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The Cochrane Database of Systematic... May 2016Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although their long-term effect is uncertain. This is an update of a review first published in 2007, and previously updated in 2009 and 2011.
OBJECTIVES
To assess the effects of corticosteroids on nerve damage in leprosy.
SEARCH METHODS
On 16 June 2015, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also checked clinical trials registers and contacted trial authors.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of corticosteroids for nerve damage in leprosy. The comparators were no treatment, placebo treatment, or a different corticosteroid regimen.
DATA COLLECTION AND ANALYSIS
The primary outcome was improvement in nerve function after one year. Secondary outcomes were change in nerve pain, limitations in activities of daily living, limitations in participation, and adverse events. Two review authors independently extracted data and assessed trial quality. When data were lacking, we contacted trial authors for additional information.
MAIN RESULTS
We included five RCTs involving 576 people. The trials were largely at low risk of bias, but we considered the quality of the evidence from these trials as moderate to low, largely due to imprecision from small sample sizes. Two out of the five trials reported on improvement in nerve function at one year. These two trials compared prednisolone with placebo. One trial, with 84 participants, treated mild sensory impairment of less than six months' duration, and the other, with 95 participants, treated nerve function impairment of 6 to 24 months' duration. There was no significant difference in nerve function improvement after 12 months between people treated with prednisolone and those treated with placebo. Adverse events were not reported significantly more often with corticosteroids than with placebo. The other three trials did not report on the primary outcome measure. One (334 participants) compared three corticosteroid regimens for severe type 1 reactions. No serious side effects of steroids were reported in any participant during the follow-up period. Another trial (21 participants) compared low-dose prednisone with high-dose prednisone for ulnar neuropathy. Two participants on the higher dose of prednisone reported adverse effects. The last (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone. The trial found no significant differences between the groups in the occurrence of adverse events.
AUTHORS' CONCLUSIONS
Corticosteroids are used for treating acute nerve damage in leprosy, but moderate-quality evidence from two RCTs treating either longstanding or mild nerve function impairment did not show corticosteroids to have a superior effect to placebo on nerve function improvement. A third trial showed significant benefit from a five-month steroid regimen over a three-month regimen in terms of response to treatment (need for additional corticosteroids). Further RCTs are needed to establish optimal corticosteroid regimens and to examine the efficacy and safety of adjuvant or new therapies for treating nerve damage in leprosy. Future trials should address non-clinical aspects, such as costs and impact on quality of life, which are highly relevant indicators for both policymakers and participants.
Topics: Glucocorticoids; Humans; Leprosy; Methylprednisolone; Peripheral Nervous System Diseases; Prednisolone; Randomized Controlled Trials as Topic; Somatosensory Disorders
PubMed: 27210895
DOI: 10.1002/14651858.CD005491.pub3 -
Hepatology International Feb 2023Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients.
METHODS
Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n = 60) 40 mg/day for 28 days (assessed at day-7 for continuation) or healthy donor FMT (n = 60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival.
RESULTS
Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65 ± 16.2 and 68 ± 14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p = 0.044, FMT HR = 0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p = 0.243, FMT HR = 0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p = 0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p = 0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p = 0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~ sevenfold, p = 0.047] and Thaumarcheota (known ammonia oxidizer, p = 0.06). Lachnospiraceae (p = 0.008), Prevotella and Viellonella communities in gut favored survival (p < 0.05).
CONCLUSION
In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy.
Topics: Humans; Prednisolone; Fecal Microbiota Transplantation; Hepatitis, Alcoholic; Microbiota; Treatment Outcome
PubMed: 36469298
DOI: 10.1007/s12072-022-10438-0 -
Frontiers in Immunology 2023Imiquimod (IMQ) is a topical agent that induces local inflammation the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in... (Randomized Controlled Trial)
Randomized Controlled Trial
Imiquimod (IMQ) is a topical agent that induces local inflammation the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in healthy volunteers for proof-of-pharmacology trials. The aim of this study was to profile the cellular, biochemical, and clinical effects of the marketed anti-inflammatory compound prednisolone in an IMQ model. This randomized, double-blind, placebo-controlled study was conducted in 24 healthy volunteers. Oral prednisolone (0.25 mg/kg/dose) or placebo (1:1) was administered twice daily for 6 consecutive days. Two days after treatment initiation with prednisolone or placebo, 5 mg imiquimod (IMQ) once daily for two following days was applied under occlusion on the tape-stripped skin of the back for 48 h in healthy volunteers. Non-invasive (imaging and biophysical) and invasive (skin punch biopsies and blister induction) assessments were performed, as well as IMQ stimulation of whole blood. Prednisolone reduced blood perfusion and skin erythema following 48 h of IMQ application (95% CI [-26.4%, -4.3%], p = 0.0111 and 95% CI [-7.96, -2.13], p = 0.0016). Oral prednisolone suppressed the IMQ-elevated total cell count (95% CI [-79.7%, -16.3%], p = 0.0165), NK and dendritic cells (95% CI [-68.7%, -5.2%], p = 0.0333, 95% CI [-76.9%, -13.9%], p = 0.0184), and classical monocytes (95% CI [-76.7%, -26.6%], p = 0.0043) in blister fluid. Notably, TNF, IL-6, IL-8, and Mx-A responses in blister exudate were also reduced by prednisolone compared to placebo. Oral prednisolone suppresses IMQ-induced skin inflammation, which underlines the value of this cutaneous challenge model in clinical pharmacology studies of novel anti-inflammatory compounds. In these studies, prednisolone can be used as a benchmark.
Topics: Humans; Imiquimod; Blister; Healthy Volunteers; Dermatitis; Prednisolone; Inflammation; Anti-Inflammatory Agents
PubMed: 37545524
DOI: 10.3389/fimmu.2023.1197650 -
Rheumatology (Oxford, England) Mar 2023To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone.
METHODS
Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex.
RESULTS
For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)].
CONCLUSION
Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA.
Topics: Humans; Female; Middle Aged; Male; Prednisolone; C-Reactive Protein; Osteoarthritis; Biomarkers; Synovitis; Pain
PubMed: 35946535
DOI: 10.1093/rheumatology/keac442 -
Respiratory Investigation Sep 2019
Topics: Disease Progression; Hamman-Rich Syndrome; Humans; Prednisolone
PubMed: 31248831
DOI: 10.1016/j.resinv.2019.05.003 -
Pain Practice : the Official Journal of... Mar 2022Many patients with complex regional pain syndrome (CRPS) experience refractory pain with severe restrictions in the activities of daily living. Oral prednisolone is... (Review)
Review
BACKGROUND
Many patients with complex regional pain syndrome (CRPS) experience refractory pain with severe restrictions in the activities of daily living. Oral prednisolone is commonly used to treat these patients.
PURPOSE
To review previous studies assessing the effects of prednisolone in CRPS patients.
METHODS AND MATERIALS
Articles published from January 1, 1980 to July 23, 2021 in the PubMed database were searched using the following key phrases: (prednisolone OR corticosteroid OR steroid) AND (complex regional pain syndrome OR reflex sympathetic dystrophy OR shoulder-hand syndrome OR causalgia). Specifically, we included those articles in which oral prednisolone or corticosteroids were used to control the CRPS symptoms.
RESULTS
In total, 11 articles were included, comprising 3 randomized trials, 5 single-arm prospective observational studies, and 3 retrospective studies. Nearly all previous studies reported that oral prednisolone can effectively control the CRPS symptoms. Moreover, though 30-100 mg/day of oral prednisolone was initially administered in these studies, 30 mg/day was also found to be effective in controlling the symptoms. Although prednisolone was usually administered for 1-3 months, short-term treatment for 1-2 weeks was also reportedly effective. Furthermore, only 0%-30% of the patients in these studies had minor side effects after prednisolone treatment.
CONCLUSIONS
Our review showed that prednisolone may be effective in alleviating the CRPS symptoms. To determine higher levels of evidence, a full systematic review with more highly qualified studies, such as randomized controlled trials, should be conducted in the future.
Topics: Activities of Daily Living; Complex Regional Pain Syndromes; Humans; Observational Studies as Topic; Prednisolone; Reflex Sympathetic Dystrophy; Retrospective Studies
PubMed: 34779145
DOI: 10.1111/papr.13090 -
Archives of Disease in Childhood Mar 2021
Review
Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-2 Receptor Antagonists; Child; Humans; Medication Adherence; Prednisolone; Status Asthmaticus; Steroids
PubMed: 32381520
DOI: 10.1136/archdischild-2020-319462 -
BMJ Case Reports Jun 2021A 75-year-old woman was admitted with sepsis and treated with broad-spectrum antibiotics until examination of her lower limbs noted necrotising wounds. Surgical...
A 75-year-old woman was admitted with sepsis and treated with broad-spectrum antibiotics until examination of her lower limbs noted necrotising wounds. Surgical intervention was advised by the plastic surgeons; however, she was deemed unsuitable for intensive care. She underwent incision and drainage of the necrotic area and biopsies were taken. She deteriorated clinically and the decision was made for best supportive care and was therefore transferred to the inpatient palliative care unit for end-of-life care. However, she stabilised, and based on culture sensitivities, antibiotics were restarted. It was also noted that the patient had a 3-month history of loose stools, which had not been addressed previously. The biopsies were suggestive of pyoderma gangrenosum, prompting a dermatology review, and prednisolone and doxycycline were started. The wounds and her loose stools improved, and with ongoing rehabilitation, she made a full recovery. Referral to gastroenterology was made.
Topics: Aged; Biopsy; Diagnosis, Differential; Drainage; Female; Humans; Prednisolone; Pyoderma Gangrenosum
PubMed: 34099445
DOI: 10.1136/bcr-2020-240133 -
Stem Cell Research & Therapy Jan 2022Regenerative medicine provides promising approaches for treating chronic liver diseases. Previous studies indicate that decellularized liver architecture is damaged by...
INTRODUCTION
Regenerative medicine provides promising approaches for treating chronic liver diseases. Previous studies indicate that decellularized liver architecture is damaged by invading non-hepatic inflammatory cells. This study aimed to use anti-inflammatory and regenerative potency of bone marrow-derived mesenchymal stem cells (BM-MSC) and prednisolone for reducing fibrosis and balancing inflammatory cell migration into the decellularized liver scaffold.
MATERIAL AND METHOD
The liver was decellularized by perfusing Sodium Lauryl Ether Sulfate (SLES), and nuclei depletion and extracellular matrix (ECM) retention were confirmed by DNA quantification, histochemical, and immunohistochemical assessments. Scaffolds were loaded with BM-MSCs, prednisolone, or a combination of both, implanted at the anatomical place in the rat partial hepatectomized and followed up for 2 and 4 weeks.
RESULTS
Labeled-MSCs were traced in the transplanted scaffolds; however, they did not migrate into the intact liver. Immunohistochemistry showed that the hepatoblasts, cholangiocytes, stellate, and oval cells invaded into all the scaffolds. Bile ducts were more abundant in the border of the scaffolds and intact liver. Stereological assessments showed a significant reduction in the number of lymphocytes and neutrophils in prednisolone-loaded scaffolds. The regeneration process and angiogenesis were significantly higher in the group treated with cell/prednisolone-loaded bioscaffolds. Collagen fibers were significantly reduced in the scaffolds pre-treated with cell/prednisolone, prednisolone, or BM-MSCs, compared to the control group.
CONCLUSION
Loading prednisolone into the scaffolds can be a worthy approach to restrict inflammation after transplantation. Although pre-loading of the scaffolds with a combination of cells/prednisolone could not alleviate inflammation, it played an important role in regeneration and angiogenesis.
Topics: Animals; Cell Movement; Extracellular Matrix; Liver; Mesenchymal Stem Cells; Prednisolone; Rats; Tissue Engineering; Tissue Scaffolds
PubMed: 35090559
DOI: 10.1186/s13287-022-02711-8 -
PLoS Neglected Tropical Diseases Jul 2022The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory...
BACKGROUND
The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions.
METHODS
A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells.
RESULTS
30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells.
CONCLUSION
The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.
Topics: Anti-Inflammatory Agents; Drug Therapy, Combination; Erythema Nodosum; Humans; Interleukin-10; Leprostatic Agents; Leprosy; Leprosy, Lepromatous; Leukocytes, Mononuclear; Longitudinal Studies; Mycobacterium leprae; Prednisolone; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha
PubMed: 35867720
DOI: 10.1371/journal.pntd.0010641