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Journal of Nuclear Cardiology :... Aug 2023Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the...
BACKGROUND
Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients.
METHODS AND RESULTS
In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups.
CONCLUSIONS
Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients.
Topics: Humans; Prednisone; Fluorodeoxyglucose F18; Methotrexate; Positron Emission Tomography Computed Tomography; Retrospective Studies; Stroke Volume; Cardiomyopathies; Radiopharmaceuticals; Ventricular Function, Left; Sarcoidosis; Positron-Emission Tomography; Myocarditis
PubMed: 36640249
DOI: 10.1007/s12350-022-03171-6 -
The Lancet. Oncology Oct 2023
Topics: Male; Humans; Abiraterone Acetate; Prostatic Neoplasms, Castration-Resistant; Phthalazines; Piperazines; Antineoplastic Combined Chemotherapy Protocols; Prednisone
PubMed: 37797626
DOI: 10.1016/S1470-2045(23)00448-5 -
BMC Urology Jul 2023Studies have suggested a positive association between bladder cancer (BC) outcome and comedication use, including nonsteroidal anti-inflammatory drugs (NSAID),...
Chronic prednisone, metformin, and nonsteroidal anti-inflammatory drug use and clinical outcome in a cohort of bladder cancer patients undergoing radical cystectomy in Québec, Canada.
BACKGROUND
Studies have suggested a positive association between bladder cancer (BC) outcome and comedication use, including nonsteroidal anti-inflammatory drugs (NSAID), metformin, and prednisone use. To validate these associations, we evaluated whether these medications were associated with clinical outcome in a Canadian cohort of BC patients.
METHODS
This is a retrospective cohort study on BC patients undergoing radical cystectomy (RC) in Québec province in 2000-2015, as registered in the provincial health administration databases. Medication use was considered chronic when prescribed for ≥ 1 year. Overall (OS), disease-specific (DSS) and recurrence-free (RFS) survival were compared using multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, hospital and surgeon annual RC volume, neoadjuvant chemotherapy use, and type of bladder diversion, as well as mutual adjustment for concomitant comedication use (statins, NSAIDs, metformin, and prednisone).
RESULTS
Of 3742 patients included, 293, 420, and 1503 patients chronically used prednisone, metformin, and NSAIDs before surgery, respectively. In multivariable analyses, preoperative prednisone use was associated with improved OS (HR 0.67, 95%CI 0.55-0.82), DSS (HR 0.58, 95%CI 0.45-0.76), and RFS (HR 0.61, 95%CI 0.47-0.78). Patients who chronically used metformin preoperatively had a worse OS (HR 1.29, 95%CI 1.07-1.55), DSS (HR 1.38, 95%CI 1.10-1.72), and RFS (HR 1.41, 95%CI 1.13-1.74). Preoperative, chronic NSAID use was not significantly associated with all clinical outcomes, with adjusted HRs for OS, DSS, and RFS of 1.10 (95%CI 0.95-1.27), 1.24 (95%CI 1.03-1.48), and 1.22 (95%CI 1.03-1.45), respectively. Directionality of findings was similar when stratifying by comedication use in the year following surgery. Results were similar after propensity-score matching too.
CONCLUSIONS
In our Canadian cohort of BC undergoing RC, chronic prednisone use was associated with improved clinical outcomes, while metformin and NSAID were not.
Topics: Humans; Urinary Bladder; Cystectomy; Quebec; Prednisone; Metformin; Retrospective Studies; Disease-Free Survival; Canada; Urinary Bladder Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Treatment Outcome
PubMed: 37452329
DOI: 10.1186/s12894-023-01287-6 -
Pharmaceuticals (Basel, Switzerland) Oct 2023Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led... (Review)
Review
Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led to an ever-increasing demand of pharmacological treatment and relief. This demand for medication, ranging from well-known groups, such as antidepressants and benzodiazepines, to more novel drugs, was followed by a rise in safety concerns of such treatment options. The validity, frequency, and diversity of such concerns are discussed in this paper, as well as their possible effect on future prescription practices. A specific caution is provided towards the psychological safety and toll of these medications, regarding suicidality and suicidal ideation. Most significantly, this paper highlights the importance of pharmacovigilance and underscores the necessity of surveillance programs when considering chronic pain medication.
PubMed: 37895968
DOI: 10.3390/ph16101497 -
Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
Hematology (Amsterdam, Netherlands) Dec 2023Antinuclear antibody (ANA)-positive immune thrombocytopenia (ITP) patients have an unsatisfactory prognosis due to the more severe conditions of these patients and poor...
Efficacy and safety of azathioprine plus prednisone versus prednisone alone as first-line treatment for antinuclear antibody-positive immune thrombocytopenia: a retrospective cohort study.
OBJECTIVE
Antinuclear antibody (ANA)-positive immune thrombocytopenia (ITP) patients have an unsatisfactory prognosis due to the more severe conditions of these patients and poor response to first-line glucocorticoids (GCs). The current study intended to compare the efficacy and safety of AZA plus prednisone and prednisone alone as first-line treatment in ANA-positive ITP patients.
METHODS
Fifteen ANA-positive ITP patients receiving AZA plus prednisone (AZA + GC group) and eighteen ANA-positive ITP patients receiving prednisone alone (GC group) as first-line treatment were retrospectively enrolled.
RESULTS
The complete response (CR) rate (60.0% versus 22.2%) (= 0.038) was increased in the AZA + GC group versus the GC group, while the overall response rate (86.7% versus 55.6%) (= 0.070) only showed an increasing trend that did not achieve statistical significance. In addition, multivariate analysis revealed that AZA + GC (versus GC) (odds ratio = 31.331, = 0.018) was independently associated with a higher possibility of achieving CR. Additionally, accumulating relapse-free duration was prolonged in the AZA + GC group versus the GC group (median: 7.8 months versus 3.4 months) (= 0.038). Additionally, the multivariate analysis suggested that AZA + GC (versus GC) (hazard ratio = 0.306, = 0.007) was independently correlated with longer accumulating relapse-free duration. The incidence of adverse events did not differ between the two groups (all > 0.05), and the common adverse events in the AZA + GC group were pneumonia (13.3%), anemia (13.3%), cough (13.3%), nausea (6.7%), and granulocytopenia (6.7%), which were all tolerable and manageable.
CONCLUSION
First-line AZA plus prednisone realizes a better hematological response and relapse-free duration with acceptable adverse events compared to prednisone alone in ANA-positive ITP patients.
Topics: Humans; Antibodies, Antinuclear; Azathioprine; Immunosuppressive Agents; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Thrombocytopenia
PubMed: 37014744
DOI: 10.1080/16078454.2023.2196864 -
JCI Insight Nov 2023New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory...
New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD. Both drugs modulated seed genes driving the DMD disease program and improved force production in fast-twitch muscle. However, only DMF showed pro-mitochondrial effects, protected contracting muscles from fatigue, improved histopathology, and augmented clinically compatible muscle function tests. DMF may be a more selective modulator of the DMD disease program than PRED, warranting follow-up longitudinal studies to evaluate disease-modifying impact.
Topics: Animals; Mice; Mice, Inbred mdx; Dimethyl Fumarate; Muscular Dystrophy, Duchenne; Prednisone; Muscles
PubMed: 37751291
DOI: 10.1172/jci.insight.165974 -
American Journal of Respiratory and... Nov 2023Spirometry is essential for diagnosis and assessment of prognosis in patients with chronic obstructive pulmonary disease (COPD). To identify FEV trajectories and their...
Spirometry is essential for diagnosis and assessment of prognosis in patients with chronic obstructive pulmonary disease (COPD). To identify FEV trajectories and their determinants on the basis of annual spirometry measurements among individuals with and without airway obstruction (AO) and to assess mortality in relation to trajectories. From 2002 through 2004, individuals with AO (FEV/VC < 0.70, = 993) and age- and sex-matched nonobstructive (NO) referents were recruited from population-based cohorts. Annual spirometry until 2014 was used in joint-survival latent-class mixed models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up. Three trajectories were identified among the subjects with AO and two among the NO referents. Trajectory membership was driven by baseline FEV% predicted (FEV%pred) in both groups and also by pack-years in subjects with AO and current smoking in NO referents. Longitudinal FEV%pred depended on baseline FEV%pred, pack-years, and obesity. The trajectories were distributed as follows: among individuals with AO, 79.6% in AO trajectory 1 (FEV high with normal decline), 12.8% in AO trajectory 2 (FEV high with rapid decline), and 7.7% in AO trajectory 3 (FEV low with normal decline) (mean, 27, 72, and 26 ml/yr, respectively) and, among NO referents, 96.7% in NO trajectory 1 (FEV high with normal decline) and 3.3% in NO trajectory 2 (FEV high with rapid decline) (mean, 34 and 173 ml/yr, respectively). Hazard for death was increased for AO trajectories 2 (hazard ratio [HR], 1.56) and 3 (HR, 3.45) versus AO trajectory 1 and for NO trajectory 2 (HR, 2.99) versus NO trajectory 1. Three different FEV trajectories were identified among subjects with AO and two among NO referents, with different outcomes in terms of FEV decline and mortality. The FEV trajectories among subjects with AO and the relationship between low FVC and trajectory outcome are of particular clinical interest.
Topics: Adult; Humans; Lung; Forced Expiratory Volume; Vital Capacity; Pulmonary Disease, Chronic Obstructive; Airway Obstruction; Spirometry; Prednisone
PubMed: 37460250
DOI: 10.1164/rccm.202211-2166OC -
Acta Neurologica Taiwanica Jun 2024Myasthenia gravis (MG) is the most common autoimmune disease that affects the neuromuscular junction and can cause weakness in various muscle groups. The most commonly...
PURPOSE
Myasthenia gravis (MG) is the most common autoimmune disease that affects the neuromuscular junction and can cause weakness in various muscle groups. The most commonly affected muscles are the eye, facial, and neck flexors. Focal or dominant weakness of the triceps muscle is rare. In this case, we aimed to describe a rare form of MG consisting of selective or dominant triceps muscle weakness.
CASE REPORT
We present a 45-year-old male patient whose initial complaints were diplopia and ptosis. Acetylcholine receptor antibody was positive. After 10 years of well-being following thymectomy, bilateral triceps weakness was added to his ocular symptoms despite regular medication (pyridostigmine and prednisone). Repetitive nerve stimulation (RNS) showed decremental responses in the right triceps muscles.
CONCLUSION
It is important to recognize this type of myasthenia gravis to facilitate diagnosis and appropriate treatment and to avoid unnecessary investigations and treatments.
Topics: Male; Humans; Middle Aged; Myasthenia Gravis; Muscle Weakness; Muscle, Skeletal; Pyridostigmine Bromide; Blepharoptosis
PubMed: 37848221
DOI: No ID Found -
Best Practice & Research. Clinical... Dec 2023Glucocorticoids (GCs) continue to be essential agents for the management of systemic lupus erythematosus, since there are no other drugs able to active remission of... (Review)
Review
Glucocorticoids (GCs) continue to be essential agents for the management of systemic lupus erythematosus, since there are no other drugs able to active remission of active disease so rapidly. However, their potential for causing irreversible damage greatly limit their use. Fortunately, some strategies may help take advantage of their huge anti-inflammatory power while limiting GC-induced side effects. This article reviews the pharmacological basis of GC action and their translation into the clinical ground. We also offer the practical approach for the use of GC in induction and maintenance therapy as well as the strategies for GC withdrawal of the respective practice of the authors. The three main basic principles are a) using methyl-prednisolone pulses to induce remission not only in severe disease; b) limiting initial doses of prednisone to ≤30 mg/d, with rapid tapering to ≤5 mg/d, which should be the dose for maintenance therapy; and c) individualizing the decision and the strategy to withdraw GCs. Long-term therapy with HCQ and the early introduction of immunosuppressive treatment would help achieve these objectives.
Topics: Humans; Lupus Erythematosus, Systemic; Glucocorticoids; Immunosuppressive Agents; Remission Induction; Methylprednisolone; Prednisone
PubMed: 37957076
DOI: 10.1016/j.berh.2023.101873