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Inflammopharmacology Oct 2023The present review critically appraised the randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone and low-dose... (Meta-Analysis)
Meta-Analysis
Intermediate- to high-dose dexamethasone versus low-dose dexamethasone in patients with COVID-19 requiring respiratory support: a systematic review and meta-analysis of randomized trials.
The present review critically appraised the randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone and low-dose dexamethasonein patients with COVID-19 and reported pooled mortality risk estimates associated with these two dosing regimens of dexamethasone. The systematic searching of electronic databases was limited to randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone with low-dose dexamethasone in patients with COVID-19 requiring respiratory support. The primary outcome of interest in this review was all-cause mortality. A total of eight trials with 1800 patients randomized to receive intermediate to high-dose dexamethasone and 1715 patients randomized to low-dose dexamethasone were included. The meta-analysis of six trials revealed no significant difference in the risk of 28-day all-cause mortality between intermediate- to high-dose dexamethasone and low-dose dexamethasone (odds ratio 1.16, 95% confidence interval, 0.77-1.74). Similarly, the meta-analysis of five trials revealed no significant difference between the two doses regarding 60-day all-cause mortality (odds ratio 0.96, 95% confidence interval 0.74-1.26). The results suggest intermediate- to high-dose dexamethasone to be as effective as low-dose dexamethasone in reducing the risk of mortality among patients with COVID-19 requiring respiratory support. However, higher dexamethasone doses could expose patients with COVID-19 to an increased risk of adverse events, such as hyperglycemia.
Topics: Humans; COVID-19; Dexamethasone; COVID-19 Drug Treatment; Randomized Controlled Trials as Topic
PubMed: 37266814
DOI: 10.1007/s10787-023-01251-8 -
Nutrients May 2023Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ... (Review)
Review
Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.
Topics: Infant; Female; Humans; Infant, Newborn; Milk, Human; Bilirubin; Jaundice, Neonatal; Breast Feeding; Hyperbilirubinemia; Jaundice
PubMed: 37242142
DOI: 10.3390/nu15102261 -
Seizure Jul 2023Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually... (Review)
Review
OBJECTIVE
Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE.
METHODS
We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency.
RESULTS
Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies.
CONCLUSIONS
Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues.
Topics: Humans; Female; Progesterone; Anticonvulsants; Menstrual Cycle; Epilepsy, Reflex; Seizures; Randomized Controlled Trials as Topic
PubMed: 37229848
DOI: 10.1016/j.seizure.2023.05.004 -
Frontiers in Endocrinology 2023The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.
METHODS
We searched for articles that evaluated ketoconazole use in Cushing's disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.
RESULTS
After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.
CONCLUSION
Ketoconazole can be considered a safe and efficacious option for Cushing's disease treatment after pituitary surgery.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).
Topics: Humans; Ketoconazole; Pituitary ACTH Hypersecretion; Cushing Syndrome; Hydrocortisone; Prospective Studies; Retrospective Studies
PubMed: 37223017
DOI: 10.3389/fendo.2023.1145775 -
PloS One 2023Laughter as an expression of humor has been recognized as good medicine for centuries. The health benefits of humor-induced well-being remain unclear and thus we... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Laughter as an expression of humor has been recognized as good medicine for centuries. The health benefits of humor-induced well-being remain unclear and thus we conducted a systematic review and meta-analysis of interventional studies to evaluate the impact of spontaneous laughter on stress response as measured by cortisol levels.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE/PubMed, EMBASE, PsycINFO, Scopus, and Clinicaltrials.gov.
ELIGIBILITY CRITERIA
Interventional studies, which could be either randomized placebo-controlled trials (RCTs) or quasi-experimental studies, conducted in adults that compared any spontaneous laughter intervention to a controlled setting and reported changes in cortisol levels were selected.
DATA EXTRACTION AND SYNTHESIS
We examined the impact of laughter on percentage change in cortisol levels by calculating pooled estimates of the absolute differences between arithmetic means before and after interventions as compared to control using random-effects model.
RESULTS
Eight studies (315 participants; mean age 38.6) met our inclusion criteria; four were RCTs and four were quasi-experiment studies. Five studies evaluated the impact of watching a humor/comedy video, two studies evaluating laughter sessions administered by a trained laughter therapist, and one study evaluating a self-administered laughter program. Pooling these data showed a significant reduction in cortisol levels by 31.9% (95%CI -47.7% to -16.3%) induced by laughter intervention compared to control group with no evidence of publication bias (P = 0.66). Sensitivity analyses demonstrated that even a single laughter session induced a significant reduction of 36.7% in cortisol (95%CI -52.5% to -20.8%). In addition, analyses including the four RCTs reinforced these results by demonstrating a significant reduction in cortisol levels promoted by laughter as compared to the placebo arm [-37.2% (95%CI -56.3% to -18.1%)].
CONCLUSIONS
Current evidence demonstrates that spontaneous laughter is associated with greater reduction in cortisol levels as compared with usual activities, suggesting laughter as a potential adjunctive medical therapy to improve well-being.
TRIAL REGISTRATION
Registration number: CRD42021267972.
Topics: Adult; Humans; Hydrocortisone; Laughter; Medicine; Allied Health Personnel; Control Groups
PubMed: 37220157
DOI: 10.1371/journal.pone.0286260 -
Harvard Review of PsychiatryRepetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical...
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical effectiveness varies substantially. The effects of sex hormone fluctuations on cortical excitability have been identified as potential factors that can explain this variability. However, data on how sex hormone changes affect clinical response to rTMS is limited. To address this gap, we reviewed the literature examining the effects of sex hormones and hormonal treatments on transcranial magnetic stimulation (TMS) measures of cortical excitability. Results show that variations of endogenous estrogen, testosterone, and progesterone have modulatory effects on TMS-derived measures of cortical excitability. Specifically, higher levels of estrogen and testosterone were associated with greater cortical excitability, while higher progesterone was associated with lower cortical excitability. This highlights the importance of additional investigation into the effects of hormonal changes on rTMS outcomes and circuit-specific physiological variables. These results call for TMS clinicians to consider performing more frequent motor threshold (MT) assessments in patients receiving high doses of estrogen, testosterone, and progesterone in cases such as in vitro fertilization, hormone replacement therapy, and gender-affirming hormonal treatments. It may also be important to consider physiological hormonal fluctuations and their impact on depressive symptoms and the MT when treating female patients with rTMS.
Topics: Humans; Female; Transcranial Magnetic Stimulation; Depressive Disorder, Major; Progesterone; Evoked Potentials, Motor; Cortical Excitability; Estrogens; Testosterone
PubMed: 37171472
DOI: 10.1097/HRP.0000000000000366 -
TheScientificWorldJournal 2023The corticosteroids have been used for preemptive management of surgical sequelae after mandibular third molar extraction. The aim of this article was to review the... (Meta-Analysis)
Meta-Analysis Review
Efficacy of Preemptive Dexamethasone versus Methylprednisolone in the Management of Postoperative Discomfort and Pain after Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.
The corticosteroids have been used for preemptive management of surgical sequelae after mandibular third molar extraction. The aim of this article was to review the efficacy of methylprednisolone versus dexamethasone in the management of postsurgical pain, swelling, and trismus after mandibular third molar surgery. Randomized, double-blinded studies from PubMed, CINAHL, Scopus, DOSS, Cochrane central, and Web of Science were identified by using a search strategy. Randomized controlled trials evaluating the efficacy of use of dexamethasone versus methylprednisolone for mandibular third molar extraction were only considered. The studies involving the use of any other corticosteroid agent were excluded. Outcomes assessed were postoperative pain, the number of rescue analgesics required, swelling, trismus, and adverse events. The search strategy yielded 1046 articles for title and abstract screening, out of which only seven studies were included in the systematic review after full text screening. There was considerable heterogeneity between the studies with regards to the method as well as the parameters assessed. Risk of bias was low in three studies and unclear in other four studies. On pooled analyses, there was no significant difference with respect to pain, rescue analgesics, and swelling in the test and the control group. Forest plot analysis showed that dexamethasone had lesser trismus in early postoperative period (postoperative day 2) as compared to methylprednisolone. None of the included studies reported any adverse effects. Both the corticosteroids have similar efficacy in reducing the postoperative pain and swelling; however, dexamethasone showed statistically significant difference from methylprednisolone in reducing trismus (estimated standardized mean difference of -0.69 mm; 95% CI: -1.01 to -0.38; < 0.0001) in the early postoperative period. However, due to statistical heterogeneity, quality of the evidence for the review was low to moderate. Hence, more studies with larger study sample and low risk of bias are needed to confirm these results.
Topics: Humans; Methylprednisolone; Dexamethasone; Molar, Third; Trismus; Adrenal Cortex Hormones; Pain, Postoperative; Edema; Tooth Extraction; Tooth, Impacted
PubMed: 37168455
DOI: 10.1155/2023/7412026 -
Scientific Reports May 2023To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with... (Meta-Analysis)
Meta-Analysis
Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis.
To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02-0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06-77.13) and resistant DME (MD 65.37, 95% CI 3.62-127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.
Topics: Humans; Macular Edema; Ranibizumab; Glucocorticoids; Endothelial Growth Factors; Bevacizumab; Vascular Endothelial Growth Factor A; Dexamethasone; Diabetic Retinopathy; Intravitreal Injections; Diabetes Mellitus
PubMed: 37156823
DOI: 10.1038/s41598-023-34673-z -
BMC Infectious Diseases May 2023The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19.
METHODS
By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO/FiO ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0.
RESULTS
Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone.
CONCLUSIONS
This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.
Topics: Humans; Glucocorticoids; Methylprednisolone; COVID-19; COVID-19 Drug Treatment; Dexamethasone
PubMed: 37147596
DOI: 10.1186/s12879-023-08280-2 -
Clinical Cardiology Jun 2023The advantages and disadvantages of using corticosteroids in children undergoing cardiac surgery is still contentious. To examine how perioperative corticosteroids... (Meta-Analysis)
Meta-Analysis Review
The advantages and disadvantages of using corticosteroids in children undergoing cardiac surgery is still contentious. To examine how perioperative corticosteroids affect postoperative mortality and clinical outcomes in pediatric cardiac surgery with cardiopulmonary bypass (CPB). We used MEDLINE, EMBASE, and the Cochrane Database to conduct a comprehensive search up through January 2023. Children aged 0-18 undergoing cardiac surgery were included in the meta-analysis of randomized controlled studies comparing perioperative corticosteroids with other therapeutic therapies, placebo, or no treatment. All-cause hospital mortality was the primary endpoint of the study. Hospitalization duration was a secondary result. The Cochrane Risk of Bias Assessment Tool was used to evaluate the research quality. Ten trials and 7798 pediatric participants were included in our analysis. Children taking corticosteroids had no significant difference in all-cause in-hospital mortality using a random-effect model with relative risk (RR) = 0.38, 95% confidence interval (CI) = 0.16-0.91, I = 79%, p = .03 for methylprednisolone and RR = 0.29, 95% CI = 0.09-0.97, I = 80%, p = .04. For the secondary outcome, there was a significant difference between the corticosteroid and placebo groups, with pooled standard mean difference (SMD) = -0.86, 95% CI = -1.57 to -0.15, I = 85%, p = .02 for methylprednisolone and SMD = -0.97, 95% CI -1.90 to -0.04, I = 83%, p = .04 for dexamethasone. Perioperative corticosteroids may not improve mortality, but they reduce hospital stay compared to placebo. Further evidence from randomized controlled studies with larger samples is required for approaching at a valid conclusion.
Topics: Child; Humans; Cardiac Surgical Procedures; Adrenal Cortex Hormones; Methylprednisolone
PubMed: 37101401
DOI: 10.1002/clc.24018