Front Cardiovasc Med. 2024 Feb 21;11:1342832. doi: 10.3389/fcvm.2024.1342832. eCollection 2024.

ABSTRACT

INTRODUCTION: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.

METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment.

RESULTS: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed.

CONCLUSION: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).

PMID:38450375 | PMC:PMC10915057 | DOI:10.3389/fcvm.2024.1342832

Cureus. 2024 Feb 5;16(2):e53642. doi: 10.7759/cureus.53642. eCollection 2024 Feb.

ABSTRACT

In a rare case, a 70-year-old female with polycythemia vera developed late-onset melanonychia, a seldom-documented side effect of hydroxyurea. Typically, melanonychia emerges within months of treatment, but this case is unique as it occurred four years into therapy. Notably, the patient, with darker skin, also had hyperpigmentation of her hands and tongue. Her history of hydroxyurea-associated ulcers and symptoms worsening with dose adjustment suggested drug involvement. While mucocutaneous hyperpigmentation from hydroxyurea is known, melanonychia and tongue hyperpigmentation are rarely reported, mostly in early treatment. This case highlights the importance of recognizing these side effects, especially in diverse populations and darker skin tones. The diverse skin tones seen in Sub-Saharan Africa add complexity to diagnosing such dermatological conditions, highlighting the need for awareness. Melanonychia can mimic severe conditions such as subungual melanoma, emphasizing the significance of accurate recognition and management without invasive tests. Educating clinicians and patients about these benign drug-related phenomena is essential for precise identification and management. This case contributes to understanding late-onset hydroxyurea-induced melanonychia and tongue hyperpigmentation, enhancing clinical knowledge in diverse populations.

PMID:38449930 | PMC:PMC10917399 | DOI:10.7759/cureus.53642

PLoS One. 2024 Mar 6;19(3):e0298984. doi: 10.1371/journal.pone.0298984. eCollection 2024.

ABSTRACT

The Western diet has undergone a massive switch since the second half of the 20th century, with the massive increase of the consumption of refined carbohydrate associated with many adverse health effects. The physiological mechanisms linked to this consumption, such as hyperglycaemia and hyperinsulinemia, may impact non medical traits such as facial attractiveness. To explore this issue, the relationship between facial attractiveness and immediate and chronic refined carbohydrate consumption estimated by glycemic load was studied for 104 French subjects. Facial attractiveness was assessed by opposite sex raters using pictures taken two hours after a controlled breakfast. Chronic consumption was assessed considering three high glycemic risk meals: breakfast, afternoon snacking and between-meal snacking. Immediate consumption of a high glycemic breakfast decreased facial attractiveness for men and women while controlling for several control variables, including energy intake. Chronic refined carbohydrate consumption had different effects on attractiveness depending on the meal and/or the sex. Chronic refined carbohydrate consumption, estimated by the glycemic load, during the three studied meals reduced attractiveness, while a high energy intake increased it. Nevertheless, the effect was reversed for men concerning the afternoon snack, for which a high energy intake reduced attractiveness and a high glycemic load increased it. These effects were maintained when potential confounders for facial attractiveness were controlled such as age, age departure from actual age, masculinity/femininity (perceived and measured), BMI, physical activity, parental home ownership, smoking, couple status, hormonal contraceptive use (for women), and facial hairiness (for men). Results were possibly mediated by an increase in age appearance for women and a decrease in perceived masculinity for men. The physiological differences between the three meals studied and the interpretation of the results from an adaptive/maladaptive point of view in relation to our new dietary environment are discussed.

PMID:38446775 | PMC:PMC10917283 | DOI:10.1371/journal.pone.0298984

IEEE J Biomed Health Inform. 2024 Mar;28(3):1773-1784. doi: 10.1109/JBHI.2024.3349570.

ABSTRACT

Drug-drug interaction (DDI) has attracted widespread attention because when incompatible drugs are taken together, DDI will lead to adverse effects on the body, such as drug poisoning or reduced drug efficacy. The adverse effects of DDI are closely determined by the molecular structures of the drugs involved. To represent drug data effectively, researchers usually treat the molecular structure of drugs as a molecule graph. Then, previous studies can use the handcrafted graph neural network (GNN) model to learn the molecular graph representations of drugs for DDI prediction. However, in the field of bioinformatics, manually designing GNN architectures for specific molecular structure datasets is time-consuming and depends on expert experience. To address this problem, we propose an automatic drug-drug interaction prediction method named AutoDDI that can efficiently and automatically design the GNN architecture for drug-drug interaction prediction without manual intervention. To this end, we first design an effective search space for drug-drug interaction prediction by revisiting various handcrafted GNN architectures. Then, to efficiently and automatically design the optimal GNN architecture for each drug dataset from the search space, a reinforcement learning search algorithm is adopted. The experiment results show that AutoDDI can achieve the best performance on two real-world datasets. Moreover, the visual interpretation results of the case study show that AutoDDI can effectively capture drug substructure for drug-drug interaction prediction.

PMID:38446657 | DOI:10.1109/JBHI.2024.3349570

J Psychosoc Nurs Ment Health Serv. 2024 Mar;62(3):7-10. doi: 10.3928/02793695-20240207-01. Epub 2024 Mar 1.

ABSTRACT

VigiBase, the World Health Organization's collaborative global pharmaco-vigilance database, provides storage for millions of adverse drug reaction (ADR) reports. Pharmacovigilance scientists use the database to detect signals, assess, and understand trends in ADRs so that potential harms can be communicated. A search for pharmacovigilance studies on psychotropic-related ADR reports published over the past 5 years in VigiBase identified the majority to be antipsychotic-related ADRs, and within the antipsychotic class, clozapine-related. The nine antidepressant-related ADR reports were reviewed in more detail and provide an example of how the science of pharmacovigilance identifies and communicates medication risks. [Journal of Psychosocial Nursing and Mental Health Services, 62(3), 7-10.].

PMID:38446626 | DOI:10.3928/02793695-20240207-01

JAMA Netw Open. 2024 Mar 4;7(3):e241342. doi: 10.1001/jamanetworkopen.2024.1342.

ABSTRACT

IMPORTANCE: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations.

OBJECTIVE: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs.

MAIN OUTCOME AND MEASURES: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing.

RESULTS: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance.

CONCLUSIONS AND RELEVANCE: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

PMID:38446478 | DOI:10.1001/jamanetworkopen.2024.1342

Eur J Hosp Pharm. 2024 Mar 6:ejhpharm-2024-004089. doi: 10.1136/ejhpharm-2024-004089. Online ahead of print.

ABSTRACT

Brentuximab vedotin (BV) is an antibody-drug conjugate, consisting of a CD30-directed antibody, conjugated by a protease-cleavable linker to a microtubule disrupting agent auristatin E (MMAE). Although the safety datasheet of BV does not warn of severe toxic effects of extravasation, we report a third case of a patient with anaplastic large cell lymphoma who developed severe epidermal necrosis after extravasation. The reason for what happened could be attributed to the fact that MMAE belongs to the group of vinca alkaloids so it should be handled like other tissue-necrotising chemotherapeutics. Reporting of all cases of extravasation involving new conjugated chemotherapeutic drugs is of the utmost importance to be able to develop updated guidelines. Hospital pharmacists can provide information on how to manage extravasation, assess the potential risk, and have a crucial role in drafting hospital protocols.

PMID:38448203 | DOI:10.1136/ejhpharm-2024-004089

Radiother Oncol. 2024 Mar 4:110194. doi: 10.1016/j.radonc.2024.110194. Online ahead of print.

ABSTRACT

High precision, image-guided radiotherapy (RT) has increased the therapeutic ratio, enabling higher tumor and lower normal tissue doses, leading to improved patient outcomes. Nevertheless, some patients remain at risk of developing serious side effects.In many clinical situations, the radiation tolerance of normal tissues close to the target volume limits the dose that can safely be delivered and thus the potential for tumor control and cure. This is particularly so in patients being re-treated for tumor progression or a second primary tumor within a previous irradiated volume, scenarios that are becoming more frequent in clinical practice.Various normal tissue 'radioprotective' drugs with the potential to reduce side effects have been studied previously. Unfortunately, most have failed to impact clinical practice because of lack of therapeutic efficacy, concern about concurrent tumor protection or excessive drug-related toxicity. This review highlights the evidence indicating that targeting the CXCL12/CXCR4 pathway can mitigate acute and late RT-induced injury and reduce treatment side effects in a manner that overcomes these previous translational challenges. Pre-clinical studies involving a broad range of normal tissues commonly affected in clinical practice, including skin, lung, the gastrointestinal tract and brain, have shown that CXCL12 signalling is upregulated by RT and attracts CXCR4-expressing inflammatory cells that exacerbate acute tissue injury and late fibrosis. These studies also provide convincing evidence that inhibition of CXCL12/CXCR4 signalling during or after RT can reduce or prevent RT side effects, warranting further evaluation in clinical studies. Greater dialogue with the pharmaceutical industry is needed to prioritize the development and availability of CXCL12/CXCR4 inhibitors for future RT studies.

PMID:38447871 | DOI:10.1016/j.radonc.2024.110194

Gynecol Oncol. 2024 Mar 5;185:186-193. doi: 10.1016/j.ygyno.2024.01.045. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer.

METHODS: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed.

RESULTS: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia.

CONCLUSIONS: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations.

PMID:38447347 | DOI:10.1016/j.ygyno.2024.01.045

Eur J Drug Metab Pharmacokinet. 2024 Mar 6. doi: 10.1007/s13318-024-00880-w. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: HEC122505 is a potent and selectively monoamine oxidase B inhibitor that is safe and well-tolerated in preclinical models of Parkinson's disease. The objectives of single ascending dose and multiple dose pharmacokinetic trials of HEC122505 oral tablets were to determine the safety and tolerability of HEC122505, and to examine the food effect on the pharmacokinetic parameters of HEC122505 and its major metabolite HEC129870.

METHODS: The phase I study (NCT04625361) consisted of three arms: single ascending dose study (5, 20, 50, 100, 200, 300 or 400 mg HEC122505 tablets or placebo), multiple ascending dose study (20, 50 or 100 mg HEC122505 tablets or placebo once daily), and food effect (100 mg HEC122505 tablets single dose after a high-fat, high-calorie meal). All subjects completed all trial arms and were analyzed as planned.

RESULTS: Pharmacokinetic analysis showed that HEC122505 rapidly absorbed with the time to peak plasma concentration (Tmax) ranged from 0.5 to 1.75 h. In addition, maximum plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose proportional manner. Food effect study showed that a high-fat, high-calorie meal had no significant effect on the pharmacokinetics of HEC122505 and its major metabolite HEC129870, suggesting that HEC122505 could be administered in both fasted and fed state in clinical trials. The subsequent multiple-dose study evaluated doses from 20 to 100 mg dose once daily for up to 8 days. HEC122505 reached steady state after approximately 5 days with a once daily dose. In these studies, all dose of HEC122505 was generally safe and well tolerated. No grade ≥ 3 drug related adverse events (AEs) occurred.

CONCLUSION: HEC122505 was generally safe and well tolerated in the single ascending dose (ranging from 5 to 400 mg) and multiple ascending dose (50 to 200 mg once daily doses) studies. All the drug related adverse events (AEs) were Grade ≤ 2. There were no deaths, no subjects discontinued the trial due to AEs, and there were no other serious AEs. The safety and pharmacokinetic profile support once daily administration of HEC122505.

PMID:38446388 | DOI:10.1007/s13318-024-00880-w

World Allergy Organ J. 2024 Mar 2;17(3):100882. doi: 10.1016/j.waojou.2024.100882. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Berotralstat is a once-daily oral inhibitor of plasma kallikrein for the prophylaxis of hereditary angioedema (HAE) in patients ≥12 years. APeX-J aimed to evaluate the efficacy and safety of berotralstat in Japan.

METHODS: APeX-J was a Phase III trial comprising 3 parts (NCT03873116). Part 1 was a randomized, placebo-controlled evaluation of berotralstat 150 or 110 mg over 24 weeks. Part 2 was a 28-week dose-blinded phase in which berotralstat-treated patients continued the same dose and placebo patients were re-randomized to berotralstat 150 or 110 mg. In Part 3, all patients remaining on study received berotralstat 150 mg in an open-label manner for up to an additional 52 weeks. The primary endpoint of Parts 2 and 3 was long-term safety and tolerability, and secondary endpoints examined effectiveness.

RESULTS: Seventeen patients entered Part 2, and 11 continued into Part 3. Treatment-emergent adverse events (TEAEs) were reported by 14/17 patients (82.4%) in Parts 2 or 3; the most common were nasopharyngitis, abdominal pain, cystitis, influenza, and vertigo. One patient (5.9%) experienced a drug-related TEAE (Grade 4 increased hepatic enzyme). No drug-related serious TEAEs were reported. For patients who completed 26 months of treatment with berotralstat 150 mg (n = 5), mean (standard error of the mean) monthly HAE attack rates and on-demand medication use decreased from baseline by 1.15 (0.09) attacks/month and 2.8 (0.64) doses/month, respectively. Sustained improvements were also observed in patient quality of life and treatment satisfaction.

CONCLUSIONS: Long-term prophylaxis with berotralstat raised no new safety signals and was effective at reducing attacks and improving patient-reported outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03873116. Registered March 13, 2019. Retrospectively registered.

PMID:38445295 | PMC:PMC10914521 | DOI:10.1016/j.waojou.2024.100882

Open Forum Infect Dis. 2024 Feb 5;11(3):ofae046. doi: 10.1093/ofid/ofae046. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized.

METHODS: This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance.

RESULTS: Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction.

CONCLUSIONS: Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.

PMID:38444818 | PMC:PMC10914364 | DOI:10.1093/ofid/ofae046

SAGE Open Med Case Rep. 2024 Mar 4;12:2050313X241235823. doi: 10.1177/2050313X241235823. eCollection 2024.

ABSTRACT

Onychomycosis is the most prevalent nail disease and is frequently encountered in clinical practice. Despite having multiple therapeutic options, of which systemic antifungals are the most effective, treatment is not always mandatory in all patients. Especially when considering systemic treatment, the risk of adverse reactions may outweigh the potential benefits of treatment. In this case report, we present a clinical case of a 49-year-old male patient with a blank past medical history who experienced a severe drug eruption from terbinafine prescribed for mild onychomycosis that required discontinuation of terbinafine, additional evaluation, and treatment of this adverse reaction.

PMID:38444697 | PMC:PMC10913523 | DOI:10.1177/2050313X241235823

J Drugs Dermatol. 2024 Mar 1;23(3):e86-e90. doi: 10.36849/jdd.7603.

ABSTRACT

Hair loss, a pervasive and often distressing condition, affects a substantial number of individuals globally. Although conventional treatments such as hair transplantation, topicals, oral medications, and injectables exist, they have limitations, including the necessity for repeated treatments, potential adverse effects, and cost barriers. Exosome therapy, an innovative and burgeoning option within regenerative medicine, offers a novel approach to hair loss treatment. Exosomes are small vesicles that are produced from the membranes of late-endosomes and secreted by cells, playing a crucial role in intercellular communication. Research on humans is limited,1-4 and animal studies have shown that exosomes derived from various cell types can stimulate hair growth, resulting in increased research and development of exosome therapy for hair loss.5 Establishing a uniform reporting method for exosome therapy is vital as research in this area continues to expand. A standardized approach to research reporting and results is essential for comprehending the underlying mechanisms, safety, and efficacy of exosome therapy. This article provides an in-depth analysis of the current state of exosome therapy for hair loss, including potential advantages, and limitations, as well as directions for future research. J Drugs Dermatol. 2024;23(3)    doi:10.36849/JDD.7603.

PMID:38443118 | DOI:10.36849/jdd.7603

Allergy Asthma Clin Immunol. 2024 Mar 5;20(1):20. doi: 10.1186/s13223-024-00877-9.

ABSTRACT

BACKGROUND: Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge.

METHODS: We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed.

RESULTS: A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs.15 [7.7%], p = 0.04) and were prescribed more frequently amongst those who received at least one antibiotic (28/46 [60.9%] vs.15/40 [37.5%], p = 0.097). In a multivariate regression analysis, the intervention groups were found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95%CI 1.29-5.02) and in those prescribed at least one antibiotic (OR 2.44, 95%CI 1.00-6.15). No drug-related adverse events were reported.

CONCLUSIONS: Proactive penicillin allergy de-labelling for inpatients was associated with a reduction in penicillin allergy labels and increased utilization of beta-lactams in the subsequent 6-months.

PMID:38444037 | DOI:10.1186/s13223-024-00877-9

Asian J Surg. 2024 Mar 4:S1015-9584(24)00375-0. doi: 10.1016/j.asjsur.2024.02.113. Online ahead of print.

ABSTRACT

The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49-0.71) and adverse events (RR: 0.96; 95%CI: 0.93-0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36-0.66), apixaban (RR: 0.54; 95%CI: 0.36-0.81) and edoxaban (RR:0.49; 95%CI: 0.32-0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80-1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33-0.65), advantage events (RR: 0.87; 95%CI: 0.82-0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53-0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.

PMID:38443248 | DOI:10.1016/j.asjsur.2024.02.113

J Anal Toxicol. 2024 Mar 5:bkae019. doi: 10.1093/jat/bkae019. Online ahead of print.

ABSTRACT

The antiviral drug acyclovir (ACV) may induce drug-induced neuropsychiatric symptoms as side effects. The detailed pathogenic mechanism remains unclear; however, it is hypothesized that 9-carboxymethoxymethylguanine (CMMG), a metabolite of ACV, is the causative compound. Therefore, the blood concentrations of ACV and CMMG should be analyzed in ACV toxicity studies. However, it is rare to find methods that can sufficiently separate the ACV and CMMG peaks during simultaneous analysis of both compounds. Therefore, we intended to develop a liquid chromatography tandem mass spectrometry method with improved peak separation of analytes. Samples were deproteinized using methanol/acetonitrile solution (6:4, v/v). Analytes were separated on an InertSustain® Amide column (3 μm, 2.1 × 150 mm). The mobile phase consisted of acetonitrile/10 mM ammonium formate (5:95, v/v) (A) and acetonitrile/10 mM ammonium formate (95:5, v/v, pH 5.0) (B) and samples were eluted in the gradient mode. The separation of analytes was satisfactory and the peak shapes were good. Linear regression models weighted 1/x2 were obtained in the range of 0.25-10 μg/mL. The range of quality control (QC) bias was between 3.6 and 19.8%, and the within-run and between-run precisions of QC were within 13.5%. Recovery ranged from 83.6 to 103.7%, but ion suppression was observed. Samples from a patient with ACV encephalopathy were analyzed using this method. The resulting blood ACV and CMMG concentrations were 8.2 and 8.5 μg/mL, respectively. This method, with sufficient separation of ACV and CMMG, proved useful for use in ACV toxicity studies.

PMID:38441245 | DOI:10.1093/jat/bkae019

Front Endocrinol (Lausanne). 2024 Feb 19;15:1294415. doi: 10.3389/fendo.2024.1294415. eCollection 2024.

ABSTRACT

While suggested, surgery is not always possible as a first-line treatment of Cushing's Disease (CD). In such cases, patients require medical therapy in order to prevent complications resulting from hypercortisolism. Although there has been a wide expansion in pharmacological options in recent years, mitotane was the agent of choice for treating hypercortisolism decades ago. Due to the introduction of other therapies, long-term experience with mitotane remains limited. Here, we report the case of a woman with CD who was treated with mitotane for 37 years. During the treatment period, biochemical and clinical disease control was achieved and the patient had two uncomplicated pregnancies. Drug-related side effects remained moderate and could be controlled by several dose adjustments. Our case highlights the ability of mitotane to allow an effective control of hypercortisolism and to represent a safe treatment option in special situations where CD requires an alternative therapeutic approach. Furthermore, we provide a literature review of the long-term use of mitotane and reported cases of pregnancy in the context of mitotane therapy.

PMID:38440784 | PMC:PMC10911286 | DOI:10.3389/fendo.2024.1294415

BMC Geriatr. 2024 Mar 4;24(1):218. doi: 10.1186/s12877-024-04844-2.

ABSTRACT

BACKGROUND: Polypharmacy and the use of potentially inappropriate medications are common among nursing home residents and are associated with negative outcomes. Although deprescribing has been proposed as a way to curtail these problems, the best way to implement multidisciplinary comprehensive medication review and deprescribing and its real impact in specific high-risk populations, such as nursing home residents, is still unclear. This multicenter randomized controlled clinical trial aims to assess the effects of a multidisciplinary mediation management program on medication use and health problems.

METHODS: A total of 1,672 residents aged ≥ 65 years from 22 nursing homes in South Korea who meet the targeted criteria, such as the use of ≥ 10 medications, are eligible to participate. The experimental group will receive a comprehensive medication review, deprescription, and multidisciplinary case conference with the help of platform. Outcomes will be measured at baseline, at the end of the intervention, as well as at 3, 6, 9, and 12 months after the end of the intervention. The primary endpoints will be the rate of adverse drug events, number of potentially inappropriate medications/potentially inappropriate medication users/two or more central nervous system drug/ central nervous system drug users, delirium, emergency department visits, hospitalization, and falls. The secondary endpoint will be the number of medications taken and polypharmacy users.

DISCUSSION: Our trial design is unique in that it aims to introduce a structured operationalized clinical program focused on reducing polypharmacy and potentially inappropriate medications in a nursing home setting with large samples.

TRIAL REGISTRATION: Ethical approval was granted by the public institutional review board of the Ministry of Health and Welfare (2022-1092-009). The study is also registered with the Clinical Research Information Service (Identifier: KCT0008157, Development and evaluation of a multidisciplinary medication management program in long-term care facility residents Status: Approved First Submitted Date: 2023/01/18 Registered Date: 2023/02/03 Last Updated Date: 2023/01/18 (nih.go.kr) https://cris.nih.go.kr/ ), which includes all items from the World Health Organization Trial Registration Dataset.

PMID:38438996 | DOI:10.1186/s12877-024-04844-2

Sci Rep. 2024 Mar 4;14(1):5304. doi: 10.1038/s41598-023-47868-1.

ABSTRACT

High temperatures (HT) and drought are two major factors restricting wheat growth in the early growth stages. This study investigated the role of glutathione (GSH) amendment (0.0, 0.5, 1.0, and 2.0 mM) to soil in mitigating the adverse effect of HT (33 °C, with 25 °C as a control), water regimes (60% of field capacity and control), and their combinations. HT decreased the length, project area, surface area, volume, and forks of the root, while drought had the reverse effect. Shoot length, leaf area, leaf relative water content, and shoot and root dry matter were significantly decreased by HT and drought, and their combined impact was more noticeable. GSH significantly promoted the root system, shoot growth, and leaf relative water content. The combined treatment reduced chlorophyll a, chlorophyll b, and total chlorophyll. However, 0.5 mM GSH raised chlorophyll a, chlorophyll b, and total chlorophyll by 28.6%, 41.4%, and 32.5%, respectively, relative to 0.0 mM GSH. At combined treatment, 0.5 mM GSH decreased malondialdehyde (MDA) by 29.5% and increased soluble protein content by 24.1%. GSH meaningfully enhanced the activity of superoxide dismutase, catalase, and ascorbate peroxide in different treatments. This study suggested that GSH could protect wheat seedlings from the adverse effects of HT and/or drought stresses.

PMID:38438398 | PMC:PMC10912748 | DOI:10.1038/s41598-023-47868-1