Fixed-Dose Combination of Canagliflozin and Metformin as an Adjunct to Diet and Exercise in Indian Adults with Type 2 Diabetes Mellitus: Results from a Multicentric, Open-Label, Single-Arm, Phase IV Study.

BACKGROUND: Canagliflozin and metformin fixed-dose combination (CANA/MET FDC), an approved treatment for type 2 diabetes mellitus (T2DM) in India, effectively lowers glycated hemoglobin (HbA1c), promotes weight loss, and improves patient adherence. As a regulatory requirement, we aimed to evaluate the safety and efficacy of CANA/MET FDC in Indian patients with T2DM. RESEARCH DESIGN AND METHODS: This prospective, multicenter, open-label, single-arm, phase IV study included Indian patients with T2DM (aged 18-65 years) inadequately controlled on diet and exercise. Patients received CANA/MET (50/500 and 50/1000 mg) immediate-release (IR) FDC twice daily for 24 weeks. The primary endpoint was safety assessment, including adverse events (AEs) and serious AEs (SAEs). The secondary endpoint included a change in HbA1c from baseline to weeks 12 and 24. Descriptive statistics were used for all continuous safety variables and efficacy parameters. RESULTS: Of the 310 patients screened, 276 were enrolled. 114/274 (41.6%) patients had ≥1 treatment-emergent AE [treatment-emergent AEs (TEAEs), among which 29 (10.6%) were related to study intervention]. The most common TEAEs were dyslipidemia (4.7%), pyrexia (4.7%), genital infections (3.3%), hypoglycemia (3.3%), and urinary tract infections (2.6%). Three (1.1%) patients had serious TEAEs, and all cases were resolved. No deaths were reported. The mean change in HbA1c from baseline was -0.92 and -0.93% at weeks 12 and 24, respectively. CONCLUSION: The study demonstrates the safety and efficacy of CANA/MET FDC in Indian patients with T2DM, presenting a safe therapeutic option for diabetes management in India.

Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

BACKGROUND: The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. MATERIALS AND METHODS: This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. RESULTS: Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. CONCLUSION: Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Real-world Experience with Favipiravir for Treatment of COVID-19 among Indian Healthcare Professionals.

INTRODUCTION: Favipiravir has shown promising results for COVID-19 globally. Though many Indian patients have received favipiravir, there is a lack of realworld data for its clinical use by the practicing physicians. Hence, a qualitative survey was conducted to understand real-world use of favipiravir in management of COVID-19. METHODS: A cross-sectional, web-based, qualitative survey was conducted between September 2020 to October 2020, among Indian physicians from various specialties involved in COVID-19 care and using favipiravir in their practice. Physicians were provided survey link having a structured questionnaire with 32 questions. They were enquired on- 1) demographics,practice information, 2) place of favipiravir in clinical practice, 3) treatment protocol for mild to moderate COVID-19, 4) dosage and duration of favipiravir, 5) effectiveness of favipiravir, 6) tolerability of favipiravir 7) global efficacy and safety assessment of favipiravir. RESULTS: A total of 500 physicians were contacted, of which 50 physicians completed the questionnaire. 25(50.0%) were from south zone followed by 12(24.0%) from west. . Majority physicians (47, 97.9%) stated that favipiravir was used for COVID-19 in outpatient setting. Favipiravir was considered as the current drug of choice for ' mild COVID-19 with fever(86.6%). All physicians agreed that favipiravir was being used as per the recommended dose.. A total of 75% & 62.5% physicians agreed to observed clinical improvement by around 3-5 days & 5-7 days in symptomatic mild & moderate COVID-19 respectively. CONCLUSION: Majority of the physicians considered favipiravir to be safe and effective in treatment of mild to moderate COVID-19.

Response surface methodology directed synthesis of luminescent nanocomposite hydrogel for trapping anionic dyes.

The present research work reveals semi-interpenetrating network (semi-IPN) synthesis using response surface methodology-central composite design (RSM-CCD) based optimization. The maximum swelling of 362.11% was obtained with monomer, crosslinker and initiator concentrations 4.39 mol L-1, 1.52 mol L-1 and 4.58 mol L-1, respectively, temperature 70 °C, time 3 h and pH 4.0. The synthesized hydrogel showed 94.16% and 95.62% removal for eosin yellow (EY) and eriochrome black-T (EBT) dyes, respectively. The incorporation of cadmium sulphide nanodots into the hydrogel network enhanced the % dye removal (96.82% EY and 98.73% EBT) along with fluorescent behavior. Various conditions optimized for EY and EBT dye removal with respect to semi-IPN were: 0.4 g adsorbent dose each, dye concentrations 10 mg L-1 and 120 mg L-1, contact time 24 h each, respectively. Adsorption studies followed langmuir theory for both dyes. Second order and first order kinetics along with intraparticle diffusion of dye molecules were favorable to EY and EBT, respectively. Thermodynamic study reveals exothermic nature of adsorption. Recyclability of the adsorbent is superior as tested by desorption-adsorption tests.

SGLT2 Inhibitors: Paradigm Shift from Diabetes Care to Metabolic Care-An Indian Perspective.

The prevalence and burden of diabetes are on the rise in India, making it 'the diabetes capital of the world'. Comorbidities such as obesity, cardiovascular (CV) complications, chronic kidney disease (CKD), non-alcoholic fatty liver disease (NAFLD), and neurodegenerative diseases are common in patients with diabetes. Recent breakthroughs in diabetes medications and continuous glucose monitoring have resulted in a paradigm shift in diabetes care. Hence, a review in the Indian context is warranted. This review focuses on the existing evidence (gathered by a systematic literature search utilising online databases such as PubMed) on the metabolic, cardio-renoprotective, and hepatoprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition, particularly in the Indian setting. The study revealed that the SGLT2 inhibitors (SGLT2i), with their numerous pleiotropic benefits, have received considerable attention recently as a novel class of antihyperglycaemic agents (AHAs) for the management of diabetes. SGLT2i play a crucial role in the transition from glycaemic control to metabolic care, particularly in the context of obesity, CV disease and renal disease. In addition to improving glycaemic control, SGLT2i have been shown to promote weight loss, reduce blood pressure and improve lipid profiles, which are key components of metabolic health. Moreover, SGLT2i have demonstrated renal protective effects, including a reduction in albuminuria and a slower decline in the estimated glomerular filtration rate (eGFR), suggesting a potential role in the management of renal dysfunction.

Biochemical interaction of human hemoglobin with ionic liquids of noscapinoids: Spectroscopic and computational approach.

In this work, we have developed noscapine based ionic liquids i.e., Noscapine (MeNOS) and 9-Bromonoscapine (MeBrNOS) as cation supported with bis(trifluoromethylsulfonyl)amide (NTf2-) as anion. We have reported the mechanism of binding interaction between noscapine based ILs and human hemoglobin (Hb) using various spectroscopic and computational techniques. The corresponding thermodynamics studies showed that the binding is exothermic in nature and major forces responsible for binding are Van der waals and hydrogen bonding interaction. The fluorescence spectra showed that the intensity of Hb decreases in the presence of [MeNOS]NTf2 and [MeBrNOS]NTf2 both shows static quenching. The secondary structural changes in Hb were observed and calculated by using CD spectroscopy. Molecular docking studies revealed that both the ILs show strong binding in ß1 fragment of the tetrameric structure of Hb, but the binding of [MeNOS]NTf2 is relatively stronger than [MeBrNOS]NTf2 and the results are supported by MD simulations.

Treatment outcomes and associated factors among patients with drug-sensitive tuberculosis on daily fixed-dose combination drugs: A cohort study from Ahmedabad, India.

Background and Aim: The National Tuberculosis Elimination Program (NTEP) has been progressive in addressing the issues related to tuberculosis (TB) control in the country, with constant programmatic changes based on evidence available from operational research. Our objectives were 1. to assess the sociodemographic and clinical characteristics, and the treatment outcomes of patients on fixed-dose combination (FDC) daily regimen and 2. to assess the factors associated with unsuccessful treatment outcomes among patients with DS-TB. Materials and Methods: A retrospective cohort study was conducted based on record review. The study population included all patients with drug-sensitive TB, registered and initiated on treatment under NTEP "new category" from January to June 2018 and under "previously treated category" from January to March 2018. Quantitative data downloaded from Nikshay in Excel format was imported. Results: A total of 8301 patients with DS-TB registered under NTEP. Mean (standard deviation [SD]) age of DS-TB patients was 35.3 + 16.9 years, and 63.2% were in the age group of 15-44 years. Also, 60.1% were male, 2.5% were human immunodeficiency virus (HIV) positive, 65.3% were pulmonary TB cases, and 70.4% obtained treatment from public providers. Proportion of "successful" and "unsuccessful" outcomes was 87.9% and 12.1%, respectively, in the new treatment category and 78.3% and 21.7%, respectively, in the previously treated category. Among the patients classified under new category, the unsuccessful treatment outcome remained significantly high after adjustments with known confounders among patients aged 45-54 years (adjusted relative risks [aRR] 1.59, 95% confidence interval [CI] 1.31-1.93) and 55-64 years (aRR 1.67, 95% CI 1.36-2.05) compared to patients aged <15 years. Conclusion: Unsuccessful treatment outcome was significantly high among patients aged 45-54 years. Various adherence mechanisms implemented can be evaluated for further upscaling and improving the program effectiveness.

Imperative persistent interaction analysis of anticancer noscapine-ionic liquid with calf thymus DNA.

In this study, we have shown the interaction between opium poppy alkaloid noscapine-based ionic liquid [Pip-Nos]OTf and ct-DNA using UV-visible absorption spectroscopy, fluorescence spectroscopy, CD, and computational studies. The absorption spectra showed a hypochromic shift with no shift in the absorption maxima suggesting groove or electrostatic binding. Fluorescence spectra showed an enhancement in fluorescence emission suggesting that the probable mode of binding should be groove binding. Ethidium bromide (EB) competitive and Ionic strength study showed the absence of intercalative and electrostatic modes of interaction. Further, CD analysis of ct-DNA suggested a groove binding mode of interaction of [Pip-Nos]OTf with ct-DNA. [Pip-Nos]OTf displayed a strong binding with the target ct-DNA with a molecular docking score of -41.47 kJ/mol with all 3D coordinates and full conformation. Also, molecular binding contact analyses depicted the stable binding of drug and ct-DNA with potential hydrogen bonds and hydrophobic interactions. The structural superimposition dynamics analysis showed the stable binding of [Pip-Nos]OTf with the ct-DNA model through RMSD statistics. Moreover, the ligand interaction calculations revealed the involvement of large binding energy along with a high static number of molecular forces including the hydrogen bonds and hydrophobic interactions in their complexation. These significant results report the potency of [Pip-Nos]OTf and its important futuristic role in cancer therapeutics.

Use of single-inhaler triple therapy in the management of obstructive airway disease: Indian medical experts' review.

Obstructive airway disease (OAD), which includes COPD and asthma, is the leading cause of morbidity and mortality in India. Long-acting bronchodilators (long-acting ß2 agonists (LABAs) and/or long-acting muscarinic antagonists (LAMAs)) and inhaled corticosteroids (ICS) have a vital role in the management of patients with OAD. While symptom burden and exacerbations are common amongst treated patients, poor adherence to inhaler therapy is a frequent challenge. Better treatment options that optimise symptom control, improve quality of life, reduce exacerbation risk and improve adherence are desired. Triple therapy (ICS/LABA/LAMA) is recommended in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 guidelines for symptomatic COPD patients on ICS/LABA or LABA/LAMA, and who are at increased risk for frequent or severe exacerbations. Similarly, add-on LAMA is recommended in uncontrolled asthma patients on medium- to high-dose ICS/LABA by the Global Initiative for Asthma (GINA) 2021 guideline. In the real world, high-risk and overlapping phenotypes exist, which necessitate early initiation of triple therapy. We aim to provide an expert review on the use of single-inhaler triple therapy (SITT) for OAD management in global and Indian settings, knowledge from which can be extrapolated for appropriate treatment of Indian patients. The OAD population in India may benefit from early optimisation to SITT characterised by a high burden of exacerbating OAD, nonsmoker COPD and asthma-COPD overlap.

Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to-severe COPD.

Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 µg/formoterol fumarate 12 µg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 µg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV1/FVC <0.70, using ICS, LAMA, or LABA for ≥1 month were included. Subjects were randomized (1:1) to GB/FF or GLY for 12 weeks. The primary efficacy endpoint was the change from baseline in peak FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI/2017/02/007814). Results: Between March 2017 and July 2018, 331 patients were enrolled and randomized into GB/FF FDC (165 patients) and GLY monotherapy (166 patients) groups. At week 12, the difference in change from baseline in the peak FEV1 for GB/FF DPI versus GLY was 0.115 L (SE = 0.02; 95% CI = 0.061, 0.170; P < 0.0001). Trough FEV1 increased significantly in the GB/FF group compared to the GLY group with a treatment difference of 0.078 L (SE = 0.02; 95% CI = 0.015, 0.14; P = 0.01). There were no significant differences in adverse events between the groups. Conclusion: FDC of GB/FF (12.5/12 µg twice daily) as a DPI provides superior bronchodilation and lung function improvement over GLY (50 µg once daily) monotherapy. It is safe and well tolerated in symptomatic COPD patients.

Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial.

BACKGROUND: The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 µg glycopyrronium (GB)/12 µg formoterol fumarate (FF)/250 µg fluticasone propionate (FP), compared to 50 µg GB co-administered with a fixed dose of 12 µg FF/250 µg FP in subjects with COPD. METHODS: This was a phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70, using mono/dual therapy with inhaled corticosteroids (ICSs), long-acting muscarinic antagonists (LAMAs), or long-acting ß-agonists (LABAs) for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. The primary efficacy end-point was the change from baseline in trough FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (identifier number: CTRI/2019/01/017156). RESULTS: Between 23 March 2019 and 14 February 2020, 396 subjects were enrolled, with 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in least-square mean (LSM) changes in pre-dose FEV1 from baseline at 12 weeks was noninferior between the groups (p<0.05). The LSM change from baseline in post-dose FEV1 was comparable (p=0.38). A superiority test showed comparable efficacy (p=0.12) for the difference in mean change from baseline in trough FEV1 between the groups. Adverse events (mild or moderate) were recorded in 25.3% and 24.9% of subjects in the GB/FF/FP and GB+FF/FP groups. CONCLUSIONS: Fixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement as open-triple therapy. It is safe and well tolerated in symptomatic COPD patients with a history of exacerbations.

Fabrication of a Gold-Supported NiAlTi-Layered Double Hydroxide Nanocatalyst for Organic Transformations.

This work is mainly focused on the synthesis of an efficient and reusable heterogeneous Au/NiAlTi layered double hydroxide (LDH) nanocatalyst and its applications in the preparation of biologically important xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives. NiAlTi LDH was designed hydrothermally and then gold was supported over the surface of LDH by using ion-exchange and NaBH4 reduction methods. The synthesized nanocatalyst was physicochemically characterized by X-ray diffractrometry, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and transmission electron microscopy (TEM). The TEM images confirmed the support of gold nanoparticles over the surface of LDH with a size distribution of 7-9 nm. The well-characterized nanocatalyst was tested for the synthesis of biologically important xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives. The advantages obtained were excellent yields in a lesser reaction time. Stability and reusability were also accessed; the catalyst was stable even after five cycles. High catalytic efficiency, easy fabrication, and recycling ability of Au/NiAlTi LDH make it a potential catalyst for the synthesis of xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives.

Selective removal of cationic dyes using response surface methodology optimized gum acacia-sodium alginate blended superadsorbent.

Gum acacia and sodium alginate were blended to synthesize highly efficient superadsorbent formed by grafting of poly(acrylic acid) (AA) used as monomer onto the hybrid of gum acacia and sodium alginate and the polymeric chains were crosslinked through N,N'-methylene bisacrylamide (MBA). The overall reaction followed free radical polymerization with ammonium persulphate (APS) used as initiator. Response surface methodology integrated with central composite design (RSM-CCD) could synthesize semi-Interpenetrating network (semi-IPN) having maximum swelling capacity of 1749.2% at MBA, APS and AA concentrations of 0.89 × 10-2 mol L-1, 3.29 × 10-2 mol L-1 and 1.46 mol L-1, respectively using 15 mL water at 70 °C for 2.5 h. The synthesized sample was found to be selective for removal of cationic dyes upto 97.49%, 95.39% and 94.56% for auramine-O (AO), malachite green (MG) and crystal violet (CV), respectively. Adsorption capacities at equilibrium were calculated experimentally as 2.01 mg g-1, 3.06 mg g-1 and 7.55 mg g-1 for AO, MG and CV, respectively. These dyes could be desorbed with 0.1 N HCl for the recyclization of semi-IPN. Adsorption mechanism involved monolayer formation with three step process of adsorption and followed first order kinetics. Exothermic nature of adsorption was revealed by thermodynamic studies.

RSM-CCD optimized sodium alginate/gelatin based ZnS-nanocomposite hydrogel for the effective removal of biebrich scarlet and crystal violet dyes.

The present work represents RSM-CCD (Response Surface Methodology integrated Central composite Design) optimized synthesis scheme of semi-IPN (semi interpenetrating network) NaAla-Gel-cl-polyAAm and ZnS nanocomposite adsorbent NaAla-Gel-cl-polyAAm/ZnS. Under optimized reaction parameters semi-IPN NaAla-Gel-cl-polyAAm showed maximum swelling percentage of 3191.73%. Maximum dye removal percentage (97.37%) was observed with ZnS nanocomposite for the removal of biebrich scarlet. The adsorption isotherm data indicated that Langmuir and Freundlich adsorption isotherm fitted well for biebrich scarlet (R2 = 0.964) and crystal violet (R2 = 0.960), respectively. ΔG°, ΔH° and ΔS° values indicated the thermodynamic feasibility of the reaction. Excellent recyclability and reusability of the adsorbent materials suggested their applicability towards textile industry and water purification purpose.

Efficient capture of eosin yellow and crystal violet with high performance xanthan-acacia hybrid super-adsorbent optimized using response surface methodology.

Blending of xanthan and acacia gives a unique hybrid that was used for the synthesis of semi-interpenetrating network (semi-IPN) in which poly(acrylamide) chains were grafted onto hybrid of xanthan-acacia followed by their cross-linking (Xan-Aca-cl-poly(AAm)). Optimization was carried out under response surface methodology-central composite design (RSM-CCD). Maximum percentage swelling of semi-IPN obtained was 496.57%. The concentrations of acrylamide, citric acid and ammonium persulphate used as monomer, cross-linker and initiator, respectively were found to be significant parameters. The blend was highly effective in removal of both cationic (crystal violet) and anionic dyes (eosin yellow) showing maximum dye removal capacity of 97.58% and 95.42%, respectively under optimized parameters - 0.4 g semi-IPN dose in 15 ml dye solution of 10 mg L-1 concentration within 16 h. Adsorption mechanism of both the dyes followed three steps in accordance with intraparticle diffusion model along with mono layer langmuir adsorption criteria. Second order kinetics was followed in case of both dyes. Thermodynamic studies gave idea about the exothermic nature of adsorption. Semi-IPN could be recycled up to eight consecutive cycles and hence, can be utilized for industrial purpose for removal of dyes.