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Brain and Behavior Jun 2023Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines... (Review)
Review
INTRODUCTION
Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan.
METHODS
We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies.
RESULTS
The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature.
CONCLUSION
Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.
Topics: Female; Humans; Male; Chorea; Anticonvulsants; Valproic Acid; Haloperidol; Dopamine Antagonists
PubMed: 37150977
DOI: 10.1002/brb3.3035 -
BMC Infectious Diseases May 2023The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19.
METHODS
By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO/FiO ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0.
RESULTS
Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone.
CONCLUSIONS
This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.
Topics: Humans; Glucocorticoids; Methylprednisolone; COVID-19; COVID-19 Drug Treatment; Dexamethasone
PubMed: 37147596
DOI: 10.1186/s12879-023-08280-2 -
Clinical Cardiology Jun 2023The advantages and disadvantages of using corticosteroids in children undergoing cardiac surgery is still contentious. To examine how perioperative corticosteroids... (Meta-Analysis)
Meta-Analysis Review
The advantages and disadvantages of using corticosteroids in children undergoing cardiac surgery is still contentious. To examine how perioperative corticosteroids affect postoperative mortality and clinical outcomes in pediatric cardiac surgery with cardiopulmonary bypass (CPB). We used MEDLINE, EMBASE, and the Cochrane Database to conduct a comprehensive search up through January 2023. Children aged 0-18 undergoing cardiac surgery were included in the meta-analysis of randomized controlled studies comparing perioperative corticosteroids with other therapeutic therapies, placebo, or no treatment. All-cause hospital mortality was the primary endpoint of the study. Hospitalization duration was a secondary result. The Cochrane Risk of Bias Assessment Tool was used to evaluate the research quality. Ten trials and 7798 pediatric participants were included in our analysis. Children taking corticosteroids had no significant difference in all-cause in-hospital mortality using a random-effect model with relative risk (RR) = 0.38, 95% confidence interval (CI) = 0.16-0.91, I = 79%, p = .03 for methylprednisolone and RR = 0.29, 95% CI = 0.09-0.97, I = 80%, p = .04. For the secondary outcome, there was a significant difference between the corticosteroid and placebo groups, with pooled standard mean difference (SMD) = -0.86, 95% CI = -1.57 to -0.15, I = 85%, p = .02 for methylprednisolone and SMD = -0.97, 95% CI -1.90 to -0.04, I = 83%, p = .04 for dexamethasone. Perioperative corticosteroids may not improve mortality, but they reduce hospital stay compared to placebo. Further evidence from randomized controlled studies with larger samples is required for approaching at a valid conclusion.
Topics: Child; Humans; Cardiac Surgical Procedures; Adrenal Cortex Hormones; Methylprednisolone
PubMed: 37101401
DOI: 10.1002/clc.24018 -
Current Fungal Infection Reports 2023Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids... (Review)
Review
PURPOSE OF REVIEW
Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids on mortality and visual outcome in different fungal diseases.
RECENT FINDINGS
Corticosteroids are a risk factor of aspergillosis for patients who have COVID-19, and they also led to a worse outcome. Similarity, corticosteroids are a risk factor for candidemia and mucormycosis. Some researchers reported that using topical corticosteroid in keratitis was associated with worse visual outcome if fungal keratitis. Some studies showed that corticosteroids are linked to a negative outcome for non-HIV patients with pneumonia (PCP), in contrast to those with HIV and PCP.
SUMMARY
In 59 references, we found that corticosteroid therapy showed a worse clinical outcome in invasive aspergillosis (IA) (HR: 2.50, 95%CI: 1.89-3.31, < 0.001) and chronic pulmonary aspergillosis (CPA) (HR: 2.74, 95%CI: 1.48-5.06, = 0.001), PCP without HIV infection (OR: 1.29, 95%CI: 1.09-1.53, = 0.003), invasive candidiasis and candidaemia (OR: 2.13, 95%CI: 1.85-2.46, < 0.001), mucormycosis (OR: 4.19, 95%CI: 1.74-10.05, = 0.001) and early in the course of fungal keratitis (OR: 2.99, 95%CI: 1.14-7.84, = 0.026). There was equivocal outcome in cryptococcal meningoencephalitis in AIDS and primary coccidioidomycosis, while corticosteroid therapy showed a better outcome in PCP in HIV-infected patients (RR: 0.62, 95%CI: 0.46-0.83, =0.001) and fungal keratitis patients after keratoplasty surgery (OR: 0.01, 95%CI: 0.00-0.41, = 0.041) and probably in cryptococcal meningoencephalitis in non-immunocompromised patients. A sub-analysis in invasive aspergillosis and CPA showed that use of more than 2 mg/kg/day of prednisolone equivalents per day is a significant factor in increasing mortality (HR: 2.94, 95%CI: 2.13-4.05, < 0.001). Corticosteroid therapy during invasive fungal disease was usually associated with a slightly or greatly increased mortality or worse visual outcome (in fungal keratitis), with two disease exceptions. Avoiding the addition of corticosteroids, or minimising dose and duration in those who require them, is likely to improve the outcome of most life- and vision-threatening fungal diseases. This review provides a cornerstone for further research in exploring the accuracy of suitable dose and duration of corticosteroids treatment in fungal diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12281-023-00456-2.
PubMed: 36852004
DOI: 10.1007/s12281-023-00456-2 -
The Cochrane Database of Systematic... Jan 2023Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry... (Review)
Review
BACKGROUND
Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications.
OBJECTIVES
To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the use of IVIG for the treatment of KD. We included studies involving treatment for initial or refractory KD, or both.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were incidence of CAAs and incidence of any adverse effects after treatment. Our secondary outcomes were acute coronary syndromes, duration of fever, need for additional treatment, length of hospital stay, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified 31 RCTs involving a total of 4609 participants with KD. Studies compared IVIG with ASA, another dose or regimen of IVIG, prednisolone, or infliximab. The majority of studies reported on primary treatment, so those results are reported below. A limited number of studies investigated secondary or tertiary treatment in IVIG-resistant patients. Doses and regimens of IVIG infusion varied between studies, and all studies had some concerns related to risk of bias. Primary treatment with IVIG compared to ASA for people with KD Compared to ASA treatment, IVIG probably reduces the incidence of CAAs in people with KD up to 30 days (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41 to 0.87; 11 studies, 1437 participants; moderate-certainty evidence). The individual studies reported a range of adverse effects, but there was little to no difference in numbers of adverse effects between treatment groups (OR 0.57, 95% CI 0.17 to 1.89; 10 studies, 1376 participants; very low-certainty evidence). There was limited evidence for the incidence of acute coronary syndromes, so we are uncertain of any effects. Duration of fever days from treatment onset was probably shorter in the IVIG group (mean difference (MD) -4.00 days, 95% CI -5.06 to -2.93; 3 studies, 307 participants; moderate-certainty evidence). There was little or no difference between groups in need for additional treatment (OR 0.27, 95% CI 0.05 to 1.57; 3 studies, 272 participants; low-certainty evidence). No study reported length of hospital stay, and no deaths were reported in either group. Primary treatment with IVIG compared to different infusion regimens of IVIG for people with KD Higher-dose regimens of IVIG probably reduce the incidence of CAAs compared to medium- or lower-dose regimens of IVIG up to 30 days (OR 0.60, 95% CI 0.40 to 0.89; 8 studies, 1824 participants; moderate-certainty evidence). There was little to no difference in the number of adverse effects between groups (OR 1.11, 95% CI 0.52 to 2.37; 6 studies, 1659 participants; low-certainty evidence). No study reported on acute coronary syndromes. Higher-dose IVIG may reduce the duration of fever compared to medium- or lower-dose regimens (MD -0.71 days, 95% CI -1.36 to -0.06; 4 studies, 992 participants; low-certainty evidence). Higher-dose regimens may reduce the need for additional treatment (OR 0.29, 95% CI 0.10 to 0.88; 4 studies, 1125 participants; low-certainty evidence). We did not detect a clear difference in length of hospital stay between infusion regimens (MD -0.24, 95% CI -0.78 to 0.30; 3 studies, 752 participants; low-certainty evidence). One study reported mortality, and there was little to no difference detected between regimens (moderate-certainty evidence). Primary treatment with IVIG compared to prednisolone for people with KD The evidence comparing IVIG with prednisolone on incidence of CAA is very uncertain (OR 0.60, 95% CI 0.24 to 1.48; 2 studies, 140 participants; very low-certainty evidence), and there was little to no difference between groups in adverse effects (OR 4.18, 95% CI 0.19 to 89.48; 1 study; 90 participants; low-certainty evidence). We are very uncertain of the impact on duration of fever, as two studies reported this outcome differently and showed conflicting results. One study reported on acute coronary syndromes and mortality, finding little or no difference between groups (low-certainty evidence). No study reported the need for additional treatment or length of hospital stay.
AUTHORS' CONCLUSIONS
The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.
Topics: Child; Humans; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Acute Coronary Syndrome; Prednisolone; Aspirin; Inflammation; Fever
PubMed: 36695415
DOI: 10.1002/14651858.CD014884.pub2 -
Journal of Nephrology Jul 2023Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of corticosteroid treatment to prevent renal scarring.
METHODS
We searched the PubMED, SCOPUS, Cochrane CENTRAL and Web of Science databases in June 2022 for (corticosteroid* or dexamethasone or prednisolone* or prednisone* or hydrocortisone*) AND pyelonephritis. Randomised controlled trials focusing on children were included. The intervention was corticosteroid treatment with antibiotics compared to antibiotics with or without a placebo. The main outcome was the presence of renal scars on dimercaptosuccinic acid scanning at follow-up. The evidence quality was assessed using the GRADE methodology and risk of bias 2.0 tool. We calculated the risk ratio (RR), absolute risk difference (RD) with 95% confidence intervals (CI) and the number needed to treat (NNT). We applied a fixed effects model due to low heterogeneity.
RESULTS
We screened 872 abstracts and included five full texts. Renal scarring at follow-up was found in 31/220 (14.1%) patients in the corticosteroid groups and 76/278 (27.3%) in the control groups (RR 0.65, CI 0.44-0.96, RD - 13.2%, NNT 8). The evidence quality was moderate. Two studies reported adverse events with no differences between the groups. The risk of bias analysis showed some concerns in four studies.
CONCLUSION
We found moderate quality evidence that adjuvant corticosteroid treatment could prevent renal scarring. Adverse events were insufficiently reported, and more research on their effectiveness and harm is therefore needed before using corticosteroids in clinical settings.
Topics: Child; Humans; Cicatrix; Adrenal Cortex Hormones; Prednisolone; Anti-Bacterial Agents; Pyelonephritis; Randomized Controlled Trials as Topic
PubMed: 36692666
DOI: 10.1007/s40620-022-01552-1 -
Journal of Osteopathic Medicine Apr 2023Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood.
OBJECTIVES
The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework.
METHODS
On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity.
RESULTS
A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002).
CONCLUSIONS
Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.
Topics: Humans; Adult; Middle Aged; Glucocorticoids; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Pneumonia
PubMed: 36691851
DOI: 10.1515/jom-2022-0177 -
Frontiers in Medicine 2022To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA).
OBJECTIVE
To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA).
METHODS
The available evidence in the field was reviewed, and the GCA working group wrote draft guidelines. These guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis and the British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA informed the development of the current guidelines.
RESULTS
A total of 13 recommendations were developed. Ultrasound is recommended as the primary diagnostic test. In patients with suspected GCA, treatment with high doses of Prednisolone (40-60 mg) should be initiated immediately. For patients with refractory disease or relapse, Methotrexate (MTX) should be used as the first-line adjunctive therapy, followed by tocilizumab (TCZ).
CONCLUSION
Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with GCA were developed.
PubMed: 36687436
DOI: 10.3389/fmed.2022.1082604 -
The Cochrane Database of Systematic... Jan 2023Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018.
OBJECTIVES
To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below.
SEARCH METHODS
We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events).
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach.
MAIN RESULTS
This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias. Any glucocorticoid compared to placebo Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence). One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children). Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone. There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review.
AUTHORS' CONCLUSIONS
The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.
Topics: Child; Humans; Croup; Dexamethasone; Epinephrine; Glucocorticoids; Prednisolone; Respiratory Tract Infections; Randomized Controlled Trials as Topic; Adolescent
PubMed: 36626194
DOI: 10.1002/14651858.CD001955.pub5 -
EClinicalMedicine Feb 2023Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in...
BACKGROUND
Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia.
METHODS
We did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179).
FINDINGS
Eighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% 68.7%, odds ratio [OR] 1.82, 95% CI 1.10-3.02). The difference was more profound for sustained response (60.5% 37.4%, OR 2.57, 95% CI 1.95-3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%).
INTERPRETATION
Our findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies.
FUNDING
National Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.
PubMed: 36578882
DOI: 10.1016/j.eclinm.2022.101777