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Topic:Pharmacology

Pharmacology in horses involves the study and application of drugs and medications to diagnose, treat, and prevent diseases and conditions in equine species. This field encompasses the understanding of pharmacokinetics and pharmacodynamics specific to horses, including how drugs are absorbed, distributed, metabolized, and excreted by the equine body. Commonly studied pharmacological agents in horses include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, sedatives, and anthelmintics. Research in equine pharmacology focuses on determining appropriate dosages, understanding drug interactions, and minimizing adverse effects. This page compiles peer-reviewed research studies and scholarly articles that investigate the efficacy, safety, and regulatory aspects of pharmacological interventions in equine veterinary practice.
Echocardiographic and clinical effects of two sedative doses of Dexmedetomidine in healthy horses.
Journal of equine veterinary science    February 9, 2025   105382 doi: 10.1016/j.jevs.2025.105382
Roustaei A, Masoudifard M, Azari O, Keshipour H, Koohestani O.The effects of dexmedetomidine (DEX), as a sedative drug, on echocardiographic measurements have been investigated in many species but not in horses. Therefore, this study aimed to evaluate the echocardiographic and clinical effects of two sedative doses of DEX in healthy horses. Six female crossbred horses weighted 250-330 kg underwent echocardiography before and after sedation by intravenous administration of a low dose of 3.5 μg/kg (LD) and a high dose of 7 μg/kg (HD) of DEX. A significant increase (p≤ 0.05) was observed in the diameters of the pulmonary artery and the left atrium measu...
Imaging flow cytometry reveals the mechanism of equine arteritis virus entry and internalization.
Scientific reports    January 25, 2025   Volume 15, Issue 1 3246 doi: 10.1038/s41598-025-87080-x
Kublicka A, Lorek D, Mikołajczyk-Martinez A, Chodaczek G, Chwirot A, Bażanów B, Matczuk AK.The process of viral entry into host cells is crucial for the establishment of infection and the determination of viral pathogenicity. A comprehensive understanding of entry pathways is fundamental for the development of novel therapeutic strategies. Standard techniques for investigating viral entry include confocal microscopy and flow cytometry, both of which provide complementary qualitative and quantitative data. Imaging flow cytometry, which integrates the advantages of both methodologies, offers significant potential in virological studies. In this investigation, we employed imaging flow ...
Screening analysis of doping agents in horse urine and plasma with dilute and shoot using liquid chromatography high resolution mass spectrometry.
The Analyst    January 23, 2025   doi: 10.1039/d4an01501k
Göktaş EF, Kabil E, Söylemez Yeşilçimen E, Dirikolu L.Various technical methodologies are required to accurately detect substances of different chemical and pharmacological properties in biological samples, which are increasing in number and variety daily. Therefore, laboratories where many samples and different factors are analyzed simultaneously need methods with easy sample preparation, short analysis times and low analysis costs. In this study, the objective was to scan substances susceptible to chemical degradation, amenable to analysis without hydrolysis, and exhibiting short-term stability by employing a straightforward, expeditious, and c...
Retrospective evaluation of the effect of xylazine infusion on survival to discharge in horses undergoing exploratory laparotomy for colic.
Veterinary anaesthesia and analgesia    January 15, 2025   S1467-2987(25)00006-6 doi: 10.1016/j.vaa.2025.01.006
Reed RA, Carroll AT, Dantino SC, Quandt JE, Barletta M, Sakai DM.To determine the influence of xylazine infusion on survival to discharge and describe the associated intraoperative requirement for isoflurane, use of positive inotropes and vasopressors, and recovery time in horses undergoing exploratory laparotomy. Methods: Retrospective cohort study. Methods: A total of 352 horses. Methods: Medical records of horses undergoing anesthesia for exploratory laparotomy from January 2018 to December 2023 were reviewed. Data collected included survival to discharge, results of diagnostic tests, end tidal isoflurane concentration (FE'Iso), use of vasopressors/inotr...
Comparing the effectiveness of four antihistamines with olopatadine in healthy Thoroughbred horses.
The Journal of veterinary medical science    January 14, 2025   doi: 10.1292/jvms.24-0412
Ikeda Y, Kuroda T, Mita H, Tamura N, Ohta M.We compared the antihistamine effect of four new antihistamines with olopatadine, which is used to treat equine allergic diseases. Six healthy Thoroughbred horses received oral doses of olopatadine (50 mg), levocetirizine (50 mg), bilastine (200 mg), rupatadine (100 mg), and desloratadine (50 mg) at >2-week intervals. The effects were investigated by measurement of the wheal area induced by histamine intradermal injection, and inhibition rate was compared with positive and negative controls. The maximum wheal inhibition rate (mean ± SD) of olopatadine (85.3% ± 7.7%) was significantly higher ...
Effect of rapid and slow intravenous injection of sodium penicillin on arterial blood pressure in isoflurane-anesthetized horses during surgery.
Veterinary anaesthesia and analgesia    January 6, 2025   S1467-2987(25)00001-7 doi: 10.1016/j.vaa.2025.01.001
Henderson ARP, Valverde A, Marchiori J, Tisotti T, Torrent A, Côté N, Gomez DE.To determine the effects of rapid (1 minute) and slow (10 minutes) intravenous (IV) injection of sodium penicillin on arterial blood pressure in anesthetized horses. Methods: Prospective randomized clinical trial. Methods: A group of 29 client-owned horses of various breeds, 1-20 years old, with body masses of 360-710 kg. Methods: General anesthesia was induced with a variety of anesthetic protocols and maintained with isoflurane under mechanical ventilation, with hourly doses of IV lidocaine and an infusion of dexmedetomidine. Horses were administered IV intraoperative penicillin every 2 hour...
Preparation of Molecularly Imprinted Electrochemical Sensors and Analysis of the Doping of Epinephrine in Equine Blood.
Sensors (Basel, Switzerland)    December 26, 2024   Volume 25, Issue 1 70 doi: 10.3390/s25010070
Wang Z, Li Y, Xi X, Zou Q, Zhang Y.In this paper, a novel molecularly imprinted polymer membrane modified glassy carbon electrode for electrochemical sensors (MIP-OH-MWCNTs-GCE) for epinephrine (EP) was successfully prepared by a gel-sol method using an optimized functional monomer oligosilsesquioxane-AlO sol-ITO composite sol (ITO-POSS-AlO). Hydroxylated multi-walled carbon nanotubes (OH-MWCNTs) were introduced during the modification of the electrodes, and the electrochemical behavior of EP on the molecularly imprinted electrochemical sensors was probed by the differential pulse velocity (DPV) method. The experimental conditi...
Analgesic efficacy of tapentadol in chronic joint disorders in horses: plasma serotonin concentration and adrenocortical response as biomarkers of pain-induced stress.
Frontiers in veterinary science    December 17, 2024   Volume 11 1505398 doi: 10.3389/fvets.2024.1505398
Costa GL, Tabbì M, Bruschetta G, Spadola F, Leonardi F, Bruno F, Iannelli NM, Licata P, Macrì F, Passino ES, Macrì D, Interlandi C.The study aimed to evaluate the analgesic efficacy of tapentadol in horses, by determining plasma serotonin concentration and adrenocortical response, as biomarkers of pain stress in chronic joint disorders. Thirty-six horses (20 females and 16 males) were divided into three groups of 12 subjects each: group A, osteoarthritis (OA), grade 3-4 lameness; group B, OA, grade 5 lameness; and group C, no OA, no lameness, were enrolled. The orthopedic examination included flexion tests, and radiological and ultrasound examinations. The degree of lameness has been estimated from 0 to 5 according to the...
Detection of Over 110 Anabolic-Androgenic Steroids, Corticosteroids and/or Their Esters in Horse Hair Using Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and Gas Chromatography-Tandem Mass Spectrometry After Solid-Supported Liquid Extraction.
Drug testing and analysis    December 10, 2024   doi: 10.1002/dta.3837
So YM, Kwok WH, Ching CCW, Wong COL, Wan TSM, Ho ENM.Anabolic-androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their duration of action. As such, the detection of intact esters of endogenous steroids in hair is particularly advantageous, as it can provide unequivocal proof of their external origin. Compared with urine and blood matrices, hair in general allows a longer detection window as long as the administered drug can be incorporated into hair and has not degraded. This can be useful in doping control of equi...
Role of cannabidiolic acid or the combination of cannabigerol/cannabidiol in pain modulation and welfare improvement in horses with chronic osteoarthritis.
Frontiers in veterinary science    December 10, 2024   Volume 11 1496473 doi: 10.3389/fvets.2024.1496473
Aragona F, Tabbì M, Gugliandolo E, Giannetto C, D'Angelo F, Fazio F, Interlandi C.Cannabidiol (CBD) is a non-psychotropic cannabinoid obtained from hemp (Cannabis sativa L.) used for pain management in companion animals including horses. The present study aimed to evaluate the efficacy of cannabidiolic acid (CBDA) and cannabigerol/cannabidiol oil (CBG/CBD) oral administration in alleviating pain in adult horses affected by chronic osteoarthritis (OA). Twenty-four horses (10 geldings and 14 mares), aged between 11 and 18 years old, were equally divided into two groups. One group received CBDA 15% oil and the other group received CBG/CBD oil (CBG20%-CBD10%) for 14 consecuti...
Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat.
Pulmonary pharmacology & therapeutics    December 5, 2024   Volume 88 102342 doi: 10.1016/j.pupt.2024.102342
Equine asthma, a prevalent chronic inflammatory condition affecting the equine population, significantly compromises the performance and quality of life in affected horses. Inhaled corticosteroids (ICS) are often the first-line pharmacological intervention due to their potent anti-inflammatory properties. This meta-analysis investigates the clinical efficacy of ICS in treating equine asthma, emphasizing the number needed to treat (NNT) and the likelihood of achieving a clinical response. A comprehensive literature search identified relevant studies comparing ICS with placebo (PCB) controlled t...
Pergolide mesylate administration does not decrease blood thyroid hormone concentrations and thyroid function in horses.
American journal of veterinary research    November 27, 2024   1-5 doi: 10.2460/ajvr.24.09.0257
Jargielo MM, Kritchevsky JE, Bertin FR.Pergolide, labeled for the treatment of pituitary pars intermedia dysfunction, is 90% protein bound and might cause a decrease in blood thyroid hormone concentrations by displacing them from binding proteins. This study investigated the effect of pergolide on the equine thyroid function. Methods: This was an analytic, observational, cohort study. Six horses (17 to 24 years old and 530 to 599 kg) received 1 mg of pergolide mesylate orally once a day from days 1 to 6. Total T4 (tT4) was measured daily from day 0 to 11 (before, during, and after pergolide treatment). Thyrotropin-releasing hormone...
The effect of intramuscular atipamezole on head height and sedation scores in detomidine-sedated horses.
Veterinary anaesthesia and analgesia    November 26, 2024   S1467-2987(24)00345-3 doi: 10.1016/j.vaa.2024.11.008
Mascarenhas C, Castro D, Lascola KM, Hofmeister E, Clark-Price SC.To assess the effect of two different doses of intramuscular atipamezole on head height (HH) in horses after sedation with detomidine. Methods: Randomized, blinded, triple crossover study. Methods: Eight healthy adult horses. Methods: Baseline HH was measured before detomidine (40 μg kg) was injected intravenously. HH was measured at 10 and 20 minutes after injection. Then, saline, atipamezole 60 μg kg (AT60) or 120 μg kg (AT120) was injected intramuscularly. HH measurements were repeated at 10 minutes intervals for 100 minutes. HH data were analyzed with a linear mixed model. Significance ...
Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation.
Journal of veterinary internal medicine    November 22, 2024   Volume 39, Issue 1 e17256 doi: 10.1111/jvim.17256
Kemp KL, Skinner JE, Bertin FR.Phenylbutazone is prescribed for laminitis-associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Objective: Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Methods: Sixteen horses, including 7 with ID. Methods: Randomized cross-over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10-day washout period, administration of the alternative trea...
Short-term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: A retrospective case series.
Domestic animal endocrinology    November 19, 2024   Volume 90 106894 doi: 10.1016/j.domaniend.2024.106894
Sundra T, Knowles E, Rendle D, Kelty E, Lester G, Rossi G.The metabolic and lipid profiles of horses treated with sodium-glucose cotransporter 2 inhibitors are not well understood. This retrospective study evaluated blood parameters in hyperinsulinemic horses treated with either ertugliflozin (0.05 mg/kg) or dapagliflozin (0.02 mg/kg) orally once daily. Blood samples were collected at baseline (day 0) and after 7 and/or 30 days of treatment. Statistical analyses were conducted using Wilcoxon signed-rank, Mann-Whitney and Spearman's rank correlation tests. Thirty-four horses received dapagliflozin and 24 received ertugliflozin. Significant (p<0.05)...
Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics.
Scientific reports    November 12, 2024   Volume 14, Issue 1 27684 doi: 10.1038/s41598-024-75734-1
Kwak YB, Seo SA, Kim M, Yoon J.Ethyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h a...
Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation.
Viruses    November 12, 2024   Volume 16, Issue 11 doi: 10.3390/v16111765
Li S, Li L, Sun Y, Khan MZ, Yu Y, Ruan L, Chen L, Zhao J, Jia J, Li Y, Wang C, Wang T.Equid herpesvirus type 8 (EqHV-8) is known to cause respiratory disease and miscarriage in horses and donkeys, which is a major problem for the equine farming industry. However, there are currently limited vaccines or drugs available to effectively treat EqHV-8 infection. Therefore, it is crucial to develop new antiviral approaches to prevent potential pandemics caused by EqHV-8. This study evaluates the antiviral and antioxidant effects of cepharanthine against EqHV-8 by employing both in vitro assays and in vivo mouse models to assess its therapeutic efficacy. To assess the effectiveness of ...
A broad-spectrum peptide screening method using an optimized solid-phase extraction and liquid chromatography-high-field asymmetric ion mobility spectrometry-mass spectrometry for doping control in equine urine.
Analytical methods : advancing methods and applications    November 6, 2024   doi: 10.1039/d4ay01477d
Ohnuma K, Hirano-Kodaira M, Bannai M, Shimizu Y, Yamada M, Kinoshita K, Ngai-Wa Leung G, Ishii H.The abuse of prohibited peptide-based drugs with a broad spectrum of chemical characteristics poses a significant concern for the horseracing industry. Recently, there has been a notable increase in positive cases of small-peptide drugs reported in equine and canine sports. In addition to small peptides, large peptides (over 2 kDa) with structural diversity have also entered the market in increasing numbers as drugs for humans and livestock. However, the simultaneous analysis of both small- and large-peptide-based drugs is still challenging. In this study, a screening method was developed to c...
Lidocaine’s Ineffectiveness in Mitigating Lipopolysaccharide-Induced Pain and Peristaltic Effects in Horses.
Animals : an open access journal from MDPI    November 2, 2024   Volume 14, Issue 21 3147 doi: 10.3390/ani14213147
Sousa LN, Winter IC, Varela DD, Luvison EZ, Guzmán JFC, Machado AMV, Figueiredo RDV, Pena GT, Dos Santos ACS, Faleiros RR, Carvalho AM.The present study involved seven horses in a randomized crossover clinical trial to evaluate the effect of lidocaine on horses with induced endotoxemia. Horses received intravenous lidocaine (1.5 mg/kg bolus, followed by 0.05 mg/kg bwt/min) or placebo (0.9% sodium chloride at the same manner) one hour before LPS administration (0.03 μg/kg, IV infusion over 30 min). We monitored clinic and hematologic parameters, abdominal auscultation, ultrasound, and pain over time. No relevant clinical differences existed between treatments regarding peristalsis, abdominal pain, or any other parameters befo...
Potential adverse effects of SGLT2i in horses.
The Veterinary record    November 1, 2024   Volume 195, Issue 6 253-254 doi: 10.1002/vetr.4726
McGorum BC, Keen JA, McCullagh S, Marr CM, MacKenzie C, Carslake H, Menzies-Gow N, Dunkel B, Hewetson M, Reed J, Knowles E.No abstract available
Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses.
Animals : an open access journal from MDPI    October 28, 2024   Volume 14, Issue 21 3102 doi: 10.3390/ani14213102
Mersich I, Bishop RC, Diaz Yucupicio S, Nobrega AD, Austin SM, Barger AM, Fick ME, Wilkins PA.Coagulopathy is common in equine critical illness, with its early recognition being crucial for patient management and prognosis. In vitro viscoelastic (VE) hypercoagulability with decreased RCM/PCV has been demonstrated in dogs but not horses. Our objective was to evaluate the effects of acepromazine-induced (0.1 mg/kg IV) decreased RCM on VE and plasma coagulation parameters using a prospective interventional study of eight adult horses. Complete blood count (CBC), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), packed cell volume (PCV), total solids (TS), and VCM Vetâ„...
Influence of acepromazine on the cardiovascular effects of dobutamine in isoflurane-anaesthetised horses premedicated with romifidine.
Veterinary anaesthesia and analgesia    October 24, 2024   S1467-2987(24)00334-9 doi: 10.1016/j.vaa.2024.10.141
Wong AM, Schier MF, Hosgood G, Drynan E, Raisis AL.To explore the influence of acepromazine on the cardiovascular effects of dobutamine in isoflurane-anaesthetised horses premedicated with romifidine. Methods: Prospective randomised clinical trial. Methods: A total of 18 horses undergoing elective arthroscopy were enrolled, of which 12 horses requiring dobutamine were included. Methods: Horses were randomised to receive acepromazine 0.02 mg kg (Group A+) intravenously (IV) or none (Group A-), 35 minutes before anaesthesia. Horses received xylazine 0.2 mg kg concurrently to facilitate IV access. Horses were premedicated with romifidine 0.08 mg ...
Effect of furosemide on comprehensive renin-angiotensin-aldosterone system activity of Thoroughbred horses.
Journal of veterinary internal medicine    October 22, 2024   doi: 10.1111/jvim.17208
Lehman ML, Domenig O, Ames MK, Morgan JM.Furosemide, a commonly used diuretic, activates the renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. Objective: To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses. Methods: 14 healthy adult thoroughbreds from a university teaching herd. Methods: Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Pro...
Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine.
Molecules (Basel, Switzerland)    October 22, 2024   Volume 29, Issue 21 4988 doi: 10.3390/molecules29214988
Elbourne M, Keledjian J, Cawley A, Fu S.Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities su...
Effect of short-term dopamine reduction on insulin sensitivity and post-prandial insulin and glucose responses in Standardbred horses.
Domestic animal endocrinology    October 20, 2024   Volume 90 106893 doi: 10.1016/j.domaniend.2024.106893
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-me...
Lipid and Corticosteroid Biomarkers Under the Influence of Bisphosphonates.
Drug testing and analysis    October 15, 2024   Volume 17, Issue 7 1107-1117 doi: 10.1002/dta.3811
Tou K, Cawley A, Noble G, Loy J, Bishop D, Keledjian J, Sornalingam K, Richards S, Fu S.Detecting the use of bisphosphonates (BPs) in equine athletes is of interest to regulators and laboratories due to the threat to welfare issues for the potential to provide analgesic effects and manipulating bone structure. The detection of BPs in biological matrices is challenging due to erratic biological elimination and inconsistent analytical recoveries. Therefore, complementary approaches are needed to provide evidence of their misuse in racehorses. BPs have two sub-classes: nitrogenous and non-nitrogenous. This study investigated plasma elimination following administration of one example...
Erratum for “Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation”.
Journal of veterinary internal medicine    October 7, 2024   Volume 38, Issue 6 3695 doi: 10.1111/jvim.17210
No abstract available
Rational quinidine dosage regimen for atrial fibrillation in Thoroughbred racehorses based on population pharmacokinetics.
Frontiers in veterinary science    October 7, 2024   Volume 11 1454342 doi: 10.3389/fvets.2024.1454342
Kuroda T, Minamijima Y, Kinman CK, Takahashi Y, Ebisuda Y, Inoue K, Ishikawa H, Mita H, Tamura N, Nukada T, Toutain PL, Ohta M.Quinidine (QND) sulfate is an effective treatment for atrial fibrillation (AF) in horses, and several dosage regimens have been proposed to address its wide variability in response and potential adverse effects. The purpose of this study was to analyze the variability in plasma quinidine concentrations using population pharmacokinetics to determine an effective and safe dosage regimen for Thoroughbred horses. Unassigned: Six healthy Thoroughbred horses were treated with 20 mg/kg quinidine sulfate dihydrate (16.58 mg/kg QND base) administered PO or 5 mg/kg quinidine hydrochloride monohydr...
Use of prototype bi-nasal prongs for noninvasive ventilation in foals.
Journal of veterinary internal medicine    October 7, 2024   Volume 38, Issue 6 3327-3336 doi: 10.1111/jvim.17170
Raidal SL, van Diggelen M, Catanchin CSM, Lehmann HS, Quinn CT.Noninvasive ventilation (NIV) provides effective respiratory support in foals, but face masks are poorly tolerated and associated with hypercapnia. Bi-nasal prongs might be a more effective device interface in foals. Objective: To compare bi-nasal prongs and masks for NIV in foals with pharmacologically induced respiratory insufficiency. Methods: Six healthy foals. Methods: In a randomized cross-over study, sedated foals received NIV delivered by mask or bi-nasal prongs, with the treatment repeated using the alternative device interface after a 3-day rest period. After periods of spontaneous v...
Antibiotics: Our part in their downfall.
Equine veterinary journal    October 4, 2024   Volume 56, Issue 6 1092-1095 doi: 10.1111/evj.14211
Bladon B.No abstract available