A Bayesian Analysis of the Molnupiravir Trial Data

On October 1st 2021, Merck issued a press release claiming that "molnupiravir (MK-4482, EIDD-2801), an investigational oral antiviral medicine, significantly reduced the risk of hospitalization or death at a planned interim analysis of the Phase 3 MOVe-OUT trial in at risk, non-hospitalized adult patients with mild-to-moderate COVID-19." Specifically, 28/385 (7.3%) of patients who received molnupiravir were hospitalized or died, compared to 53/377 (14.1%) in the placebo control group. In order to quantify the evidence that molnupiravir is indeed effective, we conducted a Bayesian logistic regression. Our Bayesian analysis confirms that the molnupiravir data are indeed promising. A default analysis raises the probability for H+ from 0.50 to about 0.97 and is robust to a range of prior specifications. Nevertheless, the evidence is not so compelling as to rule out H0 almost entirely – its strength is the statistical equivalent of throwing two consecutive sixes with a fair die.

Efficacy and Safety of Ejiao (Asini Corii Colla) in Women With Blood Deficient Symptoms: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

Equus asinus L [Equidae; Asini Corii Colla] (donkey-hide gelatin, Ejiao), a well-known traditional Chinese medicine, has been widely used to nourish the blood, especially for women. The aim of this study was to assess the efficacy and safety of Ejiao in blood-deficient patients. A total of 210 participants were recruited and randomly allocated into the placebo control group and Ejiao-treated group (6 g/day). The primary outcomes on the efficacy of Ejiao included traditional Chinese medicine symptom scores, blood indicators, and SF-36. The secondary outcomes were changes in fireness and safety evaluation. Results showed that Ejiao treatment for 8 weeks had significantly improved dizziness symptoms. Among the tested 24 blood biochemical parameters, the hematocrit and red blood cell numbers decreased in the placebo control group, but decreased significantly less in the Ejiao treatment group. The white blood cell and neutrophil counts increased in the Ejiao group but were within the normal range. In addition, the quality of life improved as the scores in SF-36 domains were significantly higher in the Ejiao group. At the same time, there was no significant change in the fire–heat symptoms score or other safety parameters. Considering all these, our study showed that Ejiao has a promising effect in women suffering from blood deficiency without obvious adverse effects.

Intravenous Dexmedetomidine Administration Prior Anesthesia Induction With Propofol at 4°C Attenuates Propofol Injection Pain: A Double-Blind, Randomized, Placebo-Controlled Trial

Background: Propofol injection pain, despite various interventions, still occurs during the anesthesia induction and causes intense discomfort and anxiety in patients. This study aimed to explore the effect of intravenous dexmedetomidine on propofol injection pain prior to anesthesia induction with propofol at 4°C.Methods: A total of 251 patients (American Society of Anesthesiologists I–II) who underwent oral and maxillofacial surgery were randomly assigned to a combination group (n = 63), lidocaine group (n = 62), dexmedetomidine group (n = 63), and placebo-control group (n = 63); they received 0.5 ug/kg dexmedetomidine prior to anesthesia induction with propofol at 4°C, 40 mg lidocaine, 0.5 ug/kg dexmedetomidine prior to anesthesia induction, and normal saline, respectively. Incidence of pain, pain intensity, and reaction to the pain stimulus were evaluated by using verbal categorial scoring (VCS), a numerical rating scale (NRS), and the Surgical Pleth Index (SPI), respectively. In addition, hemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also measured. The VCS and NRS were evaluated at 5 s after propofol injection. In addition, SPI, HR, and MAP were evaluated at three time points (before anesthesia induction and 5 and 30 s after propofol injection).Results: The incidence of pain in the combination group (51%) was significantly lower than that in the lidocaine group (71%), dexmedetomidine group (67%), or placebo-control group (94%) (p < 0.001). VCS and NRS scores in the combination group were also lower compared with the other three groups (p < 0.001), with no statistically significant differences between the lidocaine group and dexmedetomidine group (p > 0.05). The SPI of the combination group decreased significantly in comparison with the other three groups at 5 s after propofol injection (F = 96.23, p < 0.001) and 30 s after propofol injection (F = 4.46, p = 0.005). Further comparisons between HR and MAP revealed no significant differences across the groups (p > 0.05).Conclusion: Because of the sedative nature of dexmedetomidine and analgesic effect of low temperature, this study showed that intravenous dexmedetomidine prior to anesthesia induction with propofol at 4°C is highly effective in attenuating the incidence and severity of pain during injection compared with lidocaine (40 mg), dexmedetomidine 0.5 ug/kg) and placebo. This approach was not associated with any anesthesia complications.Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR-2000034663

Efficacy of Wang Nam Yen herbal tea on human milk production: A randomized controlled trial

ABSTRACTBackgroundInsufficient milk production is a common problem affecting breastfeeding women, in particular following Cesarean delivery. Wang Nam Yen herbal tea is a promising traditional Thai medicine used by postpartum women to stimulate milk production, as an alternative to pharmaceutical galactagogues. We aimed to compare the efficacy of Wang Nam Yen herbal tea, domperidone, and placebo, in increasing milk production in mothers who underwent Cesarean delivery.MethodsWomen who underwent uncomplicated cesarean delivery at Sunpasitthiprasong Hospital were randomized into three groups. The participants received the treatments daily for three consecutive days. The primary outcome was breast milk volume at 72 hours after delivery. Secondary outcomes were pregnancy and neonatal outcomes, adverse events, and participant satisfaction.ResultsOf the 1,450 pregnant women that underwent cesarean delivery, 120 women were enrolled. Their mean age and gestational ages were 28.7 years and 38.4 weeks, respectively. Breast milk volume at 72 hours postpartum was significantly different among the three groups (p = 0.030). The posthoc Bonferroni correction indicated a significant difference in breast milk volume between Wang Nam Yen herbal tea group and placebo control group (p = 0.007) while there was no difference between Wang Nam Yen herbal tea group and domperidone group (p = 0.806) and between domperidone group and placebo control group (p = 0.018). There was no difference in pregnancy and neonatal outcomes, adverse events, and participant satisfaction among the three groups.ConclusionWang Nam Yen herbal tea was effective in augmenting breast milk production at 72 hours postpartum in mothers following cesarean delivery, and there was no evidence that herbal tea and domperidone differed in terms of augmenting breast milk production.Trial registrationThe study was approved by the institutional review board of Sunpasithiprasong Hospital (No.061/2559) and was registered TCTR20170811003 with the Thai Clinical Trial Registry.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Echinococcus multilocularis infections in cats

NexGard® Combo, a novel topical endectoparasiticide formulation for cats combining esafoxolaner, eprinomectin and praziquantel, for the treatment of internal and external parasite infestations, including arthropods, nematodes and cestodes, was tested for efficacy against induced infections of Echinococcus multilocularis in cats, in two experimental studies. The two studies were performed in the United States with the same E. multilocularis isolate sourced locally. In each study, 20 cats were inoculated intra-gastrically with ~30,000 E. multilocularis protoscoleces three weeks before treatment, then ten cats were randomly allocated to a placebo control group or to the novel formulation treated group. Inoculated cats were treated topically once at the minimum recommended dose of the novel formulation, or with an identical volume of placebo. One week after treatment, cats were humanely euthanized for parasite recovery and count. The efficacy calculation was based on comparison of number of scoleces found in the control group and the novel formulation group. In the two control groups, E. multilocularis scoleces were found in five (range: 30–1025) and eight (range 2–345) cats, the geometric means inclusive of the ten cats per group were 8.9 and 28.8, respectively. In the two novel formulation-treated groups, none of the cats harbored any E. multilocularis scoleces, demonstrating 100% efficacy.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Amblyomma americanum in cats

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide product for cats. The efficacy of this novel formulation was assessed in two experimental studies against induced infestations with Amblyomma americanum, a tick species of major importance, highly prevalent in a large southeastern quarter of the United States. In each study, 10 cats were randomly allocated to a placebo control group and 10 cats to a novel formulation treated group. Infested cats were treated topically once at the minimum recommended dose. Both studies were designed to test curative efficacy on existing infestation, 72 h after treatment, and to test preventive efficacy, 72 h after subsequent weekly (Study #1) or fortnightly (Study #2) infestations for one month. For each infestation, all cats were infested with 50 unfed adult A. americanum. At each tick count, in both studies, at least 8 in 10 placebo control cats were infested with 13 (26%) or more live ticks, demonstrating adequate infestation throughout the studies. Curative efficacy of the novel formulation was 99% in both studies; preventive efficacy was 92% and 100% for at least one month.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Rhipicephalus sanguineus in cats

Esafoxolaner is a purified enantiomer of afoxolaner with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel in a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation was assessed in an experimental study against induced infestation of Rhipicephalus sanguineus ticks. Twenty cats were randomly allocated to either a placebo control group or a treated group in a 1:1 ratio. Infested cats were treated topically once at the minimum recommended dose. The study was designed to assess curative efficacy 48 h after treatment and to test preventive efficacy 48 h after weekly infestations for 2 months. At each weekly infestation, all cats were infested with 25 male and 25 unfed female R. sanguineus ticks. At each tick count, at least 6 in 10 control cats had a retention of 13 (26%) or more live ticks, demonstrating adequate infestation throughout the study. Curative efficacy on existing tick infestation was 90%; preventive efficacy over the following 6 weeks was at least 96%.

Effect of bilateral needling at an acupuncture point, ST-36 (Zusanli) on blood glucose levels in type 2 diabetes mellitus patients: A pilot randomized placebo controlled trial

BackgroundDiabetes mellitus is one of the major current public health problems. Electro-acupuncture at ST-36 showed a significant reduction in plasma glucose levels in diabetic rats. There are lacks of studies reporting its hypoglycemic effect in humans and thus, the present study was conducted to evaluate the effect of needling at ST-36 (Zusanli) on blood glucose levels in patients with type 2 diabetes mellitus (T2DM).MethodsSixty T2DM participants were recruited and randomized into acupuncture group (n=30) and placebo control group (n=30). The participants of the acupuncture group received needling at ST-36 (one finger breadth lateral to the inferior border of the tibial tuberosity), and the participants those in the placebo control group received needling at placebo point (midpoint between the apex of the patella and tibial tuberosity). For both the groups, needles were retained for 30 min. Baseline and post-test assessments were performed prior to and after each intervention. Statistical analysis was performed using SPSS version 16.ResultsThe present study showed a significant reduction in random blood glucose levels in the acupuncture group compared to the placebo control group.ConclusionThis study suggests that 30 min of bilateral acupuncture needling at ST-36 with manual stimulation is effective in reducing blood glucose levels in T2DM patients.