Production and carcass traits of high dairy genetic merit Holstein, standard dairy genetic merit Friesian and Charolais × Holstein-Friesian male cattle

peer-reviewedThe increased proportion of Holstein genetic material in the dairy herd has consequences for beef production in Ireland. A total of 72 spring-born male calves (24 Holsteins (HO), 24 Friesian (FR) and 24 Charolais × Holstein-Friesians (CH)) were reared from calfhood to slaughter. Calves were artificially reared indoors and spent their first summer at pasture following which they were assigned, on a breed basis, to a factorial combination of two production systems (intensive 19-month bull beef and extensive 25-month steer beef) and two slaughter weights (560 and 650 kg). After slaughter the pistola hind quarter was separated into fat, bone and muscle. Live-weight gain, carcass gain, kill-out proportion, carcass conformation and carcass fat scores were 830, 811 and 859 (s.e. 14.9) g/day, 540, 533, 585 (s.e. 7.7) g/day, 526, 538 and 561 (s.e. 3.0) g/kg, 1.51, 2.18 and 2.96 (s.e. 0.085), and 3.40, 4.25 and 4.06 (s.e. 0.104) for HO, FR and CH, respectively. Corresponding values for pistola weight as a proportion of carcass weight, pistola muscle proportion and pistola fat proportion were 458, 459 and 461 (s.e. 2.6) g/kg, 657, 645 and 667 (s.e. 3.7) g/kg, and 132, 161 and 145 (s.e. 4.1) g/kg. Compared with the intensive system, animals on the extensive system had a lower (P < 0.001) daily live-weight gain, kill-out proportion and a lower muscle proportion in the pistola. Increasing slaughter weight increased (P < 0.001) carcass weight and carcass fat score and reduced the proportion of muscle in the pistola. Allometric regression coefficients for pistola weight on side weight, and total bone, muscle and fat weights on pistola weight were 0.898, 0.755, 0.900 and 1.910 respectively. It is concluded that HO grew at least as fast as FR but had a lower killout proportion. Carcass conformation and fat scores were greater for FR than for HO and muscle proportion in the pistola was lower and total fat proportion was higher. Compared with FR, CH had heavier carcasses, a higher kill-out proportion and less fat and more muscle in the pistola

Body and carcass measurements, carcass conformation and tissue distribution of high dairy genetic merit Holstein, standard dairy genetic merit Friesian and Charolais x Holstein-Friesian male cattle

peer-reviewedThe increased proportion of Holstein genes in the dairy herd may have undesirable consequences for beef production in Ireland. A total of 72 spring-born calves, (24 Holstein (HO), 24 Friesian (FR) and 24 Charolais X Holstein-Friesian (CH)) were reared from calfhood to slaughter. Calves were artificially reared indoors and spent their first summer at pasture following which they were assigned to a 3 breeds (HO, FR and CH) 2 production systems (intensive 19-month bull beef and extensive 25-month steer beef) 2 slaughter weights (560 and 650 kg) factorial experiment. Body measurements of all animals were recorded at the same time before the earliest slaughter date. After slaughter, carcasses were graded and measured and the pistola hind-quarter was separated into fat, bone and muscle. HO had significantly higher values for withers height, pelvic height and chest depth than FR, which in turn had higher values than CH. HO had a longer back and a narrower chest than either FR or CH, which were not significantly different. Carcass length and depth, pistola length, and leg length were 139.2, 134.4 and 132.0 (s.e. 0.81), 52.1, 51.3 and 47.7 (s.e. 0.38), 114.4, 109.0 and 107.0 (s.e. 0.65) and 76.7, 71.9 and 71.4 (s.e. 0.44) cm for HO, FR and CH, respectively. Breed differences in pistola tissue distribution between the joints were small and confined to the distal pelvic limb and ribs. There were relatively small breed differences in the distribution of pistola muscle weight between individual muscles. Body measurements were significantly greater for animals on the intensive system (bulls) than the extensive system (steers) in absolute terms, but the opposite was so when they were expressed relative to live weight. The only significant difference in relative carcass measurements between the production systems was for carcass depth, which was lower for the intensive compared with the extensive system. Increasing slaughter weight significantly increased all carcass measurements in absolute terms but reduced them relative to weight. It is concluded that there were large differences between the breed types in body and carcass measurements, and hence in carcass shape and compactness but differences in tissue distribution were small

Non-carcass parts and carcass composition of high dairy genetic merit Holstein, standard dairy genetic merit Friesian and Charolais × Holstein-Friesian steers

peer-reviewedThe increased use of Holstein genetic material in the dairy herd has consequences for beef production. A total of 24 spring-born calves comprising 8 Holsteins (HO), 8 Friesians (FR) and 8 Charolais × Holstein-Friesians (CH) were reared from calfhood to slaughter. At the end of the second grazing season they were assigned to a 3 (breeds; HO, FR and CH) × 2 (slaughter weights; 620 and 730 kg) factorial experiment and fin¬ished indoors. After slaughter carcasses were classified for conformation and fatness, all organs and non-carcass parts were weighed, and the right side of each carcass was dissected into fat, bone and muscle. Non-carcass parts, carcass weight, kill-out propor¬tion, carcass conformation score and m. longissimus area were 405, 398 and 368 (s.e. 8.31) g/kg empty body weight, 355, 344 and 383 (s.e. 9.4) kg, 509, 520 and 545 (s.e. 8.99) g/kg, 1.0, 2.0 and 3.1 (s.e. 0.16), 7616, 7096 and 9286 (s.e. 223.4) mm2 for HO, FR and CH, respectively. Corresponding proportions of carcass muscle and fat were 631, 614 and 656 (s.e. 8.4), and 165, 200 and 165 (s.e. 10.5) g/kg. Increasing slaughter weight increased the proportion of total non-carcass parts, carcass weight, carcass fat score and fat proportion, and reduced carcass muscle and bone proportions. It is concluded that differences in kill-out proportion between the two dairy breeds was primarily due to the lower proportion of gastrointestinal tract (GIT) in FR, and the higher kill-out proportion of CH was mainly due to lower proportions of GIT, internal organs and internal fat. In terms of beef production, HO and FR were broadly comparable for most traits except carcass conformation score and carcass fat proportion, which were lower for HO. CH was superior to the dairy breeds in all important production traits

Thrombocytopenia with tedizolid and linezolid

Objective: Though thrombocytopenia is a known adverse effect with linezolid, the first-in class oxazolidinone antibiotic, some have suggested a lower risk of thrombocytopenia with tedizolid, the second-in-class oxazolidinone antibiotic. We sought to evaluate adverse event reports for thrombocytopenia with tedizolid and linezolid from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: To assess the period since tedizolid approval, we included initial FAERS reports from July 2014 through December 2016. To evaluate historical rates with linezolid prior to tedizolid approval, we assessed AERSMine data from January 2004 through June 2014. Reporting odds ratios (ROR) and proportional reporting ratios (PRR) were calculated. Results: Of all the reported events, 0.074% (n=1,468) were thrombocytopenia. Linezolid represented 0.02% (n=408) of all events, and tedizolid represented 0.002% (n=41). The ROR for thrombocytopenia with linezolid was 37.9 (95% confidence interval [CI] 20.78-69.17) and with tedizolid was 34.0 (95% CI 4.67- 247.30). The PRR for thrombocytopenia with linezolid was 36.9 (95% CI 20.56-66.28) and with tedizolid was 33.2 (95% CI 4.79- 230.10). From 2004 through June 2014, the linezolid ROR was 12.1 (95% CI 11.19-12.96) and PRR was 11.1 (95% CI 10.38-11.87). Conclusion: We observed a significantly increased risk of thrombocytopenia of similar magnitude with both linezolid and tedizolid. Thrombocytopenia with tedizolid should be assessed with real-world comparative safety studies as more patients are treated with tedizolid

The Art and Science of Drug Titration

A “one-size-fits-all” approach has been the standard for drug dosing, in particular for agents with a wide therapeutic index. The scientific principles of drug titration, most commonly used for medications with a narrow therapeutic index, are to give the patient adequate and effective treatment, at the lowest dose possible, with the aim of minimizing unnecessary medication use and side effects. The art of drug titration involves the interplay of scientific drug titration principles with the clinical expertise of the healthcare provider, and an individualized, patient-centered partnership between the provider and the patient to review the delicate balance of perceived benefits and risks from both perspectives. Drug titration may occur as up-, down-, or cross-titration depending on whether the goal is to reach or maintain a therapeutic outcome, decrease the risk of adverse effects, or prevent withdrawal/discontinuation syndromes or recurrence of disease. Drug titration introduces additional complexities surrounding the conduct of clinical trials and real-world studies, confounding our understanding of the true effect of medications. In clinical practice, wide variations in titration schedules may exist due to a lack of evidence and consensus on titration approaches that achieve an optimal benefit-harm profile. Further, drug titration may be challenging for patients to follow, resulting in suboptimal adherence and may require increased healthcare-related visits and coordination of care amongst providers. Despite the challenges associated with drug titration, it is a personalized approach to drug dosing that blends science with art, and with supportive real-world outcomes-based evidence, can be effective for optimizing pharmacotherapeutic outcomes and improving drug safety

Colistin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis reactions: a retrospective case-non-case pharmacovigilance study

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin reactions. Colistin is a last resort antibiotic with a historically poor safety profile. The association between colistin and SJS/TEN has not been previously quantified. Research design and methods: We identified colistin and SJS/TEN adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and calculated effect estimates using OpenEpi. Results: From January 2013 through March 2021, 964 adverse events were reported for colistin. Colistin was listed as a secondary suspect drug in 13 SJS/TEN adverse event reports (1.3%), with a reporting odds ratio of 29.6 (95% confidence interval [CI] 17.1–51.1), and proportional reporting ratio of 29.2 (95% CI 17.0–50.2). Limitations of any FAERS study include the voluntary nature of reporting, unclear causal relationship between drug and adverse reaction, underreporting, and wide confidence intervals for rare adverse events like SJS/TEN. Conclusions: Colistin was not the primary suspect drug in any SJS/TEN adverse event reports. We did identify a statistically significant safety signal for SJS/TEN with colistin as a secondary suspect drug. SJS/TEN is not currently included in the colistin product label. This association should be further explored in other pharmacoepidemiologic drug safety studies

470. Concomitant Antibiotic Use and Death Among a National Cohort of Veterans With Clostridium difficile Infection (CDI)

Background: Antibiotic use is a well-known risk factor for development of CDI, and there is preliminary evidence suggesting concomitant antibiotic use may result in poor outcomes, including death. This work investigated the effect of concomitant antibiotic exposure during CDI treatment on mortality among patients with CDI. Methods: We conducted a national retrospective study of Veterans with a first CDI between 2010 and 2014, defined as a positive C. difficile toxin(s) and no episode in the year prior. Those treated with guideline recommended CDI treatment were included (10–14 days of PO or IV metronidazole, PO or PR vancomycin, or fidaxomicin). The exposure of interest was any non-CDI antibiotic use during CDI treatment; and the outcome was all cause death within 30 days of the end of CDI treatment. Inverse probability of treatment weighted Cox proportional hazards models were used to estimate the effect of concomitant antibiotic use on time to mortality. Weights were derived from propensity score modeling of the probability of exposure to antibiotics during CDI treatment as a function of potential confounders. Sensitivity analyses by antibiotic class were conducted. Results: Of the 9,517 patients included in the study cohort, mean age was 65.3 years (±SD 14.6), 92.5% (n = 8,802) were male, and 75.03% (n = 7,141) were white. Half were exposed to non-CDI antibiotics during CDI treatment (51.8%, n = 4,925) and 8.9% (n = 849) died. In unadjusted and adjusted analyses, concomitant antibiotic use was associated with death (HR 5.74, 95% CI 4.75–6.93; aHR 2.39, 95% CI 2.07–2.75). Advanced generation cephalosporin (aHR 2.36, 95% CI 2.05–2.71), β-lactam/β-lactamase inhibitor combinations (aHR 1.45, 95% CI 1.16–1.82), and clindamycin (aHR 1.95, 95% CI 1.26–3.02) were associated with death, while fluoroquinolone use was not (aHR 0.97, 95% CI 0.84–1.12) Conclusion: Among our national cohort, concomitant antibiotic use was common during CDI treatment. Any concomitant antibiotic use increased the risk of death; however, results suggest risk might vary by antibiotic class. Results support continued efforts in the reduction of unnecessary antibiotic use during CDI treatment, and future studies into which antibiotics may have the least risk of death when treatment is necessary