Efficacy of carprofen on conception rates in lactating dairy cows after subcutaneous or intrauterine administration at the time of breeding

Manipulation of the reproductive tract can cause inflammatory processes in the endometrium and release of cytokines and prostaglandins. It has been shown that PGF2α has direct negative effects on embryonic survival and development. Treatment with nonsteroidal antiinflammatory drugs (e.g., ibuprofen lysinate, flunixin meglumine) might improve pregnancy rates after embryo transfer in recipient heifers. The primary objective of this study was to evaluate the effect of a nonsteroidal antiinflammatory drug on reproductive performance in lactating dairy cows when administered at the time of first-service artificial insemination (AI) based on the hypothesis that uterine manipulation during AI might be similarly intense compared with embryo transfer in its effect on prostaglandin release. A total of 970 cows (333 primiparous and 637 multiparous) from 17 Holstein dairy farms were enrolled. On the day of first AI, cows were randomly allocated to 1 of 3 treatment groups. Cows of group 1 received 1.4 mg/kg of body weight (BW) of carprofen subcutaneously immediately after AI (SC group). In group 2, 1.4 mg/kg of BW of carprofen was administered into the uterus using a sterile disposable catheter 12 to 24 h after AI (IU group). Animals of group 3 remained as untreated controls. First AI conception rate was similar for the SC group (42.2%) compared with the untreated control group (45.1%). A binary logistic regression model for the odds of conception at first AI revealed a negative effect of an intrauterine administration of carprofen on conception rate (38.3%). Cows allocated to the IU group had a lower likelihood of being pregnant within 200 d in milk than cows in the control group. In summary, subcutaneous treatment with the nonsteroidal antiinflammatory drug carprofen at the time of AI did not influence conception rate, whereas an intrauterine administration of carprofen 12 to 24 h after first AI had a negative effect on first-service conception rate in lactating dairy cows

Glucose concentration in capillary blood of dairy cows obtained by a minimally invasive lancet technique and determined with three different hand-held devices

Background Dairy cows have a massive demand for glucose at the onset of lactation. A poor adaption to this period leads to an excessive negative energy balance with an increased risk for ketosis and impaired animal health and production. Besides the measurement of ketones, analysing the glucose concentration in blood is reported as helpful instrument for diagnosis and differentiation of ketosis. Monitoring metabolic parameters requires multiple blood sampling. In other species, new blood sampling techniques have been introduced in which small amounts of blood are rapidly analysed using electronic hand-held devices. The objective of this study was to evaluate the suitability of capillary blood for blood glucose measurement in dairy cows using the hand-held devices FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini) and the WellionVet GLUCO CALEA, (WGC, MED TRUST). In total, 240 capillary blood samples were obtained from dry and fresh lactating Holstein-Friesian cows. Blood was collected from the skin of the exterior vulva by using a lancet. For method comparison, additional blood samples were taken from a coccygeal vessel and analyzed in a laboratory. Glucose concentrations measured by a standard laboratory method were defined as the criterion standard. Results The Pearson correlation coefficients between the glucose concentrations analyzed in capillary blood with the devices and the reference were 73 % for the FSP, 81 % for the GLX and 41 % for the WGC. Bland- Altman plots showed biases of −18.8 mg/dL for the FSP, -11.2 mg/dL for the GLX and +20.82 mg/dL for the WGC. The optimized threshold determined by a Receiver Operating Characteristics analysis to detect hyperglycemia using the FSP was 43 mg/dL with a sensitivity (Se) and specificity (Sp) of 76 and 80 %. Using the GLX and WGC optimized thresholds were 49 mg/dL (Se = 92 %, Sp = 85 %) and 95 mg/dL (Se = 39 %, Sp = 92 %). Conclusions The results of this study demonstrate good performance characteristics for the GLX and moderate for the FSP to detect hyperglycemia in dairy cows using capillary blood. With the study settings, the WGC was not suitable for determination of glucose concentrations

Revisited: Therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics.

In order to assess the significance of drug/substance levels measured in intensive care medicine and clinical and forensic toxicology as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. We revisited and expanded our 2012 compilation of therapeutic and toxic plasma concentration ranges as well as half-lives of now more than 1100 drugs and other xenobiotics.Data have been abstracted from original papers, text books, and previous compilations and have been completed with data collected in our own forensic and clinical toxicology laboratories. We compiled the data presented in the table and the corresponding annotations over the past 30+ years. A previous compilation was completely double-checked, revised, and updated, if necessary. In addition, more than 200 substances, especially drugs who have been introduced since 2012 to the market as well as illegal drugs and other xenobiotics which became known to cause intoxications were added. We carefully referenced all data. Moreover, the annotations providing details were updated and revised, when necessary.For more than 1100 drugs and other xenobiotics, therapeutic ("normal") and, if data was available, toxic, and comatose-fatal plasma/blood concentrations as well as elimination half-lives were compiled in a table.In case of intoxications, the blood concentration of the substance and/or metabolite better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications as well as to support forensic and clinical expert opinions

Evaluation of sensor-based health monitoring in dairy cows: Exploiting rumination times for health alerts around parturition

The use of sensor-based measures of rumination time as a parameter for early disease detection has received a lot of attention in scientific research. This study aimed to assess the accuracy of health alerts triggered by a sensor-based accelerometer system within 2 different management strategies on a commercial dairy farm. Multiparous Holstein cows were enrolled during the dry-off period and randomly allocated to conventional (CON) or sensor-based (SEN) management groups at calving. All cows were monitored for disorders for a minimum of 10 DIM following standardized operating procedures (SOP). The CON group (n = 199) followed an established monitoring protocol on the farm. The health alerts of this group were not available during the study but were later included in the analysis. The SEN group (n = 197) was only investigated when the sensor system triggered a health alert, and a more intensive monitoring approach was implemented according to the SOP. To analyze the efficiency of the health alerts in detecting disorders, the sensitivity (SE) and specificity (SP) of health alerts were determined for the CON group. In addition, all cows were divided into 3 subgroups based on their health status and the status of the health alerts in order to retrospectively compare the course of rumination time. Most health alerts (87%, n = 217) occurred on DIM 1. For the confirmation of diagnoses, health alerts showed SE and SP levels of 71% and 47% for CON cows. In SEN cows, SE of 71% and 75% and SP of 48% and 43% were found for the detection of ketosis and hypocalcemia, respectively. The rumination time of the subgroups was affected by DIM and the interaction between DIM and the status of health alert and health condition

Helium poisoning: new procedure for sampling and analysis.

An increasing number of suicidal asphyxiation with a plastic bag with inert gases, and in particular helium (He), have been reported from numerous countries over the last decade. These cases are differently managed and lead to different and variable interpretations. Based on the 12 last cases analysed in the laboratory and on the review of the most recent literature about this topic, updated autopsy guidelines for sampling have been proposed regarding to the samples choice and analytical challenges required by the gaseous state of this substance. Biological samples from airways (lungs lobe) followed by brain and cardiac blood are the best matrices to take during the autopsy to diagnose He exposure. Gaseous samples from trachea, pulmonary bronchi, gastric and cardiac areas are also recommended as alternative samples. The anatomical site of sampling must be carefully detailed, and to this end, forensic imaging constitutes a beneficial tool. Even if He detection is sufficient to conclude to He exposure, He concentrations in samples may be related to He exposure conditions (duration, breathing rate, etc.). A quantification in biological samples could be helpful to document more precisely the case. He concentrations in gaseous samples are reported up to 6.0 μmol/mL (tracheal gas), 2.4 μmol/mL (pulmonary gas), 0.64 μmol/mL (cardiac gas) and 12 μmol/mL (gastric gas). He concentrations in solid/liquid samples are reported up to 28 μmol/g (lungs) and 0.03 μmol/g (cardiac blood). The other matrices usually sampled during autopsy such as urine, peripheral blood, liver, fat matter and kidney appear as not relevant

Treatment Regimens with Ranibizumab in Neovascular Age-Related Macular Degeneration: Real-World Results from the PACIFIC Study Author List

Katrin Lorenz,1 Christos Haritoglou,2 Daniel Barthelmes,3 Armin Mir Mohi Sefat,4 Hüsnü Berk,5 Erik Beeke,6 Martin Scheffler,7 Matthias Iwersen,8 Bettina Müller,8 Focke Ziemssen9,10 On behalf of members of the PACIFIC study group1Augenklinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Germany; 2Herzog Carl Theodor Eye Hospital, Munich, Germany; 3Augenklinik, Universitäts Spital Zürich, Zurich, Switzerland; 4Klinik für Augenheilkunde, Universitätsklinikum Schleswig-Holstein, Campus Luebeck, Luebeck, Germany; 5Klinik für Augenheilkunde, St. Elisabeth-Krankenhaus GmbH, Cologne, Germany; 6Augenzentrum Osnabrueck, Osnabrueck, Germany; 7Augenheilkunde Rhauderfehn, Rhauderfehn, Germany; 8Novartis Pharma GmbH, Nuremberg, Germany; 9Klinik und Poliklinik fuer Augenheilkunde, Universitätsklinikum Leipzig, Leipzig, Germany; 10Department Fuer Augenheilkunde, Eberhard-Karls-Universität Tuebingen, Tuebingen, GermanyCorrespondence: Katrin Lorenz, Augenklinik und Poliklinik, Universitätsmedizin Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Email [email protected]: Intravitreal anti-VEGF is the gold standard for treating neovascular age-related macular degeneration (nAMD). The treatment success depends not only on drug efficacy but also on regimen feasibility for physicians and patients. The implementation of different regimen might lead to varying outcomes. “Treat-and-extend” aims to minimize undertreatment with injections at each visit and tailored intervals. This study investigates the utilization and effectiveness of ranibizumab in nAMD, focusing on different treatment regimens in real-world settings.Materials and Methods: The PACIFIC study, a non-interventional, prospective, multicenter study, included nAMD patients treated with ranibizumab at 185 sites across Germany, the Netherlands and Switzerland. Over 24 months, functional and morphological outcomes were documented for 3051 patients over 24 months, highlighting the practiced treatment regimens.Results: A pattern of an observational approach with nevertheless increasing interval extension prevailed (70.4%, 1028 pre-treated; 68.6%, 1090 treatment-naïve patients), emerging as the preferred strategy within the first 3 months. Across all regimens, the average number of injections was comparable (mean ± SD: 7.34 ±  5.30 in pre-treated; 7.26 ±  4.70 in treatment-naïve patients). The treat and extend regimen, however, demonstrated superior effectiveness in improving visual acuity, particularly among treatment-naïve patients (number of injections: 7.89 ±  5.54 pre-treated; 9.54 ±  5.42 treatment-naïve patients).Conclusion: Over 2-year observational period, the treat and extend regimen emerged as a highly effective approach, particularly for those newly diagnosed, with a low risk of undertreatment. Despite its benefits, an unconscious shift to a observe-and-extend or “monitor-and-extend” approach occurred early in treatment, highlighting the need for tailored approaches to optimize patient outcomes in clinical practice.Keywords: anti-VEGF, visual acuity, treatment regimen, functional outcome, real-world result

Identification and characterization of dairy cows with different backfat thickness antepartum in relation to postpartum loss of backfat thickness: a cluster analytic approach

The objectives of this study were (1) to characterize the interindividual variation in the relationship between antepartum (ap) backfat thickness (BFT) and subsequent BFT loss during early lactation in a large dairy herd using cluster analysis; (2) to compare the serum concentrations of metabolites (nonesterified fatty acids, β-hydroxybutyrate), metabolic hormones (leptin and adiponectin), and an inflammatory marker (haptoglobin) among the respective clusters; and (3) to compare lactation performance and uterine health status in the different clusters. An additional objective was (4) to investigate differences in these serum variables and in milk yield of overconditioned (OC) cows that differed in the extent of BFT loss. Using data from a large study of 1,709 multiparous Holstein cows, we first selected those animals from which serum samples and BFT results (mm) were available at d 25 (±10) ap and d 31 (±3 d) postpartum (pp). The remaining 713 cows (parity of 2 to 7) were then subjected to cluster analysis: different approaches based on the BFT of the cows were performed. K-means (unsupervised machine learning algorithm) clustering based on BFT-ap alone identified 5 clusters: lean (5–8 mm BFT, n = 50), normal (9–12 mm, n = 206), slightly fat (SF; 13–16 mm, n = 203), just fat (JF; 16–22 mm, n = 193), and very fat (VF; 23–43 mm, n = 61). Clustering by difference between BFT-ap and BFT-pp (ΔBFT) also revealed 5 clusters: extreme loss (17–23 mm ΔBFT, n = 16), moderate loss (9–15 mm, n = 119), little loss (4–8 mm, n = 326), no loss (0–3 mm, n = 203), and gain (−8 to −1 mm, n = 51). Based on the blood variables measured, our results confirm that cows with greater BFT losses had higher lipid mobilization and ketogenesis than cows with less BFT loss. The serum variables of cows that gained BFT did not differ from normal cows. Milk yield was affected by the BFT-ap cluster, but not by the ΔBFT cluster. Cows categorized as VF had lesser milk yield than other clusters. We further compared the OC cows that had little or no BFT loss (i.e., 2% of VF, 12% of JF, and 31% of SF, OC-no loss, n = 85) with the OC cows that lost BFT (OC-loss, n = 135). Both NEFA and BHB pp concentrations and milk yield were greater in OC-loss cows compared with the OC-no loss cows. The serum concentration of leptin ap was greater in OC-loss than in the OC-no loss cows. Overall, OC cows lost more BFT than normal or lean cows. However, those OC cows with a smaller loss of BFT produced less milk than OC cows with greater losses