-
BMC Veterinary Research Jul 2023Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting...
BACKGROUND
Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.
OBJECTIVE
The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.
ANIMALS
There were 45 dogs initially enrolled in the study.
RESULTS
At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).
CONCLUSION
This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.
Topics: Dogs; Animals; Prednisolone; Prednisone; Polyuria; Drug-Related Side Effects and Adverse Reactions; Hyperphagia; Polydipsia; Perception; Dog Diseases
PubMed: 37488543
DOI: 10.1186/s12917-023-03644-x -
Journal of Endocrinological... Jul 2023Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves' disease. First-line treatment for DON consists of high-dose intravenous... (Review)
Review
PURPOSE
Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves' disease. First-line treatment for DON consists of high-dose intravenous methylprednisolone (ivMP), followed by immediate orbital decompression (OD) if the response is poor or absent as recommended by the 2021 European Group on Graves' orbitopathy guidelines. The safety and efficacy of the proposed therapy have been proven. However, consensus regarding possible therapeutic options for patients with contraindications to ivMP/OD or resistant form of disease is missing. This paper aims to provide and summarize all available data regarding possible alternative treatment strategies for DON.
METHODS
A comprehensive literature search within an electronic database was performed including data published until December 2022.
RESULTS
Overall, 52 articles describing use of emerging therapeutic strategies for DON were identified. Collected evidence indicates that biologics, including teprotumumab and tocilizumab, may be considered as an important possible treatment option for DON patients. Rituximab should be avoided in DON due to conflicting data and risk of adverse events. Orbital radiotherapy could be beneficial for patients with restricted ocular motility classified as poor surgical candidates.
CONCLUSION
Only a limited number of studies have been dedicated to the therapy of DON, mostly retrospective with a small sample size. Clear criteria regarding diagnosis and resolution of DON do not exist, which restricts comparison of therapeutic outcomes. Randomized clinical trials and comparison studies with long-term follow-ups are necessary to verify the safety and efficacy of each therapeutic option for DON.
Topics: Humans; Graves Ophthalmopathy; Optic Nerve Diseases; Retrospective Studies; Methylprednisolone; Glucocorticoids; Graves Disease
PubMed: 36802028
DOI: 10.1007/s40618-023-02036-0 -
Annals of Medicine Dec 2023Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant...
BACKGROUND
Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population.
METHODS
We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model.
RESULTS
A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment.
CONCLUSIONS
The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.
Topics: Humans; Female; Liver Transplantation; Tacrolimus; Everolimus; Cohort Studies; Alcoholism; Risk Factors; Sirolimus; Proportional Hazards Models; Fractures, Bone; Hepatitis C; Prednisolone; Immunosuppressive Agents
PubMed: 37455447
DOI: 10.1080/07853890.2023.2230871 -
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 -
Human Molecular Genetics Jan 2024Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death....
Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death. The corticosteroids prednisone/prednisolone and deflazacort are used to treat DMD as the standard of care; however, only deflazacort is FDA approved for DMD. The novel atypical corticosteroid vamorolone is being investigated for treatment of DMD. We compared the pharmaceutical properties as well as the efficacy and safety of the three corticosteroids across multiple doses in the B10-mdx DMD mouse model. Pharmacokinetic studies in the mouse and evaluation of p-glycoprotein (P-gP) efflux in a cellular system demonstrated that vamorolone is not a strong P-gp substrate resulting in measurable central nervous system (CNS) exposure in the mouse. In contrast, deflazacort and prednisolone are strong P-gp substrates. All three corticosteroids showed efficacy, but also side effects at efficacious doses. After dosing mdx mice for two weeks, all three corticosteroids induced changes in gene expression in the liver and the muscle, but prednisolone and vamorolone induced more changes in the brain than did deflazacort. Both prednisolone and vamorolone induced depression-like behavior. All three corticosteroids reduced endogenous corticosterone levels, increased glucose levels, and reduced osteocalcin levels. Using micro-computed tomography, femur bone density was decreased, reaching significance with prednisolone. The results of these studies indicate that efficacious doses of vamorolone, are associated with similar side effects as seen with other corticosteroids. Further, because vamorolone is not a strong P-gp substrate, vamorolone distributes into the CNS increasing the potential CNS side-effects.
Topics: Animals; Mice; Prednisolone; X-Ray Microtomography; Mice, Inbred mdx; Muscular Dystrophy, Duchenne; Corticosterone; Pharmaceutical Preparations; Pregnadienediols; Pregnenediones
PubMed: 37819629
DOI: 10.1093/hmg/ddad173 -
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 -
European Urology Open Science Oct 2023Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear.
BACKGROUND
Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear.
OBJECTIVE
To assess the efficacy and safety of low-dose oral prednisolone (PSL) treatment for patients with refractory HIC.
DESIGN SETTING AND PARTICIPANTS
This retrospective observational study reviewed the clinical outcomes of 31 patients with refractory HIC who received oral PSL daily (initial dose, 5.0 or 7.5 mg) for at least 12 mo between 2016 and 2023. The dose was tapered to the minimum that maintained symptom relief during follow-up.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Treatment outcomes were evaluated using a seven-graded global response assessment (scores ≥+2, moderately or markedly improved, were defined as treatment response), O'Leary and Sant symptom and problem indices (OSSI/OSPI), overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, a quality of life (QOL) score, and frequency-volume chart variables. Related complications were also documented.
RESULTS AND LIMITATIONS
The mean follow-up period was 20.1 ± 14.6 mo. The overall response rates at 1, 3, 6, 9, and 12 mo at doses of 6.7, 6.7, 5.2, 4.0, and 3.0 mg were 38.7%, 48.4%, 54.8%, 61.3%, and 64.5%, respectively. Compared with baseline, OSSI/OSPI and pain intensity improved significantly from 1 mo after PSL induction. The OABSS, QOL score, urinary frequency, and voided volume improved significantly from 9 mo after PSL induction. No patients discontinued treatment due to adverse events, although hypertension and glucose intolerance occurred in two patients, but these were resolved by temporal medications.
CONCLUSIONS
This study showed that low-dose oral PSL significantly improves bladder pain, urinary symptoms, and QOL in patients with HIC, without serious adverse events. Further prospective evaluation is warranted to verify the potential efficacy and safety of low-dose PSL for HIC.
PATIENT SUMMARY
This retrospective observational study reviewed the clinical outcomes of 31 patients suffering from refractory Hunner-type interstitial cystitis treated with low-dose oral prednisolone. Low-dose prednisolone improved bladder pain, urinary symptoms, and quality of life significantly, without serious adverse events. The response rate of 64.5% at 12 mo was comparable with the rates reported in previous studies that used higher doses of prednisolone. This study provides a rationale for further prospective evaluation of low-dose prednisolone for this intractable disease.
PubMed: 37822513
DOI: 10.1016/j.euros.2023.07.006 -
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 -
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