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Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Rheumatology International Sep 2023The current systematic review aimed to document published cases of femoral head avascular necrosis (FHAVN) post-COVID-19, to report the COVID-19 disease characteristics...
The current systematic review aimed to document published cases of femoral head avascular necrosis (FHAVN) post-COVID-19, to report the COVID-19 disease characteristics and management patients received, and to evaluate how the FHAVN were diagnosed and treated among various reports. A systematic literature review was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through a comprehensive English literature search on January 2023 through four databases (Embase, PubMed, Cochrane Library, and Scopus), including studies reporting on FHAVN post-COVID-19. Fourteen articles were included, ten (71.4%) were case reports, and four (28.6%) case series reported on 104 patients having a mean age of 42.2 ± 11.7 (14:74) years, in which 182 hip joints were affected. In 13 reports, corticosteroids were used during the COVID-19 management plan for a mean of 24.8 ± 11 (7:42) days, with a mean prednisolone equivalent dose of 1238.5 ± 492.8 (100:3520) mg. A mean of 142.1 ± 107.6 (7:459) days passed between COVID-19 diagnosis and FHAVN detection, and most of the hips were stage II (70.1%), and concomitant septic arthritis was present in eight (4.4%) hips. Most hips (147, 80.8%) were treated non-surgically, of which 143 (78.6%) hips received medical treatment, while 35 (19.2%) hips were surgically managed, 16 (8.8%) core decompression, 13 (7.1%) primary THA, five (2.7%) staged THA and three (1.6%) had first stage THA (debridement and application of antibiotic-loaded cement spacer). The outcomes were acceptable as regards hip function and pain relief. Femoral head avascular necrosis post-COVID-19 infection is a real concern, primarily attributed to corticosteroid usage, besides other factors. Early suspicion and detection are mandatory, as conservative management lines are effective during early stages with acceptable outcomes. However, surgical intervention was required for progressive collapse or patients presented in the late stage.
Topics: Humans; Adult; Middle Aged; Treatment Outcome; Femur Head; COVID-19 Testing; COVID-19; Femur Head Necrosis; Adrenal Cortex Hormones; Decompression, Surgical
PubMed: 37338665
DOI: 10.1007/s00296-023-05373-8 -
The Journal of Allergy and Clinical... Apr 2024Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated...
BACKGROUND
Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear.
OBJECTIVE
To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids.
METHODS
We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach.
RESULTS
We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty).
CONCLUSIONS
Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more.
PubMed: 38642709
DOI: 10.1016/j.jaip.2024.04.016 -
BMC Infectious Diseases Dec 2023Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens.
METHODS
This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared.
RESULTS
In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay.
CONCLUSIONS
Considering the available evidence, this network meta‑analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19.
TRIAL REGISTRATION
PROSPERO CRD42022350407 (22/08/2022).
Topics: Humans; Glucocorticoids; COVID-19; Hydrocortisone; Network Meta-Analysis; Methylprednisolone; Dexamethasone
PubMed: 38124031
DOI: 10.1186/s12879-023-08874-w -
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 -
The Journal of Maternal-fetal &... Dec 2023There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART).
OBJECTIVE
This meta-analysis was performed to evaluate the efficiency and safety of adjuvant glucocorticoid therapy on pregnancy outcomes in infertile women undergoing ART cycles.
STUDY DESIGN
A literature search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library up to December 2022. To assess the efficacy and safety of additional glucocorticoid treatment during ovulation induction in women who underwent IVF or ICSI treatment, only randomized controlled trials were included.
RESULTS
Overall, glucocorticoid therapy during ovulation showed a nonsignificant effect of prednisolone improving the live birth rate (OR = 1.03, 95% CI [.75, 1.43], I = .0%, = .84), abortion rate (OR = 1.14, 95% CI [.62, 2.08], I = 31%, = .68), and implantation rate (OR = 1.1, 95% CI [.82, 1.5], I = 8%, = .52) of infertile women compared to the control group. The present meta-analysis revealed that the clinical pregnancy rate per cycle tended to increase after glucocorticoid treatment (OR = 1.29, 95% CI [1.02, 1.63], I = 8%, = .52).
CONCLUSIONS
The present meta-analysis suggested that ovarian stimulation prednisolone therapy does not significantly improve clinical outcomes in women undergoing IVF/ICSI. Although the results indicated that adjuvant glucocorticoid therapy during ovarian stimulation may increase the clinical pregnancy rate, subgroup analysis showed that it was affected by infertility factors, dose schedules, and length of treatment. Therefore, these results should be interpreted with caution.
Topics: Female; Pregnancy; Humans; Glucocorticoids; Infertility, Female; Ovulation Induction; Prednisolone; Adjuvants, Pharmaceutic; Dietary Supplements
PubMed: 37385781
DOI: 10.1080/14767058.2023.2227310 -
Cureus May 2024Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study... (Review)
Review
Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.
PubMed: 38854256
DOI: 10.7759/cureus.60049 -
Journal of Neuromuscular Diseases 2024The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
METHODS
This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
RESULTS
The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
CONCLUSION
Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
Topics: Muscular Dystrophy, Duchenne; Humans; Glucocorticoids; Walking; Pregnenediones; Latent TGF-beta Binding Proteins
PubMed: 38669554
DOI: 10.3233/JND-230220 -
BMJ Open Respiratory Research Jan 2024Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP.
METHODS
We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model.
RESULTS
A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I=0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I=0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia.
CONCLUSIONS
The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360.
Topics: Humans; Hydrocortisone; Adrenal Cortex Hormones; Methylprednisolone; Community-Acquired Infections; Pneumonia; Dexamethasone
PubMed: 38262670
DOI: 10.1136/bmjresp-2023-002141 -
Sarcoidosis, Vasculitis, and Diffuse... Dec 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare multi-system conditions, usually presenting in older age groups. However, younger...
BACKGROUND AND AIM
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare multi-system conditions, usually presenting in older age groups. However, younger individuals are also affected. The average increase of childbearing age and lack of studies in pregnancy necessitates this comprehensive review of data to guide the management of AAV in pregnancy. This systematic review (SR) aimed to summarise the incidence, clinical features, management and maternal and foetal outcomes in female patients with AAV.
METHODS
The protocol was registered on PROSPERO (CRD42023437482). Articles published in Medline, Embase and Cochrane Databases from 1946 until June 2023 were included. Single case reports, reviews and conference abstracts were excluded. Articles meeting inclusion criteria were examined by two authors. Data on demographics, treatment, clinical features, flares during pregnancy and maternal and foetal outcomes were extracted.
RESULTS
Eight studies were included, detailing 82 pregnancies in 64 women. The most common drugs used for remission induction pre-conception were cyclophosphamide, rituximab, prednisolone and azathioprine. Serious maternal complications in pregnancy included progressive tracheal/subglottic stenosis (n=5), renal disease (n=2), preeclampsia (n=10) and miscarriages (n=5). Foetal anomalies were rare (n=5). The mean birth weight was 3.37kgs and mean gestation age was 38.26 weeks. No maternal deaths or vasculitis in newborns were reported. Conclusions: Patients can have positive maternal and foetal outcomes following strong induction therapy, vigorous monitoring and prompt treatment of flares during pregnancy. Serious complications and flares are not associated with worse outcomes for newborns.
PubMed: 38126499
DOI: 10.36141/svdld.v40i4.15094