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British Dental Journal Sep 2021
Topics: Betamethasone; Betamethasone Valerate
PubMed: 34561568
DOI: 10.1038/s41415-021-3487-9 -
Medical Archives (Sarajevo, Bosnia and... Apr 2023Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines, the prescription... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effectiveness of Eplerenone vs Spironolactone on Left Ventricular Systolic Function, Hospitalization and Cardiovascular Death in Patients With Chronic Heart Failure-HFrEF.
BACKGROUND
Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines, the prescription of a MRA is recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure and no contraindications for this therapy.
OBJECTIVE
The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function by measuring left ventricle ejection fraction (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF.
METHODS
From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size and matched by age and gender patients in Spiron-HF group for management of chronic HFrEF. Each patient was evaluated clinically, biochemically, and echocardiographically at the beginning of treatment (baseline) after 6 months and at the end of 12th month. Echocardiography was performed to find out change in left ventricular systolic function.
RESULTS
After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P < 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P < 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P < 0.05), occurred after 12 months of treatment. Left ventricular global longitudinal strain (LV GLS) was significantly improved in Epler-HF group compared with Spiron-HF group (0.6 ± 0.4 versus 3.4 ± 0.9; P < 0.05). There were no significant differences observed in reduction of left ventricular end-diastolic volume (2.2 ± 0.5 ml versus 4.7 ± 1.1ml; P =0.103) and left ventricular diastolic diameter (1.2 ± 0.6 versus 1.7 ± 0.3; P=0.082) in both arms. The effects of both MRA agents spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34-0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44-0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73- 1.27; p= 0.675).
CONCLUSION
Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEF.
Topics: Humans; Spironolactone; Eplerenone; Heart Failure; Stroke Volume; Prospective Studies; Single-Blind Method; Mineralocorticoid Receptor Antagonists; Ventricular Function, Left; Chronic Disease; Hospitalization; Treatment Outcome
PubMed: 37260796
DOI: 10.5455/medarh.2023.77.105-111 -
Stress (Amsterdam, Netherlands) Nov 2023As the end product of the hypothalamus-pituitary-adrenal (HPA) axis, the glucocorticoid hormones cortisol and corticosterone coordinate circadian activities,... (Review)
Review
As the end product of the hypothalamus-pituitary-adrenal (HPA) axis, the glucocorticoid hormones cortisol and corticosterone coordinate circadian activities, stress-coping, and adaptation to change. For this purpose, the hormone promotes energy metabolism and controls defense reactions in the body and brain. This life-sustaining action exerted by glucocorticoids occurs in concert with the autonomic nervous and immune systems, transmitters, growth factors/cytokines, and neuropeptides. The current contribution will focus on the glucocorticoid feedback paradox in the HPA-axis: the phenomenon that stress responsivity remains resilient if preceded by stress-induced secretion of glucocorticoid hormone, but not if this hormone is previously administered. Furthermore, in animal studies, the mixed progesterone/glucocorticoid antagonist RU486 or mifepristone switches to an apparent partial agonist upon repeated administration. To address these enigmas several interesting phenomena are highlighted. These include the conditional nature of the excitation/inhibition balance in feedback regulation, the role of glucose as a determinant of stress responsivity, and the potential of glucocorticoids in resetting the stress response system. The analysis of the feedback paradox provides also a golden opportunity to review the progress in understanding the role of glucocorticoid hormone in resilience and vulnerability during stress, the science that was burned deeply in Mary Dallman's emotions.
Topics: Animals; Glucocorticoids; Feedback; Stress, Psychological; Corticosterone; Hydrocortisone
PubMed: 37589046
DOI: 10.1080/10253890.2023.2247090 -
Revista de Neurologia May 2022Catamenial pattern epilepsy is defined as an increase in the frequency of seizures during a specific stage of the menstrual cycle compared to baseline. It has been... (Review)
Review
Catamenial pattern epilepsy is defined as an increase in the frequency of seizures during a specific stage of the menstrual cycle compared to baseline. It has been described that around a third of women with epilepsy have a catamenial pattern. The changes in the seizure pattern would be explained by the influence of catamenial fluctuations, of female gonadal hormones on neuronal excitability. Progesterone through its metabolite allopregnanolone plays a protective role by increasing GABAergic transmission; however, its effect on brain progesterone receptors can increase neuronal excitability. The effects of estrogens are complex, they tend to increase neuronal excitability, although their effects depend on their concentration and exposure time. Three catamenial patterns of seizure exacerbation have been proposed: the perimenstrual pattern, the periovulatory pattern, and the luteal pattern. The diagnostic approach is carried out through a systematic process of 4 steps: a) clinical history of the pattern of the menstrual cycle and epileptic seizures; b) diagnostic methods to characterize the menstrual cycle and the pattern of seizures; c) check diagnostic criteria; and d) categorize the catamenial pattern. The treatment options studied require a higher level of evidence, and there is no specific treatment. Optimization of conventional antiseizure treatment is recommended as the first therapeutic option. Other therapeutic options, such as non-hormonal and hormonal treatments, could be useful in case the first therapeutic option proves to be ineffective.
Topics: Epilepsy, Reflex; Female; Humans; Menstrual Cycle; Pregnanolone; Progesterone; Seizures
PubMed: 35484702
DOI: 10.33588/rn.7409.2022041 -
Clinical efficacy and safety of Zuranolone (SAGE-217) in individuals with major depressive disorder.Journal of Affective Disorders Nov 2023Major depressive disorder (MDD) is a common mental disorder with a high rate of morbidity and mortality. Dysfunctional signaling of gamma-aminobutyric acid (GABA) has... (Review)
Review
Major depressive disorder (MDD) is a common mental disorder with a high rate of morbidity and mortality. Dysfunctional signaling of gamma-aminobutyric acid (GABA) has been implicated in some studies in the etiology of MDD. Zuranolone (SAGE-217) is a novel, oral neuroactive steroid and an investigational positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Herein, we aimed to evaluate the efficacy and safety of Zuranolone in individuals with MDD. We reviewed seven studies including 1662 participants with MDD. Zuranolone was investigated as an oral, once-daily, 14-day treatment course. The results of our synthesis indicate that the antidepressant effects of Zuranolone are rapid, clinically meaningful, and replicated across multiple randomized clinical trials. In addition to replicated efficacy, Zuranolone is associated with an acceptable level of treatment-emergent adverse events and discontinuation without serious adverse events. It is believed that Zuranolone's antidepressant effects arise from its ability to enhance inhibitory GABAergic signaling by increasing synaptic and extrasynaptic GABAA activity and regulation of GABAA receptor expression. Taken together, preliminary evidence suggests the potential for antidepressant effects of Zuranolone. Zuranolone has been approved by FDA for postpartum depression, and is showing efficacy in major depressive disorder. Future research vistas should seek to determine the durability of this treatment approach as well as its effects on domain-specific outcomes (e.g., anhedonia, circadian rhythm, arousal systems) along with application in other diagnostic entities (e.g., bipolar depression).
Topics: Female; Humans; Depressive Disorder, Major; Pregnanes; Antidepressive Agents; Receptors, GABA-A; Treatment Outcome
PubMed: 37557991
DOI: 10.1016/j.jad.2023.08.027 -
The American Journal of Geriatric... Jun 2020
Topics: Drug Therapy, Combination; Humans; Megestrol; Megestrol Acetate; Mental Disorders
PubMed: 32122805
DOI: 10.1016/j.jagp.2020.01.188 -
Obstetrics and Gynecology Clinics of... Mar 2023Specifically, meta-analyses of randomized trials demonstrate that vaginal progesterone reduces the risk of preterm birth in selected high-risk singleton pregnancies.... (Review)
Review
Specifically, meta-analyses of randomized trials demonstrate that vaginal progesterone reduces the risk of preterm birth in selected high-risk singleton pregnancies. 17-OHPC may also reduce the risk of recurrent preterm birth in singletons. Finally, one trial suggests that vaginal progesterone may also be beneficial in improving live birth rates in singletons with prior miscarriages and early pregnancy bleeding.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Progesterone; 17 alpha-Hydroxyprogesterone Caproate; Progestins; Hydroxyprogesterones; Premature Birth
PubMed: 36822696
DOI: 10.1016/j.ogc.2022.10.004 -
Journal of Comparative Effectiveness... Dec 2021Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense... (Meta-Analysis)
Meta-Analysis
Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54 m [95% CI: 13.799, 65.286; p = 0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Deflazacort provides clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy.
Topics: Codon, Nonsense; Humans; Muscular Dystrophy, Duchenne; Prednisolone; Prednisone; Pregnenediones; Retrospective Studies
PubMed: 34693725
DOI: 10.2217/cer-2021-0018 -
Journal of Hypertension Jul 2019
Topics: Dexamethasone; Glucocorticoids; Humans; Hydrocortisone; Hypertensive Encephalopathy; Mutation; Receptors, Glucocorticoid
PubMed: 31145708
DOI: 10.1097/HJH.0000000000002066 -
The European Respiratory Journal Apr 2023https://bit.ly/3YUkc8G
https://bit.ly/3YUkc8G
Topics: Humans; COVID-19; Methylprednisolone; COVID-19 Drug Treatment; Adrenal Cortex Hormones; Dexamethasone
PubMed: 36858444
DOI: 10.1183/13993003.00270-2023