Venous thromboembolism in patients with COVID-19. A prevalent and a preventable complication of the pandemic

Coronavirus disease 2019 or most commonly known as COVID-19 is a trending global infectious disease which a few months ago was affirmed as a global health emergency or a pandemic by the WHO Emergency Committee. The common symptoms manifested in this pandemic disease are high grade fever, cough, fatigue, shortness of breath and flu like symptom which can evolve into severe respiratory disorders such as pneumonia, acute respiratory distress syndrome (ARDS) and/or end-organ failure. Factors that contribute to the severity or high mortality rate in COVID-19 include old age, comorbidities like hypertension, diabetes, hyperlipidaemia, neutrophilia, and organ and coagulation dysfunction. Disseminated intravascular coagulation and other various coagulopathies including Venous thromboembolism have known to become a major contributing factor to high mortality rate. Venous thromboembolism is a disease which is a combination of deep vein thrombosis and pulmonary embolism. Prophylactic anticoagulation in patients prone to or with a pre-existing history of venous thromboembolism is associated with decreased mortality in severe COVID-19 pneumonia. This review article focuses upon COVID-19 and increased incidence of venous thromboembolism in patients infected by COVID-19 along with the role it has in high mortality rate in COVID-19 patients.     

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies

BackgroundData on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce.ObjectiveTo study 14-day mortality in patients who received CPT.Patients & methodsRetrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed.ResultsThe median age of the study cohort was 62 years (18–80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2–25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy.ConclusionsWe provide a large series of patients with hematological malignancies and role of CPT in this group.     

Efficacy and Safety of Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation Undergoing Elective Surgical Procedures: A Meta-analysis

Objective: The study objective was to determine if peri-operative bridging anticoagulation in patients with atrial fibrillation is beneficial or harmful.Design: Systematic review and meta-analysis.Setting: Inpatient or in-hospital setting.Participants: Adults with atrial fibrillation having a CHADS2 score >1 undergoing elective surgical procedure on anticoagulation.Methods: A systemic search of multiple databases (Cochrane, Medline, PubMed) was performed regarding studies conducted on efficacy and safety of perioperative bridging anticoagulation in patients with atrial fibrillation. Studies identified were reviewed by two authors individually before inclusion. The results were then pooled using Review Manager to determine the combined effect. Stroke/systemic embolism was considered as the primary efficacy outcome. Major bleeding was the primary safety outcome.Results: The systematic search revealed 108 potential articles. The full texts of 28 articles were retrieved for assessment of eligibility. After full text review, 25 articles were excluded. Three articles met inclusion criteria. No significant difference in stroke/systemic embolism with bridging anticoagulation was noted (risk ratio, 1.25-95% confidence interval [CI], 0.55–2.85). Bridging was associated with significantly higher risk of major bleeding (risk ratio, 3.29-95% CI, 2.25–4.81).Conclusion: An individualized approach is required when initiating peri-operative bridging anticoagulation. There is certainly a higher risk of bleeding with bridging anticoagulation and no difference in stroke/systemic embolism. However, the results cannot be extrapolated to patients who have valvular atrial fibrillation or CHADS2 score of 5 or greater.     

Challenges of acute phase neuroimaging in VA-ECMO,pitfalls and alternative imaging options

Large vessel occlusion in patients on ECMO is challenging to appreciate clinically secondary to sedation or induced paralysis, thus placing more emphasis on neurovascular imaging. However, emergent CTA and CTP are both inaccurate and unreliable in ECMO patients due to altered circuitry and interference with normal physiologic hemodynamics. In this review, the utility of DSA is discussed in evaluating the altered hemodynamics of VA-ECMO circuits and patency of major vasculature. In addition, the potential use of TCD in ECMO patients is discussed.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Instant and quantitative epoxidation of styrene under ambient conditions over a nickel(ii)dibenzotetramethyltetraaza[14]annulene complex immobilized on amino-functionalized SBA-15

Nickel(ii)dibenzotetramethyltetraaza[14]annulene complex (Nitmtaa) was synthetized and immobilized on post amino-functionalized SBA-15 (N-SBA-15) to obtain a stable and reusable nanocatalyst named as Nitmtaa@N-SBA-15. Here (3-aminopropyl)triethoxysilane (APTES) was first grafted on the surface SBA-15, then Nitmtaa was added and coordinated on the silica surface via APTES amine groups. The structure and morphology, and thermal stability of the prepared nanocatalyst was investigated using SEM, HR-TEM, BET, FT-IR, powder XRD, and TGA. HR-TEM and XRD results revealed a high dispersion of Nitmtaa on the SBA-15 surface. The catalytic activity of this nanocatalyst was evaluated in the epoxidation of styrene, under ambient conditions, using meta-chloroperoxybenzoic acid (m-CPBA) as the oxygen donor. This nanocatalyst showed an immediate and quantitative epoxidation of styrene with high turn-over-frequency ∼31.58 s⁻¹. Moreover, the superior catalytic activity and high stability of Nitmtaa@N-SBA-15 could be maintained after four successive cycles. A possible reaction mechanism is also proposed.

Immediate and quantitative epoxidation of styrene under ambient conditions catalyzed by new nanocatalyst obtained by immobilizing nickel(ii)dibenzotetramethyltetraaza[14]annulene in amino-functionalized SBA-15.     

Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films

Three factors, three levels (3³) full factorial design was used to develop venlafaxine HCl fast dissolving oral films (FDOFs) to optimize the concentrations of the film forming polymer; hydroxypropyl methylcellulose HPMC (X1), superdisintegrant; sodium starch glycolate SSG, (X2) and glycerol as the film plasticizer (X3). Effects of the three factors on the disintegration time (Y1), swelling index (Y2), and dissolution efficiency at 15 min; DE%15 (Y3) of the prepared FDOFs were evaluated by using statistical models. The optimized film formula was characterized in term of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and morphological characteristics.Disintegration time was found to increase with the increase in HPMC (X1) concentration, and the shortest disintegration time (21.67 ± 2.08 s) was observed in case of F2 formula (lowest HPMC level and highest glycerol level in absence of SSG). The highest swelling index (3.64 ± 0.59) was observed in case of film formula F1 (medium concentrations of both HPMC and glycerol and highest SSG concentration. The results also indicated that as the concentration of HPMC increased the DE%15 decreased. SSG (X2), with highest value (72.33 ± 1.71%) was recorded for in case of F12 (using 2% HPMC, 5%SSG and 1.5% glycerol). The optimized FDOF formula derived by the statistical models suggested 2% HPMC, 5% SSG, and 1% glycerol.The data obtained from DSC and XRPD revealed no interaction between drug and FDOT excipients. In addition, XRPD studies proved that the venlafaxine HCl was homogeneously dispersed in the film matrix.