Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Background: Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. Material and Methods: We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. Results: The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Conclusion: Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis.

Dermatophytosis, the most prevalent fungal infection, is witnessing a rising incidence annually. To address this challenge, we developed a terbinafine-loaded oil-in-water nanoemulsion (TH-NE) through the aqueous microtitration method. The formulation comprised olive oil (oil phase), Span 80 (surfactant), and propylene glycol (co-surfactant). Pseudo-phase ternary diagrams and thermodynamic studies underscored the stability of TH-NE. Employing the Box-Behnken design (BBD), we optimized TH-NE, which resulted in a remarkable particle size of 28.07 nm ± 0.5, a low polydispersity index (PDI) of 0.1922 ± 0.1, and a substantial negative zeta potential of -41.87 mV ± 1. Subsequently, TH-NE was integrated into a 1.5% carbopol matrix, yielding a nanoemulgel (TH-NEG). Texture analysis of TH-NEG demonstrated a firmness of 168.00 g, a consistency of 229.81 g/s, negative cohesiveness (-83.36 g), and a work of cohesion at -107.02 g/s. In vitro drug release studies revealed an initial burst effect followed by sustained release, with TH-NEG achieving an impressive 88% release over 48 h, outperforming TH-NE (74%) and the marketed formulation (66%). Ex vivo release studies mirrored these results, with TH-NEG (86%) and TH-NE (71%) showcasing sustained drug release in comparison to the marketed formulation (67%). Confocal microscopy illustrated that TH-NEG and TH-NE penetrated to depths of 30 µm and 25 µm, respectively, into the epidermal layer. Furthermore, dermatokinetic studies highlighted the enhanced drug penetration of TH-NEG compared to TH-NE through mouse skin. In summary, our study establishes TH-NEG as a promising carrier for terbinafine in treating dermatophytosis, offering improved drug delivery and sustained release potential.

Exploration of a W/O Nanoemulsion for Antibiofilm Activity against Cariogenic Enterococcus faecalis.

A ciprofloxacin-loaded water-in-oil nanoemulsion (CPX-NE) was prepared and evaluated for the antimicrobial effect against oral biofilms produced by Enterococcus faecalis. CPX-NE was prepared by ultrasonication using functional excipients oleic acid (oil phase), Span 80 (surfactant), and Transcutol P (cosurfactant). Rheological parameters (viscosity = 20 ± 1.24 cp) confirmed optimum values for CPX-NE, a pH of 6.5 ± 0.23 suggested the simulation of CPX-NE with the pH of the mouth cavity, refractive index (1.46 ± 0.22), and % transmittance (92.34 ± 0.02) indicated the isotropic nature of the NE. The droplet size (72.19 ± 1.68 nm), polydispersity index (0.142 ± 0.02), and ζ potential (-28 mV) demonstrated a narrow size distribution and electrostatically stabilized NE. The morphology of the optimized formulation showed uniform spherical nanodroplets, as seen in fluorescence microscopy. In vitro drug release showed an initial burst effect followed by sustained release for 48 h, following Fick's diffusion. The minimum biofilm inhibitory and eradication concentration (MBIC/MBEC) was determined to compare CPX-NE with ciprofloxacin plain drug solution (CPX-PS) for their efficacy. CPX-NE demonstrated a significant inhibitory and eradication effect compared to CPX-PS. It was concluded that the developed CPX-NE has effective antibiofilm activity against E. faecalis and may be useful in the prevention and treatment of dental caries.

Demographic profile of patients seeking teleophthalmology consultations through e-Sanjeevani: Retrospective analysis of 5138 patients from North India.

Purpose: To report the demographic profile of patients registered through e-Sanjeevani OPD seeking teleophthalmology services. Methods: This was a cross-sectional data analysis of patients with ocular complaints registered through the e-Sanjeevani platform at a tertiary care center. It was a doctor-to-doctor consultation, where teleophthalmology consultants provided teleconsultation services at subcenters (SCs), primary health centers (PHCs), and community health centers (CHCs). Data regarding the patient's age, gender, residential address, provisional diagnosis, and treatment prescribed were recorded from May 2021 to February 2022 (9 months). Results: In total, 5138 patients were teleconsulted from the mean age of the patients was 37.64 ± 19.34 years. Among these patients, 44% were males and 56% were females. Most of the teleconsultation calls were made from Palwal district (19.8%), followed by Hisar (14.5%) and Sonipat. The most common provisional diagnosis was dry eyes (21%), followed by allergic conjunctivitis (18%), refractive error (15%), and cataract (14%). These constituted approximately 70% of the diagnosis made through teleconsultations. The rest of the eye problems were diagnosed as stye, blepharitis, nasolacrimal duct obstruction, pterygium, subconjunctival hemorrhage, etc., The majority of the patients were managed medically (56.6%) and approximately 11.6% of the patients were referred for surgical intervention. Conclusion: e-Sanjeevani is an effective way to provide teleconsultations to patients in remote locations. The majority of the patients seeking ophthalmology consultations can be managed conservatively. Patients requiring surgical intervention can be referred timely, thus avoiding any delay in treatment.

Effectiveness-of Calcium Phosphate derivative agents on the prevention and remineralization of caries among children- A systematic review & meta-analysis of randomized controlled trials.

OBJECTIVES: Dental caries among children is a highly prevalent yet easily preventable oral health issue among children. Various calcium phosphate (CaP) derivatives are implicated to exhibit caries preventive potential; however, no study has summarized the anti-caries effectiveness of these agents. This systematic review and meta-analysis sought to assess the caries-preventive and tooth-remineralizing effect of various (CaP) derivative agents compared to no-intervention/placebo or Fluoride (F) use alone among children. MATERIALS AND METHODS: EMBASE, Ovid, PubMed, Scopus, Web of Science, Cochrane central register of controlled trials (CENTRAL), and grey literature were searched for relevant articles up to April 2021. Only English-language articles were included. Total 2636 articles were searched through different databases; out of the 2161 articles were screened after duplicate removal. 26 studies fulfilling the eligibility criteria were included in this systematic review. Methodological quality assessment and quantitative analysis were done using RevMan. GRADE was used to evaluate the certainty of evidence. RESULTS: A total of 26 trials fulfilling the eligibility criteria were included. The meta-analysis of 10 studies revealed that complete white spot lesions (WSLs) regression (RR=1.56; 95% CI, 1.27 to 1.91; P < .0001, I2=0%), post intervention active WSLs (RR=0.80; 95% CI, 0.70 to 0.90; P = .0004, I2=0%) and post intervention Salivary S. mutans count (RR= 0.69; 95% CI, 0.48 to 0.99; P = .47, I2=0%) significantly favored the CaP+F combined therapy as compared to F alone. No significant differences in the lesion area, Delta F, and DIAGNOdent values were observed between the 2 groups. Low certainty of the evidence was found in the present systematic review due to the high/unclear risk of bias, imprecision, and indirectness of included trials. CONCLUSIONS: Topical treatment using CaP+F group showed superior remineralization potential as well as the antibacterial effect on dental caries among children as compared to no intervention and/or placebo or F alone. Apart from CPP-ACP, other CaP derivatives like TCP and fTCP seem to have promising effects in remineralizing early lesions, however, very few trials exist on these potential agents. To provide definitive recommendations in this area, more clinical trials on caries preventive effectiveness of various CaP agents are warranted.

Remote Monitoring and Holistic Care of Home-Isolated COVID-19 Positive Healthcare Workers Through Digital Technology During the Omicron (B1.1.529) Wave: A Prospective Cohort Study From India.

Background: Remote monitoring through digital technology offers a promising solution for the diverse medical, psychological and social issues that plague patients with COVID-19 under home-isolation, but remain neglected due to a lack of streamlined medical services for these patients. Methods: This prospective cohort study determined the feasibility of remote telemonitoring of healthcare workers with mild COVID-19 under home isolation during the Omicron (B1.1.529) wave and characterized their clinico-demographic profile. A holistic monitoring model comprising of mandatory phone calls at the beginning and end of isolation, assisted by home oximetry, predesigned google forms, and opt-in software-based (eSanjeevani OPD) teleconsultation was employed. Factors associated with development of symptomatic disease were also determined. Results: Out of 100 COVID-19 positive healthcare workers under home-isolation, data for 94 participants was available [median age 27(20-52) years, 56(60%) females]. 93(99%) patients were previously vaccinated for COVID-19 (median time from last dose = 248 days); 34(36%) had a past history of COVID-19. Fever (67%), myalgia (69%), sore throat/dry cough (70%), and running nose (45%) were the most common symptoms. No patient progressed to moderate-severe disease or required care escalation during the remote monitoring period. Most participants reported several additional psychosocial concerns which were adequately addressed. Symptomatic patients had higher BMI (24.1 vs. 21.8kg/m2, p = 0.01) compared to asymptomatic patients. Age, past infection with COVID-19, and time since last vaccine dose were not different between symptomatic and asymptomatic patients. Conclusion: COVID-19 patients under home isolation have multi-faceted medical and psychosocial issues which can be holistically managed remotely through digital technology.

The perceived need for evidence-based COVID-19 management and Tele-education in the North-East region of India: a cross-sectional survey.

Due to the sudden rise in the cases of COVID-19 in the North-Eastern region of India, this study was conducted to survey the felt needs of the medical professionals with regards to education on the evidence-based management of COVID-19. A total of 25 North-East leaders were recruited and a baseline survey was conducted through the digital medium. Out of 25 North-East leaders, 52% were undergoing training in evidence-based medicine in the capacity-building program for evidence-based child health. Participants (48%) strongly agreed and 40% agreed on the possibility of enhanced care by capacity building in the areas of COVID-19 management through discussing cases. Out of 25 North East leaders, 48% agreed to join both as a speaker as well as a participant. Various priority topics on COVID-19 management e.g. childhood, adult, ocular manifestation, ICU management, telemedicine, vaccines, lab protocols, psychological distress, and treatment strategy have emerged. We have presented the findings of the survey which will help guide the mentoring program focusing on evidence-based management of COVID-19 in remote areas through Tele-education.

Structure of a 14-3-3ε:FOXO3apS253 Phosphopeptide Complex Reveals 14-3-3 Isoform-Specific Binding of Forkhead Box Class O Transcription Factor (FOXO) Phosphoproteins.

The transcriptional activity of Forkhead Box O3 (FOXO3a) is inactivated by AKT-mediated phosphorylation on Serine 253 (S253), which enables FOXO3a binding to 14-3-3. Phosphorylated FOXO3a binding to 14-3-3 facilitates the nuclear exclusion of FOXO3a, causing cancer cell proliferation. The FOXO3a/14-3-3 interaction has, therefore, emerged as an important therapeutic target. Here, we report a comprehensive analysis using fluorescence polarization, isothermal titration calorimetry, small-angle X-ray scattering, X-ray crystallography, and molecular dynamics simulations to gain molecular-level insights into the interaction of FOXO3apS253 phosphopeptide with 14-3-3ε. A high-resolution structure of the fluorophore-labeled FOXO3apS253:14-3-3ε complex revealed a distinct mode of interaction compared to other 14-3-3 phosphopeptide complexes. FOXO3apS253 phosphopeptide showed significant structural difference in the positions of the -3 and -4 Arg residues relative to pSer, compared to that of a similar phosphopeptide, FOXO1pS256 bound to 14-3-3σ. Moreover, molecular dynamics studies show that the significant structural changes and molecular interactions noticed in the crystal structure of FOXO3apS253:14-3-3ε are preserved over the course of the simulation. Thus, this study reveals structural differences between the binding to 14-3-3 isoforms of FOXO1pS256 versus FOXO3apS253, providing a framework for the rational design of isoform-specific FOXO/14-3-3 protein-protein interaction inhibitors for therapy.

Multisystem Inflammatory Syndrome Associated With COVID-19 in Children (MIS-C): A Systematic Review of Studies From India.

BACKGROUND: With wide clinical spectrum, multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children (MIS-C) is a relatively novel condition occurring weeks to months' post SARS-CoV-2 infection. The aim was to systematically review data on clinical features, laboratory parameters and therapeutics of MIS-C from India. Methods: This systematic review was done as per the PRISMA guidelines, and quality assessment was done using NIH tool for case-series. A systematic search through databases yielded studies whose data was pooled to calculate the mean frequencies with standard deviation using GraphPad software. RESULTS: Screening of 2548 articles published till December, 2021, yielded 11 case-series. World Health Organization case definition was used widely. There was a slight preponderance of males (57%), median (IQR) age was 7 (6,7) years, 63% (n=305) required intensive care unit admissions, and mortality rate was 10% (n=261). Clinical features included fever, mucocutaneous features (72%), and gastrointestinal problems (62%) in majority. Widely used treatment was corticosteroids (76%) and intravenous immunoglobulin (62%) with other options depending on patient's state. An increased level of inflammatory markers and derangement in other parameters corroborated with disease status. Kawasaki disease like features, not reported in many studies, ranged from 4-76% of patients. CONCLUSION: MIS-C presents with a wide spectrum clinical features, increased inflammatory markers and managed as per the disease course and presentation. Future studies monitoring the long-term effects of MIS-C are recommended.

Identification of Mtb GlmU Uridyltransferase Domain Inhibitors by Ligand-Based and Structure-Based Drug Design Approaches.

Targeting enzymes that play a role in the biosynthesis of the bacterial cell wall has long been a strategy for antibacterial discovery. In particular, the cell wall of Mycobacterium tuberculosis (Mtb) is a complex of three layers, one of which is Peptidoglycan, an essential component providing rigidity and strength. UDP-GlcNAc, a precursor for the synthesis of peptidoglycan, is formed by GlmU, a bi-functional enzyme. Inhibiting GlmU Uridyltransferase activity has been proven to be an effective anti-bacterial, but its similarity with human enzymes has been a deterrent to drug development. To develop Mtb selective hits, the Mtb GlmU substrate binding pocket was compared with structurally similar human enzymes to identify selectivity determining factors. Substrate binding pockets and conformational changes upon substrate binding were analyzed and MD simulations with substrates were performed to quantify crucial interactions to develop critical pharmacophore features. Thereafter, two strategies were applied to propose potent and selective bacterial GlmU Uridyltransferase domain inhibitors: (i) optimization of existing inhibitors, and (ii) identification by virtual screening. The binding modes of hits identified from virtual screening and ligand growing approaches were evaluated further for their ability to retain stable contacts within the pocket during 20 ns MD simulations. Hits that are predicted to be more potent than existing inhibitors and selective against human homologues could be of great interest for rejuvenating drug discovery efforts towards targeting the Mtb cell wall for antibacterial discovery.

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. METHODS: A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. RESULTS: Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. CONCLUSIONS: Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.

HIV infection is associated with a progressive decline of CD4+ T-cell numbers and increase in viral load. To keep the virus replication in check, patients need to take the antiretroviral therapy life-long, which is not without gastrointestinal discomfort. Probiotics have already shown multiple benefits ranging from reduction in diarrhea, nausea and bloating besides replenishment of CD4+ T-cells numbers. Based on this background information, we have compiled the data on probiotics among HIV-infected children. A pooled analysis from randomized clinical trials revealed significant improvement in CD4+ T-cell counts in HIV-infected children without any adverse effects. However, we recommend large and well-designed trials in future that would help in forming a concrete and high quality evidence in this context.

Burden of Attention Deficit Hyperactivity Disorder (ADHD) in Indian Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the pooled prevalence of attention deficit hyperactivity disorder (ADHD) in Indian children. METHODS: The searching of published literature was conducted in different databases (PubMed, Ovid SP, and EMBASE). The authors also tried to acquire information from the unpublished literature about the prevalence of ADHD. A screening was done to include eligible original studies, community or school-based, cross-sectional or cohort, reporting the prevalence of ADHD in children aged ≤ 18 y in India. Retrieved data were analyzed using STATA MP12 (Texas College station). RESULTS: Of 729 studies retrieved by searching different databases, 183 studies were removed as duplicates, and 546 titles and abstracts were screened. After screening, 19 studies were included for quantitative analysis. Subgroup analysis was conducted with respect to their setting (school-based/community-based). Fifteen studies performed in a school-based setting showed 75.1 (95% CI 56.0-94.1) pooled prevalence of ADHD per 1000 children of 4-19 y of age. In community-based settings, the pooled prevalence per 1000 children surveyed was 18.6 (95% CI 8.8-28.4). The overall pooled prevalence of ADHD was observed as 63.2 (95% CI 49.2-77.1) in 1000 children surveyed. Significant heterogeneity was observed in the systemic review. CONCLUSIONS: ADHD accounts for a significant health burden, and understanding its burden is crucial for effective health policy-making for educational intervention and rehabilitation.

Role of environmental lead in the occurrence of anemia in Indian children: a systematic review and meta-analysis.

Exposure to lead among children, as well as adults, is a major global health issue. With diverse routes of exposure (e.g., food, air, and water) either environmentally or occupationally, lead among children can cause mild, moderate, to severe health complications in the later stages of life. The average blood lead level reported by CDC in 2021 is 3.5 µg/dL, and the level of blood lead toxicity is ≥ 10 µg/dL. In this study, we planned to systematically analyze the association between blood lead levels (BLLs) (≥ 10 µg/dL and < 10 µg/dL) and the risk of anemia (hemoglobin level < 11 g/dL) among Indian children aged between ≥ 1 and ≤ 18 years. An online literature search of 5 databases, PubMed, Ovid, EMBASE, Web of Science, and Google Scholar was accomplished with a search updated until 8th March 2021. Study designs included cohort, cross-sectional, and case-control studies that have evaluated the association of lead toxicity or exposure with anemia (Hb < 11 g/dL) reported in urban and/or rural Indian children. Meta-analysis was performed among a total of 864 children from 4 cross-sectional studies. The association between lead toxicity (BLLs ≥ 10 µg/dL) and the risk of being anemic was not statistically significant (RR = 1.15 (95% CI: 0.86-1.55, I2 = 77%). The risks of bias in all included studies were low according to the Newcastle Ottawa Scale. Increased blood lead levels did not appear to be the major contributor to anemia in Indian Children. We need to focus primarily on improving the nutritional quality, fortified food supplements, and a balanced diet for children to reduce the anemia burden in India. Lead toxicity should be sought as an etiological factor only in areas of high environmental risk factors which were leaded paints, leaded batteries, a house near major road/traffic areas, and pesticide exposure.

Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.

BACKGROUND AND AIMS: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). RESULTS: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2  > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

Needle Fear among Children during Mass Measles Rubella (MR) Injectable Vaccination Campaign in North India: an Observational Study.

The cross-sectional observational study evaluated the prevalence and predictors of needle-fear among school-going children during mass Measles-Rubella (MR) immunization campaign (year 2017) in the north Indian city of Chandigarh. Fear of needle was assessed using a single-item self-report global question, anxiety was assessed using the Likert scale (score 1-5) and the standardized "Children Faces Scale" where facial responses were graded from 0 to 4. Out of a total sample of 2568 school children, 1225 (47.7%) reported needle fear (95% CI: 45.8%-49.6%) on a global single item assessment. On an anxiety related Likert scale, 52.3% did not respond (mainly younger children) and among those who responded, 42.6% (523/1226) showed significant anxiety (score of ≥3 on Likert scale of 1 to 5). Finally, 17.4% children (95% CI: 15.9%-18.9%) (n = 446/2568) scored 2 or above (indicating significant needle fear) on the 'Children Faces Scale' during the actual vaccination procedure. The needle fear were significantly increased among girl students as compared to boys (adjusted OR 2.58; 95% CI: 2.05-3.24, p < 0.001) as well as children accompanied by their parents (adjusted OR 2.05; 95% CI:1.57-2.69, p < 0.001). On the other hand, needle fear was significantly lowered in children studying in private schools as compared to public school children (adjusted OR 0.45; 95% CI: 0.28-0.74, p = 0.002). The needle fear, which was an overriding concern in the minds of girls, children accompanied by their parents, and public-school students, must be proactively addressed for successful mass vaccination campaigns. These findings assume further importance with recent international roll out of COVID 19 vaccine.

Exploring the role of bacillus calmette-guerin vaccination in protection against COVID-19.

BACKGROUND: In recent studies, it has been established that countries having Bacillus Calmette-Guerin (BCG) vaccination programs reported less COVID-19 cases and deaths per population Preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers. METHODS: The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in the hospital. The Graph Pad statistical analysis tool was used to determine the association of preliminary BCG vaccination with their COVID-19 status. RESULTS: A total of 200 health care workers working in different departments of the hospital were enrolled in the study. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated was 0.79 (0.50-1.25). There was also a significant negative correlation between two groups. The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44-0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56-2.09). CONCLUSION: The present study did not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

Evaluation of Tele-rheumatology during the COVID-19 Pandemic in Asian Population: A Pilot Study.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune condition associated with a potential for deformities. It is one of the common conditions to seek health care. Hence, the present study was conducted to assess the telemedicine services for patients suffering from rheumatoid arthritis during the COVID-19 pandemic in an Asian Indian population. METHODS: A prospective study was conducted (March 2020-June 2020) in the telemedicine department of a premier northern Indian tertiary care institution. Out of the total patients enrolled (N = 7577) in telemedicine services, 122 rheumatoid arthritis patients (1.6%) were followed for 1 month to assess change in functional status by modified Health Assessment Questionnaire (mHAQ). Telephonic interviews of the enrolled patients were conducted to determine the level of understanding of advice given by consultants, barriers during the consultation, and satisfaction with teleconsultations for rheumatology clinics. RESULTS: For the native people, language of the clinicians was the main barrier (20%) in telerheumatology. Saving of time and money was observed as beneficial factors for patients. More than three-quarters of all rheumatoid arthritis patients were ready to use teleconsultation in the near future. A similar proportion of patients were in support for the recommendation of these services to other persons. CONCLUSION: We report the successful use of telemedicine services in the evaluation and management of rheumatic diseases in the current COVID-19 pandemic situation.

Paracetamol exposure and asthma: What does the evidence say? An overview of systematic reviews.

OBJECTIVE: To conduct an umbrella review collating the existing evidence to determine whether there is an association between exposure of Paracetamol in-utero or in infancy and the development of childhood Asthma. METHODS: In this review, systematic reviews with or without meta-analysis that reported the association between paracetamol and asthma in children were included. To identify relevant reviews, a search was performed in the electronic databases PubMed, the Cochrane Library, and Ovid MEDLINE. The protocol was registered in PROSPERO CRD42020156023. A separate search was conducted for primary studies from the last 5 years not yet included in systematic reviews reporting the association from January 2016 to March 2021. RESULTS: The electronic searches identified 1966 review titles. After the removal of 493 duplicates, 1475 titles and abstracts were screened against the eligibility criteria. Full-text screening yielded six systematic reviews to be included in this review. The search for primary studies in the last 5 years yielded 1214 hits, out of which 5 studies were found suitable for inclusion. Three of them, that were not included in the systematic reviews, and have been summarised in this paper. The odds ratios (ORs) for the outcome of asthma in offspring of mothers with prenatal paracetamol consumption in any trimester were 1.28 (1.13-1.39) and 1.21 (1.02-1.44). For first trimester exposures, they were 1.12 (0.99-1.27), 1.39 (1.01-1.91), and 1.21 (1.14-1.28), for the second or third trimester, they were 1.49 (1.37-1.63) and 1.13 (1.04-1.23). For the third trimester only, the figure was 1.17 (1.04-1.31). Of the six reviews included, 1 had a low risk of bias, 2 had an unclear risk while 3 had a high risk of bias assessed using the ROBIS tool. There was no significant increased risk of asthma with early infancy exposure. The inter-study heterogeneity varied from I2 = 41% to I2 = 76% across reviews. In the primary studies, the OR for prenatal exposure ranged from 1.12 (0.25-4.98) to 4.66 (1.92-11.3) and for infancy exposure was 1.56 (1.06-2.30). All three included primary studies were adjudged to be of high quality using the Newcastle Ottawa scale. CONCLUSIONS: There is a modest association between paracetamol exposure in-utero and the future development of asthma. Exposure in infancy has a less consistant association. All the studies done thus far are observational in nature, with their inherent biases. Further research, preferably randomized controlled trials are recommended to answer this pertinent question.

Synopsis of Pharmotechnological Approaches in Diagnostic and Management Strategies for Fighting Against COVID-19.

Nanoparticles (NPs) are projected to play a significant role in the fight against coronavirus disease (COVID-19). The various properties of NPs like magnetic and optical can be exploited to build diagnostic test kits. The unembellished morphological and physiochemical resemblances of SARS-CoV-2 with synthetic NPs make them a potent tool for mediation. Nanoparticles can be analytically functionalized with different proteins, polymers, and functional groups to perform specific inhibitory functions, while also serving as delivery vehicles. Moreover, NPs can also be employed to prepare broad-spectrum respiratory drugs and vaccines that can guard seasonal flu and prepare the human race for the pandemic in the future. The present review outlines the role of NPs for detection, diagnostic and therapeutic purposes against members of the coronavirus family. We emphasize nanomaterial-based approaches to address coronaviruses in general and SARS-CoV-2 in particular. We discuss NPs based detection systems like graphene (G-FET), biosensors, and plasmonic photothermal associated sensors. The therapeutic approaches exploiting NPs such as inorganic, organic virus-like & self-assembly protein (VLP), and inactivation of SARS-CoV-2 employing photodynamic are also presented.

Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis. LAY SUMMARY: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.