FORMULATION OPTIMIZATION AND CHARACTERIZATION OF AQUEOUS INJECTION CONTAINING POORLY SOLUBLE DRUG USING MIXED HYDROTROPIC SOLUBILIZATION

Objective: Mefenamic acid (MFA) is an NSAID that exhibits anti-inflammatory analgesic and antipyretic activity. Peak plasma levels are attained in 2-4 h and the elimination half-life approximates 2 h, repetitive administration of tablets for 3-5 times a day is desired. It is supplied only in the form of tablets for oral administration. In acute conditions drug administered parenterally could give rapid relief from severe symptoms like pain. Thus, formulation of injectable formulation of MFA could be better alternative compared to conventional tablet dosage form. The low aqueous solubility of MFA precludes its use in parenteral formulation development. Methods: In this work attempt were made to enhance the aqueous solubility of mefenamic acid using mixed solvency technique. For that different hydrotropic agents such as Urea, Sodium acetate, sodium benzoate, sodium citrate and their blends were evaluated. Optimal concentration of hydrotropic agent in blend was determined using D-optimal mixture experimental design. The optimized bled was used to develop the aqueous injection of mefenamic acid. The developed injection was subjected for various quality control tests and stability of developed formulation was also evaluated. Results: The aqueous solubility in optimized blend of hydrotropic agent batches (U: SA: SB: SC, 4:4:23:9 %w/v) showed 835.71-fold compared to MFA solubility in distilled water. The quality control tests for parenteral formulation and accelerated stability study were found to be within prescribed limits and stable. Conclusion: The inadequate solubility of MFA was overcome, and aqueous injection was successfully developed which can be serve as cost effective treatment in various indications

In-Hospital Outcome In Patients With Acyanotic Congenital Heart Disease Undergoing Transcatheter Aortic Valve Replacement.

The purpose of the study was to determine the in-hospital outcome and resource utilization in patients with acyanotic congenital heart disease (ACHD) undergoing transcatheter aortic valve replacement (TAVR). Current guidelines from professional societies do not support TAVR in patients with ACHD, likely from a lack of supportive evidence. Temporal trends in patients with ACHD undergoing TAVR were determined using the 2016-2018 National Inpatient Sample database appropriate ICS-10-PCS code. Stata 16.0 was used for statistical analysis. 0.87% of patients undergoing TAVR had concomitant ACHD, with ASD being the most common (78%). After matching, there was no increased risk of mortality in ACHD patients undergoing TAVR compared to patients without ACHD (OR 1.43, P = 0.59). Additionally, no difference was found in the incidence of overall cardiac complications between patients with ACHD and patients without ACHD, except STEMI (OR 4.16, 95% CI, 1.08-16.00, P = 0.038), which is likely due to more comorbidity burden in the later cohort. Complications such as acute kidney injury, ischemic stroke, and bleeding were similar. Hospital resource utilization was higher in the ACHD group in the form of increased length of stay and higher mean total cost. The comparable in-hospital all-cause mortality and complication rate in ACHD patients undergoing TAVR compared to patients without ACHD is encouraging and will be helpful to design future randomized controlled trials

Predictors and mortality risk of venous thromboembolism in patients with COVID-19: systematic review and meta-analysis of observational studies

Introduction: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19. Methods: We searched PubMed, EMBASE, Google Scholar, and Ovid databases for relevant observational studies of VTE in COVID-19 disease. The effect size for predictors of VTE was calculated using a random-effects model and presented as forest plots. Heterogeneity among studies was expressed as Q statistics and I2. Bias was assessed using the Newcastle Ottawa Scale for all identified observational studies. Publication bias was assessed with funnel plot analysis. Results: We identified 28 studies involving 6053 patients with suspected or confirmed COVID-19. The overall pooled prevalence of VTE events was 20.7%. Male sex was associated with a higher risk of VTE events, whereas prior history of VTE, smoking, and cancer were not. VTE events were significantly higher in severely ill patients, mechanically ventilated patients, those requiring intensive care admission, and those with a low PaO2/FiO2 ratio (P/F ratio). Chronic comorbidities, including cardiovascular disease, heart failure, renal disease, and pulmonary disease, did not increase the risk of VTE events. Patients with VTE had higher leukocyte counts and higher levels of D-dimer, C-reactive protein, and procalcitonin. The occurrence of VTE was associated with increased length of stay but did not impact mortality. Therapeutic and prophylactic doses of anticoagulation were not protective against VTE. Conclusion: VTE in COVID-19 is associated with male gender and severe disease but not with traditional risk factors for VTE. The occurrence of VTE does not appear to be mitigated by either prophylactic or therapeutic anticoagulation. The occurrence of VTE in this population is associated with an increased length of stay but does not appear to impact mortality

Proposed Pathogenesis, Characteristics, and Management of COVID-19 mRNA Vaccine-Related Myopericarditis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus causing coronavirus disease 2019 (COVID-19), has affected human lives across the globe. On 11 December 2020, the US FDA granted an emergency use authorization for the first COVID-19 vaccine, and vaccines are now widely available. Undoubtedly, the emergence of these vaccines has led to substantial relief, helping alleviate the fear and anxiety around the COVID-19 illness for both the general public and clinicians. However, recent cases of vaccine complications, including myopericarditis, have been reported after administration of COVID-19 vaccines. This article discusses the cases, possible pathogenesis of myopericarditis, and treatment of the condition. Most cases were mild and should not yet change vaccine policies, although prospective studies are needed to better assess the risk-benefit ratios in different groups

Impact of Pulmonary Hypertension in Patients With Hypertrophic Cardiomyopathy Presented With Cardiogenic Shock/Acute Decompensated Heart Failure

There have been no studies focusing on how pulmonary hypertension (PH) affects inpatient outcomes in patients with hypertrophic cardiomyopathy (HCM) hospitalized for acute decompensated heart failure or cardiogenic shock. This study explores inpatient outcomes of patients with HCM, and concomitant PH compared to patients with HCM. Based on the National Inpatient Sample (NIS) 2016-2018, patients admitted with a primary diagnosis of acute decompensated heart failure or cardiogenic shock were selected. The patients diagnosed with concomitant HCM were identified and divided into 2 groups based on the presence or absence of PH. After propensity matching 1545 matched pairs were generated. Patients with PH had a higher prevalence of chronic kidney disease (P \u3c 0.001), anemia (P \u3c 0.001), coagulopathy (P \u3c 0.001), atrial fibrillation (P = 0.031), and valvular disease (P \u3c 0.001) (Table 1). The primary outcome (all-cause in-hospital mortality) occurred in 110 patients (2.6%) without PH and 95 patients (5.2%) with PH, which was not statistically significant after propensity matching (odds ratio [OR]:1.53; 95% confidence interval [CI]: 0.70-3.33; P = 0. 28) (Table 3). Patients with PH had a higher incidence of transient ischemic attack (TIA) (OR: 9.52; 95% CI: 3.38-26.78; P \u3c 0.001)] and respiratory failure [(OR: 1.49; 95% CI:1.05-2.11; P = 0.027], although with no difference in requirement for mechanical ventilation (= 0.64), as compared to patients without PH. PH in patients with HCM is associated with increased morbidity, including increased risk of TIA and respiratory failure

Association of Atrial Fibrillation with Outcomes in Patients Hospitalized with Inflammatory Bowel Disease: an Analysis of the National Inpatient Sample

INTRODUCTION: We aimed to determine in-hospital outcomes, length of hospital stay (LOS) and resource utilization in a contemporary cohort of patients with inflammatory bowel disease (IBD) and atrial fibrillation (AFIB). MATERIAL AND METHODS: The National Inpatient Sample database October 2015 to December 2017 was utilized for data analysis using the International Classification of Diseases, Tenth Revision codes to identify the patients with the principal diagnosis of IBD. RESULTS: Of 714,863 IBD patients, 64,599 had a diagnosis of both IBD and AFIB. We found that IBD patients with AFIB had a greater incidence of in-hospital mortality (OR = 1.3; 95% CI: 1.1-1.4), sepsis (OR = 1.2; 95% CI: 1.1-1.3), mechanical ventilation (OR = 1.2; 95% CI: 1.1-1.5), shock requiring vasopressor (OR = 1.4; 95% CI: 1.1-1.9), lower gastrointestinal bleeding (LGIB) (OR = 1.09, 95% CI: 1.04-1.1), and hemorrhage requiring blood transfusion (OR = 1.2, 95% CI: 1.17-1.37). Mean LOS ± SD, mean total charges and total costs were higher in patients with IBD and AFIB. CONCLUSIONS: In this study, IBD with AFIB was associated with increased in-hospital mortality and morbidity, mean LOS and resource utilization