Systemic therapy timing and use in patients with advanced melanoma at the end of life: A retrospective cohort study.

Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017-June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision-making.

A novel concept for the control of Aujeszky's disease: experiences in two vaccinated pig herds.

A study was conducted to examine the usefulness of a glycoprotein I (gI)-ELISA to monitor Aujeszky's disease virus infection in two vaccinated pig herds; the gI-ELISA can differentiate between pigs infected with Aujeszky's disease virus and pigs vaccinated against Aujeszky's disease with gI-negative vaccines. The two herds had been vaccinated with gI-negative vaccines for several years. The first survey, in September 1986, revealed that approximately 10 per cent of the breeding pigs in a large multiplier herd were seropositive for antibodies to gI of Aujeszky's disease virus, and it was decided to try to eliminate the virus from the herd by gI-ELISA testing and culling of gI-seropositive pigs. A one month quarantine period for incoming stock was established, and only gI-seronegative pigs were admitted to the herd. After two rounds of testing and culling the herd appeared to be free of wild-type Aujeszky's disease virus, and neither Aujeszky's disease virus nor antibodies could be detected either in 21 sentinel pigs placed on the farm or in 347 stillborn piglets or piglets that died shortly after birth. The herd probably remained free of Aujeszky's disease virus until the end of the 27-month period of monitoring except for two of 639 breeding pigs that were unexpectedly found to be positive in the gI-ELISA in November 1987. These sows were culled. A second breeding herd was monitored for antibodies to gI of Aujeszky's disease virus for two years. The gI-seropositive sows constituted approximately 30 per cent of the herd's breeding pigs, but they were not culled.(ABSTRACT TRUNCATED AT 250 WORDS)

A longitudinal study of starvation in piglets and the introduction of a modified liver biopsy technique.

The effect of starvation on blood glucose, muscle glycogen and liver glycogen concentration was measured in a group of newborn piglets. Liver biopsies were obtained by using a modified version of the Menghini technique. No difference in length of survival time was observed between piglets that received water and those that did not. Piglets with higher birth weight survived longer. No relationship was found between initial liver glycogen content and survival time. Moreover, we concluded that plasma glucose levels are not reliable indicators of length of survival time. The interrelated changes in liver glycogen, muscle glycogen, and plasmaglucose concentrations found in this study correspond with those reported elsewhere. Moreover, the number of experimental animals needed for the study was markedly reduced. We conclude that the liver biopsy technique is valuable in longitudinal hypoglycaemia studies of piglets.

Comparison of blood glucose concentrations measured by enzymatic and reflectance photometric methods in fasting piglets.

During a metabolic study of 22 fasting newborn piglets, blood glucose concentrations were measured by enzymatic and reflectance photometric methods. Use of the reflectance photometer is an accurate method of determining blood glucose levels even in hypoglycaemic range. In addition, the minimal quantity of blood needed for measurement allows the use of the same newborn piglets in longitudinal studies in which samples must be taken frequently.

Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows.

Following intravenous administration of an oxytetracycline-HC1 and an oxytetracycline-dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three-compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration. The recovery of OTC in the urine in the 72-h period was in the range of 73% to 96% of the available dose administered. The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.

Comparative pharmacokinetics and bioavailability of eight parenteral oxytetracycline-10% formulations in dairy cows.

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%-formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4.1 micrograms/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 micrograms/ml, were achieved 12 to 24 h p.i. The OTC milk concentration-time profile ran parallel to the OTC plasma concentration-time profile. After intravenous administration the time for the appearance of OTC in milk was shorter (1-2 hours p.i.), the peak milk OTC concentration was higher (1.7-1.9 micrograms/ml) and achieved earlier (6-8 h p.i.), and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability. The plasma and milk protein binding for OTC was respectively 71.7 +/- 7.4% and 84.8 +/- 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.