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Background: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. Methods: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days − 7, − 2, 21, and 28, and tick counts were performed on day − 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. Results: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24–48 h earlier for lotilaner compared with sarolaner or afoxolaner. Conclusions: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period. [ABSTRACT FROM AUTHOR]

Objective: There is substantial inter‐individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer‐term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit. Methods: Client charts of adults with overweight or obesity (N = 748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss. Results: The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2 ± 75.2% vs. 82.3 ± 82.4, p < 0.01) compared with those who did not meet the 2% threshold. Conclusions: Lower 4‐week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals. This analysis adds to the growing evidence suggesting that weight loss during the early weeks of an intervention may be predictive of longer‐term success. To our knowledge, this analysis is also the first to evaluate the sensitivity and specificity of various weight loss thresholds within the context of a commercial weight loss program. An additional unique aspect of this study, not typically evaluable in clinical trials that have a defined study length or within research trials which incentivize participants for study completion, is the evaluation of the relationship between early weight loss and time spent in the program. [ABSTRACT FROM AUTHOR]

Objective: There is substantial inter-individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer-term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit., Methods: Client charts of adults with overweight or obesity ( N  = 748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss., Results: The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2 ± 75.2% vs. 82.3 ± 82.4, p  < 0.01) compared with those who did not meet the 2% threshold., Conclusions: Lower 4-week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals., Competing Interests: CDC, JRK, and SSJ are employees of Medifast, Inc. JLU is a member of the Medifast Scientific Advisory Board and receives consulting fees associated with that appointment. Within the prior 24 months, KCM has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio; he also has current research grant funding from the National Dairy Council, Hass Avocado Board, Greenyn, the Indiana University Foundation, Naturmega, Cargill, and National Cattlemen's Beef Association. MLW and LLG are employees of and MB is a contractor for Midwest Biomedical Research, which has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio., (© 2023 Jason Pharmaceuticals, Inc and The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)