Pharmacokinetics/pharmacodynamics cut-off determination for fosfomycin using Monte Carlo simulation in healthy horses.

Fosfomycin (FOM) is an approved veterinary medicinal product for large animals in Japan, but Clinical breakpoint (CBP) for antimicrobial susceptibility test (AST) is not defined for animals. This study aimed at conducting a pharmacokinetics/pharmacodynamics (PK/PD) analysis to determine the PK/PD cutoff for the CBP in horses. Drug concentrations following single intravenous administration (IV) of 20 mg/kg body weight (BW) FOM in nine horses were measured using liquid chromatography/mass spectrometry. The data were modelled using a nonlinear mixed-effects model, followed by Monte Carlo simulations. A 90% probability of target attainment for a PK/PD target of the ratio of Area Under the free plasma concentration-time curve divided by the minimal inhibitory concentration (MIC) >24 hr was set as PK/PD cut-off. The PK/PD cutoff for FOM 20 mg/kg BW q12 hr IV was estimated with the MIC value of ≤16.0 mg/L, and this regimen was considered effective against E. coli (MIC90; 16.0 mg/L) in healthy horses based on the MIC90 values of the wild population. Owing to the relevance of FOM to human health, veterinarians should use q 12 hr FOM 20 mg /kg against E. coli infections with an MIC <16 µg/mL, as suggested by our PK/PD cutoff after AST.

Reinstrumentation for progressive hyper-kyphotic deformity after implant removal despite obtaining physiological alignment by posterior corrective surgery for adolescent idiopathic scoliosis with flat back: a case report.

This case report describes a 13-year-old female patient with adolescent idiopathic scoliosis (AIS) and flat back who experienced progressive kyphotic deformity after implant removal despite obtaining physiological alignment postoperatively. The patient underwent multiple surgeries, and a late-developing infection complicated her treatment course. Despite hard bracing to prevent kyphotic change, the kyphosis progressed to 74° within a year after implant removal, leading to a decrease in patient height and back pain. Revision surgery was eventually necessary. Possible factors for the kyphotic progression include injury to paraspinal back muscles due to multiple surgeries or insufficient bony fusion from late-developing infection. This case highlights the importance of thorough evaluation and follow-up for optimal patient outcomes after implant removal in AIS patients, particularly those with flat back.

Incidence of surgical site infection after internal fixation of the first phalangeal bone and the third metacarpal/metatarsal bone fractures in Thoroughbred racehorses.

Surgical site infection (SSI) is one of the major complications of equine fracture surgery. The purpose of this study was to investigate the incidence of and risk factors for SSI after internal fixation of the first phalangeal bone (P1) and the third metacarpal/metatarsal bone (MC3/MT3) fractures in Thoroughbred racehorses. Between 2011 and 2020, 451 cases underwent surgery with screws or a locking compression plate (LCP) for sagittal fractures of P1 or condylar fractures of MC3/MT3. Overall, 2.9% (13/451) of the cases developed an SSI. The incidence was significantly higher in plate fixation (21.4%) than in screw fixation (2.3%). There was no significant association with other variables, such as sex, age, number of screws, experience of surgeon, or prophylactic antimicrobials. The median duration of hospitalization for screw fixation was 14 days without an SSI and 20 days with an SSI, and those for plate fixation were 26 and 25-88 days, respectively, indicating that the development of SSI prolongs the duration of hospitalization. On the other hand, there were no significant differences in discharge and race resumption rates between cases with and without an SSI. These data indicate that the incidence of SSI in this study was low and that it was higher following plate fixation than screw fixation.

One-Year Outcome of Patients with Chest Pain in the Rule-Out Group According to the 0-Hour/1-Hour Algorithm.

The European Society of Cardiology recommends the 0/1-hour algorithm for risk stratification of patients with suspected non-ST-elevation myocardial infarction as class I, level B; however, there are few reports on the long-term prognosis, resulting in a rule-out group. We aimed to determine whether implementation of the 0-hour/1-hour algorithm is safe and effective in emergency department (ED) patients with possible acute coronary syndrome (ACS) through a 1-year follow-up period. Our study analyzed the 1-year follow-up data from a prospective pre-post study of 1106 ED patients with possible ACS from 4 hospitals in Japan and Taiwan. Patients were 18 years or older. Accrual occurred for 1 year after implementing the 0-1-hour algorithm from November 2014 to December 2018. Overall, 520 patients were stratified into the rule-out group. Major advanced cardiovascular events (all-cause death, acute myocardial infarction [AMI], stroke, unstable angina, and revascularization) at 1-year were determined using data from health records and phone calls. The 0-1-hour algorithm stratified 47.0% of patients in the rule-out group. Over the 1-year follow-up period (follow-up rate = 86.9%), cardiovascular death and subsequent AMI did not occur in the rule-out group. Among the 27 patients who underwent the procedure within 30 days post-index visit, 3 patients (0.7%) had a stroke, 6 patients (1.3%) died of non-cardiovascular cause, and 30 patients (6.7%) underwent coronary revascularization within 1 year. At the 1-year follow-up, implementation of the 0-hour/1-hour algorithm was associated with very low rates of adverse event among patients in the rule-out group.

Preliminary study of heart rate variability in Criollo horses for the elucidation of their neurophysiological characteristics of autonomic nerve function.

The Criollo is an Argentine horse breed with a calm temperament. Although its temperament is considered to be related to its neurophysiological characteristics, the details of this are unknown. Therefore, we analyzed the heart rate variability in Criollos as a preliminary study to deepen the neurophysiological understanding of their autonomic function. Electrocardiograms were recorded from Criollos and Thoroughbreds, and the power spectrum of heart rate variability was analyzed. Compared with Thoroughbreds, Criollos showed (i) a significantly higher high-frequency component, which is an index of parasympathetic nerve activity, and (ii) tendency toward a lower ratio of low- to high-frequency power, which is an index of the autonomic balance. These results revealed that parasympathetic nerves might be more active in Criollos compared with Thoroughbreds.

Characteristic Inflammatory Biomarkers in an Equine Model of Persistent Synovitis Induced By the Intra-Articular Administration of Monoiodoacetic Acid.

Persistent synovitis damages the articular cartilage in horses. To evaluate the effectiveness of treatment for synovitis using a model induced by intra-articular administration of monoiodoacetic acid (MIA), it is necessary to identify inflammatory biomarkers characteristic of the MIA model. Synovitis was induced by administering MIA into the unilateral antebrachiocarpal joints of five horses, and saline was injected into the contralateral joints as a control on day 0. Clinical and ultrasonographic examinations and synovial fluid collection were performed on days 0, 1, 2, 7, 14, 21, 28, and 35. Leukocyte, lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and transforming growth factor-ß1 (TGF-ß1) concentrations in the synovial fluid were measured. Synovium was obtained after euthanasia on day 42 and histologically examined before quantification of the gene expression of inflammatory biomarkers by real-time PCR. Acute inflammatory symptoms persisted for approximately 2 weeks before returning to control levels. However, some indicators of chronic inflammation remained elevated until day 35. On day 42, synovitis continued histologically, with osteoclasts. The expressions of matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), receptor activator of nuclear factor kappa-Β ligand (RANKL), and collagen type I α2 chain (Col1a2) were significantly higher in the MIA model than in the control. In the MIA model, representative inflammatory biomarkers in the chronic inflammatory stage were persistently expressed in both synovial fluid and tissue, suggesting that they may be useful for the assessment of the anti-inflammatory effect of drugs.

Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations.

A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5 mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC-MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10 mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by Monte Carlo simulations to establish a rational dosage regimen. A 90% Probability of Target Attainment (PTA) for a PK/PD target of a free plasma concentration exceeding MIC90 (fT > MIC ) for 40% of the dosing interval was set for selecting an effective dosing regimen. The typical half-life of absorption and bioavailability after IM administration were 1.25 h and 96.8%, respectively. A CEZ dosage regimen of 5 mg/kg BW q12h IM administration achieved therapeutic concentrations to control both Streptococcus zooepidemicus and Staphylococcus aureus. For the same dose, the fT > MIC after IM administration was significantly longer than after IV administration, and the IM route should be favoured by clinicians for its efficiency and convenience.

Pharmacokinetic/pharmacodynamic analysis of cephalothin after intramuscular administration in Thoroughbred horses.

A pharmacokinetic/pharmacodynamic (PK/PD) approach was used to determine a dosage regimen of cephalothin (CET) after intramuscular (IM) administration in horses. CET plasma concentrations were measured in eight horses after a single IM administration of 11 mg/kg bwt of CET. The data were modeled using a nonlinear mixed-effect model, and the probability of target attainment (PTA) of the PK/PD target was calculated for 5,000 horses generated by Monte Carlo simulations. IM administrations of CET at 11 mg/kg bwt q 8 hr and q 6 hr achieved a PTA of 90% against the MIC90 of S. zooepidemicus and S. aureus, respectively, and were considered to be effective dosage regimens. The total dose for the IM administration recommended in this study was lower than that for intravenous (IV) administration in previous studies.

Temporary Monosegmental Fixation Using Multiaxial Percutaneous Pedicle Screws for Surgical Management of Bony Flexion-Distraction Injuries of the Thoracolumbar Spine: A Technical Note.

Introduction: The efficacy of minimally invasive surgeries for thoracolumbar flexion-distraction injuries (FDIs) has been reported, but those surgeries were monosegmental fusion surgeries of two adjacent vertebrae with bone grafts or temporary fixations using percutaneous pedicle screws (PPSs) that were at least bisegmental. Our idea was to fuse the fracture itself, not to fuse the fractured vertebra with an adjacent vertebra or to stabilize the fractured vertebra by bridging rostrally/caudally adjacent intact vertebrae, specifically when the displacement is minimal. This study aimed to present the surgical techniques of reduction and temporary monosegmental fixation of neurologically intact thoracolumbar bony FDIs using multiaxial PPSs, which can minimize the surgical invasiveness and preserve all motion segments, as well as report three cases treated with this procedure. Technical Note: When the fracture extended from the vertebral body to the spinous process at the same level, screws were placed into the fractured vertebra rostrally to the fracture along the rostral endplate, and the caudally adjacent vertebra was instrumented beyond the fracture line. When the fracture extended from the vertebral body to the spinous process of the rostrally adjacent vertebra, screws were placed into the fractured vertebra caudally to the fracture line, and the rostrally adjacent vertebra was instrumented. The kyphotic deformity was reduced through ligamentotaxis by using MPPSs in the rostral vertebra as rigid joysticks to apply direct buttress leverage to the rostral endplate. Intraoperative blood loss was minimal. The correction of kyphotic deformity and its durability were acceptable, and the segmental range of motion of the two affected vertebrae from flexion to extension was maintained after implant removal. Conclusions: This surgery can act as the least-invasive option for the management of thoracolumbar bony FDIs to allow early ambulation without external bracing and to preserve all the motion segments.

Concentration of cephalothin in body fluids and tissue samples of Thoroughbred horses.

Cephalothin (CET) concentrations in body fluids (plasma, synovial fluid, pleural fluid, peritoneal fluid, and aqueous humor) and tissue samples (bone, lung, jejunum, hoof, and subcutaneous tissue) were investigated to consider the treatment of infectious diseases in horses. CET 22 mg/kg body weight was intravenously administered to 12 horses. Samples were collected from four different horses at 1, 3, and 5 hr after administration. The CET concentration in body fluids other than aqueous humor was maintained above the MIC90 values of Streptococcus zooepidemicus and Staphylococcus aureus until 5 hr, but it was not maintained above that of S. aureus in bone. CET (22 mg/kg twice a day) is effective for septic arthritis, pleuritis, and peritonitis caused by gram-positive bacteria but ineffective for osteomyelitis.

Comparison of surgical outcomes of posterior surgeries between cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To compare the surgical outcomes and complications of posterior decompression between individuals with cervical spondylotic myelopathy (CSM) and those with ossification of the posterior longitudinal ligament (OPLL). SETTING: Seventeen medical institutions in Japan. METHODS: This study included 814 individuals with CSM (n = 636) and OPLL (n = 178) who underwent posterior decompression. Propensity score matching of the baseline characteristics was performed to compare surgical outcomes and perioperative complications between the CSM and OPLL groups. RESULTS: Before propensity score matching, the OPLL group had higher percentage of male individuals, body mass index, and number of stenosis levels and longer duration of symptoms (P < 0.01, P < 0.01, P < 0.01, and P < 0.01, respectively). After matching, the baseline characteristics were comparable between the CSM (n = 98) and OPLL (n = 98) groups. The postoperative Japanese Orthopaedic Association (JOA) scores, preoperative-to-postoperative changes in the JOA scores, and JOA score recovery rates were not significantly different between the groups (P = 0.42, P = 0.47, and P = 0.09, respectively). The postoperative visual analog scale (VAS) score for neck pain and preoperative-to-postoperative changes in the VAS score for neck pain were not significantly different between the groups (P = 0.25 and P = 0.50, respectively). The incidence of perioperative complications was comparable between groups. CONCLUSION: Neurological improvement and complication rates after surgery were comparable between individuals with CSM and those with OPLL, suggesting similar effectiveness and safety of posterior decompression for both conditions.

Incidence of carpal fractures and risk factors for recurrent fractures after arthroscopic removal of carpal chip fracture fragments in Thoroughbred racehorses.

BACKGROUND: We aimed to investigate the recent incidence of carpal fractures and the risk factors for recurrent ipsilateral fractures after arthroscopic removal of clinically active unilateral carpal chip fracture fragments in Thoroughbred racehorses. METHODS: The findings for horses managed under the Japan Racing Association that developed carpal bone fractures between 2014 and 2018 were retrospectively reviewed. The proportion of cases that developed a recurrent carpal fracture in the originally affected joint was calculated, and the risk factors for recurrent fractures were analysed. RESULTS: In total, 2858 carpal fractures were recorded in the study period (incidence, 0.8%). Of the 554 horses that resumed racing after the treatment of the unilateral major carpal chip fracture, 144 had a recurrent fracture (26.0%). Chip fractures of the third carpal bone (odds ratio [OR]: 3.7) or a combination of the distal end of the radius and intermediate carpal bone (OR: 3.0) were associated with a significantly higher risk of recurrent fractures than the distal aspect of the radial carpal bone. CONCLUSIONS: The incidence of carpal fractures remained similar to that reported in Japan in the 1990s. The rate of recurrent ipsilateral fractures differed among lesion sites.

Platelet Lysate Enhances Equine Skeletal Muscle Regeneration in A Bupivacaine-Induced Muscle Injury Model☆.

This study aimed to verify the effects of platelet lysate (PL) administration on the repair of injured horse tissue. Skeletal muscle injuries were induced in 26 Thoroughbreds by bupivacaine administration. PL or saline was administered 1 day (1D) after injury. Muscle samples from 22 horses injected with PL or saline were obtained by needle biopsy at 2, 3, 4, or 7 days (2D, 3D, 4D, or 7D, respectively) after injury, and growth-factor concentrations and muscle regeneration-associated gene expression levels were determined. Intact samples were similarly collected before injury, and samples of injured muscle not treated with PL or saline (sham samples) were also obtained at 1D, 2D, 3D, 4D, and 7D as references for comparison. Samples from the remaining 4 horses were obtained by surgical incision following euthanasia at 5 days (5D) and 7D after injury, followed by histological analysis. Although increased growth factor levels caused by PL administration were observed for up to 1-day post-administration (2D), gene expressions were enhanced for up to 6 days post-administration (7D). Moreover, the number of embryonic myosin heavy chain (MHC-e)-positive myofibrils at 5D was higher in the PL-treated group than in the saline-treated group, whereas no significant between-group difference in the number of myofibrils was recorded at 7D. Thus, PL administration in muscle injury upregulated the expression of various genes associated with muscle regeneration and promoted morphological regeneration within 6 days of treatment, although growth factor levels from PL decreased at the injected site by approximately 2 days post-administration.

Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations.

BACKGROUND: For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. OBJECTIVE: To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. STUDY DESIGN: Experimental study. METHODS: Drug plasma and urine concentrations following single intravenous administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 hours for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the international screening limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/mL, urine; 100 ng/mL). RESULTS: For a regimen of 1.1 mg/kg BW q 24 hours, the IPC and IUC values were 2.0 and 73.0 ng/mL respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 hours after a single 1.1 mg/kg dose administration, 149 and 199 hours after multiple doses over 5 days at either 24- or 12-hour intervals respectively. Corresponding detection times in urine were 46, 68 and 104 hours respectively. MAIN LIMITATION: Only female horses were investigated. CONCLUSIONS: Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.

Minimally invasive anteroposterior combined surgery using lateral lumbar interbody fusion without corpectomy for treatment of lumbar spinal canal stenosis associated with osteoporotic vertebral collapse.

OBJECTIVE: Various reconstructive surgical procedures have been described for lumbar spinal canal stenosis (LSCS) with osteoporotic vertebral collapse (OVC); however, the optimal surgery remains controversial. In this study, the authors aimed to report the clinical and radiographic outcomes of their novel, less invasive, short-segment anteroposterior combined surgery (APCS) that utilized oblique lateral interbody fusion (OLIF) and posterior fusion without corpectomy to achieve decompression and reconstruction of anterior support in patients with LSCS-OVC. METHODS: In this retrospective study, 20 patients with LSCS-OVC (mean age 79.6 years) underwent APCS and received follow-up for a mean of 38.6 months. All patients were unable to walk without support owing to severe low-back and leg pain. Cleft formations in the fractured vertebrae were identified on CT. APCS was performed on the basis of a novel classification of OVC into three types. In type A fractures with a collapsed rostral endplate, combined monosegment OLIF and posterior spinal fusion (PSF) were performed between the collapsed and rostral adjacent vertebrae. In type B fractures with a collapsed caudal endplate, combined monosegment OLIF and PSF were performed between the collapsed and caudal adjacent vertebrae. In type C fractures with severe collapse of both the rostral and caudal endplates, bisegment OLIF and PSF were performed between the rostral and caudal adjacent vertebrae, and pedicle screws were also inserted into the collapsed vertebra. Preoperative and postoperative clinical and radiographical status were reviewed. RESULTS: The mean number of fusion segments was 1.6. Walking ability improved in all patients, and the mean Japanese Orthopaedic Association score for recovery rate was 65.7%. At 1 year postoperatively, the mean preoperative Oswestry Disability Index of 65.6% had significantly improved to 21.1%. The mean local lordotic angle, which was -5.9° preoperatively, was corrected to 10.5° with surgery and was maintained at 7.7° at the final follow-up. The mean corrective angle was 16.4°, and the mean correction loss was 2.8°. CONCLUSIONS: The authors have proposed using minimally invasive, short-segment APCS with OLIF, tailored to the morphology of the collapsed vertebra, to treat LSCS-OVC. APCS achieves neural decompression, reconstruction of anterior support, and correction of local alignment.

Ultrasound-guided puncture reduces bleeding-associated complications, regardless of calcified plaque, after endovascular treatment of femoropopliteal lesions, especially using the antegrade procedure: A single-center study.

BACKGROUND: A common complication of endovascular treatment for femoropopliteal lesions is bleeding at the vascular access site. Although risk factors of bleeding-associated complications at the approach site have been reported, the results have been inconclusive. Hence, this study aimed to assess the predictors of bleeding-associated complications at the approach site in patients undergoing endovascular treatment for femoropopliteal lesions. METHODS: This retrospective, single-center, observational study included consecutive patients who underwent endovascular treatment (n = 366, 75% male, 72.4±9.9 year) for peripheral arterial disease with claudication and critical limb ischemia in our hospital from January 2010 to December 2017. We divided the patients into bleeding and non-bleeding groups, depending on whether bleeding-associated complications occurred at the approach site. Bleeding-associated complications were defined according to the Bleeding Academic Research Consortium criteria types 2, 3, and 5. RESULTS: Altogether, 366 endovascular treatment procedures and 404 arterial accesses were performed for femoropopliteal lesions in 335 peripheral arterial disease patients with claudication and 69 critical limb ischemia patients. We recorded 35 postprocedural bleeding-associated complications at the approach site (9%), all of which were hematomas. The predictors of increased bleeding-associated complications were age ≥ 80 years (bleeding vs. non-bleeding group, 43% vs. 25%, p<0.05) and antegrade cannulation of the common femoral artery (48% vs. 69%, p<0.05). Ultrasound-guided puncture reduced bleeding-associated complications (odds ratio, 0.28; 95% confidence interval, 0.004-0.21; p<0.05). In contrast, there was no significant difference in puncture site calcification between the groups (bleeding vs. non-bleeding groups, 29% vs. 21%, p = 0.29). CONCLUSION: Ultrasound-guided puncture is associated with a decrease in bleeding-associated complications at the approach site, regardless of the presence of calcified plaque. It is particularly effective and should be more actively used in patients aged ≥80 years and for antegrade cannulation of the common femoral artery.

Clinical Evaluation of a New High-Sensitivity Cardiac Troponin I Assay for Diagnosis and Risk Assessment of Patients with Suspected Acute Myocardial Infarction.

INTRODUCTION: Current assays based on the 0-hour/1-hour (0-/1-h) algorithm using high-sensitivity cardiac troponin (hs-cTn) are limited to only Abbott Architect hs-cTnI, Siemens Vista hs-cTnI, and Roche Elecsys hs-cTnT. OBJECTIVE: This study aimed to evaluate this new hs-cTnI assay, LumipulsePresto hs Troponin I, for diagnosis of acute myocardial infarction (AMI) on admission and on 0-/1-h algorithm to stratify AMI patients precisely. METHODS: This prospective cohort study included 442 patients with suspected non-ST-elevation myocardial infarction in three hospitals in Japan and Taiwan from June 2016 to January 2019. We enrolled patients presenting to the emergency department with symptoms suggestive of AMI and collected blood samples on admission and 1 hour later. Two independent cardiologists centrally adjudicated final diagnoses; all clinical information was reviewed twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) and Lumipulse Presto Lumipulse Presto, second, using the Lumipulse Presto hs-cTnI measurements. At first, we compared diagnostic accuracy quantified using receiver operating characteristic (ROC) curves for AMI. Then, we evaluated major adverse cardiovascular events (cardiac death, AMI) in the rule-out group according to a 0-hour/1-hour algorithm at the 30-day follow-up. RESULTS: Diagnostic accuracy at presentation by the ROC curve for AMI was very high and similar for the LumipulsePresto hs-cTnI and hs-cTnT,(area under the curve [AUC]: LumipulsePresto hs-cTnI, 0.89, 95% confidence interval [CI] 0.86-0.93; hs-cTnT, 0.89, 95% CI 0.85-0.93; p = 0.82). In early presenters, the LumipulsePresto hs-cTnI appeared to maintain the diagnostic performance of hs-cTn for patients with <3 h (AUC: LumipulsePresto hs-cTnI, 0.87, 95% CI 0.81-0.92; hs-cTnT, 0.86, 95% CI 0.80-0.92; p = 0.81). The algorithm using the LumipulsePresto hs-cTnI ruled out AMI in 200 patients with negative predictive value and sensitivity of 100% (95% CI 97.3%-100%) and 100% (95% CI 92.7%-100%), respectively, in the rule-out group. CONCLUSION: Diagnostic accuracy and clinical utility of the novel LumipulsePresto hs-cTnI assay are high and comparable with the established hs-cTn assays.

Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.

BACKGROUND: First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. OBJECTIVE: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. STUDY DESIGN: Experimental study with single administration. METHODS: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. RESULTS: The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. MAIN LIMITATIONS: Small sample size only in healthy horses. CONCLUSIONS: For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6-12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10-22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses.