TO COMPARE THE EFFICACY OF INTRA CERVICAL FOLEY’S CATHETER WITH INTRA CERVICAL DINOPROSTONE GEL IN CERVICAL RIPENING FOR THE SUCCESSFUL INDUCTION OF LABOR

Background: This study compared the efficacy and safety of the intracervical Foley catheter and dinoprostone insert for cervical ripening to achieve successful labor induction. Methods: This was a randomized controlled study conducted. Group A received Dinoprostone cervical gel 0.5mg instilled in the cervical canal. Maximum of three doses (1.5mg dinoprostone) could be administered 6 hours apart. Patients randomized to group B were subjected to Foleys catheter insertion. Primary efficacy parameter was change in Bishops score as compared to baseline. Conclusion: Our study showed that for pre induction cervical ripening there was no difference in efficacy between intracervical Foleys catheter and PGE2 gel. Keywords: Foleys catheter, Induction of labour, Prostaglandins

Peroxynitrous Acid Generated In Situ from Acidified H2O2 and NaNO2. A Suitable Novel Antimicrobial Agent?

Peroxynitrite (ONOO−) and peroxynitrous acid (ONOOH) are known as short acting reactive species with nitrating and oxidative properties, which are associated with their antimicrobial effect. However, to the best of our knowledge, ONOOH/ONOO- are not yet used as antimicrobial actives in practical applications. The aim is to elucidate if ONOOH generated in situ from acidified hydrogen peroxide (H2O2) and sodium nitrite (NaNO2) may serve as an antimicrobial active in disinfectants. Therefore, the dose-response relationship and mutagenicity are investigated. Antimicrobial efficacy was investigated by suspension tests and mutagenicity by the Ames test. Tests were conducted with E. coli. For investigating the dose-response relationship, pH values and concentrations of H2O2 and NaNO2 were varied. The antimicrobial efficacy is correlated to the dose of ONOOH, which is determined by numerical computations. The relationship can be described by the efficacy parameter W, corresponding to the amount of educts consumed during exposure time. Sufficient inactivation was observed whenever W ≥ 1 mM, yielding a criterion for inactivation of E. coli by acidified H2O2 and NaNO2. No mutagenicity of ONOOH was noticed. While further investigations are necessary, results indicate that safe and effective usage of ONOOH generated from acidified H2O2 and NaNO2 as a novel active in disinfectants is conceivable.

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration–time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration–time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056

Effect of PARP Inhibitors as Maintenance Treatment on Restricted Mean Survival Time in Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review and Meta-analysis

Background Earlier trials on the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors in platinum-sensitive relapsed ovarian cancer used the hazard ratio (HR) as an efficacy parameter. Objective The present meta-analysis was focused on improving the robustness and clinical interpretability of the efficacy evaluation of PARP inhibitors using the restricted mean survival time (RMST). Methods A search for relevant studies published up to July 31, 2020, was performed in electronic databases to identify eligible trials comparing PARP inhibitors with placebo. The difference in RMST was used as a PARP inhibitor efficacy parameter. Combined differences in RMST with 95% CIs across studies were calculated using a random-effects model. Results Four trials (6 articles) were assessed, including 1079 patients treated with PARP inhibitors and 598 with placebo. The combined RMST differences for up to 360 days (PARP inhibitors minus placebo: point estimate and 95% CI) among all patients and the patients of subgroups with BRCA mutations, homologous recombination-deficient (HRD) carcinoma, and BRCA wild-type carcinoma were 87 days (95% CI = 71, 102), 112 days (95% CI = 96, 129), 99 days (95% CI = 80, 119), and 69 days (95% CI = 47, 92), respectively. The combined RMST differences for up to 660 and 720 days were also larger among patients with BRCA mutations than among those with HRD carcinoma. Conclusion and Relevance Based on using the RMST difference as an alternative measure to the HR, this meta-analysis suggests that PARP inhibitors are the most effective for patients with BRCA mutations, followed by patients with HRD carcinoma.

Comparative analysis of efficacy and safety of Bilastine 20 mg and Levocetirizine 5 mg in the treatment of Allergic Rhinoconjunctivitis

Objective: The present study was conducted to assess the efficacy and safety of bilastine 20 mgand compare the results with that of levocetirizine 5 mg in the treatment of allergicrhinoconjunctivitis. Material and Methods: It was a prospective study conducted in theDepartment of Ophthalmology and Department of Otorhinolaryngology at a tertiary institute ofsouthern Rajasthan, India during the period of 6 months from September 2019 to February 2020.100 patients of chronic allergic rhinoconjunctivitis were included in the study, of which 50 weretreated with Bilastine 20 mg, and the rest 50 patients were treated with levocetirizine 5 mg. Theprimary assessment was done by calculating the total symptom score (TSS) before and after the 7thand 14th post-treatment day. Results: The age of the patients ranges from 10 years to 65 yearswith a mean age of 32±5.2 years. The primary efficacy parameter for assessment was a reduction intotal symptom score (TSS). Both bilastine 20 mg and levocetirizine 5 mg significantly reduced theTSS on the 7th and 14th post-treatment days (p-value< 0.001). There was no significant differencebetween TSS of bilastine and levocetirizine after 7 days (p-value= 0.41) and after 14 days treatment(p-value= 0.68). Adverse events were reported by 10% of patients in the bilastine group and by38% of patients in the levocetirizine group. Conclusion: Bilastine is a selective H1 antihistaminewith good efficacy and excellent safety profile and it is highly recommended to use it as a first-linetreatment for allergic rhinoconjunctivitis.

Melting points of one- and two-component molecular crystals as effective characteristics for rational design of pharmaceutical systems

Based on the review of the literature results the database of the fusion temperatures of two-component molecular crystals (1947 co-crystals) and individual components thereof was built up. To improve the design of co-crystals with predictable melting temperatures, the correlation equations connecting co-crystals and individual components melting points were deduced. These correlations were discovered for 18 co-crystals of different stoichiometric compositions. The correlation coefficients were analysed, and the conclusions about the main/determinative and slave components of a co-crystal were made. The comparative analysis of the melting points of co-crystals composed from the same components but with different stoichiometry showed a co-crystal melting temperature growth when increasing the content of a high-melting component. The differences in the melting temperatures were determined and discussed for the following: (a) monotropic polymorphic forms, (b) two-component crystals with the same composition and different stoichiometry, and (c) two-component crystals based on racemates and enantiomers. The database analysis revealed the active pharmaceutical ingredients (APIs) and co-formers (CFs) more particularly used for co-crystal design. The approach based on an efficacy parameter allowing the prediction of co-crystals with melting points lower than those of individual compounds was developed.

COMPARISON OF PRE AND POST INDUCTION BISHOPS SCORE IMPROVEMENT IN INTRACERVICAL FOLEY’S CATHETER AND PGE2 GEL

Background: Aim-The success of labor induction depends on the cervical status at the time of induction. Objective- For effective cervical ripening both foley catheter and a dinoprostone gel are used. The aim of this study was to compare the efficacy and safety of the intracervical Foleys catheter and dinoprostone gel in cervical ripening for successful induction of labor. Methods: It was a randomized controlled study conducted in the obstetrics department at SMS Medical College, Jaipur. 100 Women were enrolled with a bishops score <5with various indication for induction of labour. They intracervical Foleys catheter insertion and group B received Dinoprostone gel 0.5mg instilleted intracervical. Maximum of 2 doses dinoprostone gel could be administered 6 hours apart. Primary efficacy parameter was change in Bishops score as compared to baseline. Results: The groups were comparable with respect to maternal age, gestation age, indication of induction and initial Bishop's score. Both the groups showed significant change in the Bishop's score at 12 hr,8.02 ± 3.22 and 7.1 ± 4.48 in Foleys catheter and Dinoprostone gel, respectively, But p value was not statistically significant(0.242). Conclusion- This study shows that both Foleys catheter and Dinoprostone are equally effective in cervical ripening.

A new kinetic method for measuring agonist efficacy and ligand bias using high resolution biosensors and a kinetic data analysis framework

ABSTRACTThe kinetics/dynamics of signaling are of increasing value for G-protein-coupled receptor therapeutic development, including spatiotemporal signaling and the kinetic context of biased agonism. Effective application of signaling kinetics to developing new therapeutics requires reliable kinetic assays and an analysis framework to extract kinetic pharmacological parameters. Here we describe a platform for measuring arrestin recruitment kinetics to GPCRs using a high quantum yield, genetically encoded fluorescent biosensor, and a new analysis framework to quantify the recruitment kinetics. The sensor enabled high temporal resolution measurement of arrestin recruitment to the angiotensin AT1 and vasopressin V2 receptors. The analysis quantified the initial rate of arrestin signaling (kτ), a biologically-meaningful kinetic drug efficacy parameter, by fitting time course data using routine curve-fitting methods. Biased agonism was assessed by comparing kτ values for arrestin recruitment with those for Gq signaling via the AT1 receptor. The kτ ratio values were in good agreement with bias estimates from existing methods. This platform potentially improves and simplifies assessment of biased agonism because the same assay modality is used to compare pathways (potentially in the same cells), the analysis method is parsimonious and intuitive, and kinetic context is factored into the bias measurement.

A pilot-study of hypnotherapy as complementary treatment for pain in chronic pancreatitis

BackgroundChronic pain is the hallmark symptom of chronic pancreatitis (CP). Its treatment is complicated, and often the patients have side-effects notwithstanding that pain is not ameliorated in many cases. Hypnotherapy has been shown to improve symptoms of irritable bowel syndrome including abdominal pain and, as such, may serve as a remedy to relive pain. The aim of this open-label pilot-study was to test the effect of hypnotherapy for pain in patients with CP. MethodsFour patients with CP and chronic abdominal pain were included and followed for four consecutive weeks. The primary efficacy parameter was pain relief. After 1 week of baseline patients received a 1-h session of hypnotherapy. This was repeated at day 15 and day 23 and supplemented by self-administered hypnotherapy. ResultsThree of four participants completed the trial and experienced short lasting pain reduction during the trial. The reported pain relief was in the range of 20%–39% compared to baseline. Hypnotherapy improved self-reported sleep, vitality, and social life. ConclusionsThe results suggest that hypnotherapy may reduce pain related to CP. Furthermore, no adverse effects were reported and the majority of participants completed the trial. Further prospective controlled trials are warranted to examine the potential of hypnotherapy.

Synergistic Effects of Doxorubicin and Cardenolid Glycosides of Calotropis Gigantea Root on Cervical Cancer Hela Cell Line

Cardenolid glycosides (CGs) has been known has high anticancer activity against several types of cancers, for example, breast cancer, lung cancer, prostate cancer, melanoma, neuroblastoma, myeloma and leukemia in the in vitro and in vivo research. The aim of our study was to know the synergistic potency of CGs improving the efficacy of doxorubicin in cervical cancer. Activities from combination of doxorubicin and CGs was measured by MTT colorimetric methode. Combination Index was used as combination efficacy parameter. The results showed that the IC50 of CGs was 1,023 μg/mL. CGs demonstrated selective activity in inhibiting the growth of HeLa cells by selectivity index > 3 (241.9). Combination test for CGs and Doxorubicin showed strong synergistic effect in doses 200 ug/mL Doxorubicin and 1.79 ug/mL CGs. The synergistic effect has been shown by 10 combination doses for the doses below the IC50. CGs increases the efficacy of Doxorubicin for the doses below the IC50, thus CGs can be recommended as co chemotherapy in cervical cancer treatment.