Importance of epidemic severity and vaccine mode of action and availability for delaying the second vaccine dose

Following initial optimism regarding the potential for rapid vaccination, delays and shortages in vaccine supplies have occurred in many countries. Various strategies to counter this gloomy reality and speed up vaccination have been set forth, of which the most popular approach has been to delay the second vaccine dose for a longer period than originally recommended by the manufacturers. Controversy has surrounded this strategy, and overly simplistic models have been developed to shed light on this issue. Here we use three different epidemic models, all accounting for the actual COVID-19 epidemic in the Czech Republic, including the rise and eventual prevalence of the B.1.1.7 variant of SARS-CoV-2 virus and real vaccination rollout strategy, to explore when delaying the second vaccine dose from 21 days to 42 days is advantageous. Using the numbers of COVID-19-related deaths as a quantity for comparing various model scenarios, we find that vaccine mode of action at the beginning of the infection course (preventing contagion and symptom appearance), mild epidemic and sufficient vaccine supply rate call for the original inter-delay scenario of 21 days regardless of vaccine efficacy. On the contrary, for vaccine mode of action at the end of infection course (preventing severe symptoms and death), severe epidemic and low vaccine supply rate, the 42-day inter-dose period is preferable, at any plausible vaccine efficacy.

Analysis of gaps in feline ectoparasiticide purchases from veterinary clinics in the United States

Background The study objective was to examine cat owner ectoparasiticide purchases in the United States and estimate the impact of purchase gaps on timely ectoparasite protection administration. These purchase gaps lead to periods of time when cats are unprotected from ectoparasites. Methods Ectoparasiticide purchase transactions for individual cats from 671 U.S. veterinary clinics from January 1, 2017 through June 30, 2019 were evaluated to determine time “gaps” between doses of ectoparasiticides purchased in a defined 12-month period. Ectoparasiticides examined were topically applied products that contained fluralaner, fipronil/(S)-methoprene/pyriproxyfen, imidacloprid/pyriproxyfen or selamectin as active ingredients. The duration of protection following administration of one dose was 8–12 weeks for the fluralaner-containing product and one month for the other products. Results Ectoparasiticide purchase records were obtained from 114,853 cat owners and analysis found that most owners bought ≤ 6 months of protection during the year, with 61–75% (depending on the product) purchasing just 1–3 months of protection. The size of the average purchase gap was determined for all dose combinations out to 12 months of protection (5–7 doses for fluralaner and 12 doses for the other three products dosed monthly. The largest gaps occurred between the first and second doses and the second and third doses. Average purchase gaps for the four different products between doses 1 and 2 ranged from 11.2 to 13.9 weeks and between doses 2 and 3 ranged from 7.7 to 12.2 weeks. The fraction of purchases separated by gaps and the average length of the gap tended to decrease with increasing number of doses purchased. Owners purchasing the 8 to 12-week duration product containing fluralaner provided ectoparasite protection (“doses plus gap period”) for a larger proportion of each 2-dose period compared with owners purchasing products administered monthly. Conclusions When cat owners purchase flea and tick medication, gaps between subsequent purchases reduces the proportion of time ectoparasite protection can be provided. The duration of the gap between doses has an impact on the effectiveness of flea/tick medication because it inserts a period without flea and tick protection between doses of flea and tick medication. The gaps between purchases were shorter and the period of ectoparasite protection was larger for owners purchasing a 12-week product than for owners purchasing a monthly product.

Self-blinding citizen science to explore psychedelic microdosing

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Analysis of Gaps in Feline Ectoparasiticide Purchases from Veterinary Clinics in the United States.

Background:The study objective was to examine cat owner ectoparasiticide purchases in the United States and estimate the impact of purchase gaps on timely ectoparasite protection administration. These purchase gaps lead to periods of time when cats are unprotected from ectoparasites. Methods:Ectoparasiticide purchase transactions for individual cats from 671 U.S. veterinary clinics from January 1, 2017 through June 30, 2019 were evaluated to determine time “gaps” between doses of ectoparasiticides purchased in a defined 12-month period. Ectoparasiticides examined were topically applied products that contained fluralaner, fipronil/(S)-methoprene/pyriproxyfen, imidacloprid/pyriproxyfen or selamectin as active ingredients. The duration of protection following administration of one dose was 12 weeks for the fluralaner-containing product and one month for the other products.Results:Ectoparasiticide purchase records were obtained from 114,853 cat owners and analysis found that most owners bought < 6 months of protection during the year, with 61-75% (depending on the product) purchasing just 1-3 months of protection. The size of the average purchase gap was determined for all dose combinations out to 12 months of protection (5 doses for fluralaner and 12 doses for the other three monthly products. The largest gaps occurred between the first and second doses and the second and third doses. Average purchase gaps for the four different products between doses 1 and 2 ranged from 11.2 - 13.9 weeks and between doses 2 and 3 ranged from 7.7- 12.2 weeks. The fraction of purchases separated by gaps and the average length of the gap tended to decrease with increasing number of doses purchased. Owners purchasing the 12-week duration product containing fluralaner provided ectoparasite protection (“doses plus gap period”) for a larger proportion of each 2-dose period compared with owners purchasing products administered monthly. Conclusions: When cat owners purchase flea and tick medication, gaps between subsequent purchases reduces the proportion of time ectoparasite protection can be provided. The duration of the gap between dose has an impact on the effectiveness of flea/tick medication because it inserts a period without flea and tick protection between doses of flea and tick medication. The gaps between purchases were shorter and the period of ectoparasite protection was larger for owners purchasing a 12-week product than for owners purchasing a monthly product.

Topical 5% lidocaine patches for treating postherpetic neuralgia: a survey among nurses and patients

Introduction: Postherpetic neuralgia (PHN) is associated with moderate to severe pain with peripheral and central mechanisms. While there is no clear-cut first-line therapeutic approach to PHN pain control, lidocaine patches are frequently used as monotherapy or part of a multimodal pain regimen. Methods: An online survey, the first of its kind, was conducted among PHN patients (n = 153) and nurses (n = 151) in order to determine clinical and patient knowledge, attitudes and practices toward the lidocaine patch and current unmet needs. Results: Results of the survey indicated that PHN patients are prescribed a mean of 2.6 medications to control their PHN pain, including the lidocaine patch. There were negative responses related to the patches’ ability to adhere to the skin. Patients reported the use of tape to hold the patches in place and/or patches that detached completely, truncating the therapeutic dose period. Most nurses (53%) found the biggest obstacle to PHN pain control was noncompliance and 98% stated that reliable patch adhesion for the intended 12-hour application was “somewhat important” or “very important” for PHN pain control. Forty-five percent of nurses said that poor patient adherence to PHN analgesic regimens was related to poor adhesion of the lidocaine patch. Conclusion: A new bioequivalent lidocaine patch has been developed with better adhesive characteristics, nine-fold greater bioavailability, and improved form factor.

0752 JZP-258 Dose Titration and Transition from Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Narcolepsy With Cataplexy

Introduction Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate (at same concentration as SXB) with 92% less sodium. JZP-258 dose adjustment during titration was evaluated. Methods At study entry, participants were taking SXB only, SXB+other anticataplectics, anticataplectics other than SXB, or were cataplexy treatment-naive. JZP-258 treatment began during a 12-week, open-label optimized treatment and titration period. Participants taking SXB only or SXB+other anticataplectics transitioned to JZP-258 at the same gram-for-gram dose as SXB and titrated to an efficacious and tolerable (optimal) dose from weeks 3-12. Participants taking other anticataplectics or who were anticataplectic-naive initiated JZP-258 at 4.5 g/night and were titrated to an optimal dose at 1-1.5 g/night/week (maximum total dose, 9 g/night). A 2-week stable-dose period and 2-week, double-blind, randomized withdrawal period followed. Results During the stable-dose period, total nightly JZP-258 dose (median [range]) was higher in participants taking SXB at study entry (SXB-only, 7.5 g [4.5-9.0], n=45; SXB+other anticataplectics, 9.0 g [6.0-9.0], n=14) compared with those not taking SXB (other anticataplectics, 7.5 g [4.5-9.0], n=23; anticataplectic-naive, 7.0 g [3.0-9.0], n=67), and dose adjustments were fewer. In most (69%) participants taking SXB at study entry who entered the stable-dose period, no change in dose was required (median [range] number of adjustments was 0 ([0-8]); for those with a change in dose, most changes were within one titration step (1.5 g/night). In participants not taking SXB at study entry, the median (range) number of adjustments was 3.0 (0-7). Conclusion Most participants taking SXB at study entry transitioned to JZP-258 treatment at the same dose with retained effectiveness. Participants not previously taking SXB achieved a tolerable and efficacious dose of JZP-258 after a median of 3 adjustments. Support Jazz Pharmaceuticals

0950 Effects of Sodium Oxybate (SXB) on Body Mass Index (BMI) in Pediatric Patients With Narcolepsy

Introduction Obesity is a common comorbidity of pediatric narcolepsy. SXB is a standard of care for cataplexy and excessive daytime sleepiness in narcolepsy. BMI decreases have been observed with SXB treatment. We examined BMI changes by BMI percentile category at study entry in pediatric participants. Methods Participants were aged 7-17 years with narcolepsy with cataplexy. SXB-naive participants were titrated to an optimal SXB dose, then entered a 2-week stable-dose period; participants taking SXB at study entry entered a 3-week stable-dose period. After a 2-week, placebo-controlled, double-blind, randomized-withdrawal period, all participants entered an open-label safety period (total study duration: ≤1 year). Weight categories were defined using BMI percentiles at study entry based on growth charts from the Centers for Disease Control. BMI percentile was categorized as: underweight (&lt;5%ile), normal (≥5%ile to &lt;85%ile), overweight (≥85%ile to&lt;95%ile), obese (≥95%ile). Results Among SXB-naive participants, median (Q1, Q3) BMI percentile decreased with SXB treatment in participants who were categorized as normal-weight and overweight/obese at baseline (normal-weight, n=16: 76.5 [57.8, 82.4] at baseline, 35.0 [20.5, 62.6] at week 52; overweight/obese, n=35: 97.6 [93.6, 99.1] at baseline, 86.7 [72.5, 97.9] at week 52). Of participants who were normal-weight at baseline, 15/16 remained normal-weight at week 52. Of participants who were overweight at baseline, 9/10 were normal-weight at week 52. Of participants who were obese at baseline, 7/25 were normal-weight, 3/25 were overweight, and 15/25 remained obese at week 52. Among participants taking SXB at study entry, BMI percentile decreased, but to a lesser degree. Decreased weight or weight loss was reported as an adverse event in 13 participants (11 SXB-naive; 1 participant withdrew). Four participants became underweight during the study but returned to normal-weight by study end. Conclusion Decreases in BMI percentile and category were observed with SXB treatment in pediatric participants with narcolepsy. Support Jazz Pharmaceuticals