Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural intestinal nematode infections in dogs presented as veterinary patients in Europe.

BACKGROUND: A randomised, blinded, positive controlled, multicentre, Good Clinical Practice-compliant, pivotal field study was conducted to evaluate the effectiveness and safety of a new combination of lotilaner + milbemycin oxime tablets (Credelio® Plus; Elanco Animal Health) administered orally to client-owned dogs naturally infected with intestinal nematodes. METHODS: Client-owned dogs presenting to veterinary clinics from households in France, Hungary and Germany were screened for intestinal nematodes. Dogs with an initial positive faecal egg count that was subsequently confirmed with a follow-up faecal examination to demonstrate the presence of naturally occurring mixed or mono-infections with Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum were enrolled on Day 0 into the study. Households were randomised in an approximately 2:1 ratio to receive either an investigational product (IP; Credelio Plus tablets) or control product (CP; Nexgard Spectra® tablets) as treatment. Dogs were administered the IP (n = 278) or CP (n = 117) once on Day 0 at a dose rate of 0.75-1.56 mg/kg bodyweight milbemycin oxime and 20.0-41.5 mg/kg bodyweight lotilaner (IP) or as recommended (CP). Effectiveness of the IP and CP treatments was based on the post-treatment reduction in geometric mean faecal egg counts on Day 8 (range Day 7-10) after treatment as compared to their pre-treatment nematode faecal egg counts. RESULTS: Geometric mean (GM) faecal egg counts for T. canis, A caninum and T. vulpis were reduced by ≥ 97.2% in the Credelio Plus group and by ≥ 95.3% in the afoxolaner + milbemycin oxime group. There were insufficient data to calculate a percentage reduction in GM faecal egg counts between Day 0 and Day 8 for T. leonina due to low prevalence. Credelio Plus was well tolerated in this field study. Of the 355 total doses administered, 82.3% were accepted free choice in the IP group compared to 80.8% in the CP group. CONCLUSIONS: This study demonstrated effectiveness (≥ 97.2% reduction), safety and tablet acceptance of a combination of milbemycin oxime and lotilaner (Credelio Plus) administered orally to dogs with natural intestinal infections of T. canis, A. caninum and T. vulpis.

Field evaluation of the efficacy and safety of a combination of spinosad and milbemycin oxime in the treatment and prevention of naturally acquired flea infestations and treatment of intestinal nematode infections in dogs in Europe.

Two separate randomised, blinded, multicentre field trials were conducted to evaluate the efficacy and safety of a combination of spinosad and milbemycin oxime (MO) (Trifexis(®), Elanco Animal Health) in the treatment and prevention of naturally acquired flea infestations and intestinal nematode infections in European dogs. Treatments using Trifexis(®) and each control veterinary product (CVP) were administered once on Day 0 in both field studies. In the flea field trial, 11 veterinary clinics in France participated in the study. On Day 0, whole body flea comb counts were conducted on all dogs being evaluated for enrolment. Dogs with ≥7 fleas on Day 0 were enrolled, treated once on Day 0 with spinosad/MO or the CVP (Stronghold(®); selamectin) and then underwent post-treatment flea counts on Days 14 and 30. There were 150 spinosad/MO treated dogs and 71 CVP treated dogs included in the flea effectiveness population. Effectiveness against fleas (% reduction in geometric means; GM) was 98.97% and 97.37% for the spinosad/MO treated dogs, and 97.43% and 93.96% for the CVP dogs on Days 14 and 30, respectively, compared to the pre-treatment baseline flea counts. Of the spinosad/MO dogs, 89.3% and 80.0% had no live fleas on Days 14 and 30, compared to 77.5% and 70.4% of the CVP dogs, respectively. In the nematode field trial, data from 10 veterinary clinics in France and 19 in Ireland were pooled. Faecal samples from dogs at each clinic were analysed. A positive result at screening (parasite eggs from Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum) allowed for enrolment. Dogs were randomised to spinosad/MO or the CVP (Milbemax(®); MO/praziquantel). On Day 8, a post-treatment faecal sample was taken and analysed. Of 2333 dogs screened for nematode eggs, 238 dogs were positive with one or more of these nematodes, and 229 were enrolled in the study. Of the 229 dogs, 151 were treated with a single dose of spinosad/MO, and 77 were treated with a single dose of CVP. Post-treatment effectiveness against all nematodes (% reduction GM) was achieved with reductions of 98.57% and 97.57% for the spinosad/MO treated dogs and CVP dogs, respectively, as compared to the pre-treatment baseline faecal egg counts. Trifexis(®) was shown to be safe and effective against natural infestations of fleas as well as mixed and single intestinal nematode infections in client owned dogs in Europe when administered as a single oral administration at the recommended dose.

Confirmation of the efficacy of a combination tablet of spinosad and milbemycin oxime against naturally acquired infections of canine intestinal nematode parasites.

Four separate controlled and blinded studies were conducted to confirm the dose of spinosad and milbemycin oxime (MO) administered orally in combination to dogs for the treatment and control of naturally acquired infections of adult whipworm (Trichuris vulpis), hookworm (Ancylostoma caninum) and ascarids (Toxocara canis, Toxascaris leonina). Dogs were allocated randomly based on pre-treatment quantitative nematode egg counts of each species of interest to one of two treatment groups of 10 or 11 animals each. In each study, spinosad and MO in combination, was given orally to dogs using the lower half (30-45 mg/kg spinosad; 0.5-0.75 mg/kg MO) of the US commercial dose band (30-60 mg/kg spinosad; 0.5-1.0mg/kg MO) of each active ingredient on Day 0 using a tablet formulation. A corresponding vehicle control group was treated similarly in each individual study. Dogs were necropsied post-treatment on Day 7/8. All nematodes in the intestinal tract collected at necropsy were identified and counted by species and stage. The spinosad and MO combination group demonstrated significantly different adult intestinal nematode efficacy in each individual study as compared to the vehicle control group. Efficacy values for whipworm, hookworm, T. canis and T. leonina were 100%, 99.8%, 100%, 93.3%, respectively. Minor non-serious adverse events were observed in a small number of control and treated dogs that were attributed primarily to the natural nematode infections. In summary, flavored spinosad and MO combination tablets administered orally to dogs were both safe and highly efficacious delivering >93% up to 100% adult intestinal nematode control in naturally infected dogs.

Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas.

Despite major advances in the treatment of non-Hodgkin lymphoma (NHL), including the use of chemotherapeutic agents and the anti-CD20 antibody rituximab, the majority of patients eventually relapse, and salvage treatments with non-cross-resistant compounds are needed to further improve patient survival. Here, we evaluated the antitumor effects of the microtubule destabilizing agent monomethyl auristatin E (MMAE) conjugated to the humanized anti-CD19 antibody hBU12 via a protease-sensitive valine-citrulline (vc) dipeptide linker. hBU12-vcMMAE induced potent tumor cell killing against rituximab-sensitive and -resistant NHL cell lines. CD19 can form heterodimers with CD21, and high levels of CD21 were reported to interfere negatively with the activity of CD19-targeted therapeutics. However, we observed comparable internalization, intracellular trafficking, and drug release in CD21(low) and CD21(high), rituximab-sensitive and -refractory lymphomas treated with hBU12-vcMMAE. Furthermore, high rates of durable regressions in mice implanted with these tumors were observed, suggesting that both rituximab resistance and CD21 expression levels do not impact on the activity of hBU12-vcMMAE. Combined, our data suggest that hBU12-vcMMAE may represent a promising addition to the treatment options for rituximab refractory NHL and other hematologic malignancies, including acute lymphoblastic leukemia.

A theoretical model for treatment of soft tissue injuries: treatment of an ankle sprain in a college tennis player.

OBJECTIVE: To present theories of manual treatment approaches to soft tissue injuries using an example case report. CLINICAL FEATURES: A college tennis player with an ankle sprain for 6 weeks, not responding to standard treatment, was unable to play tennis or compete in tournaments. INTERVENTION AND OUTCOME: Soft tissue treatment was applied to the ankle for 2 visits. The patient experienced complete resolution of the problem and returned to play without relapse during a 9-month follow-up period. Theories of myofascial distortion treatment are discussed. CONCLUSION: This treatment approach may have potential for soft tissue problems that are not amenable to current therapy approaches.

Effect of a topical herbal cream on osteoarthritis of the hand and knee: a pilot study.

OBJECTIVE: To compare the efficacy of an herbal ointment to a sham ointment for relieving pain and stiffness associated with osteoarthritis of the hand and knee. METHOD: Single-blind, randomized controlled clinical trial conducted in 3 chiropractic medicine practices. Subjects were solicited from patients attending the 3 centers. Selection of subjects with osteoarthritis of the hand or knee was based on the criteria developed by the American College of Rheumatology. Subjects were randomized to an active (n = 17) or a sham (n = 19) group. Subjects applied the herbal ointment to the affected joint(s) for 42 consecutive days and recorded level of pain and stiffness daily on visual analog scales. RESULTS: Thirty subjects completed the study (15 active and 15 sham). Significant differences in pain (P = 0.003) and stiffness (P = 0.0008) were found between the first 21 days of application and the last 21 days of application for the experimental group but not for the sham group. Gain scores between the experimental and sham groups were significant for pain (P = 0.026) and stiffness (P = 0.042). CONCLUSION: An herbal ointment showed significant improvement in pain and stiffness for patients with hand and knee osteoarthritis who applied the ointment to the affected joint(s) for 42 consecutive days.

Effect of a topical herbal cream on the pain and stiffness of osteoarthritis: a randomized double-blind, placebo-controlled clinical trial.

This study compared the efficacy of an herbal ointment to a placebo ointment in relieving the pain and stiffness of osteoarthritis. The herbal preparation contained substances believed by alternative practitioners to be helpful in treating osteoarthritis. This study was a double-blind randomized placebo-controlled clinical trial. Subjects were solicited from patients attending an arthritis clinic in Dallas, Texas. Selection of subjects with osteoarthritis was based on the criteria developed by the American College of Rheumatology. Subjects were randomized to an active (n = 11) or a placebo (n = 8) group. Herbal ointment and control contained small amounts of capsaicin and menthol and were similar when applied. Subjects graded their levels of pain and stiffness for a 1-week no-treatment baseline. Subjects then applied the herbal or sham ointment to the involved joint(s) for 28 consecutive days and recorded their levels of pain and stiffness daily on visual analog scales. Significant differences between the active and placebo groups for pain (P < 0.05) and stiffness (P < 0.05) were found when the baseline phase was compared with the fourth week. An herbal ointment was shown to be effective in relieving the pain and stiffness of osteoarthritis without adverse effects. If future studies confirm effectiveness of this treatment, it may have a role as an adjunct to standard drug therapy.

Effectiveness of a selected bedding system on quality of sleep, low back pain, shoulder pain, and spine stiffness.

OBJECTIVE: To determine whether clinical and statistically significant changes in back pain, shoulder pain, spine stiffness, and quality of sleep may be documented after use of a prescribed bedding system. DESIGN: Quasi-experimental field study of single group pretest-posttest design with subjects serving as their own controls. SETTING: Two chiropractic clinics and the Oklahoma State University Program of Health and Human Performance. SUBJECTS: Convenience sample of 22 subjects (women, n = 13; men, n = 9) between the ages of 25 and 75 years with documented disturbed sleep, shoulder pain, low back pain, and spine stiffness of a chronic nature. OUTCOME MEASURES: Pretest and posttest 28-day Visual Analog Scales for pain, spine stiffness, and quality of sleep. MAIN RESULTS: The experimental bedding system reduced back pain by 57.21% (P =.000001), reduced shoulder pain by 60.83% (P =.000005), reduced back stiffness by 59.12% (P =.000004), and improved quality of sleep by 60.73% (P =.000001). CONCLUSIONS: Results suggest that subjects obtain significant improvement in shoulder and back pain, back stiffness, and quality of sleep after 28 days of prescribed bedding system use as compared with 28 days of personal bedding use. Female subjects and those with lower body weight were more likely to significantly improve than heavier and more obese subjects.