Rationalized Approach for Formulation and Optimization of Ebastine Microemulsion Using Design Expert for Solubility Enhancement

Ebastine is available as an oral antihistamine formula for allergic disorders such as tablets and syrup. Oral ebastine causes unfavorable effects on heart like QT prolongation, severe gastric distress, decreased tear production, resulting in dryness of the ocular surface, which exacerbates ocular discomfort and increasing susceptibility of eye to irritation. To avoid systemic side effects and ocular discomfort, topical ocular therapy could prove to be superior to systemic therapy in treating ocular allergies. Hence, topical formulation was developed to achieve onsite exposure of ebastine for ocular allergies. Moreover, conjunctiva is more accessible to hydrophilic molecules than lipophilic molecules. This creates challenge for a lipophilic molecule such as ebastine for topical ocular development. Successful dissolution of ebastine in o/w microemulsion allows its use in more convenient soluble form. Initially, solubility of drug in various oils, surfactant and cosurfactant was determined, followed by pseudo-ternary phase diagram to find microemulsion area. The D-optimal mixture design was employed for optimization of formulation. The optimized microemulsion formulation was characterized for its transparency, drug content, droplet size, zeta potential, viscosity, isotonicity, osmolarity and surface tension etc. The optimum physicochemical properties were observed to be eye-fitting. Carboxy methyl cellulose and sodium hyaluronate were used as gelling agents at different concentrations to increase residential time at the site of action. In vitro drug release study revealed that ebastine release from microemulsion gel in a sustained manner up to 24 hrs. for the purpose of providing prolonged therapy for ocular allergy. Hence, prepared microemulsion had great potential as an alternative to customary oral formulations of poorly soluble drug. Keywords:  Ebastine, Microemulsion, D-optimal mixture design, Solubilit

Type 2 diabetes mellitus and coronary artery stenosis: a risk pattern association study

Aim: Cardiovascular diseases (CVD) are the leading cause of death globally. In the condition of type 2 diabetes mellitus (T2DM), the prevalence of CVD increase parallel with the rise of metabolic complication and higher incidence of coronary artery stenosis. The aim of this study was to compare the level of percent stenosis in coronary arteries in patients with coronary artery disease (CAD) with and without T2DM, and to measure the severity of CVD using Gensini score (GS) through angiographic data. Methods: The current study was conducted in tertiary care specialized hospital in Delhi, India. The level of percent stenosis in coronary arteries was compared in patients with CAD with and without T2DM. The patients were divided into two groups: group I included 100 patients with T2DM, and group II included 100 non-diabetic CAD patients who underwent coronary angiography by Judkin’s technique. The severity of CVD was measured by GS through angiographic data. The serum levels of glycated haemoglobin (HbA1c) ≥ 6.5% were considered diabetic. Results: Significant difference was observed in serum HbA1c, and random blood sugar levels between group I and group II were also observed (P ≤ 0.001). Serum HbA1c shows a significant positive association with GS (r = 0.36, P = 0.007). Conclusions: The study shows a significant level of stenosis in coronary arteries of CAD diabetic patients. However, further prospective analysis of a larger population size will be needed to strengthen the findings and the significant association

COVID 19-related burnout among healthcare workers in India and ECG based predictive machine learning model: Insights from the BRUCEE- Li study

OBJECTIVES: COVID-19 pandemic has led to unprecedented increase in rates of stress and burn out among healthcare workers (HCWs). Heart rate variability (HRV) has been shown to be reflective of stress and burnout. The present study evaluated the prevalence of burnout and attempted to develop a HRV based predictive machine learning (ML) model to detect burnout among HCWs during COVID-19 pandemic. METHODS: Mini-Z 1.0 survey was collected from 1615 HCWs, of whom 664, 512 and 439 were frontline, second-line and non-COVID HCWs respectively. Burnout was defined as score ≥3 on Mini-Z-burnout-item. A 12-lead digitized ECG recording was performed and ECG features of HRV were obtained using feature extraction. A ML model comprising demographic and HRV features was developed to detect burnout. RESULTS: Burnout rates were higher among second-line workers 20.5% than frontline 14.9% and non-COVID 13.2% workers. In multivariable analyses, features associated with higher likelihood of burnout were feeling stressed (OR = 6.02), feeling dissatisfied with current job (OR = 5.15), working in a chaotic, hectic environment (OR = 2.09) and feeling that COVID has significantly impacted the mental wellbeing (OR = 6.02). HCWs with burnout had a significantly lower HRV parameters like root mean square of successive RR intervals differences (RMSSD) [p < 0.0001] and standard deviation of the time interval between successive RR intervals (SDNN) [p < 0.001]) as compared to normal subjects. Extra tree classifier was the best performing ML model (sensitivity: 84%) CONCLUSION: In this study of HCWs from India, burnout prevalence was lower than reports from developed nations, and was higher among second-line versus frontline workers. Incorporation of HRV based ML model predicted burnout among HCWs with a good accuracy

Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS)

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody–Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results: At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21–1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57–3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22–26 vs. 22–27) and fewer with reduced GC (median, 23; IQR, 20–25) versus standard GC (median, 26; IQR, 25–28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions: Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality.publishedVersio

Umbilical venous catheter retrieval in a 970 gm neonate by a novel technique

Umbilical venous catheterization is a necessity for the advanced care of very low birth weight neonates. Even with utmost care, few complications cannot be avoided. Fractured and retained catheter fragments are one of them. Endoluminal retrieval of such a catheter is an uncommon and challenging procedure for the interventionist. The only alternative is an open exploration of these patients. Various techniques have been described for retrieval of such foreign bodies. We describe a novel technique for percutaneous retrieval of an embolized umbilical venous catheter from a very low birth weight neonate

Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-α with rheumatic mitral stenosis and subsequent pulmonary hypertension

Background: Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.Methods: Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo) and 79 normal healthy volunteers (group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA &gt;1 cm2 and MVA &lt;1 cm2) (subgroup Aa and Ab)] and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP &gt;36 mm Hg) (subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) levels were assessed in both groups.Results: Mean IL-6, IL-10, IL-18, TNF-α and hs-CRP in group A and group B was 6.57±3.53 and 2.73±1 (p≤0.001), 8.185±2.8 and 3.51±0.86 (p≤0.001), 136.31±89.0 and 47.96±9.76 (p≤0.001), 21.26±18.59 and 5.36±3.57 (p≤0.001), 4.69±6.3 and 2.63±2.22 (p≤0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71±16.84, while in subgroup Ab was 7.56±1.93 (p≤0.001). Mean IL-10 in subgroup Ac and Ad was 8.74±3.29 and 7.47±1.82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.Conclusions: This study finds increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-α levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels. </jats:p