Digital dermatitis is an infectious disease that causes lameness in dairy cattle, a primary welfare concern of the dairy industry. One of the common treatments for this painful hoof disease is through the application of an antibiotic bandage that must be removed following treatment. The objectives of this randomized clinical trial were to determine if topical application of tetracycline hydrochloride in a paste would be as therapeutically effective for the treatment of digital dermatitis as a powdered form of tetracycline hydrochloride held in place by a bandage, and to quantify pain associated with digital dermatitis lesions. Two hundred and fourteen Holstein cow hooves with digital dermatitis lesions were randomly assigned to 1 of 3 treatments: a tetracycline hydrochloride paste, tetracycline hydrochloride powder held in place with a bandage for 2 d, or a negative (untreated) control. Lesions were examined at 2 time periods: 3 to 7 d posttreatment and 8 to 12 d posttreatment to determine healing rates. Nociceptive thresholds were measured using a pressure algometer to quantify the pain at the lesion site. The tetracycline hydrochloride paste was as effective as the powdered bandage treatment in terms of healing rates, with 47.4 and 57.1% hooves healed at 8 to 12 d posttreatment, respectively. Both treatments were more effective than the control, in which no lesions healed 8 to 12 d following initial examination. Mean (±SE) nociceptive thresholds for active, healing, and healed lesions differed, with limb-withdrawal response occurring at 7.45 (±0.67) kg, 12.84 (±1.85) kg, and censored to 25 kg (maximum value of algometer) of force applied, respectively. However, active lesions were not consistently associated with pain, as maximum force was tolerated when applied to 19% of active lesions, perhaps due to variability in stoicism between individual cattle or due to changes in pain during the progression of infection. In conclusion, tetracycline hydrochloride paste was as effective as tetracycline hydrochloride bandage, eliminating the need for bandage removal following treatment application. Digital lesions can be painful during both active and healing stages, suggesting the need for treatment and husbandry interventions for pain mitigation.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.
ImportanceRetinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated.ObjectiveTo investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO.Design, Setting, and ParticipantsThis economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021.InterventionsBevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6).Main Outcomes and MeasuresIncremental cost-utility ratio.ResultsThe simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health.Conclusions and RelevanceWhile there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.
Papillomatous digital dermatitis (PDD) is a contagious and painful foot lesion causing lameness in cattle. One of the common treatments for PDD is oxytetracycline powder held onto the hoof with a bandage wrap. The objective of this study was to determine if application of oxytetracycline in a topical paste without bandaging would be as effective as the wrap for the treatment of PDD.
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