SYNCHRONOUS FLUORESCENCE SPECTROSCOPY COUPLED WITH CONTINUOUS WAVELET TRANSFORMS AND SAVITZKY-GOLAY DERIVATIZATION TECHNIQUE FOR THE SIMULTANEOUS DETERMINATION OF TADALAFIL AND DAPOXETINE HCl.

Objective: A novel combination of Tadalafil (TAD) and Dapoxetine HCl (DAP) has been recently introduced into the market for the treatment of premature ejaculation. The aim of this work is the development and validation of simple, sensitive and accurate analytical methods for the determination of TAD and DAP in their binary mixture without prior separation.Methods: Synchronous fluorescence spectroscopic (SFS) methods coupled with continuous wavelet transforms (CWT) and Savitzky-Golay (SAVGOL) derivatization technique have been developed.Results: Under optimum conditions, TAD and DAP were determined in the concentration ranges of 0.01–3 µg/ml and 0.01–1.2 µg/ml, respectively.Conclusion: The developed methods have the requisite accuracy, selectivity, sensitivity and precision and were satisfactorily applied for the simultaneous determination of TAD and DAP in bulk powder and pharmaceutical preparations. The results obtained for the analysis of both drugs in their pure forms by the proposed methods were statistically compared to those obtained by applying a reported high performance liquid chromatographic method (HPLC) method. The statistical comparison showed that there is no significant difference between the proposed methods and the reported one with respect to accuracy and precision.Keywords: Synchronous fluorescence spectroscopy, Tadalafil, Dapoxetine HCl, Continuous wavelet transforms, Savitzky-Golay techniqu

Clinical and angiographic outcomes with drug-coated balloons for de novo coronary lesions: A meta-analysis of randomized clinical trials

Background The role of drug-coated balloons (DCBs) in the treatment of de novo coronary lesions is not well established. Methods and Results Electronic databases and major conference proceedings were searched for randomized controlled trials that compared DCBs with stents or angioplasty for de novo coronary lesions. The primary outcome was target lesion revascularization. Summary estimates were conducted using random-effects analysis complemented by several subgroup and sensitivity analyses. A total of 14 randomized controlled trials with 2483 patients were included. At a mean follow up of 12 months, DCBs were associated with no difference in the incidence of target lesion revascularization as compared with alternative strategies (risk ratio [RR], 0.79; 95% CI, 0.35-1.76). There was no difference in treatment effect based on the indication (ie, small-vessel disease, myocardial infarction, bifurcation, or high bleeding risk) (Pinteraction=0.22). DCBs were associated with lower target lesion revascularization compared with bare metal stents and similar target lesion revascularization compared with drug-eluting stents (Pinteraction=0.03). There was no difference between DCBs and control in terms of major adverse cardiac events, vessel thrombosis, or cardiovascular mortality. However, DCBs were associated with a lower incidence of myocardial infarction (RR, 0.48; 95% CI, 0.25-0.90) and all-cause mortality (RR, 0.45; 95% CI, 0.22-0.94). Conclusions In patients with de novo coronary lesions, use of DCBs was associated with comparable clinical outcomes irrespective of the indication or comparator device. DCBs had a similar rate of target lesion revascularization compared with drug-eluting stents. A randomized trial powered for clinical outcomes and evaluating the role of DCBs for all-comers is warranted

On the identifiability of steady-state induction machine models using external measurements

A common practice in induction machine parameter identification techniques is to use external measurements of voltage, current, speed, and/or torque. Using this approach, it has been shown that it is possible to obtain an infinite number of mathematical solutions representing the machine parameters. This paper examines the identifiability of two commonly used induction machine models, namely the T-model (the conventional per phase equivalent circuit) and the inverse Γ-model. A novel approach based on the alternating conditional expectation (ACE) algorithm is employed here for the first time to study the identifiability of the two induction machine models. The results obtained from the proposed ACE algorithm show that the parameters of the commonly employed T-model are unidentifiable, unlike the parameters of the inverse Γ-model which are uniquely identifiable from external measurements. The identifiability analysis results are experimentally verified using the measured operating characteristics of a 1.1-kW three-phase induction machine in conjunction with the Levenberg-Marquardt algorithm, which is developed and applied here for this purpose

Mechanical Thrombectomy for Acute Ischemic Stroke A Meta-Analysis of Randomized Trials

AbstractBackgroundAcute ischemic stroke is a leading cause of serious disability and death worldwide. Individual randomized trials have shown possible benefits of mechanical thrombectomy after usual care compared with usual care alone (i.e., intravenous thrombolysis) in the management of acute ischemic stroke patients.ObjectivesThis study systematically determined if mechanical thrombectomy after usual care would be associated with better outcomes in patients with acute ischemic stroke caused by large artery occlusion.MethodsThe authors included randomized trials that compared mechanical thrombectomy after usual care versus usual care alone for acute ischemic stroke. Random effects summary risk ratios (RR) were constructed using a DerSimonian and Laird model.ResultsNine trials with 2,410 patients were available for analysis. Compared with usual care alone, mechanical thrombectomy was associated with a higher incidence of achieving good functional outcome, defined as a modified Rankin scale (mRS) of 0 to 2 (RR: 1.45; 95% confidence interval [CI]: 1.22 to 1.72; p < 0.0001) and excellent functional outcome defined as mRS 0 to 1 (RR: 1.67; 95% CI: 1.27 to 2.19; p < 0.0001) at 90 days. There was a trend toward reduced all-cause mortality with mechanical thrombectomy (RR: 0.86; 95% CI: 0.72 to 1.02; p = 0.09). The risk of symptomatic intracranial hemorrhage was similar with either treatment modality (RR 1.06: 95% CI: 0.73 to 1.55; p = 0.76).ConclusionsIn acute ischemic stroke due to large artery occlusion, mechanical thrombectomy after usual care was associated with improved functional outcomes compared with usual care alone, and was found to be relatively safe, with no excess in intracranial hemorrhage. There was a trend for reduction in all-cause mortality with mechanical thrombectomy

Ligand-based design, synthesis, computational insights, and in vitro studies of novel N-(5-Nitrothiazol-2-yl)-carboxamido derivatives as potent inhibitors of SARS-CoV-2 main protease

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series o

Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study)

Introduction: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. Methods: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo. The primary end point was change in angina at 16 weeks as assessed by the Seattle Angina Questionnaire (SAQ). Results: Between September 2014 and January 2016, 25 subjects were randomized to ranolazine versus 25 to placebo. The most common reason for eligibility was CTO (72%), while the remainder had myocardial ischemia documented by low FFR. The mean FFR was 0.57 ± 0.12. Sixty-eight percent of subjects were on two or more anti-angina medications at baseline. Study medication was discontinued in 32% (eight of 25) of the ranolazine group versus 36% (nine of 25) of the placebo group. By intention-to-treat, 46 subjects had baseline and follow-up SAQ data completed. Ranolazine was not associated with an improvement in angina compared with placebo at 16 weeks. The results were similar among 33 subjects that completed study medication. The incidence of ischemia-driven hospitalization or catheterization was 12% (three of 25) of the ranolazine group versus 20% (five of 25) in the placebo group (p \u3e 0.05). Conclusions: In subjects with chronic stable angina and documented myocardial ischemia, ranolazine did not improve angina symptoms at 16 weeks

Efficacy and safety of Elagolix in the treatment of endometriosis associated pain: a systematic review and network meta-analysis

Background: Endometriosis commonly presents with dysmenorrhea, non-menstrual pelvic pain, and infertility. Elagolix is an oral, short-acting, gonadotropin-releasing hormone antagonist acting through complete estrogen suppression. Objective: To evaluate the evidence from published randomized controlled trials (RCTs) about the efficacy and safety of Elagolix in the treatment of endometriosis associated pain. Search strategy: Electronic databases containing articles published between January 2000 and February 2020 were searched using the MeSH terms (Elagolix OR gonadotropin-releasing hormone antagonist OR GnRH antagonist OR antigonadotropin) AND (endometriosis) AND (pelvic pain). Selection criteria: All RCTs assessing the efficacy of Elagolix in the treatment of pain associated with endometriosis were considered for this network meta-analysis, where five studies were deemed eligible for this review. Data collection and analysis: The mean difference (MD) and confidence intervals (95% CI) for continuous outcomes including analgesic use, dysmenorrhea, non-menstrual pelvic pain, and quality of life were calculated. Main results: Elagolix 250 mg reduced dysmenorrhea significantly, as compared to placebo, (MD = -0.41, 95% CI [-0.7, -0.13]) at 12 weeks, while Elagolix 200 mg reduced dysmenorrhea significantly (MD= -1.2, 95% CI [-1.9, -0.57]) compared to placebo after 24 weeks of treatment. Conclusions: Elagolix 200 mg seems to be an effective drug with fewer side effects when used to reduce dysmenorrhea and non-menstrual pelvic pain after 24 weeks of treatment in patients with endometriosis

Sex Differences in Trends and In-Hospital Outcomes among Patients with Critical Limb Ischemia: A Nationwide Analysis

Background Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and is associated with significant mortality and morbidity. Contemporary data comparing the sex differences in trends, revascularization strategies, and in-hospital outcomes among patients with CLI are scarce. Methods and Results Using the National Inpatient Sample database years 2002 to 2015, we identified hospitalizations for CLI. Temporal trends for hospitalizations for CLI were evaluated. The differences in demographics, revascularization, and in‐hospital outcomes between both sexes were compared. Among 2 400 778 CLI hospitalizations, 43.6% were women. Women were older and had a higher prevalence of obesity, hypertension, heart failure, and prior stroke. Women were also less likely to receive any revascularization (34.7% versus 35.4%, P\u3c 0.001), but the trends of revascularization have been increasing among both sexes. Revascularization was associated with lower in‐hospital mortality among women (adjusted odds ratio [OR], 0.76; 95% CI, 0.71–0.81) and men (adjusted OR, 0.69; 95% CI, 0.65–0.73). On multivariable analysis adjusting for patient‐ and hospital‐related characteristics as well as revascularization, women had a higher incidence of in‐hospital mortality, postoperative hemorrhage, need for blood transfusion, postoperative infection, ischemic stroke, and discharge to facilities compared with men. Conclusions In this nationwide contemporary analysis of CLI hospitalizations, women were older and less likely to undergo revascularization. Women had a higher incidence of in‐hospital mortality and bleeding complications compared with men. Sex‐specific studies and interventions are needed to minimize these gaps among this high‐risk population