Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous?-A retrospective cohort study

BackgroundHypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterized by the presence of hypoxia without dyspnea.. Silent hypoxia has been shown to affect the outcomes in previous studies. Research QuestionAre the outcomes in patients presenting with silent hypoxia different from those presenting with dyspneic hypoxia? Study design and MethodsThis was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory, and treatment parameters in patients with silent hypoxia and dyspneic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. ResultsAmong 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2<94% at the time of presentation. 174 (21.45%) did not have dyspnea since the onset of COVID-19 symptoms. 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspneic hypoxic patients (P=0.202). The odds ratio of death was 1.1 (95% CI 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment, and in-hospital complications, which did not reach statistical significance (P=0.851). InterpretationSilent hypoxia may be the only presenting feature of COVID-19. Since the case fatality rate is comparable between silent and dyspneic hypoxia, it should be recognized early and treated as aggressively. Since home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry at the home setting to identify these patients.

Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India-A cohort study

BackgroundThe second wave of the COVID-19 pandemic hit India from early April 2021 to June 2021 and more than 400,000 cases per day were reported in the country. We describe the clinical features, demography, treatment trends, baseline laboratory parameters of a cohort of patients admitted at the All India Institute of Medical Sciences, New Delhi with SARS-CoV-2 infection and their association with the outcome. MethodsThis was a retrospective cohort study describing the clinical, laboratory and treatment patterns of consecutive patients admitted with SARS-CoV-2 infection. Multivariate logistic regression models were fitted to identify the clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay and death. FindingsA total of 2080 patients were included in the study. The case fatality rate was 19.5%. Amongst the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 Acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged 45-60 years [OR (95% CI): 1.8 (1.2-2.6)p =0.003] and those aged >60 years [OR (95%CI): 3.4 (2.3-5.2), p<0.001] had a higher odds of death as compared to the 18-44 age group. Vaccination reduced the odds of death by 30% [OR (95% CI): 0.7 (0.5-0.9), p=0.036]. Patients with hyper inflammation at baseline as suggested by leucocytosis [OR (95% CI): 2.1 (1.4-3.10), p <0.001], raised d-dimer >500 mg/dL [OR (95% CI): 3.2 (2.2-4.6), p <0.001] and raised C-reactive peptide >0.5 mg/L [OR (95% CI): 3.8 (1.1-13), p=0.037] had higher odds of death. Patients who were admitted in the second week had lower odds of death and those admitted in the third week had higher odds of death. InterpretationThis is the largest cohort of patients admitted with COVID-19 from India reported to date and has shown that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Strategies should be made to improve vaccination rates and early admission of patients with moderate and severe COVID-19 to improve outcomes. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic has been ravaging the world since December 2019 and the cases in various regions are being reported in waves. We found that the case fatality rates ranging from 1.4% to 28.3% have been reported in the first wave in India. Older age and the presence of comorbidities are known predictors of mortality. There are no reports regarding the effectiveness of vaccination, correlation of mortality with the timing of admission to the health care facility and inflammatory markers in the second wave of the COVID-19 pandemic in India. Added-value of this studyThis study reports the real-world situation where patients get admitted at varying time points of their illness due to the mismatch between the availability of hospital beds and the rising number of COVID-19 patients during the pandemic. It reports the odds of developing severe hypoxia necessitating oxygen therapy and death thus helping identify priority groups for admission. Implications of all the available evidenceThis study found increased odds of requiring oxygen support or death in patients older than 45 years of age, with comorbidities, and those who had hyper-inflammation with raised C-reactive peptide, d-dimer or leukocytosis. Patients who were admitted in the second week of illness had lower odds of death as compared to those admitted in the third week implying that treatment with corticosteroids in the second week of the illness during the inflammatory phase could lead to reduced mortality. These findings would help triage patients and provide guidance for developing admission policy during times where hospital beds are scarce. Vaccination was found to reduce the odds of deterioration or death and should be fast-tracked to prevent further waves of the pandemic.

Aceclofenac delivery by microencapsulation using LBL self-assembly for delayed release.

Colonic targeting has gained increasing interest over the past years, not just for the transport of drugs for the treatment of local diseases associated with the colon but also for its potential for transporting peptides and proteins, particularly low molecular weight peptide drugs. Without protection, such peptide drugs are usually digested within the gastric and small intestinal sections. In the present work Layer-By-Layer (LBL) self-assembly was utilized to make Aceclofenac single bilayer microcapsules produced by sequential adsorption of positively charged chitosan and negatively charged Pectin on the external surface of negatively charged Aceclofenac microcrystals. Taguchi approach was applied to determine the best concurrence of composition factors that is concentration of chitosan, pectin, centrifugation speed and incubation time. The microcapsules were characterized for encapsulation efficiency, particle size, zeta potential, scanning electron microscopy and in-vitro release kinetics. Surface electric potential of Aceclofenac microcrystals was found to be negative with zeta potential -1.39 mV, in acetate buffer of pH 4. The primary and the secondary deposit layer of chitosan and pectin was found to have a positive and negative charge with zeta potential of +5.57 mV and -22.8 mV respectively. The sequential changing of surface zeta potential after each deposition is a satisfactory indication of the LBL self-assembly of the oppositely charged polyelectrolytes. The average size and encapsulation efficiency of the optimized single bilayer microcapsules (F5) was found to be 20µm and 63.83%, respectively. The ex-vivo percentage cumulative drug release of (F5) in Phosphate buffer pH 6.8 containing 2-4% w/v colonic fecal matter of male albino rat was found to be 98.40%. The optimized batch of microcapsules showed first order release kinetics (R(2)= 0.950) in presence of colonic fecal matter.

Development of meloxicam formulations utilizing ternary complexation for solubility enhancement.

Meloxicam (an oxicam derivative), a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water (8µg/ml), which directly influences the C(max), T(max), as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using ß-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC (methocel IH), methylcellulose (400cps), PVP K30, HPMC (K(4)M), HPMC (50cps). It is reported that when small amount of water soluble polymer is added to ß-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of ß-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility (90 µg/ml) of the drug and results in superior formulations of the drug by using ß-cyclodextrin blended with 0.12% w/w HPMC (Methocel IH). Ternary complexation is a valuable tool for solubility enhancement of drugs.