Abstract Background Specific studies on the epidemiology of necrotic enteritis in turkeys are absent in the literature. Necrotic enteritis is common in turkeys and a leading cause of use of therapeutic antibiotics. This study describes the incidence of necrotic enteritis in turkey farms, and the association between incidence and bird age, season, faecal oocyst counts, grow-out size and feed mill. Results Necrotic enteritis was diagnosed post mortem in 20.2 % of 545 grow-outs of commercial female and male B.U.T. 10 turkeys started during the years 2010–2016. 80 % of all cases occurred at four to seven weeks of age. Median (minimum-maximum) age at disease detection was 37 (18–115) days. Turkey age at detection was influenced by season, and varied from 33 days among grow-outs hatched in February to 42 days among those hatched in July-August. The incidence also varied with season, showing peak occurrence among grow-outs hatched during February-March and the lowest incidence in turkeys hatched in July-August. 59 % of all cases were detected in 25 % of the farms. The incidence per farm varied from below 4 to 59 %. A multilevel mixed-effects logistic regression model indicated clear impacts of farm and season on incidence, and border-line impacts of grow-out size and feed mill. Grow-outs diagnosed with necrotic enteritis had higher counts of faecal Eimeria oocysts than grow-outs without a diagnosis. This difference was particularly clear during the high-risk period at five to seven weeks of age. Necrotic enteritis was the cause of treatment with therapeutic antibiotics in 88.2 % of all cases of treatment. Conclusions Our data indicate that necrotic enteritis incidence in turkeys can be substantially influenced by risk factors at farm level. The incidence showed two seasonal peaks; a moderate peak in turkeys hatched in October/November and a marked peak in turkeys hatched during February/March. Mitigation measures at the farm may therefore be of particular importance during these months in farms located in the Northern temperate zone. Measures which effectively reduce counts of faecal Eimeria oocyst are likely to be among the more promising actions to take both at the farm and at population level.
Metomidate was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously at a dose of 3 mg/kg bodyweight, as a bath treatment at a dose of 9 mg/L water for 5 min to study the disposition of metomidate, and as bath treatment (9 mg/L) for 10 min to study the absorption and effect of metomidate on respiration and balance/motor control. Additionally, turbot were given metomidate orally at a dose of 7 mg/kg. The studies were performed in seawater at a temperature of 10.3 +/- 0.4 degrees C (halibut) and 18.0 +/- 0.3 degrees C (turbot). Pharmacokinetic modeling of the data showed that metomidate had shorter elimination half-life and higher plasma concentrations in turbot compared with halibut, both species displaying a rapid uptake, distribution and excretion. Following intravenous administration, the volumes of distribution at steady state (Vd(ss)) were 0.21 L/kg (halibut) and 0.44 L/kg (turbot). Plasma clearances (Cl) were 0.099 L/h.kg in halibut and 0.26 L/h.kg in turbot and the elimination half-lives (t(1/2)lambdaz) were calculated to be 5.8 h and 2.2 h in halibut and turbot, respectively. Mean residence times (MRT) were 2.2 h in halibut and 1.7 h in turbot. Following oral administration, the t(1/2)lambdaz was 3.5 h in turbot. The maximum plasma concentration (Cmax) was 7.8 mg/L in turbot 1 h after administration. The oral bioavailability (F) was calculated to 100% in turbot. Following 5 min bath the maximum plasma concentrations (Cmax), which were observed immediately after end of the bath, were 9.5 mg/L and 13.3 mg/L in halibut and turbot, respectively. Metomidate rapidly immobilized the fish, with respiratory depression, reduced heart rate, and loss of balance/motor control within 1 min (mean). Recovery was slow, with resumed balance/motor control after 26.4 min. Opercular respiration movements were resumed more rapidly with a recorded mean of 1.7 min. Oral administration was demonstrated to be a way of immobilizing fish, for example in large aquariums, without exposing them to unwanted stress.
Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.
Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction. Purpose To examine ASCVD risk by composition of non-HDL-C. Methods Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022. Results The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups. Conclusions The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2
Knowledge of the pharmacokinetic properties of drugs to combat bacterial infections in the European eel ( Anguilla anguilla ) is limited. One antimicrobial agent likely to be effective is flumequine. The aim of this study was to investigate the pharmacokinetic properties of flumequine in European eels in fresh water. Flumequine was administered to eels ( Anguilla anguilla ) intravenously (i.v.) and orally (p.o.) at a dose of 10 mg/kg body weight, and as a bath treatment at a dose of 10 mg/L water for 2 h. The study was performed in fresh water with a temperature of 23±0.3 °C, pH 7.15. Identical experimental designs were used. Two additional bath treatments were also performed, one in which the pH in the water was lowered by approximately 1 unit to 6.07 (dose: 10 mg/L) and one at a dose of 40 mg/L for 2 h in a full‐scale treatment. Following i.v. administration, the volume of distribution at steady state was 3.4 L/kg. Total body clearance was 0.012 L/h per kg and the elimination half‐life ( t 1/2 λz ) was calculated to be 314 h. Mean residence time was 283 h. Following oral administration, the t 1/2 λz was 208 h. Maximal plasma concentration ( C max) was 9.3 mg/L, at 7 h after administration ( C max). The oral bioavailability ( F ) was calculated to be 85%. Following bath administration in 10 mg/L for 2 h, maximal plasma concentration was 2.1 mg/L, observed immediately after the end of the bath. The ‘bioavailability’ in eel following a 2‐h bath treatment was 19.8%. Reducing the pH in the bath to 6.07 produced a maximal plasma concentration of 5.5 mg/L, observed immediately after the end of the bath. The ‘bioavailability’ was increased to 41% by the lowering of the pH. A similar effect was observed in a full‐scale treatment (1 kg eels/L water). The CO2 produced by the eel lowered the pH and increased ‘bioavailability’ to 35%.
Abstract Background The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) trial has randomized 17,605 non-diabetic patients with a body mass index (BMI) ≥27 kg/m2 to treatment with semaglutide versus placebo. Follow-up will be terminated on March 31, 2023. In consecutive myocardial infarction (MI) patients representing daily clinical practice, the prevalence of SELECT-eligible patients and the incidence of the three-point major adverse cardiovascular events (MACE; MI, ischemic stroke, and cardiovascular death) are not known. Purpose To assess the prevalence of SELECT-eligibility and the incidence of 5-year MACE in SELECT-eligible patients in a contemporary semi-nationwide European MI cohort representing daily clinical practice. Methods We identified 34,385 patients with a first-time MI and followed the in- and exclusion criteria for the SELECT trial as outlined in the Figure. Concordant with the SELECT trial, follow-up started on day 60 and maximum follow-up time was 5 years. We estimated adjusted hazard ratios (aHR) for the SELECT-eligible cohort using patients with a BMI from 20 to <27 kg/m2 as reference group. Moreover, we stratified the SELECT-eligible cohort by BMI ≥27 to <33 kg/m2 and ≥33 kg/m2. Results As depicted in the Figure, 10,769 patients with a BMI ≥27 kg/m2 were eligible for SELECT (SELECT-eligible cohort), which corresponds to a prevalence of 31% in the entire 34,385 MI cohort. The normoweight reference group included 11,011 patients. At baseline, the median age was 64 years for the SELECT-eligible cohort and 68 years for the reference group. Stratification of the SELECT-eligible cohort showed median age of 65 years for the BMI ≥27 to <33 kg/m2 and 63 years for the BMI ≥33 kg/m2 subgroups. The cumulative 5-year incidence of MACE was 10.7% for SELECT-eligible and 13.2% for reference patients (aHR 0.96, 95% CI 0.88-1.04). When stratifying the SELECT-eligible cohort, those with BMI ≥27 to <33 and ≥33 kg/m2 had cumulative 5-year incidence of 10.9% (aHR 0.95, 95% CI 0.87-1.04) and 9.9% (aHR 0.99, 95% CI 0.84-1.16). Conclusions In a large contemporary semi-nationwide cohort of consecutive MI patients, approximately 3 out of 10 were eligible for the SELECT trial and the estimated 5-year MACE incidence in SELECT-eligible patients was just above 10%. SELECT-eligible patients experienced the index MI up to 7 years earlier than the reference group. However, the 5-year incidence of MACE did not suggest that overweight/obese patients fulfilling SELECT eligibility criteria were associated with an excess MACE risk when compared to a normoweight reference group.
