Drug Des Devel Ther. 2024 Nov 19;18:5255-5268. doi: 10.2147/DDDT.S492913. eCollection 2024.

ABSTRACT

PURPOSE: To investigate the safety and effectiveness of naltrexone-bupropion in Korean adults with obesity.

PATIENTS AND METHODS: This was a prospective, observational multicenter study from April 29, 2016, to April 28, 2022. Individuals with obesity with a body mass index of ≥30 kg/m2 or ≥27 kg/m2 who had obesity-related comorbidities were included. The naltrexone-bupropion dose was gradually titrated weekly from 8/90 to 32/360 mg and maintained at the maximum tolerated dose. In total, 612 and 300 individuals were evaluated for safety and effectiveness, respectively.

RESULTS: In total, 41.34% individuals reported drug-related adverse reactions, such as nausea (19.12%), headache (7.68%), and dizziness (5.23%). Older age and comorbidities were significantly associated with adverse events. At 12 weeks after reaching the maintenance dose, naltrexone-bupropion 32/360 mg resulted in the greatest weight reduction (-7.21%) compared with other doses, which persisted at week 24 (-7.69%). The naltrexone-bupropion 16/180 mg resulted in significant weight reduction, achieving -5.99% and -9.18% reductions at weeks 12 and 24, similar to that with naltrexone-bupropion 32/360 mg. Young age and no comorbidities were significantly associated >5% weight reduction.

CONCLUSION: Naltrexone-bupropion demonstrated marked stability and weight loss effectiveness, particularly in young individuals with obesity without comorbidities. Therefore, individualized treatment is necessary when prescribing naltrexone-bupropion.

PMID:39583631 | PMC:PMC11585262 | DOI:10.2147/DDDT.S492913

Cureus. 2024 Oct 25;16(10):e72344. doi: 10.7759/cureus.72344. eCollection 2024 Oct.

ABSTRACT

Suxamethonium is commonly used as a muscle relaxant during electroconvulsive therapy (ECT). Prolonged apnoea associated with suxamethonium, mostly caused by pseudocholinesterase deficiency, is rare, but it can sometimes pose a great challenge in managing emergency situations due to patients' inability to breathe; occasionally, it can result in serious complications, including death. We report a case of a young male who had no prior exposure to suxamethonium and developed prolonged apnoea after induction with it. There was no record of any sensitivity or adverse reactions to any drugs for this patient or his family. ECT is a well-known treatment for many psychiatric disorders when other treatments are ineffective. This case emphasizes the need for a comprehensive pre-procedural assessment, careful consideration, and the gathering of crucial information about potential sensitivities and adverse reactions associated with medications commonly used during the ECT procedure, especially when administering these medications for the first time.

PMID:39583407 | PMC:PMC11585840 | DOI:10.7759/cureus.72344

Sci Prog. 2024 Jul-Sep;107(3):368504241263534. doi: 10.1177/00368504241263534.

ABSTRACT

OBJECTIVES: Patients with drug-related problems are at high risk for perioperative complications. The study aimed to determine the prevalence, number, characteristics, clinical significance and the involved drugs of drug-related problems in inpatients, who were admitted to elective surgery, as well as their burden of comorbidity.

METHODS: The study design was a retrospective, observational study across nine different surgical sites. Patients at admission for elective surgery with ≥ 1 drug-related problem, a hospital stay of ≥ 24 h and at age ≥ 18 years were included. The outcomes of interest were the prevalence and nature of drug-related problems, assessed by pharmacists at hospital admission. The Pharmaceutical Network Europe classification V9.1, the Hatoum scale of clinical significance, the Anatomical-Therapeutic-Chemical classification scheme of the World Health Organization were engaged to categorize drug-related problems and their clinical significance. The Charlson Comorbidity Index was applied to assess the comorbidity of participants.

RESULTS: The final data set included 11,176 elective surgical inpatients. Of these, a sample of 284 (2.54%) patients was analysed. It was found that 9.89% of the patients showed at least one drug-related problem (average 1.43, SD 0.7). Major causes were drug-drug interactions (30.3%) and supra-therapeutic doses (18.0%). Most drug-related problems were referred to a prescriber for intervention (61.3%). Eighty-two percent of drug-related problems were rated as clinically significant. Cardiovascular drugs were of major concern. Participants' most common comorbidities were tumour diagnosis (34%), diabetes mellitus with end organ damage (26%) and peripheral vascular diseases (19%).

CONCLUSIONS: Although the prevalence of drug-related problems in this diverse study population was low, drug-related problems were of great importance in terms of their cause and clinical significance. Patients with drug-related problems showed a moderate burden of physiological illness. Study results suggest a need to identify exposed patients with drug-related problems.

PMID:39582158 | DOI:10.1177/00368504241263534

Arch Dis Child. 2024 Nov 23:archdischild-2024-327416. doi: 10.1136/archdischild-2024-327416. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the efficacy of addition of melatonin or triclofos to sleep deprivation as compared with sleep deprivation with placebo for conduct of successful sleep electroencephalogram (EEG) among children between 6 months and 12 years of age.

DESIGN, SETTING AND PATIENTS: 486 children aged between 6 months and 12 years who were uncooperative or referred for sleep EEG were enrolled for this double-blind, placebo-controlled randomised trial between 30 June 2022 and 31 March 2023.

INTERVENTION: On the day of sleep EEG, participants were sleep deprived by 25% of their regular sleep duration and then randomly assigned to receive either triclofos (50 mg/kg), melatonin (weight ≤15 kg=3 mg; weight >15 kg=6 mg) or placebo.

OUTCOME: Primary outcome was the conduct of a successful sleep EEG.

RESULTS: 486 children were randomly assigned to intervention with triclofos (n=165), melatonin (n=161) or placebo (n=160). Sleep EEG success (p<0.001) with different interventions was: triclofos=145/165(88%); melatonin=123/161 (76%) and placebo=65/160 (41%). Sleep EEG's success rate was better with triclofos than melatonin (OR=2.2; 95% CI 1.2 to 4.1) or placebo (OR=10.6; 95% CI 6.1 to 19.0). Melatonin was better than placebo in the rate of successful sleep EEG (OR=4.7; 95% CI 2.9 to 7.7). Beta artefacts were significantly more with triclofos (51/145) than melatonin (19/123) and placebo (12/65), but the readability of EEG was not impacted. Movement/unwanted arousal artefacts were significantly more with placebo (37/65) than with triclofos (37/145) and melatonin (34/123). Drug-related adverse events were comparable between triclofos and melatonin. Neither of the drugs was associated with any serious adverse events.

CONCLUSIONS: Both triclofos and melatonin are individually better than sleep deprivation alone for conducting successful sleep EEGs. Triclofos is significantly better than melatonin for conducting sleep EEGs, with no significant increase in adverse events.

TRIAL REGISTRATION NUMBER: CTRI/2022/05/042479; Clinical Trials Registry of India.

PMID:39580155 | DOI:10.1136/archdischild-2024-327416

Artif Intell Med. 2024 Nov 17;159:103023. doi: 10.1016/j.artmed.2024.103023. Online ahead of print.

ABSTRACT

Accurate identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods for drug-target interactions prediction are more popular in recent years. Conventional computational methods almost simply view heterogeneous network constructed by the drug-related and protein-related dataset instead of comprehensively exploring drug-protein pair (DPP) information. To address this limitation, we proposed a Double Multi-view Heterogeneous Graph Neural Network framework for drug-target interaction prediction (DMHGNN). In DMHGNN, one multi-view heterogeneous graph neural network is based on meta-paths and denoising autoencoder for protein-, drug-related heterogeneous network learning, and another multi-view heterogeneous graph neural network is based on multi-channel graph convolutional network for drug-protein pair similarity network learning. First, a meta-path-based graph encoder with the attention mechanism is used for substructure learning of complex relationships from heterogeneous network constructed by proteins, drugs, side-effects and diseases, obtaining key information that is easy to be ignored in global learning of heterogeneous networks, and multi-source neighbouring features for drugs and proteins are learned from heterogeneous network via denoising auto-encoder model. Then, multi-view graphs of drug-protein pairs (DPPs) including the topology graph, semantics graph and collaborative graph with shared weights are constructed, and the multi-channel graph convolutional network (GCN) is utilized to learn the deep representation of DPPs. Finally, a multi-layer fully connection network is trained to predict drug-target interactions. Experiments have demonstrated its effectiveness and better performance than state-of-the-art methods.

PMID:39579417 | DOI:10.1016/j.artmed.2024.103023

Chin J Integr Med. 2024 Nov 22. doi: 10.1007/s11655-024-3918-y. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) Zihua Wenfei Zhisou Granule (ZWZG) in postinfectious cough (PIC) patients with CM syndrome of wind-cold invading Fei (Lung, WCIF).

METHODS: This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase II clinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory Departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A (ZWZG-matched placebo 15 g), group B (active ZWZG 15 g), and group C (active ZWZG 10 g plus ZWZG-matched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score (CSS), cough Visual Analog Scale (VAS) value, Cough-Specific Quality of Life Questionnaire (CQLQ) score, and CM syndrome score from baseline (day 0) to post-treatment (day 14). Adverse events (AEs) in each group were recorded.

RESULTS: A total of 198 patients were included in the full analysis set (FAS) and safety analysis set (SS), while 183 were enrolled in the per-protocol analysis set (PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85% in groups A, B, and C, respectively; while the cough disappearance rate was 31.34%, 72.31% and 68.18%, respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A (P<0.0001). Both the median time to cough relief and cough disappearance in groups B and C were shorter than group A (P<0.0001). Compared with group A, groups B and C showed significantly greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS (P<0.05). There were no significant differences in changes from baseline to post-treatment in CQLQ and CM syndrome scores among 3 groups (P>0.05). Results in the PPS population were consistent with those in the FAS population. Groups B and C showed lower incidence in AEs than group A (P<0.05), while there was no significant difference between groups B and C (P>0.05). No drug-related severe AEs were reported.

CONCLUSIONS: ZWZG can increase cough disappearance rate and cough relief rate; and it is beneficial in shortening cough duration and reducing cough severity and frequency in patients suffering from PIC. It is safe and generally well tolerated. (Registration No. ChiCTR1900022078).

PMID:39576445 | DOI:10.1007/s11655-024-3918-y

Cureus. 2024 Oct 22;16(10):e72098. doi: 10.7759/cureus.72098. eCollection 2024 Oct.

ABSTRACT

Lyell syndrome, also known as toxic epidermal necrolysis (TEN), is a rare but life-threatening skin condition, often triggered by certain medications. Antiepileptics, allopurinol, and some nonsteroidal anti-inflammatory drugs are the most common causes. Some antibiotics are also common culprits, although tetracyclines are rarely linked to this condition. We hereby report a case of TEN induced by doxycycline in an 18-year-old girl who was taking the drug for the treatment of acne.

PMID:39574993 | PMC:PMC11581461 | DOI:10.7759/cureus.72098

Cureus. 2024 Oct 22;16(10):e72147. doi: 10.7759/cureus.72147. eCollection 2024 Oct.

ABSTRACT

Hydralazine has been used for decades for the management of hypertension. However, hydralazine has been associated with various side effects, including autoimmune diseases such as hydralazine-induced antineutrophil cytoplasmic antibody-associated vasculitis (ANCA-vasculitis) and lupus-like syndrome characterized by multiorgan involvement and complex clinical manifestations. We present four cases of hydralazine-induced vasculitis (sometimes referred to as drug-induced lupus or DIL) with different presentations, including diffuse alveolar hemorrhage, hemoptysis, and skin rash. Based on variable manifestations, diagnosis can be difficult, and a high index of suspicion is of paramount importance. The final diagnosis is made by kidney biopsy, and treatment includes discontinuation of the offending agent and frequent immunosuppression. We urge caution with the use of hydralazine and choosing alternative antihypertensives when possible.

PMID:39574988 | PMC:PMC11581442 | DOI:10.7759/cureus.72147

BMJ Med. 2024 Oct 22;3(1):e000854. doi: 10.1136/bmjmed-2024-000854. eCollection 2024.

ABSTRACT

OBJECTIVE: To assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent girls and boys in Denmark.

DESIGN: Self-controlled case series study.

SETTING: Population based study of linked nationwide health registers in Denmark for HPV vaccination and hospital diagnosis data, 1 October 2017 (or age 10 years) to 31 December 2022 or censored. Personal data were obtained from the Central Person Register. Information on dates of HPV vaccination and type of vaccine were obtained from the Danish Vaccination Register. Primary or secondary diagnoses of inpatient or outpatient hospital contact were sourced from the Danish National Patient Register.

PARTICIPANTS: Source cohort 854 586. 350 687 individuals aged 10-17 years living in Denmark received at least one dose of HPV9 vaccine. Self-controlled case series analysis of 3354 individuals (1913 girls and 1441 boys) who received at least one dose of HPV9 vaccine and had at least one outcome.

MAIN OUTCOME MEASURES: Rate ratios of the study outcomes in a 28 day or 180 day risk period (depending on the type of outcome) after HPV9 vaccination compared with the reference period were calculated. 47 immune mediated diseases, myocarditis, pericarditis, and seven thromboembolic outcomes were assessed. A safety signal for a specific outcome was identified if at least three outcomes were seen in the risk period after vaccination, the rate ratio was significantly increased (lower bound of the 95% confidence interval (CI) for the self-controlled case series rate ratio >1.0), and the false discovery rate adjusted P value was significant (<0.05).

RESULTS: 696 776 doses of any HPV vaccine were given during the study period, including 673 530 doses of HPV9 vaccine in 350 687 individuals who received at least one dose. In the self-controlled case series analysis, rate ratios of all immune mediated outcomes combined were 0.99 (95% CI 0.86 to 1.13) and 1.03 (0.89 to 1.20) in girls and boys, respectively, after HPV9 vaccination. Rate ratios for any of the 47 analysed immune mediated outcomes were not increased in the risk periods in girls after vaccination. The only increased rate ratio seen was for Raynaud's disease (rate ratio 2.62, 95% CI 1.07 to 6.40) after HPV9 vaccination in boys, which did not fulfil the criteria of a safety signal. These findings should be interpreted in the light of the study limitations. None of the other 55 outcomes examined showed an association with HPV9 vaccination.

CONCLUSIONS: The results of this study did not suggest an association between HPV9 vaccination and the study outcomes in adolescent boys and girls aged 10-17 years. This study contributes to the evidence on the safety of the HPV9 vaccine.

PMID:39574421 | PMC:PMC11579538 | DOI:10.1136/bmjmed-2024-000854

Rev Med Inst Mex Seguro Soc. 2024 Sep 2;62(5):1-6. doi: 10.5281/zenodo.12667969.

ABSTRACT

BACKGROUND: COVID-19 is a severe acute respiratory syndrome caused by SARS-CoV-2. This disease had a high mortality rate and turned into a pandemic, which is why it was considered a severe public health problem. In this context, pregnant patients were a vulnerable group and, consequently, an effective vaccine was necessary.

OBJECTIVE: To categorize the events attributable to the application of Vaxzevria vaccine in pregnant patients.

MATERIAL AND METHODS: Retrospective, cross-sectional, descriptive and observational study carried out at No. 55 Family Medicine Unit in Puebla, Puebla. 300 patients between 15 and 44 years of age who received the first dose of Vaxzevria vaccine were included. The Format of Notification of Events Presumably Attributable to Vaccination was reviewed.

RESULTS: The most representative general symptoms were headache in 44.3%; fever in 30.7%; asthenia and adynamia in 19.3%; adynamia in 19%, and limitation of movement in 3%. Concerning local symptoms and signs, 23% presented localized pain on the site where the vaccine was administered. Finally, regarding systemic symptoms, 21.7% had arthralgias and 20.7% myalgias.

CONCLUSIONS: The symptoms and signs were of less severity for pregnant patients, and resolved in a few days, which is why it was safe the administration of Vaxzevria vaccine.

PMID:39571084 | DOI:10.5281/zenodo.12667969

PLoS One. 2024 Nov 21;19(11):e0309781. doi: 10.1371/journal.pone.0309781. eCollection 2024.

ABSTRACT

BACKGROUND: Several diseases co-exist with diabetes such as hypertension, and dyslipidemia, leading to cases of non-adherence, several drug interactions, and an increased risk of adverse drug reactions among patients, which are often termed as drug-related problems (DRPs). The role of pharmacists in high-income countries is well-defined in identifying DRPs among type 2 diabetes patients. However, these roles still need to be explored within low- and middle-income countries. The study aimed to identify DRPs in Type 2 diabetic patients.

METHODS: A community-based cross-sectional study was conducted in the Sunwal Municipality, Lumbini Province, Nepal from April to November 2021 where a stratified random sampling technique was employed to collect the data. The study included patients aged ≥ 18 years of either gender with type 2 diabetes who were prescribed at least one anti-diabetic medication. Patients were visited at their homes once identified through the community pharmacies, and a prescription review was conducted to identify the DRPs by using the Pharmaceutical Care Network Europe (PCNE) V8.02 tool and pertinent guidelines.

RESULTS: Among 182 patients, 97 (53.3%) had DRPs. Most of the patients were 50-60 years (n = 46; 25.3%), with a mean ± SD age of 55.43±14.46, as most were female (n = 94; 51.6%). Biguanides and sulfonylureas were the common classes of drugs prescribed. The major class of drug associated with DRPs were biguanides (n = 85; 49.7%), followed by sulfonylureas (n = 42; 24.6%). Metformin was the major drug associated with DRPs (n = 85; 49.4%). The major type of DRP identified was treatment effectiveness (n = 82; 79.61%), while patients not adhering to drug therapy (n = 97; 71.85%) was the leading cause of DRPs. DRPs were significantly associated with the duration of diabetes (p = .007) and the number of fruit servings (p = .007).

CONCLUSION: The majority of the patients were found to have DRPs. The visiting patients at home by the pharmacists helped in identifying the DRPs and associated factors among type 2 diabetes patients, which may aid in the prevention and management of the disease.

PMID:39570842 | DOI:10.1371/journal.pone.0309781

Harefuah. 2024 Jul;163(7):457-461.

ABSTRACT

Sex- and Gender-Conscious Medicine aims to raise awareness among the general public and among professionals to the phenomenon that the function of all body systems in women and men can be different. The differences may be small but significant for the health and disease and also affect pharmacokinetics and pharmacodynamics. Since medications are still studied mostly in men and the results are applied to women, pharmacokinetics and pharmacodynamics of men have actually become the "gold standard", which is applied in practice to both sexes. This is the case, despite the fact that the body weight of women is usually lower than that of men and the compartmental distribution of fat, muscle and water is different between the sexes. In addition, metabolism and clearance of drugs through the kidneys can differ between them. As a result, women sometimes find themselves undertreated or over-treated with regard to various medications and suffer twice as much from adverse drug reactions than men. Even the involvement of regulatory institutions such as the FDA in the USA was not enough to change the situation decisively. In this review, I will discuss various aspects of the problem, present examples of different groups of drugs and will especially refer to the problem of the side effects of medications in women.

PMID:39569956

Front Immunol. 2024 Nov 6;15:1478545. doi: 10.3389/fimmu.2024.1478545. eCollection 2024.

ABSTRACT

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01-0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.

PMID:39569195 | PMC:PMC11576437 | DOI:10.3389/fimmu.2024.1478545

JMIR Med Inform. 2024 Nov 20;12:e45289. doi: 10.2196/45289.

ABSTRACT

BACKGROUND: Social networking services (SNS) closely reflect the lives of individuals in modern society and generate large amounts of data. Previous studies have extracted drug information using relevant SNS data. In particular, it is important to detect adverse drug reactions (ADRs) early using drug surveillance systems. To this end, various deep learning methods have been used to analyze data in multiple languages in addition to English.

OBJECTIVE: A cautionary drug that can cause ADRs in older patients was selected, and Korean SNS data containing this drug information were collected. Based on this information, we aimed to develop a deep learning model that classifies drug ADR posts based on a recurrent neural network.

METHODS: In previous studies, ketoprofen, which has a high prescription frequency and, thus, was referred to the most in posts secured from SNS data, was selected as the target drug. Blog posts, café posts, and NAVER Q&A posts from 2005 to 2020 were collected from NAVER, a portal site containing drug-related information, and natural language processing techniques were applied to analyze data written in Korean. Posts containing highly relevant drug names and ADR word pairs were filtered through association analysis, and training data were generated through manual labeling tasks. Using the training data, an embedded layer of word2vec was formed, and a Bidirectional Long Short-Term Memory (Bi-LSTM) classification model was generated. Then, we evaluated the area under the curve with other machine learning models. In addition, the entire process was further verified using the nonsteroidal anti-inflammatory drug aceclofenac.

RESULTS: Among the nonsteroidal anti-inflammatory drugs, Korean SNS posts containing information on ketoprofen and aceclofenac were secured, and the generic name lexicon, ADR lexicon, and Korean stop word lexicon were generated. In addition, to improve the accuracy of the classification model, an embedding layer was created considering the association between the drug name and the ADR word. In the ADR post classification test, ketoprofen and aceclofenac achieved 85% and 80% accuracy, respectively.

CONCLUSIONS: Here, we propose a process for developing a model for classifying ADR posts using SNS data. After analyzing drug name-ADR patterns, we filtered high-quality data by extracting posts, including known ADR words based on the analysis. Based on these data, we developed a model that classifies ADR posts. This confirmed that a model that can leverage social data to monitor ADRs automatically is feasible.

PMID:39565685 | DOI:10.2196/45289

Oman Med J. 2024 May 30;39(3):e631. doi: 10.5001/omj.2024.75. eCollection 2024 May.

ABSTRACT

OBJECTIVES: The objective of this study was to boost pharmacovigilance activity in our psychiatry referral hospital and highlight the pharmacist's role in preventing, detecting, and managing adverse drug reactions (ADRs). Our goal was to promote patient safety and compliance with psychotropic medication by identifying ADR patterns among hospitalized patients in our psychiatry hospital. We aimed to assess and evaluate the causality, severity, and management of documented ADRs along with establishing a hospital-based ADR reporting platform.

METHODS: We enrolled adult patients (18-60 years) admitted to our psychiatric facility between 1 September 2020 and 30 September 2021 who received at least one psychotropic agent for at least two months. Patients with a history of substance abuse, pregnant females, and patients on clozapine were excluded. Medical records were examined for demographics, clinical details, and psychotropic-related ADRs. ADRs were analyzed for causality using Naranjo's algorithm, for severity using modified Hartwig and Siegel, and for preventability using modified Schumock and Thornton scales.

RESULTS: Among 506 admitted patients, 327 suspected psychotropic-related ADRs corresponding to 217 (42.9%) patients, were recorded. Hormonal ADRs were five times higher in men, while the odds of neurological ADRs were significantly higher for women. Otherwise, other ADRs were not statistically affected by gender. Combined therapy was associated with high odds of ADRs, whereas cardiovascular and neurological ADRs were statistically related to monotherapy. Neurological (47.4%) ADRs predominated, followed by cardiovascular (18.7%), and hormonal (15.0%). ADRs were more prevalent among antipsychotics, followed by antidepressants, then mood stabilizers. According to the Naranjo algorithm, some (22.9%) of ADRs were definite, while the majority (74.3%) were probable. As per the Hartwig severity scale, the majority (74.0%) of ADRs were moderate, and the rest (26.0%) were mild. The Modified Schumock and Thornton assessment questionnaire revealed that 75.2% of ADRs were unpreventable, 19.3% were probably preventable, and 5.5% were preventable. In 46.8% of the cases, a new medication was required to manage the emerging ADRs; one-third of ADRs necessitate the replacement of the suspected medication. Close monitoring without any pharmacological intervention was sufficient in 23.2% of cases, while dose reduction was the solution in 7.6% of cases.

CONCLUSIONS: ADR monitoring in the psychiatry setting by a multidisciplinary team helps recognize the initial signs of ADRs, contributing to better compliance. Hospital-based reporting programs or data-capturing tools will aid in the spontaneous and active assessment of ADRs by healthcare practitioners.

PMID:39564097 | PMC:PMC11574781 | DOI:10.5001/omj.2024.75

Future Oncol. 2024 Nov 20:1-11. doi: 10.1080/14796694.2024.2431479. Online ahead of print.

ABSTRACT

AIM: We conducted a meta-analysis of published randomized controlled trials to compare the effectiveness and safety of eribulin versus paclitaxel for patients with breast cancer.

METHODS: We systematically searched multiple databases including Cochrane, PubMed, Medline, and Embase. The primary outcomes analyzed were overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), and adverse events (AEs). These outcomes were evaluated using RevMan5.3 software.

RESULTS: A total of 5 studies were included in the analysis. Compared to paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs not only extended the overall survival of patients but also improved the disease control rate (DCR) [risk ratio (RR) 0.98, (95% confidence intervals (CI): 0.70, 1.38), p = 0.92]. Hematological system diseases [RR 1.18 (95% CI: 1.07, 1.31), p = 0.002] were the most frequently observed adverse event with eribulin, while paclitaxel was more likely to cause nervous system lesion [RR 0.66 (95% CI: 0.54, 0.80), p < 0.0001].

CONCLUSION: Compared with paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs can also prolong the PFS and OS of BC patients. Our recommendation is to use eribulin plus other chemotherapy drugs to treat advanced BC and to continuously monitor and manage the drug-related adverse events.

PMID:39563608 | DOI:10.1080/14796694.2024.2431479

EJNMMI Res. 2024 Nov 19;14(1):112. doi: 10.1186/s13550-024-01173-8.

ABSTRACT

BACKGROUND: Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extracted from brown algae with nanomolar affinity for P-selectin. This first-in-human study evaluated in healthy volunteers the safety, whole-body biodistribution, and dosimetry of 99mTc-fucoidan (Good Manufacturing Practices grade). We also investigated whether we could observe binding of 99mTc-fucoidan to human thrombi ex vivo and in vivo. In ten healthy volunteers, conjugate whole-body scans were performed up to 24 h following intravenous injection of 99mTc-fucoidan (370 MBq). Moreover, 99mTc-fucoidan uptake in ex vivo human thrombi (n = 11) was measured by gamma counting. Additionally, three patients with a newly diagnosed deep vein thrombosis (DVT) were subjected to 99mTc-fucoidan SPECT/CT imaging.

RESULTS: 99mTc-fucoidan was well tolerated in all participants without any drug-related adverse events. The total-body absorbed dose in males was comparable to females (0.012 ± 0.004 vs. 0.011 ± 0.005 mSv/MBq; p = 0.97). Gamma counting experiments demonstrated binding of tracer to ex vivo human thrombi that was 16% lower after blocking with a natural P-selectin ligand, Sialyl Lewis X. 99mTc-fucoidan demonstrated specific uptake at the thrombus site in one out of three scanned patients with DVT.

CONCLUSIONS: 99mTc-Fucoidan has a favorable biodistribution and safety profile. 99mTc-fucoidan exhibited specific binding to human thrombi in both in vivo and ex vivo settings. Nonetheless, the in vivo results do not support further clinical investigation of 99mTc-fucoidan as an imaging modality for DVT. Other clinical implementations of a technetium- 99m-labeled P-selectin tracer should be considered.

TRIAL REGISTRATION: Clinicaltrials,NCT03422055.Registered 01/15/2018. URL: https://clinicaltrials.gov/study/NCT03422055 Landelijk Trial Register, NL7739. Registered 4/2/2019 . https://onderzoekmetmensen.nl/en/trial/26785.

PMID:39562382 | DOI:10.1186/s13550-024-01173-8

J Infect. 2024 Nov 17:106352. doi: 10.1016/j.jinf.2024.106352. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to evaluate the usefulness of antistaphylococcal penicillin (ASP) or cephazolin-based combinations versus monotherapy in patients with native-valve infective endocarditis (IE) caused by methicillin-susceptible Staphylococcus aureus (MSSA).

METHODS: Post-hoc analysis of a multicentre prospective cohort. We include patients from 2008 to 2022, with definite native-valve, left-side IE due to MSSA treated primarily with ASP/cephazolin. Patients were categorized according to whether they initially received monotherapy or combination therapy for more than 72 hours. A propensity score-matched cohort was planned.

RESULTS: Out of 420 included cases, 94 (22.4%) received monotherapy and 326 (77.6%) combination. Median combination duration was 14 days (interquartile range 10-20). Sixty-eight combination cases were matched with 68 monotherapy controls. Baseline characteristics were well balanced. There were no differences in in-hospital or one-year mortality between groups (OR 0.85, 95%CI 0.33-2.18 and HR 0.68, 95%CI 0.35-1.31, respectively). Endocarditis relapses and persistent bacteraemia rates were similar (0% vs 1.5%, p=1.000; and 19.1% vs 13.2%, p=0.352, respectively). Drug-related adverse events were more frequent in combination group (15.0% vs 1.1%, p<0.001).

CONCLUSIONS: Antibiotic combination for patients with native valve left-sided MSSA endocarditis did not improve patient's outcomes. Drug-related adverse events were more frequent in combination patients.

PMID:39561880 | DOI:10.1016/j.jinf.2024.106352

Medicine (Baltimore). 2024 Nov 15;103(46):e40470. doi: 10.1097/MD.0000000000040470.

ABSTRACT

Following improved accessibility to medical services, the phenomenon of polypharmacy in elderly patients with comorbidity has been increasing globally. Polypharmacy patients are prone to drug interactions, adverse drug reactions, and even the risk of death etc. Therefore, there is an urgent need to fully understand the current status and characteristics of drug use in elderly patients with chronic diseases, focusing on polypharmacy factors to ensure that medications for elderly patients are effective and safe. To collect and analyze the characteristics of the current drug use situation in elderly patients with chronic diseases in Chongqing and further explore the influencing factors for polypharmacy, providing references for formulating more effective and safe medication regimens for elderly patients. Most elderly patients affected with chronic diseases in Chongqing were willing to go to hospitals or pharmacies to buy medicines. However, they were not familiar with their disease conditions and drug-related adverse reactions and could not be regularly followed up or monitored. The number of diseases, medications, and adverse drug reactions increased with the increasing age of elderly patients. The problem of irrational use of drugs in elderly patients with chronic diseases was relatively prominent, especially the use of traditional Chinese medicines. The medication situation in elderly patients with chronic diseases was not optimistic, and the problem of polypharmacy was relatively prominent. Further large-scale studies are needed to provide a certain reference for improving the current status of drug use in elderly patients.

PMID:39560587 | DOI:10.1097/MD.0000000000040470

Int J Nanomedicine. 2024 Nov 14;19:11847-11858. doi: 10.2147/IJN.S490400. eCollection 2024.

ABSTRACT

PURPOSE: Abraxane (nanoparticle albumin-bound paclitaxel) is a chemotherapeutic employed commonly for the management of various cancers including breast cancer, non-small cell lung cancer, and pancreatic adenocarcinoma. Although it has clinically beneficial properties, Abraxane is accompanied by multiple adverse events (AEs) that require close observation. This study aims to evaluate the AE profile of Abraxane using recently available data from January 2004 through December 2023 in the FDA Adverse Event Reporting System (FAERS).

PATIENTS AND METHODS: The data for Abraxane-related AEs were obtained from the FAERS database. The dataset consisted of patient demographic characteristics as well as information on the types and outcomes of AEs reported. Reporting odds ratios (ROR) as well as proportional reporting ratio (PRR), considering the used definition of anti-cancer agent and AEs, were calculated to investigate any association with Abraxane.

RESULTS: A total of 10,310 reports associated with Abraxane AEs were identified. Blood and lymphatic system disorders were the most frequent (ROR 6.44), followed by hepatobiliary (ROR 3.16), infections (ROR 1.45), and gastrointestinal disorders (ROR 1.42). Serious outcomes included hospitalization in 36.35% and death in 29.76% of cases. The top adverse reactions matched known profiles, including peripheral sensory neuropathy (ROR: 49.48). The analysis also found new adverse reactions, such as scleroderma-like reactions (ROR: 95.4) and vascular pseudoaneurysm ruptures (ROR: 87.71).

CONCLUSION: Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.

PMID:39558918 | PMC:PMC11572439 | DOI:10.2147/IJN.S490400