S D Med. 2023 Jul;76(7):311-313.

ABSTRACT

INTRODUCTION: Increasing and easy availability of so-called natural/herbal supplements pose the unique challenge of identifying associated side effects, including arrhythmias in otherwise-healthy individuals.

CASE PRESENTATION: A 25-year-old female patient presented to the emergency department with fatigue and lightheadedness. The electrocardiogram showed complete AV block with a junctional escape rhythm at 55 beats per minute with QT prolongation (542ms). One week ago, she started to use a herbal medication (Muscle Eze Advanced) for muscle cramps after workouts. Extensive cardiac testing, including complete blood count, complete metabolic panel, TSH, transthoracic echocardiography, urine drug analysis, Lyme antibody were negative. Normal sinus rhythm was restored spontaneously within 1 day of discontinuing the herbal medication. PR and corrected QT intervals returned to baseline over the next two weeks.

CONCLUSION: Muscle Eze Advanced consists of seven ingredients, including Melissa officinalis and Valeriana officinalis that have negative chronotropic, negative dromotrophic and QT prolonging effects. Recognizing the association between certain over-the-counter supplements and brady-arrhythmias may circumvent need for permanent pacemakers - an important consideration especially in the young.

PMID:37733962

S D Med. 2023 Jul;76(7):305-308.

ABSTRACT

Cytochrome P450 polymorphisms have gathered much attention regarding personalized psychopharmacological care. It is well documented that these drug metabolizing enzymes lead to interpatient variability in pharmacokinetic profiles. It appears that less functional genotype may increase of risk of higher side-effect burden. Here we highlight the importance of genetic polymorphisms to potentially predict a toxicity related phenotype after an intentional overdose. Genotyping may have a role in predicting serious side effects to help clinicians educate patients and their families, and implement more intensive monitoring and institute prophylactic treatment as needed.

PMID:37733961

Science. 2023 Sep 22;381(6664):1316-1323. doi: 10.1126/science.abq1053. Epub 2023 Sep 21.

ABSTRACT

Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially through CI, provides proof of concept of ETC rewiring to achieve antitumor responses without side effects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion.

PMID:37733872 | DOI:10.1126/science.abq1053

Sci Rep. 2023 Sep 20;13(1):15576. doi: 10.1038/s41598-023-42514-2.

ABSTRACT

Cancer is one of the leading causes of death, which has attracted the attention of the scientific world to the search for efficient methods for treatment. With the great development and regeneration of nanotechnology over the last 25 years, various nanoparticles in different structures, shapes and composites provide good potential for cancer therapy. There are several drugs approved by FDA used in breast cancer treatment like Cyclophosphamide, Doxorubicin Hydrochloride, Femara, Herceptin, etc. Each has several side effects as well as treatment, which limits the use of drugs due to heart failure, pulmonary dysfunction, or immunodeficiency. Recently, such side effects are greatly reduced by using innovative delivery techniques. Some drugs have been approved for use in cancer treatment under the concept of drug delivery, such as Doxil (liposomal loaded doxorubicin). The purpose of this study is to investigate the effect of copper nanoparticles (CuNPs) as a drug model for cancer treatment, either in their free form or encapsulated in Soy lecithin liposomes (SLP) from plant origin as a cheap source of lipids. CuNPs were prepared by the chemical reduction method and loaded onto SLP through the thin film hydration method. The drug model Cu/SLP was successfully combined. The characteristics of the free CuNPs, liposomes, and the combined form, zeta potential, size distribution, drug encapsulation efficiency (EE%), drug release profile, Fourier transform infrared (FTIR), and transmission electron microscopy (TEM), were checked, followed by an in vitro study on the breast cancer cell line Mcf-7 as a model for cytotoxicity evaluation. The optimal Cu/SLP had a particle mean size of 81.59 ± 14.93 nm, a negative zeta potential of - 50.7 ± 4.34 mV, loaded CuNPs showed an EE% of 78.9%, a drug release profile for about 50% of the drug was released after 6 h, and FTIR analysis was recorded. The cytotoxicity assay showed that the IC50 of Cu/SLP is smaller than that of free CuNPs. These results give clear evidence of the efficacy of using the combined Cu/SLP rather than CuNPs alone as a model drug carrier prepared from plant origin against cancer, both medically and economically.

PMID:37730859 | DOI:10.1038/s41598-023-42514-2

Sci Rep. 2023 Sep 20;13(1):15578. doi: 10.1038/s41598-023-42555-7.

ABSTRACT

Since 1990 and in particular, after the implementation of the Water Frame Directive, many positive effects of pro-ecological projects are evident; unfortunately, examples of adverse effects have also been observed. This study aims to indicate how some ill-considered actions, called "pro-ecological", may lead to habitat degradation and the disappearance of valuable hydrobiont species. Two watercourses, representing the lowland gravel stream and sandy stream type, were selected for the study. Literature indicated that in the past, these watercourses were characterized by an excellent ecological status and the presence of valuable rheophilic fauna and flora. Environmental parameters were recorded, macroinvertebrates and ichthyofauna were sampled and analyzed, and finally, indexes were calculated. The results were compared with literature data. In the course of studies conducted in 2011-2015, drastic habitat deterioration and extensive changes in the species structure of ichthyofauna and aquatic invertebrates were observed. Changes in the Smolnica stream have been caused by the three retention basins constructed in 2000, along the lower and middle course; while in Kiszewko, however, the factor for habitat deterioration was connected with the excessive expansion of the Eurasian beaver (Castor fiber), which created a beaver pond 20 m in width, with impoundment elevations of up to 2 m.

PMID:37730846 | DOI:10.1038/s41598-023-42555-7

Hum Vaccin Immunother. 2023 Aug;19(2):2253589. doi: 10.1080/21645515.2023.2253589. Epub 2023 Sep 21.

ABSTRACT

Vaccine hesitancy, spurred by misinterpretation of Adverse Events (AEs), threatens public health. Despite sporadic reports of oral AEs post-COVID-19 vaccination, systematic analysis is scarce. This study evaluates these AEs using the Australian Database of Adverse Event Notifications (DAEN). A secondary analysis of DAEN data was conducted, with the analysis period commencing from the start of the COVID-19 vaccination rollout in February 2021 and the inception of the influenza vaccine database in 1971, both through until December 2022. The focus of the analysis was on oral AEs related to COVID-19 and influenza vaccines. Reports were extracted according to a predefined schema and then stratified by vaccine type, sex, and age. Oral paresthesia was the most common oral AE after COVID-19 vaccination (75.28 per 10,000 reports), followed by dysgeusia (73.96), swollen tongue (51.55), lip swelling (49.43), taste disorder (27.32), ageusia (25.85), dry mouth (24.75), mouth ulceration (18.97), oral hypoaesthesia (15.60), and oral herpes (12.74). While COVID-19 and influenza vaccines shared most oral AEs, taste-related AEs, dry mouth, and oral herpes were significantly more common after COVID-19 vaccination. mRNA vaccines yielded more oral AEs than other types. Females had higher oral AE incidence. Most oral AEs did not differ significantly between COVID-19 and influenza vaccination. However, specific oral AEs, particularly taste-related, dry mouth, and oral herpes, were more prevalent after COVID-19 vaccination compared with seasonal influenza, especially in females and mRNA vaccine recipients.

PMID:37734344 | DOI:10.1080/21645515.2023.2253589

Drug Ther Bull. 2023 Sep 21:dtb-2023-000047. doi: 10.1136/dtb.2023.000047. Online ahead of print.

NO ABSTRACT

PMID:37734922 | DOI:10.1136/dtb.2023.000047

Adv Ther. 2023 Sep 21. doi: 10.1007/s12325-023-02633-8. Online ahead of print.

ABSTRACT

INTRODUCTION: The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors.

METHODS: In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m2 [G1-G2 subcohort] and 30 to < 60 mL/min/1.73 m2 [G3 subcohort]).

RESULTS: In total, 93 patients were evaluated (G1-G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (- 11.8 ± 10.8/- 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (- 12.9 ± 10.5/- 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, - 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1-G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L.

CONCLUSION: Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug's efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination.

CLINICAL TRIAL REGISTRATION: jRCTs031200273.

PMID:37733211 | DOI:10.1007/s12325-023-02633-8

Clin J Pain. 2023 Sep 19. doi: 10.1097/AJP.0000000000001160. Online ahead of print.

ABSTRACT

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20-40% of hemorrhoidectomy patients. Compared to morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain.

METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale (VAS) pain intensity scores.

RESULTS: VAS results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P=0.0301). According to Brief Pain Inventory Short Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group (P<0.0001). Drug-related adverse events were mild-to-moderate and resolved by treatment end. No drug-related severe adverse events were observed.

DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe pain and may provide another option for patients to control their pain.

PMID:37732966 | DOI:10.1097/AJP.0000000000001160

Front Pharmacol. 2023 Sep 4;14:1257842. doi: 10.3389/fphar.2023.1257842. eCollection 2023.

ABSTRACT

Background: Inferring drug-related side effects is beneficial for reducing drug development cost and time. Current computational prediction methods have concentrated on graph reasoning over heterogeneous graphs comprising the drug and side effect nodes. However, the various topologies and node attributes within multiple drug-side effect heterogeneous graphs have not been completely exploited. Methods: We proposed a new drug-side effect association prediction method, GGSC, to deeply integrate the diverse topologies and attributes from multiple heterogeneous graphs and the self-calibration attributes of each drug-side effect node pair. First, we created two heterogeneous graphs comprising the drug and side effect nodes and their related similarity and association connections. Since each heterogeneous graph has its specific topology and node attributes, a node feature learning strategy was designed and the learning for each graph was enhanced from a graph generative and adversarial perspective. We constructed a generator based on a graph convolutional autoencoder to encode the topological structure and node attributes from the whole heterogeneous graph and then generate the node features embedding the graph topology. A discriminator based on multilayer perceptron was designed to distinguish the generated topological features from the original ones. We also designed representation-level attention to discriminate the contributions of topological representations from multiple heterogeneous graphs and adaptively fused them. Finally, we constructed a self-calibration module based on convolutional neural networks to guide pairwise attribute learning through the features of the small latent space. Results: The comparison experiment results showed that GGSC had higher prediction performance than several state-of-the-art prediction methods. The ablation experiments demonstrated the effectiveness of topological enhancement learning, representation-level attention, and self-calibrated pairwise attribute learning. In addition, case studies over five drugs demonstrated GGSC's ability in discovering the potential drug-related side effect candidates. Conclusion: We proposed a drug-side effect association prediction method, and the method is beneficial for screening the reliable association candidates for the biologists to discover the actual associations.

PMID:37731739 | PMC:PMC10507253 | DOI:10.3389/fphar.2023.1257842

Clin J Oncol Nurs. 2023 Sep 15;27(5):565-570. doi: 10.1188/23.CJON.565-570.

ABSTRACT

Patients receiving radiation therapy (RT) for cancer are at greater risk for falls because of age, treatment, pharmacologic side effects, and cognitive or motor deficits. The Timed Up and Go (TUG) Test is a validated, objecti.

PMID:37729459 | DOI:10.1188/23.CJON.565-570

Clin J Oncol Nurs. 2023 Sep 15;27(5):491-495. doi: 10.1188/23.CJON.491-495.

ABSTRACT

IV oncology treatments are associated with severe side effects (SEs) that can decrease patients' quality of life and lead to increased hospitalizations. However, improved reporting with remote monitoring systems (RMSs) may.

PMID:37729457 | DOI:10.1188/23.CJON.491-495

Clin J Oncol Nurs. 2023 Sep 15;27(5):463-467. doi: 10.1188/23.CJON.463-467.

ABSTRACT

During the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment. ICI-related side effects occur via direct overactivation of the immune system, and patients can experience sym.

PMID:37729456 | DOI:10.1188/23.CJON.463-467

Clin J Oncol Nurs. 2023 Sep 15;27(5):479-485. doi: 10.1188/23.CJON.479-485.

ABSTRACT

Taste alteration is a common side effect of chemotherapy and can have a direct impact on patients' quality of life. Consistent evaluation of alteration in taste is lacking in clinical practice. The literature strongly suppo.

PMID:37729452 | DOI:10.1188/23.CJON.479-485

J Fam Pract. 2023 Sep;72(7):292-303. doi: 10.12788/jfp.0657.

ABSTRACT

These agents are as effective as traditional acute and preventive treatments, cause fewer adverse effects, and can simplify regimens.

PMID:37729144 | DOI:10.12788/jfp.0657

Rev Med Suisse. 2023 Sep 20;19(842):1707-1712. doi: 10.53738/REVMED.2023.19.842.1707.

ABSTRACT

Antipsychotics are known to produce frequent and/or potentially serious adverse effects, including neurological, cardiovascular, metabolic and endocrine effects. The side-effects of antipsychotics vary according to their affinity for different central and peripheral receptors, and individual vulnerabilities. Some of these side-effects are dose-dependent, while others are little or not ; thus, management strategies need to be adapted. Good management of adverse events is important to encourage patients' medication adherence and to reduce the cardiovascular morbidity and mortality of side effects. Good collaboration between psychiatrists and general practitioners or specialists is essential.

PMID:37728265 | DOI:10.53738/REVMED.2023.19.842.1707

Int J Nanomedicine. 2023 Sep 14;18:5243-5264. doi: 10.2147/IJN.S423412. eCollection 2023.

ABSTRACT

Cancer is the second leading cause of death worldwide. Its incidence has been increasing in recent years, and it is becoming a major threat to human health. Conventional cancer treatment strategies, including surgery, chemotherapy, and radiotherapy, have faced problems such as drug resistance, toxic side effects and unsatisfactory therapeutic efficacy. Therefore, better development and utilization of biomaterials can improve the specificity and efficacy of tumor therapy. Algae, as a novel living material, possesses good biocompatibility. Although some reviews have elucidated several algae-based biomaterials for cancer treatment, the majority of the literature has focused on a limited number of algae. As a result, there is currently a lack of comprehensive reviews on the subject of anticancer algae. This review aims to address this gap by conducting a thorough examination of algal species that show potential for anticancer activity. Furthermore, our review will also elucidate the engineering strategies of algae and discuss the challenges and prospects associated with their implementation.

PMID:37727650 | PMC:PMC10506609 | DOI:10.2147/IJN.S423412

BMC Nephrol. 2023 Sep 20;24(1):277. doi: 10.1186/s12882-023-03332-w.

ABSTRACT

BACKGROUND: Hemodialysis (HD) patients commonly receive polypharmacy leading to increased likelihood of drug related problems (DRPs) and poor quality of life. Medication Therapy Management (MTM) services discover and resolve DRPs and may specifically improve Medication-burden Quality of life (MBQoL) in HD patients. We aimed to assess the effect of MTM services on DRPs and MBQoL among HD patients.

METHODS: A prospective pre-post study was conducted on 104 patients in an HD unit in Alexandria, Egypt. MBQoL was assessed at baseline and after three months of MTM sessions, using the Arabic, validated version of the Patient Reported Outcomes Measure of Pharmaceutical Therapy (PROMPT) questionnaire. Cohen's d test and multiple linear regression were used to assess the effect size of MTM and the factors affecting MBQoL, respectively. DRPs, adverse events and adherence were also monitored.

RESULTS: MBQoL improved significantly after the implementation of MTM (Cohen's d=0.88, p < 0.01) with the largest effect size in the "medicine information and relation with healthcare providers" domain. DRPs decreased significantly after MTM implementation (11.97 ± 4.65 versus 7.63 ± 3.85 per patient, p<0.001). The mean adverse events per patient were also reduced (9.69 ± 4.12 versus 6.56 ± 3.77, p < 0.001).

CONCLUSION: Applying MTM services presents an opportunity to improve care for HD patients by improving MBQoL, decreasing DRPs and adverse events.

PMID:37730586 | DOI:10.1186/s12882-023-03332-w

JHEP Rep. 2023 Jul 18;5(10):100851. doi: 10.1016/j.jhepr.2023.100851. eCollection 2023 Oct.

ABSTRACT

BACKGROUND & AIMS: Checkpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI).

METHODS: Prescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI.

RESULTS: Out of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2-15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have 'life-threatening' grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases.

CONCLUSIONS: The real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care.

IMPACT AND IMPLICATIONS: Using prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.

PMID:37727807 | PMC:PMC10505983 | DOI:10.1016/j.jhepr.2023.100851

BMC Med Inform Decis Mak. 2023 Sep 19;23(1):189. doi: 10.1186/s12911-023-02287-0.

ABSTRACT

BACKGROUND: The exponential growth of digital healthcare data is fueling the development of Knowledge Discovery in Databases (KDD). Extracting temporal relationships between medical events is essential to reveal hidden patterns that can help physicians find optimal treatments, diagnose illnesses, detect drug adverse reactions, and more. This paper presents an approach for the extraction of patient evolution patterns from electronic health records written in Catalan and/or Spanish.

METHODS: We propose a robust formulation for extracting Temporal Association Rules (TARs) that goes beyond simple rule extraction by considering the sequence of multiple visits. Our highly configurable algorithm leverages this formulation to extract Temporal Association Rules from sequences of medical instances. We can generate rules in the desired format, content, and temporal factors while accounting for different levels of abstraction of medical instances. To demonstrate the effectiveness of our methodology, we applied it to extract patient evolution patterns from clinical histories of multimorbid patients suffering from heart disease and stroke who visited Primary Care Centers (CAP) in Catalonia. Our main objective is to uncover complex rules with multiple temporal steps, that comprise a set of medical instances.

RESULTS: As we are working with real-world, error-prone data, we propose a process of validation of the results by expert practitioners in primary care. Despite our limited dataset, the high percentage of patterns deemed correct and relevant by the experts is promising. The insights gained from these patterns can inform preventive measures and help detect risk factors, ultimately leading to better treatments and outcomes for patients.

CONCLUSION: Our algorithm successfully extracted a set of meaningful and relevant temporal patterns, especially for the specific type of multimorbid patients considered. These patterns were evaluated by experts and demonstrated the ability to predict risk factors that are commonly associated with certain diseases. Moreover, the average time gap between the occurrence of medical events provided critical insight into the term of these risk factors. This information holds significant value in the context of primary healthcare and preventive medicine, highlighting the potential of our method to serve as a valuable medical tool.

PMID:37726756 | PMC:PMC10510308 | DOI:10.1186/s12911-023-02287-0