Comparison of a portable, pneumotach flow-sensor-based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients-a randomized, crossover study.

BACKGROUND: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. METHODS: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).

Safety and clinical outcomes of remdesivir in hospitalised COVID-19 patients: a retrospective analysis of active surveillance database.

BACKGROUND: Real-world data on safety and clinical outcomes of remdesivir in COVID-19 management is scant. We present findings of data analysis conducted for assessing the safety and clinical outcomes of remdesivir treatment for COVID-19 in India. METHODS: This retrospective analysis used data from an active surveillance programme database of hospitalised patients with COVID-19 who were receiving remdesivir. RESULTS: Of the 2329 patients included, 67.40% were men. Diabetes (29.69%) and hypertension (20.33%) were the most common comorbidities. At remdesivir initiation, 2272 (97.55%) patients were receiving oxygen therapy. Remdesivir was administered for 5 days in 65.38% of patients. Antibiotics (64.90%) and steroids (47.90%) were the most common concomitant medications. Remdesivir was overall well tolerated, and total 119 adverse events were reported; most common were nausea and vomiting in 45.40% and increased liver enzymes in 14.28% patients. 84% of patients were cured/improved, 6.77% died and 9.16% showed no improvement in their clinical status at data collection. Subgroup analyses showed that the mortality rate was significantly lower in patients < 60 years old than in those > 60 years old. Amongst patients on oxygen therapy, the cure/improvement rate was significantly higher in those receiving standard low-flow oxygen than in those receiving mechanical ventilation, non-invasive ventilation, or high-flow oxygen. Factors that were associated with higher mortality were age > 60 years, cardiac disease, diabetes high flow oxygen, non-invasive ventilation and mechanical ventilation. CONCLUSION: Our analysis showed that remdesivir is well tolerated and has an acceptable safety profile. The clinical outcome of cure/improvement was 84%, with a higher improvement in patients < 60 years old and on standard low-flow oxygen.

Efficacy and safety of glycopyrronium/formoterol delivered via a dry powder inhaler in patients with moderate to severe chronic obstructive pulmonary disease: Results from a multi-centre, open-label, randomised study.

Background: We designed this randomised, open-label, parallel group, multi-centre study to investigate the efficacy and safety of glycopyrronium/formoterol, a long-acting muscarinic antagonist/long-acting ß2-agonist fixed dose combination, delivered through a dry powder inhaler (DPI) in patients with chronic obstructive pulmonary disease (COPD). Material and Methods: We randomised (1:1) patients with moderate to severe COPD (N = 356) to receive glycopyrronium 25 µg/formoterol 12 µg via DPI twice daily (GF-DPI) or glycopyrronium 50 µg monotherapy via DPI once daily (G-DPI). The primary study endpoint was the mean change from the baseline in pre-dose trough-forced expiratory volume in one second (FEV1) at 12 weeks. Results: At week 12, the mean increase from the baseline in pre-dose trough FEV1 was higher in the GF-DPI group (120 ml) than in the G-DPI (60 ml) group. The mean difference (MD) between treatment groups was 0.06 L (95% CI: 0.00-0.12 L, P < 0.0001 for non-inferiority). At week 12, the mean pre-dose forced vital capacity (FVC), 1 hour post-dose FEV1, and post-dose FVC increased significantly from the baseline only in the GF-DPI group (p < 0.0001). The reduction in the COPD assessment test score was greater in the GF-DPI group (p = 0.0379). The average daily number of puffs of rescue medication and the reduction in mean modified Medical Research Council scale, COPD, and Asthma Sleep Impact Scale score at week 12 were similar between groups (p > 0.05). Overall, 35 adverse events and two serious adverse events unrelated to study drugs were reported. Both groups had similar results for overall drug safety. Conclusion: The results demonstrate efficacy and safety of GF-DPI in Indian patients with moderate to severe COPD. Treatment with GF-DPI significantly improved the lung function and quality of life and was well tolerated.

Hydrogen Evolution Reaction by Atomic Layer-Deposited MoNx on Porous Carbon Substrates: The Effects of Porosity and Annealing on Catalyst Activity and Stability.

Molybdenum-based compounds are considered as a potential replacement for expensive precious-metal electrocatalysts for the hydrogen evolution reaction (HER) in acid electrolytes. However, coating of thin films of molybdenum nitride or carbide on a large-area self-standing substrate with high precision is still challenging. Here, MoNx is uniformly coated on carbon cloth (CC) and nitrogen-doped carbon (NC)-modified CC (NCCC) substrates by atomic layer deposition (ALD). The as-deposited film has a nanocrystalline character close to amorphous and a composition of approximately Mo2 N with significant oxygen contamination, mainly at the surface. Among the as-prepared ALD-MoNx electrodes, the MoNx /NCCC has the highest HER activity (overpotential η≈236 mV to achieve 10 mA cm-2 ) owing to the high surface area and porosity of the NCCC substrate. However, the durability of the electrode is poor, owing to the poor adhesion of NC powder on CC. Annealing MoNx /NCCC in H2 atmosphere at 400 °C improves both the activity and durability of the electrode without significant change in the phase or porosity. Annealing at an elevated temperature of 600 °C results in formation of a Mo2 C phase that further enhances the activity (η≈196 mV to achieve 10 mA cm-2 ), although there is a huge reduction in the porosity of the electrode as a consequence of the annealing. The structure of the electrode is also systematically investigated by electrochemical impedance spectroscopy (EIS). A deviation in the conventional Warburg impedance is observed in EIS of the NCCC-based electrode and is ascribed to the change in the H+ ion diffusion characteristics, owing to the geometry of the pores. The change in porous nature with annealing and the loss in porosity are reflected in the EIS of H+ ion diffusion observed at high-frequency. The current work establishes a better understanding of the importance of various parameters for a highly active HER electrode and will help the development of a commercial electrode for HER using the ALD technique.

A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy.

BACKGROUND: Vitamin B12 deficiency has been associated with peripheral neuropathy, loss of sensation in the peripheral nerves, and weakness in the lower extremities. Methylcobalamin is the most effective analogue of vitamin B12 used to treat or prevent the complications associated with vitamin B12 deficiency. The current study aimed to compare the serum cobalamin levels after administration of two different regimes of methylcobalamin in peripheral neuropathy patients. METHODS: The present study was a prospective, randomized, comparative study. The study consisted of two parallel groups, group A (methylcobalamin 500 µg injection intramuscularly three times a week) and group B (methylcobalamin 1500 µg injection intramuscularly once a week). A control group of healthy volunteers was also included. RESULTS: A total of 24 patients (12 in each group) were included in the study. Five healthy volunteers were also included as a control in each group. At the end of treatment, serum cobalamin levels were significantly (P = 0.028) higher in group A (1892.08 ± 234.50) as compared with group B (1438.5 ± 460.32). The serum cobalamin levels in Group A healthy volunteers were also two times higher than that of group B (P = 0.056). Both the LANSS scale and DN4 questionnaire reported similar results at end of treatment. CONCLUSIONS: The 500 µg methylcobalamin thrice weekly regime is more effective in increasing the serum cobalamin levels as compared to the 1500 µg methylcobalamin once weekly regime.

Porous synthetic hectorite clay-alginate composite beads for effective adsorption of methylene blue dye from aqueous solution.

The present study deals with the preparation and characterization of mesoporous synthetic hectorite (MSH) clay which further encapsulated with Na-alginate for the preparation of mesoporous synthetic hectorite-alginate beads (MSH-AB) where Ca2+ act as a cross-linking agent. The detail characterization of MSH and MSH-AB were carried out by various physicochemical techniques. The thermogravimetric analysis study showed better thermal stability results for MSH-AB. The textural properties results of MSH and MSH-AB showed the high surface area 468, 205m2/g, and the pore volume of 0.34, 0.29cm3/g respectively. The applicability of powder MSH and MSH-AB in wet (W) and dry (D) forms were assessed for the removal of cationic dye, methylene blue (MB) by optimizing various batch adsorption parameters. The Langmuir monolayer adsorption capacity obtained for MSH-AB-W showed significant high adsorption efficacy (i.e., 785.45mgMB/g) compared to the MSH-AB-D (357.14mgMB/g) and powder MSH materials (196.00mgMB/g). The adsorption isotherm studies showed that the Langmuir isotherm model was best suitable for MSH, whereas the Freundlich model was utilised to describe the adsorption behavior of organized hydrogel composite beads. The pseudo-second-order kinetics model was observed best for MB sorption onto MSH, whereas pseudo-first order useful to describe the kinetic behavior of MSH-AB. The regeneration experimental results revealed that MSH-AB-W could be recycled more than six cycles with high MB removal efficiency. Furthermore, the adsorption property of the MSH-AB-W was examined for the binary mixture of MB with other dye solutions such as Methyl Red (MR), Methyl Orange (MO), Alizarine Yellow (AY), and Remazol Brilliant Blue (RBB) to evaluate the selective adsorption efficiency. The MSH composite beads were found potentially suitable as an efficient, selective and recyclable adsorbent for the removal of MB from the aqueous solutions.

Metal-Free Carbon-Based Materials: Promising Electrocatalysts for Oxygen Reduction Reaction in Microbial Fuel Cells.

Microbial fuel cells (MFCs) are a promising green approach for wastewater treatment with the simultaneous advantage of energy production. Among the various limiting factors, the cathodic limitation, with respect to performance and cost, is one of the main obstacles to the practical applications of MFCs. Despite the high performance of platinum and other metal-based cathodes, their practical use is limited by their high cost, low stability, and environmental toxicity. Oxygen is the most favorable electron acceptor in the case of MFCs, which reduces to water through a complicated oxygen reduction reaction (ORR). Carbon-based ORR catalysts possessing high surface area and good electrical conductivity improve the ORR kinetics by lowering the cathodic overpotential. Recently, a range of carbon-based materials have attracted attention for their exceptional ORR catalytic activity and high stability. Doping the carbon texture with a heteroatom improved their ORR activity remarkably through the favorable adsorption of oxygen and weaker molecular bonding. This review provides better insight into ORR catalysis for MFCs and the properties, performance, and applicability of various metal-free carbon-based electrocatalysts in MFCs to find the most appropriate cathodic catalyst for the practical applications. The approaches for improvement, key challenges, and future opportunities in this field are also explored.

Potential Risks and Mitigation Strategies Before the Conduct of a Clinical Trial: An Industry Perspective.

Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials.

Anchoring Mechanism of ZnO Nanoparticles on Graphitic Carbon Nanofiber Surfaces through a Modified Co-Precipitation Method to Improve Interfacial Contact and Photocatalytic Performance.

A facile three-step co-precipitation method is developed to synthesize graphitic carbon nanofibers (CNFs) decorated with ZnO nanoparticles (NPs). By interchanging intermediate steps of the reaction processes, two kinds of nanohybrids are fabricated with stark morphological and physicochemical differences. The morphologies differ because of the different chemical environments of the NP/nanocluster formation. The hybrid with larger and non-uniform ZnO nanocluster size is formed in liquid phase and resulted in considerable interfacial defects that deteriorate the charge-transfer properties. The hybrid with smaller and uniform ZnO NPs was formed in a dry solid phase and produced near-defect-free interfaces, leading to efficient charge transfer for superior photocatalytic performance. The results broaden the understanding of the anchoring/bonding mechanism in ZnO/CNF hybrid formation and may facilitate further development of more effective exfoliation strategies for the preparation of high-performance composites/hybrids.

Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common therapeutic products used for the management of inflammation and pain. However, their use is associated with gastrointestinal (GI), cardiovascular and renal complications. Although prevalence data regarding NSAID-induced complications are available worldwide, but none of the study has assessed the prevalence of GI, cardiac and renal complications in India. This study aimed to assess the point prevalence of GI, cardiac and renal complications associated with the use of NSAIDs in India. The study also aimed to evaluate the association between the risk factors and GI, renal and cardiac complications in patients using NSAIDs. METHODS: This prospective, cross-sectional, multi-centric study was conducted in eight medical colleges across India (North, East, West, South and Central India). Data related to GI complications including gastric, duodenal and gastroduodenal erosions/ulcers/gastritis, renal complications including acute and chronic renal failure or cardiac complications including acute coronary syndrome (ACS), acute myocardial infarction (AMI) and cardiac failure, were collected from patients. RESULTS: The cut-off date for interim data analysis was July 7, 2014. A total of 2,140 patients out of 3,600 were enrolled from eight centers at the time of interim analysis. The NSAID-associated point prevalence of GI complications was 30.08%; cardiac complication was 42.77%; and renal complication was 27.88%. CONCLUSIONS: Results of the present interim analysis show that the prevalence of GI, cardiac and renal complications among patients is high due to exaggerated usage; however, the final analysis would provide the overall prevalence of these complications.

Safety reporting through a comprehensive and pragmatic pharmcovigilance process for India and emerging markets: an industry perspective.

INTRODUCTION: Pharmacovigilance (PV) deals with the drug-related adverse reactions ensuring patients' safety. Emerging markets of India, South East Asia (SEA), Russia, Latin America (LA), Middle East and North Africa (MENA) have developed their own PV programs. However, under/manual reporting accompanied with lack of awareness regarding adverse drug reactions (ADRs) are major drawbacks that continue to exist due to lack of co-ordination and disparity in the regulatory approach. AREAS COVERED: Of the 118 studies identified using various databases, 60 were included for the review. The authors discuss the present PV scenario of India, SEA, Russia, LA and MENA, and explain a basic process for uniform PV data input-output across industry, which includes data collection, analysis, processing, causality assessment and data distribution systems. EXPERT OPINION: As the number of clinical trials conducted are rising in the emerging markets, there is a need to understand and implement a robust PV system, where electronically globalized, evidence based, public health oriented and regulatory compliant PV system is established. This would also improve transparency in system and ensure enhancement in safety data reporting ensuring premature and trouble-free detection of ADRs. It might result in implementing various PV boosting activities, which could yield robust patient safety data from India and emerging markets.

A dechlorination pathway for synthesis of horn shaped carbon nanotubes and its adsorption properties for CO2, CH4, CO and N2.

Using metallic copper as reductant and tetrachloroethylene as carbon precursor, a simple, low temperature solvothermal method for the synthesis of horn shaped carbon nanotubes is reported. The detail study of reaction parameters such as temperature, time, carbon precursor amount, type and catalyst proportion has been carried out to optimize the conditions wherein that the copper metal (10 g) mediated reduction of tetrachloroethylene (25 mL) at 200°C for 5h resulted in the horn shaped carbon nanotubes with high yield and structural selectivity. The adsorption properties of horn shaped carbon nanotubes were investigated for carbon dioxide, methane, carbon monoxide and nitrogen as adsorbate by volumetric measurements up to 850 mm Hg. The prepared horn shaped carbon nanotubes showed good adsorption capacity for CO(2) (45 cm(3)/g) and CO (17 cm(3)/g), at 303 K and 850 mm Hg pressure, with high equilibrium selectivity (73.3 for CO(2) and 110.7 for CO at 318 K) and capacity selectivity (9.1 for CO(2) and 3.1 for CO at 850 mm Hg and 318 K) over nitrogen which provides the tool for the separation of CO(2) from its mixture with nitrogen observed in flue gas of thermal power plants and boilers, as well as with CO such as syngas.