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Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.European Journal of Pediatrics May 2022The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents...
UNLABELLED
The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.
CONCLUSIONS
Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.
WHAT IS KNOWN
• The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear.
WHAT IS NEW
• Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
Topics: Adolescent; COVID-19; Child; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Respiration, Artificial; Systemic Inflammatory Response Syndrome; COVID-19 Drug Treatment
PubMed: 35192051
DOI: 10.1007/s00431-022-04388-w -
Cureus Feb 2022Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood vessels and is more commonly seen in the geriatric population. ANCA-associated vasculitis (AAV) is typically characterized as necrotizing vasculitis and includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The mortality rate remains high, with especially cardiovascular disease, infections, and malignancies being the leading causes of death. Existing treatment options depend heavily on the use of glucocorticoids (GCs), often in combination with cyclophosphamide (CYC); however, as the multitude of adverse effects associated with these agents has increased, numerous studies are being conducted to reduce not only these harmful effects but also improve remission rates. Rituximab, avacopan, corticosteroids, including intravenous pulse methylprednisolone, plasma exchange, and immunological targeting are among the emerging treatments. The purpose of this review is to emphasize the pathogenesis and traditional treatment modalities and give insights into the recent advances in managing this disorder in an attempt to spare the adverse effects of conventional therapies while achieving better remission rates with combination therapies as well. The authors explored multiple databases, employing appropriate keywords, satisfying the quality appraisal, after which a total of 14 reports were included in this review. Upon overall analysis, it can be concluded that rituximab and CYC, when used in combination, provided a safer alternative to GCs while exhibiting equal, if not superior, effectiveness and results, thus, paving the way for additional in-depth research in a larger population of interest.
PubMed: 35155037
DOI: 10.7759/cureus.21814 -
Daru : Journal of Faculty of Pharmacy,... Jun 2022Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to estimate the efficacy of tocilizumab and the corticosteroids particularly dexamethasone and methylprednisolone and to identify possible determinants of their efficacy.
METHODS
Five electronic databases were searched for studies involving tocilizumab, dexamethasone, and methylprednisolone in treating COVID-19. We included case-control and randomized or partially randomized trials. Meta-regression for patient baseline characteristics, co-medications, and tocilizumab dose regimens was performed to identify contributing factors to drug efficacy.
RESULTS
Thirteen randomized controlled trials (RCTs) and twenty-four case-control studies were included in our meta-analysis involving 18,702 patients. Meta-analysis among the RCTs showed that a summary estimate favoring mortality reduction (OR 0.71, 95%CI 0.55 - 0.92) contributed mainly by tocilizumab and dexamethasone. Among case-control studies, meta-analysis showed mortality reduction (OR 0.52, 95%CI 0.36 - 0.75) contributed by tocilizumab and tocilizumab-methylprednisolone combination. Methylprednisolone alone did not reduce mortality except for one study involving high dose pulse therapy. Meta-analysis also found that all three drugs did not significantly reduce mechanical ventilation (OR 0.72, 95%CI 0.32 - 1.60).
CONCLUSION
Tocilizumab and dexamethasone emerge as viable options in reducing mortality in severe COVID-19 patients. A tocilizumab-corticosteroid combination strategy may improve therapeutic outcome in cases where single therapy fails.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Dexamethasone; Humans; Methylprednisolone; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35084705
DOI: 10.1007/s40199-021-00430-8 -
Annals of Medicine and Surgery (2012) Feb 2022Vasculitis is one of the complications of COVID-19. We conducted a systematic review analysing the association of COVID-19 with vasculitis. We searched Google Scholar... (Review)
Review
Vasculitis is one of the complications of COVID-19. We conducted a systematic review analysing the association of COVID-19 with vasculitis. We searched Google Scholar and PubMed from December 1, 2019, to October 11, 2021. The review included 8 studies (7 case reports and 1 case series) reporting 9 cases of vasculitis secondary to COVID-19. The mean age was 29.17 ± 28.2 years, ranging from 6 months to 83 years. The male to female ratio was 4:5. Maculopapular, violaceous, papular and erythematous rash were common. Heparin(n = 2), corticosteroids (n = 6) (methylprednisolone) and intravenous immunoglobulin (n = 4) were prescribed in these patients. Significant clinical improvement was observed in 8 out of 9 patients. One person died during treatment. Our study discusses vasculitis as one of the complications of COVID-19. Furthermore, the pathophysiology, clinical presentation, and management of COVID-19 associated vasculitis is discussed.
PubMed: 35039779
DOI: 10.1016/j.amsu.2022.103249 -
International Journal of Molecular... Dec 2021Clinical and experimental data have shown that prolonged exposure to GCs leads to bone loss and increases fracture risk. Special attention has been given to existing...
Clinical and experimental data have shown that prolonged exposure to GCs leads to bone loss and increases fracture risk. Special attention has been given to existing emerging drugs that can prevent and treat glucocorticoid-induced osteoporosis GIOP. However, there is no consensus about the most relevant animal model treatments on GIOP. In this systematic review, we aimed to examine animal models of GIOP centering on study design, drug dose, timing and size of the experimental groups, allocation concealment, and outcome measures. The present review was written according to the PRISMA 2020 statement. Literature searches were performed in the PubMed electronic database via Mesh with the publication date set between April, 2011, and February 2021. A total of 284 full-text articles were screened and 53 were analyzed. The most common animal species used to model GIOP were rats (66%) and mice (32%). In mice studies, males (58%) were preferred and genetically modified animals accounted for 28%. Our work calls for a standardization of the establishment of the GIOP animal model with better precision for model selection. A described reporting design, conduction, and selection of outcome measures are recommended.
Topics: Animals; Biomechanical Phenomena; Bone Resorption; Bone and Bones; Disease Models, Animal; Female; Glucocorticoids; Male; Mice, Inbred C57BL; Osteoporosis; Rats, Sprague-Dawley; Mice; Rats
PubMed: 35008803
DOI: 10.3390/ijms23010377 -
Translational Pediatrics Nov 2021Hormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the...
BACKGROUND
Hormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the clinical treatment of PMD, have been reported in several clinical studies.
METHODS
Chinese and English databases were respectively searched using "randomized controlled trials", "Duchenne-type myotonic dystrophy", "glucocorticoids", Prednisone", "Prednisolone", and "Methylprednisolone", and "Defibrotide" were used as search terms. The meta-analysis was performed using the RevMan 5.3 and Stata 13 software provided by the Cochrane system.
RESULTS
this study included five randomized controlled trials, all of which described the correct randomization method. There were four detailed descriptions of hidden distribution schemes. There were four literatures using blind method. Heterogeneity analysis showed that there was some heterogeneity between the results of the mean prognostic muscle strength, walking time of 9 meters, and 4 flights of stairs climbing between the glucocorticoid-treated group (the experimental group) and the placebo group (the control group). There were no significant differences between the experimental group and the control group in average muscle strength level, walking time of 9 meters and climbing time of 4 flights of stairs (MD =1.77; 95% CI: -0.95 to 4.48; P=0.20>0.05), (MD =-12.27; 95% CI: -35.94 to 11.40; P=0.31>0.01), (MD =-3.09; 95% CI: -11.16 to 4.99; P=0.45>0.05). In addition, glucocorticoid treatment significantly increased creatine kinase level in patients with PMD (MD =-0.28, 95% CI: -0.57 to 0.00; P=0.05). In terms of the incidence of adverse reactions, glucocorticoid treatment significantly increased the prognostic probability of acne, rapid hair growth, and emotional irritability in PMD patients (OR =2.40; 95% CI: 1.09 to 5.27; P=0.03<0.05), (OR =3.05; 95% CI: 1.55 to 5.99; P=0.001<0.05), (OR =4.04; 95% CI: 1.82 to 10.63; P=0.001<0.05). There was no significant difference in the incidence of prognostic depression between the experimental group and the control group (OR =5.11; 95% CI: 0.80 to 32.79; P=0.09>0.05).
DISCUSSION
The results suggest that glucocorticoids have a significant effect on PMD patients, but to a certain extent they increase the incidence of adverse reactions in patients after treatment. However, due to the lack of complete clinical data in some ongoing studies, our conclusions may not be fully representative.
PubMed: 34976770
DOI: 10.21037/tp-21-461 -
American Journal of Physical Medicine &... Dec 2022The aim of the study was to compare the efficacy and safety of ultrasound-guided versus anatomic landmark-guided corticosteroid injection for the treatment of... (Meta-Analysis)
Meta-Analysis
Effectiveness of Ultrasound-Guided Versus Anatomic Landmark-Guided Corticosteroid Injection on Pain, Physical Function, and Safety in Patients With Subacromial Impingement Syndrome: A Systematic Review and Meta-analysis.
OBJECTIVE
The aim of the study was to compare the efficacy and safety of ultrasound-guided versus anatomic landmark-guided corticosteroid injection for the treatment of subacromial impingement syndrome.
DESIGN
PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov , CBM, CNKI, and Wanfang databases were searched from inception to August 15, 2021, for randomized controlled trials comparing ultrasound-guided versus anatomic landmark-guided injections of corticosteroids for the treatment of subacromial impingement syndrome.
RESULTS
Twelve randomized controlled trials with 891 patients were included in this study; 454 patients received ultrasound-guided injections and 437 received anatomic landmark-guided injections. Pooled results showed that ultrasound-guided injection was more beneficial for pain relief (10 trials; mean difference = -0.58; 95% confidence interval = -1.05 to -0.10; P = 0.017) and functional improvement (11 trials; standard mean difference = -0.84; 95% confidence interval = -1.41 to -0.27; P = 0.004). There was no significant difference in shoulder range of motion. In the subgroup analysis, there was a significant difference in pain relief and functional improvement at 6-8 wks and with methylprednisolone.
CONCLUSIONS
Ultrasound-guided injection of corticosteroids is potentially superior to anatomic landmark-guided injection in improving the clinical symptoms of subacromial impingement syndrome; however, these findings should be interpreted with some caution as the quality of evidence was rated as moderate to very low.
Topics: Humans; Shoulder Impingement Syndrome; Anatomic Landmarks; Adrenal Cortex Hormones; Shoulder Pain; Ultrasonography, Interventional; Injections, Intra-Articular; Randomized Controlled Trials as Topic
PubMed: 34966059
DOI: 10.1097/PHM.0000000000001940 -
Medical Journal of the Islamic Republic... 2021Bullous pemphigoid (BP) is a widely recognized autoimmune blistering disease (AIBD) linked with a high incidence of morbidity and mortality. The aim of this study was... (Review)
Review
Bullous pemphigoid (BP) is a widely recognized autoimmune blistering disease (AIBD) linked with a high incidence of morbidity and mortality. The aim of this study was to evaluate the available findings of randomized clinical trial studies to update interventions for Bullous pemphigoid. This article provides an updated overview of interventions for BP. A literature search was performed using Cochrane Central Register of Clinical Trials, MEDLINE, Scopus, and Web of Science from August 2010 to December 2020. All randomized clinical trials (RCTs) were done on adults and investigated the effectiveness of administered topical or systemic medications versus placebos or controls included in the current systematic review. Three RCTs comprising 363 patients were included in the systematic review. One of the eligible studies was placebo-controlled. All of the included studies used various interventions including, methylprednisolone plus azathioprine versus methylprednisolone plus dapsone, doxycycline versus prednisolone, and intravenous immunoglobulin (IVIG). Following their potentials in disease control, no difference was observed between dapsone and azathioprine; although, dapsone had a higher corticosteroid-sparing potential. The evaluation of the effect of doxycycline in short-term blister control in comparison to corticosteroids showed that the medication was not inferior to prednisolone, although it had a higher long-term safety. Therapeutic outcome of IVIG for steroid-resistant patients was satisfactory. Moreover, the effectiveness and reliability of various immunosuppressive drugs and tetracyclines are investigated by blinded RCTs for the treatment of BP.
PubMed: 34956957
DOI: 10.47176/mjiri.35.111 -
Journal of Primary Care & Community... 2021COVID-19 was initially considered to be a respiratory illness, but current findings suggest that SARS-CoV-2 is increasingly expressed in cardiac myocytes as well....
BACKGROUND
COVID-19 was initially considered to be a respiratory illness, but current findings suggest that SARS-CoV-2 is increasingly expressed in cardiac myocytes as well. COVID-19 may lead to cardiovascular injuries, resulting in myocarditis, with inflammation of the heart muscle.
OBJECTIVE
This systematic review collates current evidence about demographics, symptomatology, diagnostic, and clinical outcomes of COVID-19 infected patients with myocarditis.
METHODS
In accordance with PRISMA 2020 guidelines, a systematic search was conducted using PubMed, Cochrane Central, Web of Science and Google Scholar until August, 2021. A combination of the following keywords was used: SARS-CoV-2, COVID-19, myocarditis. Cohorts and case reports that comprised of patients with confirmed myocarditis due to COVID-19 infection, aged >18 years were included. The findings were tabulated and subsequently synthesized.
RESULTS
In total, 54 case reports and 5 cohorts were identified comprising 215 patients. Hypertension (51.7%), diabetes mellitus type 2 (46.4%), cardiac comorbidities (14.6%) were the 3 most reported comorbidities. Majority of the patients presented with cough (61.9%), fever (60.4%), shortness of breath (53.2%), and chest pain (43.9%). Inflammatory markers were raised in 97.8% patients, whereas cardiac markers were elevated in 94.8% of the included patients. On noting radiographic findings, cardiomegaly (32.5%) was the most common finding. Electrocardiography testing obtained ST segment elevation among 44.8% patients and T wave inversion in 7.3% of the sample. Cardiovascular magnetic resonance imaging yielded 83.3% patients with myocardial edema, with late gadolinium enhancement in 63.9% patients. In hospital management consisted of azithromycin (25.5%), methylprednisolone/steroids (8.5%), and other standard care treatments for COVID-19. The most common in-hospital complication included acute respiratory distress syndrome (66.4%) and cardiogenic shock (14%). On last follow up, 64.7% of the patients survived, whereas 31.8% patients did not survive, and 3.5% were in the critical care unit.
CONCLUSION
It is essential to demarcate COVID-19 infection and myocarditis presentations due to the heightened risk of death among patients contracting both myocardial inflammation and ARDS. With a multitude of diagnostic and treatment options available for COVID-19 and myocarditis, patients that are under high risk of suspicion for COVID-19 induced myocarditis must be appropriately diagnosed and treated to curb co-infections.
Topics: COVID-19; Contrast Media; Gadolinium; Humans; Myocarditis; SARS-CoV-2
PubMed: 34854348
DOI: 10.1177/21501327211056800 -
Journal of Neuroimmunology Jan 2022Since the emergency use approval of different types of COVID-19 vaccines, several safety concerns have been raised regarding its early and delayed impact on the nervous...
BACKGROUND
Since the emergency use approval of different types of COVID-19 vaccines, several safety concerns have been raised regarding its early and delayed impact on the nervous system.
OBJECTIVE
This study aims to systematically review the reported cases of CNS demyelination in association with COVID-19 vaccination, which has not been performed, to our knowledge.
METHODS
A systematic review was performed by screening published articles and preprints of cases of CNS demyelination in association with COVID-19 vaccines in PubMed, SCOPUS, EMBASE, Google Scholar, Ovid and medRxiv databases, until September 30, 2021. This study followed PRISMA guidelines. Descriptive findings of reported cases were reviewed and stratified by demographic and clinical findings, diagnostic work-up, management, and overall outcome.
RESULTS
A total of 32 cases were identified, with female predominance (68.8%) and median age of 44 years. Eleven cases were reported after Pfizer vaccine, 8 following AstraZeneca vaccine, 6 following Moderna, 5 following Sinovac/ Sinopharm vaccines, and one following each of Sputnik and Johnson&Johnson vaccines. The majority of cases (71.8%) occurred after the first dose of the vaccine, with neurological symptoms manifesting after a median of 9 days. The most common reported presentations were transverse myelitis (12/32) and MS-like pictures (first diagnosis or a relapse) in another 12/32 cases, followed by ADEM- like (5/32), and NMOSD- like (3/32) presentations. History of a previous immune-mediated disease was reported in 17/32 (53.1%) cases. The mRNA-based vaccines resulted in the greatest number of demyelinating syndromes (17/32), followed by viral vector vaccines (10/32), and inactivated vaccines (5/32). Most MS-like episodes (9/12) were triggered by mRNA-based vaccines, while TM occurred following both viral vector and mRNA-based vaccines. Management included high dose methylprednisolone, PLEX, IVIg, or a combination of those, with a favorable outcome in the majority of case; marked/complete improvement (25/32) or stabilized/ partial recovery in the remaining cases.
CONCLUSION
This systematic review identified few cases of CNS demyelination following all types of approved COVID-19 vaccines so far. Clinical presentation was heterogenous, mainly following the first dose, however, half of the reported cases had a history of immune-mediated disease. Favorable outcome was observed in most cases. We suggest long-term post-marketing surveillance for these cases, to assess for causality, and ensure the safety of COVID-19 vaccines.
Topics: COVID-19; COVID-19 Vaccines; Demyelinating Autoimmune Diseases, CNS; Humans; SARS-CoV-2
PubMed: 34839149
DOI: 10.1016/j.jneuroim.2021.577765