Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study.Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].

Meta-analysis of the efficacy and safety of finerenone in diabetic kidney disease

Background: The Phase III clinical trial of the non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been completed, aiming to investigate renal and cardiovascular (CV) outcomes in type 2 diabetes (T2D) with chronic kidney disease (CKD). However, the efficacy and safety of finerenone in renal function remain controversial. The purpose of this study was to explore the efficacy and safety of finerenone in treating the patients with diabetic kidney disease (DKD). Methods: Databases of PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) on patients with DKD receiving finerenone treatment from inception to September 2021. Data including patient characteristics and interested outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean differences (MD) with 95% CIs, respectively. Results: A total of 4 RCTs involving 13945 patients were included in this meta-analysis. Analysis results demonstrated that patients receiving finerenone showed a significant decrease in changing urinary albumin-to-creatinine ratio (UACR) from baseline (MD: ﹣0.30; 95%CI [﹣0.33, ﹣0.27] P=0.46, I2=0%) (P＜0.05). The number of patients with ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline in the finerenone group was significantly smaller than that in the placebo group (RR: 0.85; 95%CI [0.78, 0.93] P=0.60, I2=0%) (P＜0.05). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95%CI [0.98, 1.01] P = 0.94, I2=0%) (P=0.65). The incidence of hyperkalemia was higher in the finerenone group than that in the placebo group (RR: 2.03; 95%CI [1.83, 2.26] P = 0.95, I2=0%) (P＜0.05). Conclusion: Finerenone contributes to the reduction of UACR and can ameliorate the deterioration of renal function in patients with T2D and CKD. The higher risk of hyperkalemia was found in the finerenone group compared with placebo, however, there was no difference in the risk of overall adverse events.

Double-blind, Randomized, Placebo-Controlled study to evaluate the Efficacy of an early treatment with Herbal Supplement based in the Prevention of Post-Traumatic Stress Disorder in emergency department (PHYTéS Study)

Introduction: The prevention from Post-traumatic stress disorder (PTSD) is therefore of major public health interest and one of the concerns of any emergency physician. The purpose of our study was to evaluate the efficacy and safety of an herbal supplement to prevent the occurrence of PTSD in high-risk patients. Methods: It is a randomized, double-blind, prospective, interventional study including patients exposed to a potentially traumatic event that meets DSM-V Criterion A and has a Peri-traumatic Distress Inventory score or the Questionnary for traumatic dissociation experiments (PDEQ) and/or L.Crocq score higher than the thresholds between day 1 and day 3. Two hundred patients were included randomly assigned into two groups: Aleozen group and placebo group. Patients included in aleozen group received Aleozen® for 10 days while patients in placebo group received Placebo. A CAPS-5 assessment was performed for all patients at different moments. The main objective was to assess the efficacy of Aleozen after 90 days of an exposition to traumatic events according to PTSD. Secondary objectives were to evaluate the safety of Aleozen® at 10 and 30 days after its administration and PTSD in the study population after one year of inclusion. Results: No statistical differences were noted between the two groups in term of baseline characteristics including age, sex and the ISS score. After 90 days of follow-up, and according to the CAPS-5 scale, 85 patients (42.5%) of the population study showed PTSD. Concerning primary endpoint, less PTSD were seen in intervention group compared to placebo group (38.8% versus 61.2% respectively; p<0.001). During the study, no adverse events were noted. Conclusion: Results of this work suggest the potential preventive effects of an herbal supplement on PTSD for traumatic patient in emergency. Further confirmatory studies are needed.

Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype

Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs ( PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene–gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.

Granisetron Augmentation of Sertraline in Obsessive-Compulsive Disorder: A Double-Blind Placebo-Controlled, Randomized Clinical Trial

Background: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20–30%, and satisfactory treatment is obtained in 40–60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients’ function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms.In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. Methods: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS.Results: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron and 27.5 to 19.3 for placebo group with a slightly greater drop for granisetron group), while the granisetron group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57)=4.52,p-value=0.01). Moreover, in comparison with the placebo group, the proportion of the patients showing complete response was considerably higher among the granisetron group (P-value <0.01). No major adverse effects were observed in any of the groups. Conclusion: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.Trial registration: The trial was registered at the Iranian Registry of Clinical Trials on 27/03/2019 (www.irct.ir; IRCT ID: IRCT20170123032145N3).

The Effectiveness of 0.2% Chlorhexidine Gel on Early Wound Healing after Tooth Extraction: A Randomized Controlled Trial

Objective This study aimed to evaluate the effect of 0.2% chlorhexidine (CHX) gel on wound healing after tooth extraction. Materials and Methods A single blind, randomized controlled trial was performed recruiting 32 participants who underwent dental extractions. Patients were randomly allocated for CHX group or placebo group. The primary outcomes were wound closure measured with calipers and healings were assessed by Landry et al index after 7 days of topical application of allocated gels on extraction sites. Results The wound closures were greater in CHX group compared with placebo group and healing scores were correlated with the use of CHX gel (p-value < 0.05). Conclusion In a population of healthy nonsmoker adults, application of 0.2% CHX gel twice a day for 7 days after tooth extraction has a beneficial effect on wound healing.

Delta Tocotrienol as a Supplement to FOLFOXIRI in First Line Treatment of Metastatic Colorectal Cancer. A Randomized, Double-blind, Placebo-controlled Phase II Study

Purpose Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with its possible neuroprotective and anti-inflammatory effects reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo controlled trial in mCRC patients receiving first line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI).Methods We randomly assigned 70 mCRC patients to FOLFOXIRI plus δ-tocotrienol or FOLFOXIRI plus placebo. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo x 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy.Results Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio (HR) of 0.70 (95% CI 0.36-1.36, p=0.29)). In the placebo group 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p=0.047).Conclusion The addition of δ-tocotrienol to FOLFOXIRI did not significantly prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different between the two groups. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.Clinicaltrials.gov identifier NCT02705300. Date of registration March 10, 2016.

Effects of luteolin-rich chrysanthemum flower extract on purine base absorption and blood uric acid in Japanese subjects

Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels. Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE. Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia. Trial Registration: UMIN-CTR: UMIN000042327Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd. Keywords: Chrysanthemum, luteolin, uric acid, purine base

Finally, an FDA Approval for an Immunization Against COVID-19: Hope on the Horizon

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018—October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.