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Nutrients Dec 2023Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and... (Review)
Review
BACKGROUND
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
METHODS
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
RESULTS
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
CONCLUSIONS
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Topics: Humans; Plant Extracts; Withania; Hydrocortisone; Plants, Medicinal; Antioxidants
PubMed: 38140274
DOI: 10.3390/nu15245015 -
Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Journal of Critical Care Apr 2024The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP.
METHODS
The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model.
RESULTS
Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty).
CONCLUSIONS
Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.
Topics: Adult; Humans; Adrenal Cortex Hormones; Community-Acquired Infections; Hydrocortisone; Pneumonia; Randomized Controlled Trials as Topic
PubMed: 38128217
DOI: 10.1016/j.jcrc.2023.154507 -
BMC Infectious Diseases Dec 2023Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens.
METHODS
This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared.
RESULTS
In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay.
CONCLUSIONS
Considering the available evidence, this network meta‑analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19.
TRIAL REGISTRATION
PROSPERO CRD42022350407 (22/08/2022).
Topics: Humans; Glucocorticoids; COVID-19; Hydrocortisone; Network Meta-Analysis; Methylprednisolone; Dexamethasone
PubMed: 38124031
DOI: 10.1186/s12879-023-08874-w -
Neurology(R) Neuroimmunology &... Jan 2024We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
BACKGROUND AND OBJECTIVES
We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
METHODS
Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included.
RESULTS
From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy.
DISCUSSION
Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Brain Diseases; COVID-19; Methylprednisolone; SARS-CoV-2; Seizures; Aged
PubMed: 38086061
DOI: 10.1212/NXI.0000000000200186 -
Human Reproduction Open 2023What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as... (Review)
Review
STUDY QUESTION
What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards?
SUMMARY ANSWER
Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare.
WHAT IS KNOWN ALREADY
In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend.
STUDY DESIGN SIZE DURATION
The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*').
PARTICIPANTS/MATERIALS SETTING METHODS
The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found.
MAIN RESULTS AND THE ROLE OF CHANCE
A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ultimately, 69 studies were included in the final sample. The key results concerned four aspects relevant to the research goals. (i) The studies showed discrepancies in defining who is an APA parent. (ii) There was an imbalance in the empirical evidence produced for different participant groups (mothers, fathers, and offspring), with offspring being the most studied study subjects. (iii) The research topics studied underlined the increased risks of neuro-developmental and psychotic disorders among offspring. (iv) The observed advantages and disadvantages were varied and could not be compared, especially for the offspring of APA parents.
LIMITATIONS REASONS FOR CAUTION
Only English-language studies, published between 2000 and 2021, found in the above-mentioned databases were considered for this review.
WIDER IMPLICATIONS OF THE FINDINGS
More research is necessary to understand the risks and benefits of building a family at an APA for the offspring when they reach adulthood. Furthermore, studies that explore the perspective of older fathers and older parents from non-Western societies would be highly informative.
STUDY FUNDING/COMPETING INTERESTS
The writing of this manuscript was permitted by financial support provided by the Swiss National Science Foundation (Weave/Lead Agency funding program, grant number 10001AL_197415/1, project title 'Family Building at Advanced Parental Age: An Interdisciplinary Approach'). The funder had no role in the drafting of this manuscript and the views expressed therein are those of the authors. The authors have no conflicts of interest.
REGISTRATION NUMBER
This systematic review is registered in Prospero: CRD42022304564.
PubMed: 38045093
DOI: 10.1093/hropen/hoad042 -
Journal of Human Hypertension Feb 2024Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating... (Meta-Analysis)
Meta-Analysis Review
Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.
Topics: Humans; Renin-Angiotensin System; Renin; Aldosterone; Blood Pressure; Norepinephrine; Epinephrine; Angiotensin II; Potassium; Sodium; Exercise
PubMed: 38017087
DOI: 10.1038/s41371-023-00872-4 -
PloS One 2023Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential... (Meta-Analysis)
Meta-Analysis
Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Adrenal Cortex Hormones; Budesonide; Treatment Outcome
PubMed: 38015868
DOI: 10.1371/journal.pone.0294872 -
ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
Respiratory Medicine Jan 2024Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to...
Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting β-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.
INTRODUCTION
Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting β-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted.
METHODS
Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis.
RESULTS
The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs.
CONCLUSION
A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.
Topics: Humans; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Randomized Controlled Trials as Topic; Meta-Analysis as Topic
PubMed: 38008385
DOI: 10.1016/j.rmed.2023.107478