Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure," "virological cure," "death or clinical worsening of disease," "radiological progression," and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.
The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (þ) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on 'docking score'. These tophits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class 'bronchodilators' and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations.
The aim of the study was to examine the dimensions of hallucinations and delusions in affective (manic episode, bipolar affective disorder, and depressive episode) and nonaffective disorders (schizophrenia, acute and transient psychotic disorders, and unspecified psychosis). Sixty outpatients divided equally into two groups comprising affective and nonaffective disorders were taken up for evaluation after screening, as per inclusion and exclusion criteria. Scores of 3 or above on delusion and hallucinatory behavior subscales of positive and negative syndrome scale were sufficient to warrant rating on the psychotic symptom rating scales with which auditory hallucination and delusion were assessed on various dimensions. Insight was assessed using the Beck cognitive insight scale (BCIS). There were no significant differences between the two groups on age, sex, marital status, education, and economic status. There were significant differences in total score and emotional characteristic subscale, cognitive interpretation subscale, and physical characteristic subscale of auditory hallucination scales in between the two groups. Correlation between BCIS-total and total auditory hallucinations score was negative (Spearman Rho −0.319; P < 0.05). Hallucinating patients, more in nonaffective group, described a negative impact of hallucinating voices along with emotional consequences on their lives which lead to distress and disruption.
Purpose:Bloodstream infections (BSIs) are one of the major life-threatening infections in hospitals. They are responsible for prolonged hospital stays, high healthcare costs, and significant mortality. The epidemiology of BSIs varies between hospitals necessitating analysis of local trends. Few studies are available on trauma patients, who are predisposed due to the presence of multiple invasive devices.Materials and Methods:A prospective surveillance of all BSIs was done at a level 1 trauma center from April, 2011 to March, 2012. All patients admitted to the different trauma intensive care units (ICUs) were monitored daily by attending physicians for subsequent development of nosocomial BSI. An episode of BSI was identified when patients presented with one or more of the following signs/symptoms, that is, fever, hypothermia, chills, or hypotension and at least one or more blood culture samples demonstrated growth of pathogenic bacteria. BSIs were further divided into primary and secondary BSIs as per the definitions of Center for Disease Control and Prevention. All patients developing nosocomial BSIs were followed till their final outcome.Results:A total of 296 episodes of nosocomial BSIs were observed in 240 patients. A source of BSI was identified in 155 (52%) episodes. Ventilator-associated pneumonia was the most common source of secondary BSI. The most common organism was Acinetobacter sp. (21.5%). Candida sp. accounted for 12% of all blood stream organisms. A high prevalence of antimicrobial resistance was observed in Gram-negative and-positive pathogens.Conclusions:Trauma patients had a high prevalence of BSIs. Since secondary bacteremia was more common, a targeted approach to prevention of individual infections would help in reducing the burden of BSIs.
Cutaneous mucormycosis is an uncommon disease and it usually affects immunocompromised, diabetic, and trauma patients with contaminated wounds or patients with underlying malignancies. It is very rare to find this disease in immunocompetent, nondiabetic patients. We herein report a case of primary cutaneous mucormycosis in an immunocompetent and nondiabetic patient. Our patient was a 50-year-old veterinary doctor. He was diagnosed to have cutaneous mucormycosis of the anterior abdominal wall, and was treated with multiple debridements of the wound and intravenous amphotericin B therapy. He received a total of 1000 mg of amphotericin B. A high index of clinical suspicion and early institution of therapy in the form of surgical debridements and antifungal drugs are required to achieve a successful outcome.
This survey demonstrates that there is universal deficiency in both the knowledge and practice of pediatricians in the field of PID. Implementation of strategies to improve the awareness of pediatricians about PID is critical so early therapeutic interventions can be done to improve the health and prevent morbidity and mortality.
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