Gamithromycin in swine: Pharmacokinetics and clinical evaluation against swine respiratory disease.

The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half-life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3-12 mg/kg BWT. No gender-related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for 'treatment success' or 'treatment failure' (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non-inferiority hypothesis test (non-inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%).

Bordetella bronchiseptica experimental model development in pigs and efficacy evaluation of a single intramuscular injection of gamithromycin (Zactran® for Swine) against Bordetella bronchiseptica-associated respiratory disease in experimentally infected piglets.

In the Bordetella bronchiseptica infection model development study, twenty-eight piglets were inoculated with B. bronchiseptica strain of either canine (109  CFU/ml) or swine (108 and 109  CFU/ml) origin; swine origin strain at 109  CFU/ml was chosen for the efficacy assessment study due to higher incidence and severity of gross and histopathological lesions compared with other strains. To assess efficacy of gamithromycin against B. bronchiseptica, forty piglets were experimentally inoculated on Day 0 and clinical signs were scored as per severity. Animals were then treated either with gamithromycin or saline on Day 3. The Global Clinical Scores in gamithromycin-treated group were consistently lower than the saline-treated control group from Day 4 onwards and were 0 and 40 in the gamithromycin-treated and saline-treated control groups, respectively, on Day 6. Severity and frequency of gross and histopathological observations were significantly lower in gamithromycin-treated animals compared with saline-treated controls. The efficacy of Zactran® for Swine at the label dose for the treatment of B. bronchiseptica-associated respiratory disease was demonstrated based on the faster reduction in clinical signs as early as 1 day post-gamithromycin treatment and based on the significant difference in the severity of macroscopic and microscopic lung lesions 10 days post-gamithromycin treatment.

Prevention of canine ocular thelaziosis (Thelazia callipaeda) with a combination of milbemycin oxime and afoxolaner (Nexgard Spectra®) in endemic areas in France and Spain.

In the past decade, canine thelaziosis due to Thelazia callipaeda has been diagnosed in an increasing number of European countries, with endemic areas being identified. A multi-center field trial was conducted in endemic areas in France and Spain to evaluate the efficacy of monthly administrations of the oral milbemycin oxime/afoxolaner combination (NexGard Spectra®) for the prevention of T. callipaeda infection in at-risk dogs. A total of 79 dogs negative for T. callipaeda and with a clinical history of eyeworm infection in the past two years completed the study. Dogs were randomly allocated either to a negative control group (42 dogs) or to the NexGard Spectra® treated group (37 dogs). All dogs were followed up for a 6-month period and assessed monthly for the presence of nematodes on the eyes and for the signs of ocular thelaziosis (e.g., conjunctivitis, keratitis, and ocular discharge). When the presence of nematodes was confirmed, the conjunctival fornix was flushed with a saline solution for parasite recovery and counting, and the dogs were treated appropriately. Recovered parasites were stored in 70% alcohol for subsequent morphological identification. During the course of the study, 57.1% (24/42) of the control dogs were diagnosed positive for Thelazia infection, which illustrates a high incidence rate of parasite infection. Conversely, no eyeworm was recovered from any of the 37 dogs that received NexGard Spectra®. All parasites sampled were confirmed to be T. callipaeda. This clinical field study demonstrated that monthly administrations of NexGard Spectra® provided 100% preventive efficacy against canine thelaziosis.

Medical and Economic Evaluation of FOREseal Bioabsorbable Reinforcement Sleeves Compared With Current Standard of Care for Reducing Air Leakage Duration After Lung Resection for Malignancy: A Randomized Trial.

OBJECTIVE: The objective of this study was to determine the efficacy of alginate staple-line reinforcement of fissure openings as compared with stapling alone, with or without tissue sealant or glue, in reducing the incidence and duration of air leakage after pulmonary lobectomy for malignancy. SUMMARY BACKGROUND DATA: No randomized trial evaluating alginate staple-line reinforcement has been performed to date. METHODS: The Staple-line Reinforcement for Prevention of Pulmonary Air Leakage study was a multicenter randomized trial, with blinded evaluation of endpoints. Patients over 18 years of age scheduled for elective open lobectomy or bilobectomy for malignancy were eligible for enrollment. At thoracotomy, patients were deemed ineligible if an unanticipated pneumonectomy was indicated, or if air leakage occurred after the liberation of pleural adhesions. Otherwise, if the fissure was incomplete or the lung had an emphysematous appearance, patients were randomized to either standard management or interventional procedure consisting of fissure opening with linear cutting staplers buttressed with paired alginate sleeves (FOREseal). The number of eligible patients necessary in each randomization arm was estimated to be 190, and an outcomes analysis was performed on an intention-to-treat basis. RESULTS: Of the 611 patients consented to study enrollment, 380 met the inclusion criteria and were randomized. Based on an intention-to-treat analysis, the primary endpoint of air leak duration was not different between the 2 groups: 1 day (range: 0-2 d) in the FOREseal group and 1 day (range: 0-3 d) in the control group (P = 0.8357). In addition, the 2 groups were similar in terms of the proportion of patients presenting with prolonged air leakage (7.8% in the FOREseal group vs 11.3% in the control group, P = 0.264) and the average duration of chest drainage (P = 0.107). Procedure costs were comparable for both groups. CONCLUSIONS: FOREseal did not demonstrate a significant advantage over standard treatment alone.

Monthly administrations of milbemycin oxime plus afoxolaner chewable tablets to prevent Angiostrongylus vasorum infection in dogs.

BACKGROUND: Infection of dogs with the cardiopulmonary nematode Angiostrongylus vasorum may result in severe clinical disease therefore adequate prevention is necessary. A randomized, negative control, blinded study was conducted to evaluate the efficacy in the prevention of canine A. vasorum infection after monthly administrations of NexGard Spectra®, a novel chewable tablet formulation combining the insecticide and acaricide afoxolaner and the anthelmintic milbemycin oxime, in a multiple challenge (trickle infection) model. METHODS: Twenty beagle dogs were challenged orally with doses of approximately 32-43 third-stage larvae of A. vasorum once every other week on seven occasions (Study Days -7, 7, 21, 35, 49, 63 and 77). Ten dogs were administered NexGard Spectra® as close as possible to the minimum recommended dose of afoxolaner and milbemycin oxime, i.e. 2.5 mg/kg body weight and 0.5 mg/kg body weight, respectively, four times at monthly intervals (Study Days 0, 28, 56 and 84) while the remaining ten dogs served as untreated controls. For parasite recovery and count, dogs were euthanized humanely and necropsied six to eight days following the last treatment (Study Days 90-92). Beginning six weeks after first inoculation, faeces were collected on a bi-weekly basis and examined for first-stage larvae of A. vasorum. RESULTS: Untreated dogs harboured 39-95 adult A. vasorum (geometric mean, 66.4), while zero to 24 adult A. vasorum were recovered from the treated dogs (geometric mean, 3.4; P < 0.0001). Thus, efficacy of NexGard Spectra® administered at monthly intervals against incoming A. vasorum was 94.9 %. Compared to the untreated controls, larval excretion of the treated dogs was reduced by 99.9 % (P < 0.0001). CONCLUSION: Results of this study demonstrate that NexGard Spectra®, when administered at monthly intervals, can effectively prevent canine A. vasorum infection.

Repellency and acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs.

BACKGROUND: A blinded, controlled laboratory study was conducted to assess the repellency and acaricidal activity of a topical spot on formulation, a combination of fipronil and permethrin, against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs. METHODS: A group of 16 adult mixed breed dogs were randomly divided into treatment and control groups based on pre-treatment live tick counts. On Day 0, the topical spot on formulation of fipronil + permethrin (commercialized under the name Frontline Tri-Act®/Frontect®) was administered to dogs in the treatment group at the minimum recommended dose of 0.1 mL/kg, corresponding to 6.76 mg fipronil/kg and 50.48 mg/kg permethrin. Tick infestations were performed with I. ricinus (50 females, 50 males) and R. sanguineus (25 females, 25 males) on each dog on Days 2, 7, 14, 21, and 28. Dogs were sedated prior to exposure and confined to crates for approximately 4 h following tick challenge. Ticks were released next to the sedated dogs and tick counts were performed at 4 h and 24 h after the start of exposure for tick counts and removal. RESULTS: Repellency at 4 h against I. ricinus was 72.6, 96.3, 92.8, 89.0, and 88.7 % on Days 2, 7, 14, 21, and 28, respectively. Repellency was 100 % 24 h after exposures on Days 2, 7, and 14 and 99.6 % after exposures on Days 21 and 28. For R. sanguineus, repellency at 4 h was 78.0, 96.8, 91.5, 88.0, and 56.8 % on Days 2, 7, 14, 21, and 28, respectively. Repellency at 24 h was 98.6, 100, 98.7, 96.1, and 95.1 % for exposures on Days 2, 7, 14, 21, and 28, respectively. For I. ricinus, acaricidal efficacy recorded at 4 h was ≥ 91.1 % during the full month and was ≥ 99.5 % for the full month when counted at 24 h. Acaricidal efficacy against R. sanguineus was ≥ 94.7 % at 4 h from Day 2 to Day 21 and was 71.4 % on Day 28. Acaricidal efficacy at 24 h, was > 97.7 % during the month. Tick counts were statistically significantly reduced in treated dogs at all time-points during the study. CONCLUSIONS: A combination of fipronil and permethrin was highly effective at rapidly repelling and killing both I. ricinus and R. sanguineus ticks on dogs for at least 4 weeks, with a significant effect at 4 and 24 h after tick exposure.

Acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks.

BACKGROUND: Two blinded, controlled laboratory studies were conducted to assess the acaricidal efficacy of a new combination of fipronil and permethrin (Frontline Tri-Act/Frontect) against two tick species. Study A evaluated the efficacy of the product against both Ixodes ricinus and Rhipicephalus sanguineus and Study B evaluated the efficacy against R. sanguineus only. METHODS: 16 (Study A) and 12 (Study B) healthy adult dogs were allocated to two groups in each study. Dogs in Group 1 served as untreated controls. Dogs in Group 2 were treated with a new topical spot-on formulation containing 6.76% (w/v) fipronil + 50.48% (w/v) permethrin once on Day 0. Each dog of study A was infested with 50 unfed adult ticks of each species and each dog of study B was infested with 50 unfed adult Rhipicephalus sanguineus prior to treatment (Day -2 in Study A, Day -1 in Study B) and post treatment on Days 7, 14, 21 and 28. The ticks were removed and counted 48 h after treatment (Day 2) or subsequent infestations (Days 9, 16, 23 and 30). Acaricidal efficacy was defined as the percent reduction in the number of live ticks in the treated group compared to the untreated control group. RESULTS: The percent efficacy in the treated group for R. sanguineus was 100%, 100%, 100%, 100% and 96.7% in Study A, and 94.4%, 100%, 100%, 98.7% and 98.0% in Study B, for counts performed on Days 2, 9, 16, 23 and 30, respectively. For I. ricinus, in Study A, the percent efficacy of the treatment was 100%, 100%, 100%, 100% and 99.2% for counts performed on Days 2, 9, 16, 23 and 30, respectively. There was a significant difference of the geometric mean numbers of live ticks between the treated and control groups at each time point in each study (p = 0.005 for every day in Study A, and p < 0.005 for every day in Study B). CONCLUSIONS: A single topical administration of a combination of fipronil and permethrin provides excellent acaricidal efficacy against both I. ricinus and R. sanguineus for at least 4 weeks.

Repellency, prevention of attachment and acaricidal efficacy of a new combination of fipronil and permethrin against the main vector of canine babesiosis in Europe, Dermacentor reticulatus ticks.

BACKGROUND: Dermacentor reticulatus is a European hard tick of major veterinary importance because it is the vector of canine babesiosis due to Babesia canis. The efficacy against this particular tick species is therefore a key characteristic for an acaricidal solution for dogs. The repellency, prevention of attachment and acaricidal efficacy of Frontline Tri- Act/Frontect, a new combination of fipronil and permethrin against induced infestations of Dermacentor reticulatus ticks on dogs were evaluated after a single topical administration. METHODS: A group of 20 dogs were allocated to two treatment groups. Ten dogs were treated with a topical spot-on formulation containing 6.76% w/v fipronil + 50.48% w/v permethrin once on Day 0 and 10 dogs served as untreated controls. Tick infestations were performed by placing 50 D. reticulatus ticks next to sedated dogs confined to infestation crates on days 1, 7, 14, 21 and 28. Thumb counts on dogs were conducted at 4, 12 and 24 h post-challenge. Tick removal counts were performed 48 h after each infestation. Repellency, prevention of attachment and acaricidal efficacy were calculated. RESULTS: The new combination provided repellency ranging between (56.5-73.5%) at 4 h post-infestation (pi), between (76.3-92.9%) at 12 h pi and between (83.9-96.5%) at 24 h pi, up to 4 weeks post-treatment. Prevention of attachment ranged between (64.1-79.7%) at 4 h pi, between (79.1-94.2%) at 12 h pi and between (84.2-99.6%) at 24 h pi, up to 4 weeks post-treatment. Acaricidal efficacy against D. reticulatus ticks was ≥99.5% for 4 weeks post-treatment. CONCLUSION: The new combination of fipronil and permethrin demonstrated excellent repellency, prevention of attachment and acaricidal efficacy against D. reticulatus for at least 4 weeks. The results suggest that in endemic areas of canine babesiosis, the application of the new combination can significantly reduce the potential for transmission of B. canis as well as other tick-borne diseases.

Repellent and insecticidal efficacy of a new combination of fipronil and permethrin against the main vector of canine leishmaniosis in Europe (Phlebotomus perniciosus).

BACKGROUND: Two successive laboratory experiments (A and B) were conducted to confirm the efficacy of a new fipronil and permethrin combination to repel and kill Phlebotomus perniciosus sandflies when applied once topically on dogs. METHODS: Due to the difficulty to get enough available dogs and sandflies in one run, the study was divided into 2 experiments which had exactly the same design, and were conducted at the same place, with the same technicians. They compared dogs treated with a combination containing 67.6 mg/mL fipronil + 504.8 mg/mL permethrin (Frontect/Frontline Tri-Act, Merial) to untreated dogs. The treatments were applied topically once on Day 0. Sandfly exposures were performed on Days 1, 7, 14, 21 and 29 with 80 P. perniciosus female sandflies. After 60 min, sandflies were assessed for vitality and engorgement status. Live sandflies were kept in an insectary and observed for mortality counts 4 h after the exposure period ended. RESULTS: Percent sandfly repellency on treated dogs was 98.2, 98.5, 99.2, 90.9 and 90.3%, for Days 1, 7, 14, 21, and 29, respectively. There was a significant difference (p ≤ 0.05) between the treated and control groups in both experiments and for the pooled data on every assessment day. Insecticidal efficacy on treated dogs at 4 h post-exposure on Days 1, 7, 14, 21 and 29 was 98.7, 99.7, 96.8, 93.4, and 78.9%, respectively. There was a significant difference between the treated and control groups for live sandflies observed at 4 h post-exposure for all assessment days (p < 0.05). CONCLUSIONS: A single topical administration of a new combination of fipronil and permethrin demonstrated a significant repellent effect (i.e., > 80%) against P. perniciosus which lasted for 29 days after application. The repellent effect was accompanied by a significant insecticidal effect on sandflies. The results suggest that in endemic areas, the application of the fipronil-permethrin combination could be integrated into canine leishmaniosis prevention program.

Efficacy of a new combination of fipronil and permethrin against Ctenocephalides felis flea infestation in dogs.

BACKGROUND: Five studies were conducted to evaluate the effect of a new combination of fipronil and permethrin on cat fleas, Ctenocephalides felis, when applied to dogs, including dogs that underwent water exposure or shampooing. METHODS: In each study, 16 dogs were allocated to two groups. Each dog was infested with 100 unfed adult fleas on Days -1, 7, 14, 21 and 28. Eight dogs were treated with a new topical spot-on formulation containing 6.76% w/v fipronil + 50.48% w/v permethrinon Day 0; and eight dogs served as untreated controls. Twenty-four or 48 h after treatment or subsequent infestation, each dog was combed to remove and count live fleas. In addition, the dogs were subjected to different levels of water or shampoo exposure. In study 1, dogs were not subjected to any water exposure or shampooing; in study 2, dogs were water immersed twice during the month on Days 10 and 24; in study 3, dogs were water immersed three times on Days 10, 17 and 24; and in studies 4 and 5, dogs were shampooed once on Day 17. RESULTS: All groups of dogs administered a single topical treatment with a combination of fipronil and permethrin had significantly (p < 0.005) lower flea counts than untreated controls 24 h and 48 h post-treatment or post-infestation, regardless of whether they underwent water exposure/shampooing or not. The reductions in C. felis counts were between 98.4% and 100% at all time points in all studies. CONCLUSIONS: The new topical spot-on formulation of fipronil and permethrin maintains a high level of protection of dogs against C. felis flea infestations even when the dogs are exposed to environmental factors that are believed to adversely affect efficacy, such as water exposure or shampooing.

Repellent and insecticidal efficacy of a new combination of fipronil and permethrin against three mosquito species (Aedes albopictus, Aedes aegypti and Culex pipiens) on dogs.

BACKGROUND: Three laboratory studies were conducted to assess the repellent and insecticidal efficacy of a combination of fipronil and permethrin (Frontline Tri- Act/Frontect) against three mosquito species (Aedes albopictus, Aedes aegypti and Culex pipiens) on dogs. METHODS: In each study, 16 healthy adult dogs were allocated to two groups. Eight dogs were treated with the new topical spot-on combination of fipronil and permethrin on Day 0 and the other eight dogs served as untreated controls. Each dog was exposed to mosquitoes on Days 1, 7, 14, 21 and 28 (and also on Day 35 in the A. aegypti study). After a 1-h exposure period, all mosquitoes were counted and categorized as live or dead and fed or non-fed. Live mosquitoes were kept in an insectary and observed for mortality counts 4, 24 and 48 h post-exposure (PE) for Aedes spp. and 24 and 48 h PE for C. pipiens. Repellency and insecticidal efficacies were defined as the percent reduction in the number of fed and live mosquitoes, respectively, in the treated group as compared to the untreated control group. RESULTS: Repellency against A. albopictus was ≥93.4% through Day 21 and 86.9% on Day 28. It was ≥91.0% through Day 35 against A. aegypti and ≥90.4% through Day 28 against C. pipiens. Insecticidal efficacy against A. albopictus was ≥97.1% at 24 h PE from Day 7 to Day 28. It was ≥98.0% for the first 3 weeks and still 75.7% on Day 35 against A. aegypti at 24 h PE. For C. pipiens, insecticidal efficacy ranged from 93.8% (Day 7) to 30.9% (Day 28) at 48 h PE. CONCLUSIONS: A single topical administration of the combination of fipronil and permethrin provides repellency against mosquitoes on dogs for at least 4 weeks. The product may therefore significantly reduce the potential for the transmission of vector-borne pathogens through the inhibition of mosquito feeding, as well as the discomfort associated with mosquito bites. Moreover, mosquito mortality was induced by contact with the treated dogs, which could aid in the control of mosquitoes, and hence the control of mosquito-borne diseases, in the local vicinity of treated dogs.

Evaluation of the curative and preventive efficacy of a single oral administration of afoxolaner against cat flea Ctenocephalides felis infestations on dogs.

The efficacy of orally administered afoxolaner for treatment and prevention of repeated infestations with adult Ctenocephalides felis on dogs was evaluated in two studies after administration of a beef-flavored soft chew. In each study, 32 dogs were divided randomly into four equal groups. Dogs in Groups 1 and 3 were not treated and served as controls. Dogs in Groups 2 and 4 were treated on Day 0 with a combination of chewable tablets to be as close as possible to the minimum therapeutic dose of 2.5mg/kg. All animals were infested experimentally with unfed C. felis (100 ± 5) on Days -1, 7, 14, 21, 28 and 35. Flea killing efficacy was evaluated in both studies while, efficacy against flea egg production was assessed in Study 1. Live fleas were counted at 12 (Groups 1 and 2) and 24h (Groups 3 and 4), after treatment or after weekly infestations. In Study 1, flea eggs were collected and counted at either 12 or 24h after each flea infestation on Days 7, 14, 21, 28 and 35. The results of both studies demonstrate the long lasting and rapid efficacy of afoxolaner against C. felis, when administered as a single oral dose to dogs. For flea counts conducted 24h after treatment or infestation, efficacy was 100% for all time points up to Day 36 in both studies, except for one time point (99.9% on Day 22) for Study 2. For flea counts performed 12h after treatment or infestation, efficacy was ≥ 95.2% until Day 21 in both studies. Efficacy at 12h was ≥ 93.0% on Day 35 in Study 1 and ≥ 89.7% on Day 35 in Study 2. The treated groups had significantly fewer fleas than untreated control dogs in both studies for all flea counts (p=0.003 Study 1, p=0.0006 Study 2). In Study 1, for all egg counts performed at or beyond Day 7, efficacy in egg reduction was >99% for all time points between Days 7 and 35.

Evaluation of the efficacy of afoxolaner against two European dog tick species: Dermacentor reticulatus and Ixodes ricinus.

The acaricidal efficacy of a novel oral formulation of afoxolaner (NEXGARD(®), Merial) against two European tick species was assessed in dogs experimentally infested with Ixodes ricinus and Dermacentor reticulatus. Three studies, each characterized by a negative controlled randomized block design, were conducted with a total of 52 beagle or mongrel dogs of both sexes. Starting 2 days before treatment, each dog was infested weekly with approximately 50 ticks. The number of live ticks was counted at 48 h post-treatment (Day 2) as well as 48 h following each infestation on Days 9, 16, 23, and 30. Afoxolaner, administered at an average dose of 2.7 mg/kg bodyweight (range 2.5-2.9 mg/kg), rapidly eliminated the pre-existing tick infestations with over 99% acaricidal efficacy and controlled the weekly re-infestations for up to 30 days post treatment with over 96% efficacy on both tick species. Afoxolaner provides excellent acaricidal efficacy against these two major European tick species using the oral route of administration.

Assessment of the efficacy of orally administered afoxolaner against Rhipicephalus sanguineus sensu lato.

Two studies were conducted to confirm that a single oral dose of the novel insecticide/acaricide afoxolaner is efficacious against existing infestations of Rhipicephalus sanguineus sensu lato in dogs and can control re-infestation for up to 35 days. Each study utilized 16 purpose bred adult dogs using a controlled randomized block design. One or two days prior to treatment, all dogs were infested with 50 unfed adult ticks. On Day 0 one group was treated with an oral chewable formulation of afoxolaner at a dose as close as possible to the minimum dose of 2.5mg/kg. Weekly re-infestations with 50 adult unfed ticks were repeated for five weeks. Forty-eight hours after treatment and after each re-infestation, the number of remaining live ticks on each dog was counted. Treatment with afoxolaner resulted in efficacies of 98.8-100% within 48 h on existing tick infestations, while the efficacy against new tick infestations was >95.7% over five weeks.

Curative and preventive efficacy of orally administered afoxolaner against Ctenocephalides canis infestation in dogs.

The efficacy of orally administered afoxolaner against adult dog fleas, Ctenocephalides canis, was evaluated in a controlled, blinded study. A total of 32 dogs were infested with 100 adult unfed fleas approximately 24h prior to treatment and then at weekly intervals for 5 weeks after treatment. Live fleas were counted upon removal at 12h (for 16 dogs) and 24h (for the remaining 16 dogs) after treatment (for counts performed the first week) or after infestation (for counts performed on subsequent weeks). In addition, flea eggs were collected from each pen and counted for the dogs with flea removal at 24h. Dosing of individual dogs was achieved using a combination of the chewable tablets to be as close as possible to the minimum effective dose of 2.5mg/kg. The percent efficacy of the afoxolaner treatment was ≥ 99.0% for all 24-h flea counts. For flea counts performed 12h after treatment or infestations, the percent efficacy was ≥ 94.1% up to Day 21. After Day 1, no flea eggs were recovered from the afoxolaner treated group, providing 100% reduction in numbers of flea eggs recovered versus untreated control group. This study confirmed that a single oral treatment with afoxolaner provided excellent efficacy against infestations by C. canis within 12-24h after treatment, prevented re-infestations, and completely prevented egg production from new flea infestations for up to 5 weeks.

Efficacy of a topical application of Certifect® (fipronil 6.26% w/v, amitraz 7.48% w/v, (S)-methoprene 5.63% w/v) for the treatment of canine generalized demodicosis.

The efficacy of the treatment with Certifect ® (containing fipronil 6.26% w/v, amitraz 7.48% w/v, (S)-methoprene 5.63% w/v) applied topically was assessed in 18 dogs diagnosed with clinical generalized demodicosis. Three treatment regimens were compared over a 3-month period. Starting at Day 0, dogs were treated monthly (group 1) or every two weeks (group 2) with the combination of fipronil, amitraz, and (S)-methoprene or with monthly topical applications of the combination of amitraz and metaflumizone (group 3, reference treatment). Clinical examinations including deep skin scrapings were performed every month in order to evaluate the resolution of clinical signs and the reduction in mite counts. On Day 84, the percentage reduction of mite counts in group 1 was 99.8%, whereas no Demodex canis could be detected in groups 2 and 3 (i.e. 100% parasitological efficacy). As a result of the Demodex mite count reduction, the skin condition of the dogs improved significantly in all groups. This study illustrates, that both monthly and bi-weekly treatments with Certifect were effective in treating dogs with generalized demodicosis over a 3-month period.

Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung.

Expression of the KLK13 and KLK14 genes was examined at the mRNA and protein levels in a cohort of 57 patients with non-small-cell lung cancer (NSCLC). The mRNA levels, assessed by real-time RT-PCR, were significantly different in malignant tissues compared to adjacent non-malignant tissues (KLK13, p=0.006; KLK14, p=0.022). KLK13 and KLK14 mRNA overexpression in tumors (1/3 of the patients) was associated with a positive nodal status in multivariate analysis (p=0.018 and p=0.069, respectively). KLK13 and KLK14 were localized in the cytoplasm of epithelial cells of normal bronchus and NSCLC, as determined by immunohistochemistry. Moreover, positive staining was significantly associated with adenocarcinoma histotype (KLK13, p=0.014) and tumor size (KLK14, p=0.048). Although the results are marginally significant, patients with high KLK13 expression at the mRNA or protein level had lower overall survival.

Side effects and complications of surgery for hyperhidrosis.

Most of the difficulties associated with hyperhidrosis surgery are due to unavoidable side effects and unforeseeable and unacceptable complications. Careful patient selection is important before surgery so surgeons can avoid some of these pitfalls. Patients should also be fully informed of all potential side effects and complications before surgical treatment.

Long-term results of thoracoscopic sympathectomy for hyperhidrosis.

BACKGROUND: Thoracoscopic sympathectomy is now the reference treatment for severe palmar hyperhidrosis, but this is offset by the occurrence of compensatory sweating. It has been studied in this series to improve the indications and information given to patients. METHODS: A retrospective review of 124 patients who were previously afflicted with bilateral thoracoscopic sympathectomy 6 years earlier was conducted. Patients were interviewed by postal questionnaire regarding the results and side effects. RESULTS: The series consisted of 89 females (72%) and 35 males and the mean age was 28 years. The main indication was palmo-plantar hyperhidrosis (34%). The mean operating time was 36 minutes and there were no intraoperative complications. Postoperative pneumothorax occurred in 9 patients and 3 patients required a chest drain. The hospital stay was 36 hours for 87.6% of the patients. Postoperative pain occurred in 78% of the patients. Neurologic complications (Horner syndrome, radial paralysis, and dysesthesia of the arm) occurred in 3 patients and disappeared after 2-6 months. Two patients required single-side reoperation because of failure with the first intervention. Eighty-nine replies to questionnaires were received (72%). The results for hands were favorable in 98% and in 63% for axillae. Compensatory sweating occurred in 87% of the patients (serious in 36% and incapacitating in 6%). Despite this 90% of the patients were satisfied or very satisfied. CONCLUSIONS: This study confirms that thoracoscopic sympathectomy is a suitable method of treatment for severe palmar hyperhidrosis but emphasizes the need to offer the patient more informative information, especially regarding compensatory sweating which seems inescapable.