Mg In Terms Research Articles

Glycaemic control, body weight, and safety of tirzepatide versus dulaglutide by baseline glycated haemoglobin level in Japanese patients with type 2 diabetes: A subgroup analysis of the SURPASS J-mono study.

To evaluate glycaemic control, body weight, and safety outcomes following treatment with tirzepatide or dulaglutide in patients with type 2 diabetes (T2D) with a baseline haemoglobin (HbA1c) level of ≤8.5% (≤69 mmol/mol) versus >8.5% (>69 mmol/mol). SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, phase 3 study conducted in Japan. In this exploratory subgroup analysis of SURPASS J-mono, we examined mean change in HbA1c and body weight and the incidence of adverse events (AEs) in patients with a baseline HbA1c of ≤8.5% versus >8.5% after treatment with tirzepatide (5, 10 or 15 mg) or dulaglutide 0.75 mg. Of 636 randomized participants, 203 had a baseline HbA1c of >8.5% and 433 had a baseline HbA1c of ≤8.5% (range ≥7.0% to ≤10.0%). Both subgroups showed significantly greater reductions in HbA1c and body weight with any-dose tirzepatide versus dulaglutide 0.75 mg, with greater HbA1c reductions observed in patients with a baseline HbA1c of >8.5% treated with tirzepatide (least squares mean [LSM] differences of -3.13% to -3.86%) or dulaglutide (LSM -1.81%) compared with patients with a baseline HbA1c of ≤8.5% (LSM -2.00% to -2.32%) or dulaglutide (LSM -1.05%; treatment-by-baseline HbA1c subgroup interaction P ≤ 0.001). For the tirzepatide treatment arms, LSM change from baseline in body weight ranged from -6.7 to -10.7 kg for the baseline HbA1c ≤8.5% subgroup and from -4.0 to -10.6 kg for the baseline HbA1c >8.5% subgroup, compared with -0.6 kg and -0.4 kg, respectively, for the dulaglutide arm. The incidence of hypoglycaemia was low, with no substantial difference in hypoglycaemia or treatment-emergent AEs between subgroups. Regardless of baseline HbA1c (≤8.5% or >8.5%), tirzepatide at doses of 5, 10 and 15 mg is effective in Japanese patients with T2D compared with dulaglutide 0.75 mg in terms of glycaemic control and body weight reduction, with an adequate safety profile consistent with previous reports.

Effect of Al addition on corrosion behavior of high-purity Mg in terms of processing history

Effect of Al addition on corrosion behavior of high-purity Mg in terms of processing history

Abstract PD17-12: Primary efficacy and safety results from the AMALEE trial evaluating 600 mg vs 400 mg starting doses of first-line ribociclib in patients with HR+/HER2− advanced breast cancer

Abstract Background: In the Phase III MONALEESA (ML)-2, -3 and -7 trials, a 600 mg dose of ribociclib (RIB) demonstrated significant overall survival benefit in patients (pts) with HR+/HER2− advanced breast cancer (ABC) but was associated with QTcF (>480 ms, 3%-7%) and neutropenia (G3/4, 57%-64%) adverse events (AEs) which were managed by dose reductions. The Phase II AMALEE study was performed as a postmarketing commitment to assess whether reducing the starting dose of RIB from the recommended dose (3 wk on, 1 wk off) of 600 mg/day to 400 mg/day decreases QTcF prolongation without compromising the efficacy of first-line RIB in pts with HR+/HER2− ABC. Here, we present efficacy and safety results from the primary analysis of AMALEE. Methods: AMALEE is a randomized Phase II open-label study including pre- and postmenopausal pts with HR+/HER2− ABC with no prior therapy for ABC. Pts received RIB 400 mg + nonsteroidal aromatase inhibitor (NSAI) or RIB 600 mg + NSAI. The primary endpoint is to determine whether overall response rate (ORR) in the 400 mg arm is noninferior to the 600 mg arm. The key secondary endpoint is QTcF prolongation at cycle 1, day 15 (C1D15) 2 hours post dose. Additional endpoints included safety, progression-free survival (PFS), duration of response (DOR), time to response (TTR), and pharmacokinetics. Results: A total of 376 pts were randomized 1:1 to receive RIB at either 400 mg or 600 mg doses. Baseline (BL) characteristics and prior antineoplastic therapy were balanced across treatment (tx) arms. At the time of the data cutoff (June 11, 2021), median follow-up was 14.9 mo (min, 6.1; max, 23.8), and all pts had been treated for ≥6 months from randomization or had discontinued study tx. ORR for RIB was 41.5% (95% CI, 34.4-48.7) with 400 mg vs 45.3% (95% CI, 38.1-52.6) with 600 mg (ORR ratio for RIB 400 mg vs 600 mg, 0.921 [90% CI, 0.757-1.121]). The lower 90% CI boundary did not meet the prespecified noninferiority (NI) margin of 0.814. Results for ORR by subgroups were consistent with the overall analysis set. RIB plasma exposure was lower at 400 mg than 600 mg; the geometric mean Cmax and AUC0-24h at C1D15 were approximately 28% and 43% lower in the 400 mg than the 600 mg arm (Cmax 1080 vs 1500 ng/mL and AUC0-24h 16400 vs 28600 ng × h/mL). This study met the key secondary endpoint, change in QTcF at C1D15 in the RIB 400 mg group with a 90% CI upper boundary of < 20 ms. Mean change in QTcF from BL to C1D15 2 hours post dose was lower in the 400 mg (12.5 ms, 90% CI, 10.9-14.1) than the 600 mg arm (19.7 ms, 90% CI, 17.4-22.0). QTcF ≥501 ms occurred in 1.6% of pts in the 400 mg arm vs 0.5% in the 600 mg arm. Rates of G3/4 neutropenia were lower in the 400 mg (31.4%) than the 600 mg arm (46.3%). Other safety results were consistent with those previously reported for RIB in the ML trials. Median duration of exposure to RIB was 8.0 mo (min, 0.1; max, 23.7) in the 400 mg arm vs 8.8 mo (min, 0.5; max, 20.8) in the 600 mg arm. Dose reductions of RIB were more frequent in the 600 mg group with 30.5% vs 13.8% of pts requiring 1 dose reduction in the 600 mg and 400 mg groups, respectively. Dose reductions were primarily attributable to AEs, with neutropenia being the most frequently reported AE requiring a dose modification. Rates of discontinuation due to AEs were similar in the 400 mg vs 600 mg arms (8.5% vs 9.6%). PFS, DOR, and TTR data are currently immature. Conclusions: RIB at the 400 mg dose shows a better safety profile vs 600 mg in terms of key AEs that are RIB concentration dependent (neutropenia and QTcF prolongation). ORR was 3.8% lower with 400 mg than 600 mg. The lower 90% CI boundary of the ORR ratio did not meet the NI margin, thus this study was unable to demonstrate statistical NI of the 400 mg vs 600 mg dose of RIB using ORR as the endpoint. Updated results with additional follow-up and the clinically relevant endpoint PFS will be presented at the congress. Citation Format: Fatima Cardoso, William Jacot, Sherko Küemmel, Sudeep Gupta, Rama Balaraman, Liudmila Lebedeva, Yan Ji, Aparna Lakshmanan, Khalid Amin, Zheng Li, Joseph Sparano. Primary efficacy and safety results from the AMALEE trial evaluating 600 mg vs 400 mg starting doses of first-line ribociclib in patients with HR+/HER2− advanced breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD17-12.

A unique formulation of sodium bicarbonate buffered pantoprazole powder for oral suspension: perspectives from an active controlled cross-over bioequivalence study

Background: The aim was determining bioequivalence between pantoprazole buffered powder for oral suspension and pantoprazole enteric coated tablets under fasting conditions in healthy volunteers.Methods: In randomized cross-over study, participants were administered a single oral dose of pantoprazole powder as suspension 40 mg (sodium bicarbonate as buffer) or one enteric coated tablet of pantoprazole 40 mg, with 240±2 ml of water as per the randomization schedule in each study period. Blood samples were collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12-, 14-, 16- and 24-hours post-dose. Plasma concentration of pantoprazole was determined with LC-MS and various pharmacokinetic parameters like Cmax, AUC0-t, AUC0-inf were compared between test and reference groups.Results: Amongst 41 samples, Cmax (3752.4±1084.6 vs. 3521.7±1099.5 ng/ml) was achieved higher in less Tmax time (1 (0.28) vs. 2.3 (0.83) hrs) with test drug as compared to reference drug. The ratios of geometric least square mean and its 90% confidence interval on log transformed Cmax, AUC0-t and AUC0-inf for pantoprazole fall within the acceptance criteria of 80% to 125%. No adverse events were observed.Conclusions: Pantoprazole powder for oral suspension 40 mg (sodium bicarbonate as buffer) was well tolerated and bioequivalent with pantoprazole enteric coated tablets IP 40 mg in terms of rate and extent of absorption under fasting conditions. At same time, the shift in AUC to the left with reduction in Tmax with the new formulation is suggestive of faster rate of absorption.

Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis.

Janus kinase (JAK) inhibitors have become promising treatments for atopic dermatitis (AD), however no study directly comparing JAK inhibitors with each other has been reported. We conducted this network meta‐analysis to determine the comparative efficacy and safety of three common oral JAK inhibitors including abrocitinib, baricitinib, and upadacitinib for moderate‐to‐severe AD. We first identified eligible studies from published meta‐analyzes, then we searched PubMed to obtain additional studies published between February and July 2021. Clinical efficacy and safety were evaluated as primary and secondary outcome, respectively. After extracting data and assessing methodological quality, we utilized ADDIS 1.4 software to conduct pair‐wise and network meta‐analyzes. Ten eligible studies were included in the final analysis. Pooled results that abrocitinib, baricitinib, and upadacitinib obtained higher investigator global assessment (IGA), eczema area, and severity index (EASI) response, however abrocitinib and upadacitinib caused more treatment‐emergent adverse events (TEAEs) regardless of doses, compared with placebo. Network meta‐analyzes revealed that upadacitinib 30 mg was superior to all regimens and upadacitinib 15 mg was better than remaining regimens except for abrocitinib 200 mg in terms of IGA and EASI response. Moreover, abrocitinib 200 mg was superior to abrocitinib 100 mg, baricitinib 1 mg, 2 mg, and 4 mg for clinical efficacy. However, upadacitinib 30 mg caused more TEAEs. Abrocitinib, baricitinib, and upadacitinib were consistently effective therapies in adult and adolescent patients with AD; however, upadacitinib 30 mg may be the optimal option in short‐term studies. More efforts should be done to reduce the risk of TEAEs caused by upadacitinib 30 mg.

On FTMP-based Interpretation of Kink Formation MFS Materials

Based on the prominent descriptive capability of the FTMP-based kink simulations, the ultimate goal is ought to be an overall reproduction of the experimentally-documented complex behavior of LPSO Mg in terms of kink band formations. This study examines one of the possible viewpoint for it to be done about their “scale-free” nature of the energy-releasing characteristics reported with respect to the AE measurement based on FTMP interaction field formalism. Demonstrated preliminarily are a significant change in the kink morphology, while maintaining appropriate “primary strengthening”, together with an improved return map characteristic.

Sympathometabolic profile of a fixed combination of lercanidipine with enalapril in the treatment of obese hypertensive patients (study review)

The publication highlights the main possibilities of fixed combinations of angiotensin-converting enzyme inhibitors with calcium channel blockers in the treatment of hypertension and the advantages of the combination of enalapril 20 mg / lercanidipine 10 mg in terms of sympathomodulatory properties. Clinical data are provided that indicate the benefit of using this combination in patients with hypertension and concomitant obesity

Some groups of drugs which use is associated with development of drug-induced atrial fibrillation

Recently, more and more attention has been paid to the problem of drug‑induced (DI) atrial fibrillation (AF). It is known that the development of DI AFcan be associated with the intake of cardiovascular and anticancer drugs, drugs that affect the central nervous system or respiratory organs. However,there are other drugs that can provoke DI AF, which practitioners are less aware of. This article is a review of the current literature on DI AF associated withthe intake of other groups of drugs and individual drugs that are not included in the above groups. Analysis of the available literature has shown that theincidence of DI AF reaches 6.9% when taking zoledronic acid and 1.5% when taking alendronate, although data from different authors regarding thecausal relationship between bisphosphonate therapy and the development of AF are ambiguous. The use of high doses of glucocorticosteroids (at a dailydose of ≥ 7.5 mg in terms of prednisolone) is also associated with an increased risk of AF (OR = 6.07; 95% CI: 3.90–9.42). Treatment with non‑steroidal anti‑inflammatory drugs is also associated with a higher risk of developing DI AF compared to those who do not use it – the incidence rate is 1.17 (95% CI:1.10–1.24) for nonselective and 1.27 (95% CI: 1.20–1.34) for cyclooxygenase‑2 inhibitors. The literature contains a description of clinical cases of DI AF whiletaking immunosuppressants (azathioprine, methotrexate + etanercept, fingolimod, cyclosporine), drugs that affect the genitourinary system (vardenafil,sildenafil, yohimbine hydrochloride, hexoprenaline), local anesthetics, bupacaero testosterone, stanozolol, testosterone cypionate, nandrolone decanoateextraboline) and nicotine‑containing products (nicotine‑containing chewing gum).

Is the effect of atorvastatin 60 mg on stabilization of lipid-rich plaque equivalent to that of rosuvastatin 10 mg? A serial optical coherence tomography combined with intravascular ultrasound imaging.

This study aimed to compare the effect of atorvastatin 60 (AT60) mg to that of rosuvastatin 10 (RT10) mg on the morphological changes in lipid-rich plaques (LRPs) and plaque volume, using serial optical coherence tomography (OCT) and intravascular ultrasound imaging (IVUS). Intensive lipid lowering therapy by statin provides more clinical benefit compared to that of moderate lipid lowering therapy. Fifty patients who underwent OCT and IVUS at baseline, 6, and 12 months were grouped by statin therapy into the AT60 mg (n = 27) and RT10 mg (n = 23) groups. The relationships between absolute and percentage changes in biomarkers and fibrous cap thickness (FCT) during follow-up were investigated using a simple regression analysis. At 6 months, the mean low-density lipoprotein cholesterol level reduced from 113.5 to 65.5 mg/dl (AT60 mg group) and 100.2 to 72.2 mg/dl (RT10 mg groups). A continuous increase in FCT from baseline to 12 months was observed in both groups (p < .001, p < .001, respectively). Mean lipid arc significantly decreased in both AT60 mg (189.0 ± 55.9°, 170.9 ± 60.2°, 155.6 ± 50.6°, p < .001) and RT10 mg (160.0 ± 45.6°, 151.2 ± 48.5°, 141.1 ± 52.9°, p = .010) groups. Plaque burden did not change significantly in both groups. Lipid-lowering therapy effect with AT60 mg was equivalent to that of RT10 mg in terms of change in plaque morphology. AT60 mg showed more intensive low-density lipid cholesterol level reduction compared to RT10 mg while RT10 mg was effective in increasing the high-density lipid cholesterol level. Both statin therapies could effectively stabilize LRPs.

Lithium-modified MAO coating enhances corrosion resistance and osteogenic differentiation for pure magnesium

In this study, the MAO coating with and without Li addition was fabricated on pure Mg to enhance corrosion resistance and osteogenic differentiation for pure Mg. The SEM, XRD and XPS were used to analyze the microstructure and chemical composition of the MAO coatings. The immersion test were conducted to evaluate the degradation behavior of the MAO coated Mg in term of pH and hydrogen evolution. MTT and quantitative PCR (qPCR) analysis were performed to assess osteogenic differentiation of the MAO coatings. The results showed that the addition of Li could decrease the number of micropores and cracks on the MAO coating. Accordingly, the Li-MAO coating with less micropores and cracks was found to exist better corrosion resistance compared with Li free MAO coating. More importantly, the in vitro results of MTT and quantitative PCR (qPCR) analysis suggested that Li addition on MAO could promote the osteogenic-related genes expression with respect to Li free MAO coating, indicating a better osteogenic ability of Li-MAO coating.

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis.

The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up.

ObjectivesThe aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole–trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP).MethodsAdult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, has been reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate and adverse events.ResultsFifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8–100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 vs 47.2%, P = 0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%, P = 0.007) and ES (20.3%, P = 0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (P = 0.007).ConclusionSMX/TMP 200/40 mg had a high PCP prevention rate and was superior to SMX/TMP 400/80 mg in terms of drug retention and safety.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.

A comparative study between two different doses of oral pregabalin in attenuating hemodynamic response to laryngoscopy and endotracheal intubation

Background: Laryngoscopy and endotracheal intubation is usually associated with exaggerated haemodynamic response. The aim of our study was to compare and evaluate the efficacy of two different doses of oral pregabalin in attenuating hemodynamic response to laryngoscopy and endotracheal intubation along with preoperative level of sedation.&#x0D; Methodology: This prospective randomized study was conducted on one hundred patients, aged 18 to 55 years of either sex belonging to American Society of Anesthesiologists (ASA) physical status I and II, posted for various elective surgical procedures under general anesthesia. They were randomly allocated into two groups ( Group P1 and Group P2) of 50 patients each by computer generated tables of random numbers. Group P1 and P2 received oral pregabalin 75 mg and 150 mg respectively 1 hour prior to induction of anesthesia. Anesthesia technique was standardized and both groups were assessed for hemodynamic changes (HR,SBP, DBP and MAP ) after premedication, before and after induction, immediately after intubation and at the end of 1, 3, 5, 10 and 15 min after intubation along with preoperative sedation, side effects or complications.&#x0D; Results: The attenuation in mean HR was comparable between two groups, (p &gt; 0.05), with significant attenuation in SBP,DBP and MAP between two groups.(P&lt;0.05). The preoperative levels of sedation were higher in Group P2 but was statistically insignificant. (p &gt; 0.05) None of the patients had experienced any side effects except dizziness.&#x0D; Conclusion: Oral pregabalin 150 mg when used as a premedication 60 min prior to induction of anesthesia was found to be more effective than oral pregabalin 75 mg in terms of significant attenuation of hemodynamic pressor response to laryngoscopy and endotracheal intubation with acceptable levels of sedation and minimal side effects.&#x0D; Citation: Patodi V, Yadav RL, Sethi SK, Jain N, Singh M. A comparative study between two different doses of oral pregabalin in attenuating hemodynamic response to laryngoscopy and endotracheal intubation. Anaesth pain intensive care 2020;24(1):__&#x0D; Received : 11 September 2019;&#x0D; Reviewed : 16, 26 October 2019, 27 December 2019, February 2020;&#x0D; Revised : 26 November 2019, 31 January, 24 February 2020;&#x0D; Accepted : 29 February 2019

Radioprotective Properties of Pterocarpus santalinus Chloroform Extract in Murine Splenic Lymphocytes and Possible Mechanism.

Background: Pterocarpus santalinus popularly known as Red Sanders is an endemic species confined to Southern part of Eastern Ghats of India especially in Andhra Pradesh and has high demand for its economical importance for its use in treatment of human ailments. Materials and Methods: In the present study, the authors have examined the presence of various phytochemicals in the chloroform extract of P. santalinus heartwood (PSCE, Pterocarpus santalinus chloroform extract) by qualitative and quantitative assays. PSCE was further used to evaluate its antioxidant and metal reducing capacity. Radioprotective property was also evaluated in various subcellular and cellular model systems. Results: The phytochemical screening study showed that the extract was positive for carbohydrates, cardiac glycosides, flavonoids, phenols, tannins, saponins, and terpenoids and was negative for alkaloids, steroids, and phlobatannins. Contents of total phenol, total flavonoids, total anthocyanin, and total tannin in the PSCE are 404 μg/mg in terms of gallic acid equivalents, 22.6 μg/mg in terms of quercetin equivalents, 0.066 mg in terms of cyanidin-3-glucoside (cyn-3-glu) equivalents, and 12.477 g/L, respectively. This extract exhibited significant radical scavenging activity against model free radical 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+), 1,1-diphenyl picrylhydrazyl, and biologically important nitric oxide. It has significant metal reducing capacity as monitored by ferric and molybdenum reduction assay. PSCE showed a concentration dependent radioprotection to plasmid pBR322 DNA and lipids of the mitochondrial membranes. Their study also showed that PSCE protected splenic lymphocytes against radiation induced cell death, DNA double strand breaks, and lipid peroxidation as monitored by propidium iodide staining, γ-H2AX assay, neutral comet assay, and TBARS assay, respectively. Addition of PSCE to lymphocytes scavenged radiation derived reactive oxygen species, restored loss of thiol content, and inhibited cellular apoptosis. Conclusions: PSCE possesses high antioxidant activity and exhibited very good radioprotective property in cell free and cellular model systems.

Efficacy and safety of tamsulosin 0.4 mg single pills for treatment of Asian patients with symptomatic benign prostatic hyperplasia with lower urinary tract symptoms: a randomized, double-blind, phase 3 trial

Objective: To verify the efficacy and safety of tamsulosin 0.4 mg and tamsulosin 0.2 mg compared with those of placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).Methods: A total of 494 patients from multiple centers participated in this double-blind, randomized, phase 3 trial. Eligible patients were randomly assigned to the tamsulosin 0.4 mg group, tamsulosin 0.2 mg group or placebo group. The International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual (PVR) urine volume, blood pressure, heart rate and adverse events were compared among the three groups at 4, 8 and 12 weeks.Results: A total of 494 BPH patients were analyzed. There were no differences in the baseline characteristics among the three groups. After 12 weeks of treatment, total IPSS was improved in the 0.2 mg and 0.4 mg tamsulosin groups; however, the extent of improvement was greater in the 0.4 mg group than in the 0.2 mg group (0.4 mg: −9.59 vs. 0.2 mg: −5.61; least-squares mean difference [95% confidence interval]: −3.95 [−5.01, −2.89], p < .0001). In addition, in the patients with severe symptoms (IPSS ≥20), total IPSS was improved the most in the 0.4 mg group (−11.27 ± 5.00, p < .0001). Qmax and PVR were improved in the 0.4 mg and 0.2 mg groups; however, the differences were not statistically significant between treatment groups. No patients experienced any serious adverse effects in any of the three groups.Conclusions: Tamsulosin 0.4 mg and 0.2 mg appear to be superior to placebo treatment, and tamsulosin 0.4 mg is more effective than 0.2 mg in terms of total IPSS improvement. Tamsulosin 0.4 mg has favorable efficacy and tolerability in Asian men with symptomatic BPH.ClinicalTrials.gov Identifier: NCT02390882.

РАСТИТЕЛЬНЫЕ АДАПТОГЕНЫ В СОСТАВЕ ПРОДУКТОВ СПЕЦИАЛИЗИРОВАННОГО ПИТАНИЯ КАК ФАКТОР ГОМЕОСТАТИЧЕСКОЙ РЕГУЛЯЦИИ С УЧАСТИЕМ МИКРОБИОТЫ ОРГАНИЗМА

The aim of this study is to develop an adaptogenic drink based on the polyphenol complex of antioxidant activity optimized in terms of bioavailability. Materials and Methods. The study was performed on the base of the polyphenol complex of antioxidant activity made of taxifolin (Larix gmelinii extract with no less than 97.0 % of taxifolin) and plant extracts (Lonicera сaerulea L., Beta vulgaris L. ssp.vulgaris) obtained in the research laboratory of the department of Food and Biotechnologies in the South Ural State University. To increase solubility and bioavailability of taxifolin we used 20-minute 630 W ultrasonic impact, providing taxifolin nanostructuring. The plant extract consists of reconstituted extracts from Beta vulgaris L. ssp.vulgaris and Lonicera сaerulea L. in a 3:1 ratio with 0.1 % of taxifolin and the amount of dry substance of no less than 15 %. Taxifolin content in a final product is no less than 0.02 %. Results. It was established that taxifolin water solution is quite sensitive to ultrasonic cavitation. The morphological structure of taxifolin particles, treated with ultrasound, was close to a spherical shape. Particles were characterized by amorphous structure, which is positive for solubility and bioavailability properties. Antioxidant activity is 1.74–1.98 times higher than in the solutions obtained using a mechanical approach. This indicates the increased physiological value of solutions. The drink obtained on the base of beet and honeysuckle extracts with 0.1 % taxifolin had the total content of betanin and betaxanthine equaled 54 ± 2 mg/100 g and the total content of phenol substances of 194 ± 4 mg in terms of gallic acid. The consumption of a taxifolin plant extract-based drink results in the decrease of Streptococcus to significantly lower values. There is a shift in pH values in a range from 6.5 to 7.5 in comparison with the initial pH values of 5.5 ? 6.0 units. Conclusion. The combination of secondary metabolites (polyphenols) in the form of Lonicera сaerulea L. and Beta vulgaris L. ssp.vulgaris plant extracts with taxifolin is a very promising one for the technology of adaptogenic drinks to improve homeostatic mechanisms involving microbiota at the stage of oral intake.

Tolerability and adequate therapeutic dosage of oral clomipramine for the treatment of premature ejaculation: A randomized, double-blind, placebo-controlled, fixed-dose, parallel-grouped clinical study.

To evaluate the adequate therapeutic dosage of clomipramine 15 mg/day and clomipramine 30 mg/day in male patients with premature ejaculation (PE), this study enrolled men aged 20-65 years who met diagnostic criteria for PE including Intravaginal Ejaculation Latency Time (IELT) less than 2 min for at least 75% of their sexual intercourses. Subjects received placebo, clomipramine 15 mg, or clomipramine 30 mg prn (2~6 h before intercourse) for 4 weeks. Efficacy was assessed using fold change, percentile change, and mean change of IELT, as well as Drug Coitus Interval Time (DCIT). A total of 101 patients were randomized into the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group. Analyses of fold changes of IELT in each group revealed that the IELT of both the clomipramine 15 mg group and clomipramine 30 mg group was significantly increased 4 weeks after administration than the placebo group. Adverse events were reported by 11.76, 32.35, and 57.57% of patients in the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group, respectively. Most common adverse events in the clomipramine treatment groups were gastrointestinal disorders and psychiatric disorders of mild to moderate severity. On-demand regimen of clomipramine 15 mg resulted in a significant improvement in IELT and was superior to a regimen of clomipramine 30 mg in terms of risk-to-benefit ratio.

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis.

AimsSeveral studies reported treatment benefits of tolvaptan in patients with congestive heart failure (CHF). However, the optimal dosage remains unclear. We aimed to compare different dosage of tolvaptan to determine the optimal dosage in terms of the efficacy and safety.MethodsWe searched MEDLINE, PubMed, EMBASE, Cochrane CENTRAL and ClinicalTrials.gov through Aug 31, 2016. Randomized controlled trials (RCTs) comparing tolvaptan of different dosages or to placebo in patients with CHF were included. We used network meta-analysis to look for the optimal dosage in terms of effectiveness and safety. Urine output, body weight change and change in serum sodium were the main outcomes of efficacy. Adverse effects were the secondary outcomes. Quality was assessed by Cochrane risk-of-bias tool.ResultsTwelve RCTs reporting 14 articles with 5793 patients (mean age, 65.7 ± 11.9 years; 73.7% man) were included. Compared with placebo, the tolvaptan 30 mg had similar effects to tolvaptan 45–90 mg in terms of urine output (mean difference [MD] 2.03 liter; 95% confidence interval [CI] 1.3 to 2.71), body weight change (MD -1.12 kg; 95% CI -1.37 to -0.88) and change in serum sodium (MD 3.06 meq/L; 95% CI 2.43 to 3.68). Compared with placebo, tolvaptan of different dosage showed a non-significant higher risk of adverse effects.ConclusionsThese findings suggest that tolvaptan 30 mg and 45 mg may be the optimum dosage for CHF patients, because of its ability to provide favourable clinical results without greater adverse effects. However, tolvaptan is not beneficial for reducing all-cause mortality in CHF patients.

Tenofovir Alafenamide: A Review in Chronic Hepatitis B.

Tenofovir alafenamide (AF) [Vemlidy®], an oral prodrug of tenofovir, was developed to optimize the antiviral potency and clinical safety of the active moiety tenofovir diphosphate (selective reverse transcriptase nucleotide inhibitor). In two identically designed, ongoing, multinational trials in treatment-naive and -experienced adult patients with hepatitis B e antigen (HBeAg)-positive or -negative chronic hepatitis B virus (HBV) infection, once-daily tenofovir AF 25mg provided effective and sustained viral suppression (120-week analysis), and was generally well tolerated. In the primary 48-week analysis, tenofovir AF was noninferior to once-daily tenofovir disoproxil fumarate (DF) 300mg in terms of the proportion of patients achieving viral suppression (HBV DNA <29 IU/mL) and was associated with significantly higher alanine aminotransferase (ALT) normalization rates than tenofovir DF based on AASLD criteria (but not central laboratory criteria). In pooled analyses and/or individual trials, ALT normalization rates by AASLD and central laboratory criteria were significantly higher in tenofovir AF than tenofovir DF recipients at most assessed timepoints up to 96 weeks. Given the bone and renal safety concerns associated with long-term tenofovir DF treatment, the more favourable pharmacological profile of tenofovir AF permits a marked reduction in the dosage of this tenofovir prodrug and thereby reduces systemic exposure to tenofovir, potentially improving the bone and renal safety of tenofovir AF versus tenofovir DF. Long-term clinical experience will more definitively establish the relative bone and renal safety of these tenofovir prodrugs. With its potential for an improved safety profile, tenofovir AF is an important emerging first-line option for the treatment of chronic HBV infection in adults and adolescents (aged ≥12 years and with a bodyweight of ≥35 kg).

An open label comparison of efficacy of low dose topiramate with naltrexone in preventing alcohol relapse

Introduction: Alcohol use disorder is a relapsing and remitting disorder. Preventing alcohol relapses has been a difficult task. The available drugs do not have adequate outcome in diverse needs. Topiramate, a GABAergic anticonvulsant, has been useful for the prevention of alcohol relapse as demonstrated in western studies. We compared the efficacy of Topiramate at 100mg with Naltrexone 50 mg in preventing relapse among Nepalese alcohol dependence patients.Methods: Following an inpatient alcohol detoxification, 37 patients taking Topiramate 100 mg and 41 patients taking Naltrexone 50 mg were followed up as outpatients at 1, 4, 8 and 12 weeks in order to monitor their abstinence period, craving for alcohol and alcohol use pattern.Results: At the end of 12 weeks follow up, Topiramate is as good as Naltrexone 50 mg in terms of maintaining abstinence (27% vs 31.7%, p=0.651) and reducing the daily alcohol intake. Topiramate is better than Naltrexone in decreasing craving at 12 wks (p=0.015).Conclusion: Topiramate 100 mg is equally efficacious to Naltrexone 50 mg in reducing alcohol craving and maintaining abstinence.