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Frontiers in Neuroendocrinology Jul 2022Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment... (Meta-Analysis)
Meta-Analysis Review
Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.
Topics: Child; Child Abuse; Corticotropin-Releasing Hormone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 35202606
DOI: 10.1016/j.yfrne.2022.100987 -
Drug Delivery and Translational Research Jun 2023Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and... (Review)
Review
Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle-Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations.
Topics: Humans; Triamcinolone Acetonide; Dermatology; Keloid; Fluorouracil; Acne Vulgaris; Treatment Outcome
PubMed: 36884194
DOI: 10.1007/s13346-023-01295-x -
Journal of Hypertension Jun 2023Stress is widely considered to be a risk factor for high blood pressure (BP), but evidence on the associations between biomarkers of chronic stress and BP is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Stress is widely considered to be a risk factor for high blood pressure (BP), but evidence on the associations between biomarkers of chronic stress and BP is inconsistent. This systematic review and meta-analysis assessed the current state of the science on relationships between measures of cortisol concentration reflecting chronic stress exposure [hair cortisol concentration (HCC), nail cortisol concentration)] and BP.
METHODS
PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, and Embase were searched. Random effects models were used to assess the pooled effect size. Exploratory moderation analysis was performed.
RESULTS
Out of 34 014 identified, 16 articles met eligibility criteria and were included in the review, while 14 were included in the meta-analysis. No articles were reported on the association between nail cortisol concentration and BP. Small, positive associations were observed between HCC and SBP [ r = 0.19 (95% confidence interval (CI): 0.08-0.29)] and HCC and DBP [ r = 0.13 (95% CI: 0.04-0.22)]. Cortisol analysis method was identified as a significant moderator of the association between HCC and DBP. HCC was largely, positively associated with hypertension status [odds ratio = 3.23 (95% CI: 2.55-4.09), P < 0.001].
CONCLUSIONS
Current evidence suggests that higher HCC may be associated with elevated BP and a potential risk factor for hypertension. However, results should be interpreted with caution because HCC can be affected by hair color, hair care products, and analytic methods. Given the limitations of studies included in this review, further research is needed.
Topics: Humans; Blood Pressure; Hydrocortisone; Hypertension; Risk Factors; Hair
PubMed: 37016924
DOI: 10.1097/HJH.0000000000003412 -
Hematology (Amsterdam, Netherlands) Dec 2023Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory multiple myeloma (RRMM), whereas its optimal timing and drug combination remain unclear. In order to assess the various regimens that incorporate selinexor, a systematic review and meta-analysis was conducted.
METHODS
Clinical trials and real-world studies involving MM patients treated with selinexor were included. Pooled risk ratio (RR) was calculated to compare the rates, along with a 95% confidence interval (CI) and concurrent -value assessment. A random-effects model was employed to provide a more conservative evaluation.
RESULTS
A total of 16 studies enrolling 817 patients were reviewed. The usage of selinexor as the fifth-line or prior therapy achieved a higher objective response rate (ORR) (65.9% versus 23.4%, < 0.01) and longer pooled progression-free survival (PFS) (median: 12.5 months versus 2.9 months, < 0.01) than those after the fifth-line usage. In addition, early usage also resulted in a consistent trend of pooled overall survival (median: 22.7 months versus 8.9 months, = 0.26), compared with post-fifth-line usage. Selinexor and dexamethasone (Xd) plus either protease inhibitors (PIs) or immunomodulatory drugs (IMiDs) achieved better ORRs than the Xd-only regimen for RRMM, with ORRs of 56.1%, 52.5% and 24.6%, respectively (< 0.01).
CONCLUSION
In conclusion, using selinexor as the fifth-line or prior therapy had a beneficial impact on RRMM. The regimen of Xd plus PIs or IMiDs was recommended.
Topics: Humans; Multiple Myeloma; Immunomodulating Agents; Dexamethasone; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36920065
DOI: 10.1080/16078454.2023.2187972 -
Expert Opinion on Pharmacotherapy Apr 2024Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.
METHODS
A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.
RESULTS
The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), = 0.99] compared to placebo.
CONCLUSION
Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.
PROSPERO REGISTRATION NUMBER
CRD42023434883.
Topics: Humans; Anticonvulsants; Randomized Controlled Trials as Topic; Drug Resistant Epilepsy; Pregnanolone; Epilepsy; Treatment Outcome
PubMed: 38606458
DOI: 10.1080/14656566.2024.2342413 -
Adipocyte Dec 2023This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was... (Meta-Analysis)
Meta-Analysis Review
METHODS
This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was accomplished by searching clinical MeSH categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers examined all the findings and selected the studies that satisfied the inclusion criteria. The Downs and Black Checklist was used to assess for bias, followed by a Review Manager v5. A Forrest plot was used for the meta-analysis and sensitivity analysis. The protocol for this review was registered with PROSPERO CRD42022320252.
RESULTS
The clinical studies ( = 2) comprised 1065 patients with prediabetes and 1103 normal controls. The RAAS measurements were completed in the adipose tissue. The RAAS components, renin and aldosterone were higher in the prediabetic (PD) compared to the control [mean difference (MD) = 0.16, 95% CI 0.16 (-0.13, 0.45), = 0.25]. Furthermore, the PD group demonstrated higher triglycerides mean difference [MD = 7.84, 95% CI 7.84 (-9.84, 25.51), = 0.38] and increased BMI [MD = 0.13, 95% CI 0.13 (-0.74, 0.99), = 0.77] compared to the control. The overall quality of the studies was fair with a median score and range of 17 (16-18).
CONCLUSION
The current study highlights the relationship between increased BMI, RAAS and insulin resistance which is a predictor of prediabetes. The renin is slightly higher in the prediabetes group without any statistical significance, aldosterone is rather negatively associated with prediabetes which may be attributed to the use of anti-hypertensive treatment.
Topics: Humans; Aldosterone; Prediabetic State; Renin; Renin-Angiotensin System; Risk Factors; Adipose Tissue
PubMed: 37606270
DOI: 10.1080/21623945.2023.2249763 -
Frontiers in Endocrinology 2020Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis.
METHODS
Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient.
RESULTS
A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (=21.50 pg/ml, 95% CI (15.63, 27.37), <0.00001) and slightly increased urinary calcium levels ( = 1.65 mmol/24 h, 95% CI (1.24, 2.06), < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery.
CONCLUSIONS
PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.
Topics: Aldosterone; Bone Density; Bone and Bones; Fractures, Bone; Humans; Hyperaldosteronism; Osteoporosis; Parathyroid Hormone; Spironolactone
PubMed: 33101208
DOI: 10.3389/fendo.2020.574151 -
Journal of Affective Disorders May 2023This review systematically examined the associations between chronic stress and hair cortisol concentration (HCC) in children, and the potential modification effects of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This review systematically examined the associations between chronic stress and hair cortisol concentration (HCC) in children, and the potential modification effects of type, measurement period and scales of chronic stress, child age and sex, hair length and HCC measurement method, characteristics of study site, and congruence between time periods measured for chronic stress and HCC.
METHODS
Pubmed, Wed of Science, and APA PsycINFO were systematically searched for articles examining the association between chronic stress and HCC.
RESULTS
Thirteen studies from five countries with 1,455 participants were included in the systematic review and nine studies were included in the meta-analysis. Meta-analysis revealed that chronic stress was associated with HCC (pooled-r = 0.09, 95 % CI: 0.03, 0.16). Stratified analyses revealed that type, measurement time and scales of chronic stress, hair length and measurement method of HCC, and the congruence between time periods measured for chronic stress and HCC modified such correlations. The positive correlations between chronic stress and HCC were significant for studies measuring chronic stress as stressful life events, assessing chronic stress within the past six months, extracting HCC from 1 cm, 3 cm, or 6 cm of hair, measuring HCC by LC-MS/MS, or having congruence between time periods measured for chronic stress and HCC. The potential modifying effects of sex and country developmental status could not be concluded due to the limited number of studies included.
CONCLUSIONS
Chronic stress was positively correlated with HCC, varying by characteristics and measurements of chronic stress and HCC. HCC could be a biomarker for chronic stress among children.
Topics: Humans; Child; Stress, Psychological; Hydrocortisone; Chromatography, Liquid; Tandem Mass Spectrometry; Hair
PubMed: 36868386
DOI: 10.1016/j.jad.2023.02.123 -
Medicine Dec 2017Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs' influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes.
METHOD
A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, without any restrictions regarding the participants' characteristics.Study design, patient population, dose and duration of intervention, and the quantitative results on glycemic markers were extracted, interpreted for result synthesis, and evaluated for sources of bias. From the articles included in the qualitative analysis, a select number were used in a meta-analysis on studies having measured glycated hemoglobin (HbA1c) or risk of diabetes.
RESULTS
Seventy-two articles were selected from the Medline database and references of articles. Results on spironolactone were heterogeneous, but seemed to be disease-specific. A potential negative effect on glucose regulation was mainly observed in heart failure and diabetes trials, while a neutral or positive effect was detected in diseases characterized by hyperandrogenism, and inconclusive for hypertension. Interpretation of data from heart failure trials was limited by the small number of studies. From a meta-analysis of 12 randomized controlled studies evaluating spironolactone's impact on HbA1c in diabetic patients, spironolactone had a nonsignificant effect in parallel-group studies (mean difference 0.03 [-0.20;0.26]), but significantly increased HbA1c in crossover studies (mean difference 0.24 [0.18;0.31]). Finally, eplerenone did not seem to influence glycemia, while limited data indicated that canrenone may exert a neutral or beneficial effect.The studies had important limitations regarding study design, sample size, duration of follow-up, and choice of glycemic markers.
CONCLUSION
Spironolactone may induce disease-specific and modest alterations on glycemia. It is uncertain whether these effects are transient or not. Data from the most extensively studied population, individuals with diabetes, do not support a long-term glycemic impact in these patients. Further prospective studies are necessary to establish spironolactone's true biological effects and their clinical implications.
Topics: Blood Glucose; Canrenone; Eplerenone; Glycated Hemoglobin; Homeostasis; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone
PubMed: 29310346
DOI: 10.1097/MD.0000000000008719 -
Stroke Feb 2007Tirilazad is a candidate neuroprotective drug with reported efficacy in animal models of stroke that was, however, without benefit in clinical trials. This apparent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Tirilazad is a candidate neuroprotective drug with reported efficacy in animal models of stroke that was, however, without benefit in clinical trials. This apparent contradiction might be explained if the animal studies were falsely positive, if the clinical trials were falsely negative, or if tirilazad was not tested under the same conditions in animal and clinical studies. Here we use systematic review and meta-analysis to describe the characteristics and limits to the neuroprotective action of tirilazad in animal models of stroke.
METHODS
Systematic review and meta-analysis of studies describing the efficacy of tirilazad in animal models of focal ischemia, in which outcome was measured as infarct volume and/or neurological score. Weighted mean difference random effects meta-analysis was used to measure overall efficacy in prespecified subgroups.
RESULTS
Eighteen studies describing outcome in 544 animals were identified. Study quality (median score, 5/10; interquartile range, 4 to 6) was similar to that seen in systematic reviews of other candidate neuroprotective drugs. Tirilazad reduced infarct volume by 29.2% (95% confidence interval 21.1% to 37.2%) and improved neurobehavioral score by 48.1% (95% confidence interval 29.3% to 66.9%).
CONCLUSIONS
Tirilazad may have substantial efficacy in animal models of stroke, but this conclusion must be qualified because of the presence of potential sources of bias.
Topics: Animals; Disease Models, Animal; Humans; Pregnatrienes; Stroke
PubMed: 17204689
DOI: 10.1161/01.STR.0000254462.75851.22