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Danish Medical Journal Oct 2023The diagnosis and management of subacute thyroiditis (SAT) may be challenging, and more evidence on patient and disease characteristics is warranted.
INTRODUCTION
The diagnosis and management of subacute thyroiditis (SAT) may be challenging, and more evidence on patient and disease characteristics is warranted.
METHODS
This was a retrospective cohort study of all patients in the North Denmark Region with a SAT diagnosis in the Danish National Patient Registry, 2016-2018. The medical records and biochemical results prior to the diagnosis and during a two-year follow-up period were reviewed.
RESULTS
A total of 71 patients with a SAT diagnosis were identified, and the diagnosis was verified in 44 (62.0%) cases with an incidence rate of 2.4/100,000/year. Patients with verified SAT were predominantly females (72.7%) with a median age of 50.7 years. Biochemical results showed thyrotoxicosis at the initial examination in 69.8% and elevated C-reactive protein in 86.5% of patients. Longitudinal biochemical assessment showed a biphasic response (median thyroid-stimulating hormone, initially: 0.02 mIU/l, at three months: 4.7 mIU/l and 2.4 mIU/l after two years). Treatment with non-steroidal anti-inflammatory drugs, beta-blockers and/or prednisolone was initiated in 23 of the 38 patients (60.5%) evaluated, and ten of 33 patients (30.3%) with follow-up data received thyroid hormone replacement therapy.
CONCLUSION
In the North Denmark Region, a hospital diagnosis of SAT was verified in less than two thirds of cases. Further large studies are warranted to extend the findings concerning the treatment and outcome of SAT.
FUNDING
None.
TRIAL REGISTRATION
Not relevant.
Topics: Female; Humans; Middle Aged; Male; Thyroiditis, Subacute; Retrospective Studies; Prednisolone; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37897374
DOI: No ID Found -
The Journal of Allergy and Clinical... Nov 2023Systemic corticosteroids (SCSs) are associated with short- and long-term adverse effects. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Systemic corticosteroids (SCSs) are associated with short- and long-term adverse effects.
OBJECTIVE
To assess mepolizumab efficacy according to prior SCS use and characterize mepolizumab's SCS-sparing capabilities, in patients with severe chronic rhinosinusitis with nasal polyps.
METHODS
In the randomized, double-blind, phase III SYNAPSE trial (NCT03085797), adults with severe chronic rhinosinusitis with nasal polyps eligible for repeat sinus surgery despite standard of care treatment received mepolizumab (100 mg subcutaneously) or placebo every 4 weeks for 52 weeks. The impact of prior SCS courses (0/1/>1) on mepolizumab versus placebo treatment responses (changes from baseline in total endoscopic nasal polyp [week 52], nasal obstruction visual analog scale [weeks 49-52], and 22-item Sino-Nasal Outcome Test total [week 52] scores) was analyzed post hoc. To characterize mepolizumab's SCS-sparing capabilities, time-to-first SCS course for nasal polyps (prespecified) and total prednisolone-equivalent oral corticosteroid dose by patient baseline characteristics (post hoc, in patients with ≥1 SCS course during SYNAPSE) were assessed up to week 52.
RESULTS
Mepolizumab versus placebo improved treatment responses, irrespective of prior SCS use. By week 52, the probability of requiring SCSs for nasal polyps (Kaplan-Meier estimate [95% CI]) was lower with mepolizumab (25.4% [20.0-32.1]) versus placebo (37.5% [31.1-44.6]). In patients requiring 1 or more dose of SCSs, total (mean ± SD mg/y) prednisolone-equivalent oral corticosteroid dose was lower with mepolizumab (438.9 ± 350.40) versus placebo (505.2 ± 455.091), overall and irrespective of prior sinus surgeries, blood eosinophil count, or comorbidities.
CONCLUSIONS
Mepolizumab is associated with clinical benefits in patients with severe chronic rhinosinusitis with nasal polyps regardless of prior SCS use and has an SCS-sparing effect.
Topics: Adult; Humans; Adrenal Cortex Hormones; Chronic Disease; Nasal Polyps; Prednisolone; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 37586475
DOI: 10.1016/j.jaip.2023.08.015 -
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 -
The Cochrane Database of Systematic... Dec 2022Cataract surgery is the most common ambulatory incisional surgery performed in the USA. Cystoid macular edema (CME), the accumulation of fluid in the central retina due... (Review)
Review
BACKGROUND
Cataract surgery is the most common ambulatory incisional surgery performed in the USA. Cystoid macular edema (CME), the accumulation of fluid in the central retina due to leakage from dilated capillaries, is the most common cause of vision impairment following cataract surgery. Acute CME, defined as CME of less than four months' duration, often resolves spontaneously. CME that persists for four months or longer is termed chronic CME. Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to treat CME. This update adds new evidence and analyses to the previously published review.
OBJECTIVES
To examine the effectiveness of NSAIDs in the treatment of CME following cataract surgery.
SEARCH METHODS
We searched the CENTRAL (2022, Issue 3); Ovid MEDLINE; Embase; PubMed; LILACS; mRCT (discontinued in 2014, last searched August 2011), ClinicalTrials.gov, and WHO ICTRP databases. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 20 March 2022. SELECTION CRITERIA: We included randomized controlled trials evaluating the effects of NSAIDs for CME following cataract surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all titles and abstracts, reviewed full-text publications against eligibility criteria, independently extracted data from newly included trials and assessed risk of bias for each included trial. We contacted trial authors for clarification or to request missing information. We provided a narrative synthesis of all included trials and their results. For continuous and dichotomous outcomes, we separately performed pooled analysis and reported mean difference (MD) and risk ratio (RR) as well as the associated 95% confidence interval (CI) whenever feasible. Two review authors independently graded the overall certainty of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
We included nine trials with a total of 390 participants (393 eyes). Study participants' mean age was 72.2 years (interquartile range [IQR] 68.8 to 73.6) and 72% were women (IQR 69% to 74%). Three trials included participants with acute CME, and four included participants with chronic CME; the remaining two trials enrolled both participants with acute and chronic CME or participants with unknown CME duration. We assessed trials as having unclear (33%) or high risk of bias (67%). Visual improvement of two or more lines at the end of treatment Data from one trial in participants with acute CME show no treatment effect of topical ketorolac compared to placebo (RR 2.00, 95% CI 0.46 to 8.76; 22 participants). Data from a three-arm trial in participants with acute CME demonstrate that, when compared with topical prednisolone, topical ketorolac (RR 1.33, 95% CI 0.58 to 3.07; 17 participants) or topical ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) may have little or no effect on visual improvement. Results of subgroup analysis from two studies in participants with chronic CME suggest that, after treatment for 90 days or longer, NSAIDs may increase participants' likelihood of visual improvement by 1.87 fold (RR 2.87, 95% CI 1.58 to 5.22; I = 33%; 2 trials, 121 participants) relative to placebo. However, there was no evidence of treatment effects in the subgroup with two months of treatment or less (RR 0.72, 95% CI 0.30 to 1.73; P = 0.19, I = 41%; 2 trials, 34 participants). Overall, this evidence is very low certainty. A single-study estimate in patients with mixed CME indicates that topical diclofenac may increase the likelihood of visual improvement by 40% when compared to topical ketorolac (RR 1.40, 95% CI 1.02 to 1.94; 68 participants). However, the same trial reported no difference between the groups in mean final visual acuity in Snellen lines (MD 0.40, 95% CI -0.93 to 1.73). A three-arm trial in patients with mixed CME reporting visual changes in ETDRS letters in comparisons between ketorolac and diclofenac (34 participants) or bromfenac (34 participants) suggests no evidence of effects. Overall, NSAIDs may slightly improve visual acuity in participants with mixed CME but the evidence is very uncertain. Persistence of improvement of vision one month after discontinuation of treatment One trial of participants with chronic CME tested oral indomethacin (RR 0.40, 95% CI 0.10 to 1.60; 20 participants) and the other compared topical ketorolac to placebo (RR 4.00, 95% CI 0.51 to 31.1; 26 participants). While there is no evidence of treatment effects, evidence suggests substantial between-group heterogeneity (P = 0.07, I = 69.9%; very low-certainty evidence). None of the trials in patients with acute or mixed CME reported this outcome. Proportion of participants with improvement in leakage on fundus fluorescein angiography One three-arm trial in participants with acute CME shows that, when compared with topical prednisolone, there is no treatment benefit of topical ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or topical ketorolac and topical prednisolone combination therapy (RR 1.56, 95% CI 0.72 to 3.38; 17 participants). This evidence is very low certainty. The combined estimate from two trials in participants with chronic CME indicates NSAIDs have little to no effect over placebo on improving leakage (RR 1.93, 95% CI 0.62 to 6.02; 40 participants; very low-certainty evidence). Neither of the trials in patients with mixed CME reported this outcome. Proportion of participants with improved contrast sensitivity Very low-certainty evidence from one trial in participants with acute CME shows no treatment benefit of ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) compared with topical prednisolone. None of the trials in patients with chronic or mixed CME reported this outcome. Proportion of participants with improved central macular thickness on optical coherence tomography; measures of quality of life No included trial reported these outcomes. Adverse effects Most trials observed no differences in ocular adverse events, such as corneal toxicity or elevated intraocular pressure, between comparison groups.
AUTHORS' CONCLUSIONS
Evidence on effects of NSAIDs in patients with CME is very uncertain and further investigation is warranted. Our findings are limited by small sample sizes, and heterogeneity in interventions, assessments, and reporting of clinically important outcomes.
Topics: Humans; Female; Aged; Male; Macular Edema; Anti-Inflammatory Agents, Non-Steroidal; Ketorolac; Diclofenac; Quality of Life; Cataract; Prednisolone
PubMed: 36520144
DOI: 10.1002/14651858.CD004239.pub4 -
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 -
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 -
Cancer Epidemiology Jun 2024A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an...
BACKGROUND
A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk.
METHODS
A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use.
RESULTS
There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27).
CONCLUSIONS
In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.
Topics: Humans; Warfarin; Case-Control Studies; Esophageal Neoplasms; Prednisolone; Male; Female; Middle Aged; Aged; Administration, Oral; Anticoagulants; Risk Factors; Adult; Aged, 80 and over
PubMed: 38447250
DOI: 10.1016/j.canep.2024.102552 -
CNS Drugs Mar 2023Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a so far poorly understood underlying pathogenesis, and few effective therapies for... (Review)
Review
Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a so far poorly understood underlying pathogenesis, and few effective therapies for core symptoms. Accumulating evidence supports an association between ASD and immune/inflammatory processes, arising as a possible pathway for new drug intervention. However, current literature on the efficacy of immunoregulatory/anti-inflammatory interventions on ASD symptoms is still limited. The aim of this narrative review was to summarize and discuss the latest evidence on the use of immunoregulatory and/or anti-inflammatory agents for the management of this condition. During the last 10 years, several randomized, placebo-controlled trials on the effectiveness of (add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, N-acetylcysteine (NAC), sulforaphane (SFN), and/or omega-3 fatty acids have been performed. Overall, a beneficial effect of prednisolone, pregnenolone, celecoxib, and/or omega-3 fatty acids on several core symptoms, such as stereotyped behavior, was found. (Add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, NAC, SFN, and/or omega-3 fatty acids was also associated with a significantly higher improvement in other symptoms, such as irritability, hyperactivity, and/or lethargy when compared with placebo. The mechanisms by which these agents exert their action and improve symptoms of ASD are not fully understood. Interestingly, studies have suggested that all these agents may suppress microglial/monocyte proinflammatory activation and also restore several immune cell imbalances (e.g., T regulatory/T helper-17 cell imbalances), decreasing the levels of proinflammatory cytokines, such as interleukin (IL)-6 and/or IL-17A, both in the blood and in the brain of individuals with ASD. Although encouraging, the performance of larger randomized placebo-controlled trials, including more homogeneous populations, dosages, and longer periods of follow-up, are urgently needed in order to confirm the findings and to provide stronger evidence.
Topics: Humans; Acetylcysteine; Anti-Inflammatory Agents; Autism Spectrum Disorder; Celecoxib; Fatty Acids, Omega-3; Minocycline; Prednisolone; Randomized Controlled Trials as Topic; Immunologic Factors
PubMed: 36913130
DOI: 10.1007/s40263-023-00993-x -
Annals of Medicine 2023Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial.
INTRODUCTION
Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients.
PATIENTS AND METHODS
This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884.
RESULTS
The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (p = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups.
CONCLUSIONS
The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.KEY MESSAGESLow initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.
Topics: Adult; Humans; Prednisolone; Thyroiditis, Subacute; Anti-Inflammatory Agents, Non-Steroidal; Hypothyroidism; Pain
PubMed: 38048390
DOI: 10.1080/07853890.2023.2288941 -
BMJ Case Reports Jun 2022A man in his 70s presented with a 4-day history of bilateral frontal headache and heaviness of the face. He was unable to close either of his eyes, to wrinkle his...
A man in his 70s presented with a 4-day history of bilateral frontal headache and heaviness of the face. He was unable to close either of his eyes, to wrinkle his forehead bilaterally and to raise either corner of his mouth. The patient was admitted with a diagnosis of bilateral facial palsy. From history, epidemiology, physical and laboratory findings, Bell's palsy was considered more probable than viral infection, Guillain-Barré syndrome and sarcoidosis. Oral administration of prednisolone, valacyclovir and mecobalamin were initiated promptly, which improved his symptoms. In areas in which Lyme disease is not endemic, we believe that Bell's palsy is the most probable cause of isolated bilateral facial palsy. Patients with bilateral facial paralysis under the suspicion of Bell's palsy should be immediately started on steroid therapy.
Topics: Bell Palsy; Facial Paralysis; Guillain-Barre Syndrome; Humans; Male; Prednisolone; Valacyclovir
PubMed: 35688576
DOI: 10.1136/bcr-2022-250364