Patient weight has diverse effects on the prescribing of different antibiotics to dogs.

Introduction: Various factors including body weight-associated treatment cost may influence the probability of dispensing antibiotics to dogs in first-opinion practice, but their effect on specific drug choice remains unclear. Methods: Multiple membership regression modeling was used to investigate the probability of dispensing 12 different antibiotics to dogs of different weights in the context of various disease presentations, using anonymized data obtained from electronic health records of 18 clinics between 2020 and 2022. Data from 14,259 dogs were analyzed. Results: Treatment choice varied significantly with animal weight. Higher body weight was associated with an increased likelihood of dispensing lower cost antimicrobials such as amoxicillin and trimethoprim sulfonamide, while use of higher cost antimicrobials such as cefovecin was strongly biased to smaller animals. However, these effects were limited when restricted treatment options were available for the target condition. Conclusion: This work demonstrates that anticipated financial costs may result in different treatment choices for canine patients depending on their body weight. Further work is needed to understand the impact of financial pressures on veterinarians' treatment choices, and the implications for the optimization of antimicrobial stewardship in first opinion practice.

Female behaviour plays a critical role in controlling murine pregnancy block.

Exposure of recently mated female rodents to unfamiliar male scents during daily prolactin surges results in pregnancy failure (the 'Bruce effect'). Control of nasal contact with male scents during these narrow windows of sensitivity could allow females to maintain or terminate pregnancy, but female behavioural changes specifically during this critical period have not been investigated. We examined the approach or avoidance of familiar stud strain and unfamiliar male scents by recently mated female mice. Females that maintained pregnancy avoided both unfamiliar and familiar male scent during critical periods of susceptibility for the Bruce effect. By contrast, females that did not maintain pregnancy showed a sharp rise in the time spent with unfamiliar male scent during this critical period. Manipulation of the social status of unfamiliar and stud strain scent donors did not affect the likelihood of pregnancy block, although females spent more time with dominant male scents across all time periods. The ability to control the Bruce effect through behaviour during brief sensitivity just before dusk, when females are likely to be in nest sites, provides a mechanism by which females may adjust their reproductive investment according to nest site social stability and likelihood of offspring survival.

Host range and genetic diversity of arenaviruses in rodents, United Kingdom.

During a study to extend our knowledge of the host range and genetic diversity of arenaviruses in Great Britain, 66 of 1,147 rodent blood samples tested for antibody, and 127 of 482 tested by PCR, were found positive. All sequences most closely resembled those of previously identified lymphocytic choriomeningitis virus.

Helical tomotherapy as a means of delivering accelerated partial breast irradiation.

A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during CT. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. "Hot spots" (> or =150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study.

BACKGROUND: Infliximab (IFX) is effective therapy for ulcerative colitis and Crohn's disease, but it may be associated with side effects and loss of response. One loss of response mechanism is increased IFX clearance (IFX-CL), resulting in short half-life and decreased troughs. METHODS: Patients were recruited, and relevant demographic, clinical, and laboratory data were recorded. IFX serum concentrations and antibodies against IFX (ATI) were measured for therapeutic drug monitoring and modeled using NONMEM. RESULTS: There were 169 IFX concentrations (Crohn's disease = 73, ulcerative colitis = 92, and diagnosis undetermined = 4). Patient factors significantly associated with high IFX-CL were low albumin, high body weight, and the presence of ATI (P ≤ 0.001). Disease type did not affect IFX-CL. The typical IFX-CL was 0.381 L/d. ATI formation was associated with a 259% increase in IFX-CL. The estimated median IFX effective half-life was 5.6 ± 2.4 days. Patients with low weight are more likely to have low troughs because IFX CL is not linearly related to weight, but IFX dosing is weight-based (in mg/kg). Simulations investigating alternative dose strategies suggested that more reliably measurable concentrations over the dose interval were achieved when the dose interval was shortened than by increasing administered dose. CONCLUSIONS: IFX-CL is significantly influenced by patient factors, specifically, albumin, body weight, and ATI. There should be a decreasing IFX dose interval strategy, particularly for low albumin patients. Higher starting doses may benefit low body weight patients. Pharmacokinetic models and therapeutic drug monitoring may ensure that patients maintain measurable concentrations throughout dose intervals. Individualized dosing may improve outcomes for IFX-treated patients with Crohn's disease and ulcerative colitis.

Murine monoclonal anti-tNF antibody administration has a beneficial effect on inflammatory bowel disease that develops in IL-10 knockout mice.

Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence for the pivotal role played by tumor necrosis factor-alpha (TNF-alpha). Recent work has shown an increased concentration of TNF-alpha in both the bowel wall and in the stools of patients with IBD, and in children with that disease there are increased serum levels. Coincidental studies have shown that IL-10 knockout mice have increased levels of TNF-alpha and are known to develop a syndrome of stunted growth, anemia, bloody diarrhea, and colon tumors that mimics IBD. By injecting monoclonal antibodies intraperitoneally into IL-10 knockout mice, we were able to demonstrate significant histologic improvement of inflammation that correlates well with a resolution of diarrhea and rectal bleeding. This finding is consistent with a role for anti-TNF-alpha in the pathogenesis of IBD and suggests that this model may be of use for examining the effects of anti-TNF-alpha antibody administration.