (75.5%) were hormone receptor positive, 197 (80.4%) were human epidermal growth factor receptor 2 negative, 144 (58.6%) were of middle or lower socioeconomic status, and 114 (46.5%) had an education level lower than a college degree. DCS score was significantly reduced in the solo group compared with control (1.34 vs 1.66, respectively; Cohen d, 0.50; SD, 0.31; P < .001) and the joint group compared with control (1.31 vs 1.66, respectively; Cohen d, 0.54; SD, 0.31; P < .001).

CONCLUSIONS AND RELEVANCE: The results of this study demonstrated lower decisional conflict as measured by DCS score following use of the online, self-administered Navya-PPT among patients with early breast cancer choosing between breast-conserving surgery vs mastectomy.

TRIAL REGISTRATION: Clinical Trials Registry of India Identifier: CTRI/2017/11/010480.

PMID:37782500 | DOI:10.1001/jamanetworkopen.2023.35941

Br J Gen Pract. 2023 Jul 4:BJGP.2023.0153. doi: 10.3399/BJGP.2023.0153. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse drug reaction (ADR) related to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may negatively affect patients' treatment outcomes.

AIM: To investigate the impact of ACEIs/ARBs-related ADR consultation on cardiovascular disease (CVD) events and all-cause mortality.

DESIGN AND SETTING: Propensity score-matched cohort study of ACEIs/ARBs between 2004 and 2019 using UK IQVIA medical research data.

METHOD: ADR consultations were identified using standardised designated codes. Propensity scores were calculated based on comorbidities, concomitant medications, frailty, and polypharmacy. Cox's proportional hazard regression model was used to compare the outcomes between patients in ADR and non-ADR groups. In the secondary analysis, treatment- pattern changes following the ADR were examined and the subsequent outcomes were compared.

RESULTS: Among 1 471 906 eligible users of ACEIs/ARBs, 13 652 (0.93%) patients had ACEIs/ARBs- related ADR consultation in primary care. Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all- cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27) and secondary prevention cohorts (CVD events: aHR 1.13, 95% CI = 1.05 to 1.21; all-cause mortality: aHR 1.15, 95% CI = 1.09 to 1.21). Half (50.19%) of patients with ADR continued to use ACEIs/ARBs, and these patients had a reduced risk of mortality (aHR 0.88, 95% CI = 0.82 to 0.95) compared with those who discontinued using ACEIs/ARBs.

CONCLUSION: This study provides information on the burden of ADR on patients and the health system. The findings call for additional monitoring and treatment strategies for patients affected by ADR to mitigate the risks of adverse clinical outcomes.

PMID:37783509 | DOI:10.3399/BJGP.2023.0153

BMJ Med. 2023 Sep 21;2(1):e000352. doi: 10.1136/bmjmed-2022-000352. eCollection 2023.

ABSTRACT

OBJECTIVE: To assess the quality of reporting of adverse events in clinical trials of covid-19 drugs based on the CONSORT (Consolidated Standards of Reporting Trials) harms extension and according to clinical trial design, and to examine reporting of serious adverse events in drug trials published on PubMed versus clinical trial summaries on ClinicalTrials.gov.

DESIGN: Systematic review.

DATA SOURCES: PubMed and ClinicalTrials.gov registries were searched from 1 December 2019 to 17 February 2022.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical trials evaluating the efficacy and safety of drugs used to treat covid-19 disease in participants of all ages with suspected, probable, or confirmed SARS-CoV-2 infection were included. Clinical trials were screened on title, abstract, and text by two authors independently. Only articles published in French and English were selected. The Cochrane risk of bias tool for randomised trials (RoB 2) was used to assess risk of bias.

RESULTS: The search strategy identified 1962 randomised clinical trials assessing the efficacy and safety of drugs used to treat covid-19, published in the PubMed database; 1906 articles were excluded after screening and 56 clinical trials were included in the review. Among the 56 clinical trials, no study had a high score for quality of reporting of adverse events, 60.7% had a moderate score, 33.9% had a low score, and 5.4% had a very low score. All clinical trials with a very low score for quality of reporting of adverse events were randomised open label trials. For reporting of serious adverse events, journal articles published on PubMed under-reported 51% of serious adverse events compared with clinical trial summaries published on ClinicalTrials.gov.

CONCLUSIONS: In one in three published clinical trials on covid-19 drugs, the quality of reporting of adverse events was low or very low. Differences were found in the number of serious adverse events reported in journal articles versus clinical trial summaries. During the covid-19 pandemic, risk assessment of drugs in clinical trials of covid-19 drugs did not comply with good practice recommendations for publication of results.

SYSTEMATIC REVIEW REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) EUPAS45959.

PMID:37779893 | PMC:PMC10537984 | DOI:10.1136/bmjmed-2022-000352

Theranostics. 2023 Sep 18;13(14):5114-5129. doi: 10.7150/thno.87484. eCollection 2023.

ABSTRACT

Senescent cells in plaques emerge as a detrimental factor for atherosclerosis (AS), for which targeted senolysis might be a promising therapeutic strategy. The development of safe and efficient senolytics for senescent cell eradication by targeted delivery is greatly needed. Methods: Pro-apoptotic intelligent Bax (iBax)-overexpressing plasmid was constructed by molecular cloning, in which Bax CDS was fused to miR-122 recognition sites. Extracellular vesicle-based senolytics (EViTx) were developed to be conjugated with magnetic nanoparticles on the surface, iBax mRNA encapsulated inside, and BAX activator BTSA1 incorporated into the membrane. EViTx was characterized, and in vivo distribution was tracked via fluorescence imaging. The therapeutic effects of EViTx on AS and its systemic side effects were analyzed in ApoE-/- mice. Results: Magnetic nanoparticles, iBax mRNA and BAX activator BTSA1 were efficiently loaded into/onto EViTx. With external magnetic field navigation, EViTx was delivered into atherosclerotic plaques and induced significant apoptosis in senescent cells regardless of origins. Repeated delivery of EViTx via tail vein injection has achieved high therapeutic efficacy in ApoE-/- mice. Notably, EViTx is inevitably accumulated in liver cells, while the iBax mRNA was translationally repressed by miR-122, an endogenous miRNA highly expressed in hepatocytes, and thus the liver cells are protected from the potential toxicity of Bax mRNA. Conclusion: Our work demonstrated that magnetic EV-based delivery of iBax mRNA and the BAX activator BTSA1, efficiently induced apoptosis in recipient senescent cells in atherosclerotic plaques. This strategy represents a promising treatment approach for AS and other age-related diseases.

PMID:37771781 | PMC:PMC10526664 | DOI:10.7150/thno.87484

Pain Physician. 2023 Sep;26(5):E557-E565.

ABSTRACT

BACKGROUND: Optimal intrathecal dosing regimens for hydromorphone are not well established for analgesia after abdominal surgery.

OBJECTIVES: We reviewed intrathecal hydromorphone doses and complications because dosing variability has been observed among anesthesiologists. We hypothesized that increasing doses of intrathecal hydromorphone would be associated with improved postoperative analgesia, but with increased rates of opioid-related adverse events.

STUDY DESIGN: Retrospective analysis.

SETTING: A high-volume academic referral center in the United States.

METHODS: A retrospective study was conducted of adults undergoing abdominal surgery under general anesthesia supplemented preoperatively with intrathecal hydromorphone for postoperative analgesia from May 5, 2018, through May 31, 2021. Patients were categorized into 3 hydromorphone dosing groups: low-dose (50-100 µg), middle-dose (101-199 µg), and high-dose (200-300 µg). Multivariable logistic regression models were used to assess rates of severe postoperative pain, severe opioid-related adverse events, oversedation, and pruritus in the postanesthesia care unit (PACU) and within 24 hours after PACU discharge.

RESULTS: Of 1,846 patients identified, 1,235 (66.9%) were in the low-dose group; 321 (17.3%), middle-dose group; and 290 (15.7%), high-dose group. Patients receiving the 2 higher doses had more extensive procedures. An unadjusted analysis showed differing rates of severe pain in the PACU by group: 306 (24.8%) in the low-dose, 73 (22.7%) middle-dose, and 45 (15.5%) in the high-dose group (P = 0.003); these differences, however, were no longer significant after an adjusted analysis (P = 0.34). Ten severe opioid-related events occurred; all were recognized in the PACU. Five events each occurred in the low-dose and high-dose groups versus none in the middle-dose group (P = 0.02). No other differences were identified with adjusted analyses.

LIMITATIONS: Limitations of our study include its retrospective design and its conduct at a single center, along with the apparent, but difficult to characterize, treatment biases in hydromorphone dosing.

CONCLUSIONS: No dose response was observed between intrathecal hydromorphone dose and postoperative analgesia, a finding that may reflect treatment bias. Higher rates of severe opioid-related events were detected for patients receiving high-dose hydromorphone in the PACU, but all other safety outcomes were similar between dosing regimens.

KEY WORDS: Drug-related side effects, opioid analgesics, outcome assessment, postoperative pain, spinal injections.

PMID:37774193

Pharmacotherapy. 2023 Sep 29. doi: 10.1002/phar.2883. Online ahead of print.

ABSTRACT

INTRODUCTION: Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events.

METHODS: We conducted a secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades using MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019. Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study. Herein, we measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CIs) of modifiable statin characteristics after adjusting for baseline characteristics.

RESULTS: We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogues (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically-acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94).

CONCLUSION: Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.

PMID:37771303 | DOI:10.1002/phar.2883

BMC Health Serv Res. 2023 Sep 28;23(1):1037. doi: 10.1186/s12913-023-10028-2.

ABSTRACT

BACKGROUND: Hospital readmissions due to medication-related problems occur frequently, burdening patients and caregivers emotionally and straining health care systems economically. In times of limited health care resources, interventions to mitigate the risk of medication-related readmissions should be prioritized to patients most likely to benefit. Focusing on general internal medicine patients, this scoping review aims to identify risk factors associated with drug-related 30-day hospital readmissions.

METHODS: We began by searching the Medline, Embase, and CINAHL databases from their inception dates to May 17, 2022 for studies reporting risk factors for 30-day drug-related readmissions. We included all peer-reviewed studies, while excluding literature reviews, conference abstracts, proceeding papers, editorials, and expert opinions. We also conducted backward citation searches of the included articles. Within the final sample, we analyzed the types and frequencies of risk factors mentioned.

RESULTS: After deduplication of the initial search results, 1159 titles and abstracts were screened for full-text adjudication. We read 101 full articles, of which we included 37. Thirteen more were collected via backward citation searches, resulting in a final sample of 50 articles. We identified five risk factor categories: (1) patient characteristics, (2) medication groups, (3) medication therapy problems, (4) adverse drug reactions, and (5) readmission diagnoses. The most commonly mentioned risk factors were polypharmacy, prescribing problems-especially underprescribing and suboptimal drug selection-and adherence issues. Medication groups associated with the highest risk of 30-day readmissions (mostly following adverse drug reactions) were antithrombotic agents, insulin, opioid analgesics, and diuretics. Preventable medication-related readmissions most often reflected prescribing problems and/or adherence issues.

CONCLUSIONS: This study's findings will help care teams prioritize patients for interventions to reduce medication-related hospital readmissions, which should increase patient safety. Further research is needed to analyze surrogate social parameters for the most common drug-related factors and their predictive value regarding medication-related readmissions.

PMID:37770912 | PMC:PMC10536731 | DOI:10.1186/s12913-023-10028-2

Sensors (Basel). 2023 Sep 6;23(18):7698. doi: 10.3390/s23187698.

ABSTRACT

Augmented reality (AR) has been shown to improve productivity in industry, but its adverse effects (e.g., headaches, eye strain, nausea, and mental workload) on users warrant further investigation. The objective of this study is to investigate the effects of different instruction methods (i.e., HoloLens AR-based and paper-based instructions) and task complexity (low and high-demanding tasks) on cognitive workloads and performance. Twenty-eight healthy males with a mean age of 32.12 (SD 2.45) years were recruited in this study and were randomly divided into two groups. The first group performed the experiment using AR-based instruction, and the second group used paper-based instruction. Performance was measured using total task time (TTT). The cognitive workload was measured using the power of electroencephalograph (EEG) features and the NASA task load index (NASA TLX). The results showed that using AR instructions resulted in a reduction in maintenance times and an increase in mental workload compared to paper instructions, particularly for the more demanding tasks. With AR instruction, 0.45% and 14.94% less time was spent on low- and high-demand tasks, respectively, as compared to paper instructions. According to the EEG features, employing AR to guide employees during highly demanding maintenance tasks increased information processing, which could be linked with an increased germane cognitive load. Increased germane cognitive load means participants can better facilitate long-term knowledge and skill acquisition. These results suggested that AR is superior and recommended for highly demanding maintenance tasks since it speeds up maintenance times and increases the possibility that information is stored in long-term memory and encrypted for recalls.

PMID:37765755 | PMC:PMC10536580 | DOI:10.3390/s23187698

Nutrients. 2023 Sep 9;15(18):3922. doi: 10.3390/nu15183922.

ABSTRACT

In recent years, the consumption of energy drinks by young adults and athletes has risen significantly, but concerns have been raised about the potential health risks associated with excessive consumption. These concerns include cardiovascular problems, nervous system disorders, and the potential for addiction. This review aims to examine the reported effects of acute or chronic abuse of energy drinks on human health. The analysis shows a significant prevalence of adverse effects, particularly on the cardiovascular and neurovegetative systems. In particular, the analysis identified nine cases of cardiac arrest, three of which were fatal. The aetiology of these adverse effects is attributed to the inherent neurostimulant properties of these beverages, of which caffeine is the predominant component. A comparison of documented effects in humans with experimental studies in animal models showed an overlap in results. This review highlights the need for greater rigour in the assessment of sudden cardiac death, particularly in young people, as legal substances such as energy drinks may be involved. We propose stricter limits on the consumption of these beverages than for caffeine, based on the evidence found and the data in the literature. This review also calls for the establishment of regulations governing the consumption of these products in view of their potential impact on human health.

PMID:37764707 | PMC:PMC10535526 | DOI:10.3390/nu15183922

Molecules. 2023 Sep 16;28(18):6652. doi: 10.3390/molecules28186652.

ABSTRACT

With the advent of the aging society, osteoporosis (OP) risk increases yearly. Currently, the clinical usage of anti-OP drugs is challenged by recurrent side effects and poor patient compliance, regardless of oral, intravenous, or subcutaneous administration. Properly using a drug delivery system or formulation strategy can achieve targeted drug delivery to the bone, diminish side effects, improve bioavailability, and prolong the in vivo residence time, thus effectively curing osteoporosis. This review expounds on the pathogenesis of OP and the clinical medicaments used for OP intervention, proposes the design approach for anti-OP drug delivery, emphatically discusses emerging novel anti-OP drug delivery systems, and enumerates anti-OP preparations under clinical investigation. Our findings may contribute to engineering anti-OP drug delivery and OP-targeting therapy.

PMID:37764428 | PMC:PMC10534890 | DOI:10.3390/molecules28186652