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      COVID-19–Associated Rhino-Orbital-Cerebral Mucormycosis: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

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          Abstract

          BACKGROUND:

          Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19–associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases.

          MATERIALS AND METHODS:

          Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. “R-metafor package” was used for analysis.

          RESULTS:

          A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041–0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212–4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205–0.403) despite treatment.

          CONCLUSION:

          Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.

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          Most cited references57

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          Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.

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            Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range

            Background In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials. Methods In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.’s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials. Results We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications. Conclusions In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations. Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-14-135) contains supplementary material, which is available to authorized users.
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              Bias in meta-analysis detected by a simple, graphical test.

              Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                Nov-Dec 2021
                30 December 2021
                : 53
                : 6
                : 499-510
                Affiliations
                [1] Department of Ophthalmology, Government Medical College and Hospital, sector 32, Chandigarh, India
                [1 ] Department of Pharmacology, PGIMER, Chandigarh, India
                [2 ] Department of Management Studies, IIT Madras, Chennai, Tamil Nadu, India
                [3 ] Department of Pharmacology, Central University of Punjab, Bathinda, Punjab, India
                [4 ] Scientist, Indian Pharmacopoeia Commission, Ghaziabad, Uttar Pradesh, India
                [5 ] Microbiology, B.P. Civil hospital, Nawgaon, Assam, India
                Author notes
                Address for correspondence: Prof. Bikash Medhi, Department of Pharmacology, PGIMER, Chandigarh, India. E-mail: drbikashus@ 123456yahoo.com
                [#]

                Indicate first author

                [*]

                Indicate first author

                Both Anusuya Bhattacharyya and Phulen Sarma Contributed Equally to the Manuscript. Hence Combined First Author

                Article
                IJPharm-53-499
                10.4103/ijp.ijp_839_21
                8764981
                34975140
                2d1450bd-1e77-401a-84a4-767123f38b72
                Copyright: © 2021 Indian Journal of Pharmacology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 28 October 2021
                : 08 December 2021
                : 14 December 2021
                Categories
                Systematic Review and Meta-Analysis

                Pharmacology & Pharmaceutical medicine
                covid-19–associated mucormycosis,cerebral,covid-19,mucormycosis,orbital,rhino,rhino-orbito-cerebral mucormycosis,sars cov-2

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