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Therapeutic Apheresis and Dialysis :... Oct 2023The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We performed a meta-analysis of randomized placebo-controlled trials to evaluate the efficacy and safety of tenapanor.
METHODS
All randomized controlled trials of tenapanor were searched up to 1 August 2022. The primary endpoint was the change in serum phosphorus level from baseline with tenapanor and placebo. Data on drug-related adverse events (AEs), gastrointestinal AEs and diarrhea were collected to determine the safety of tenapanor.
RESULTS
There were 533 patients throughout five trials that were eligible. Tenapanor significantly lowered blood phosphorus level by 1.79 mg/dl in the mean difference than the placebo. Diarrhea, gastrointestinal AEs, and drug-related AEs were more severe than placebo.
CONCLUSIONS
This meta-analysis showed that although drug side effects were common, tenapanor significantly reduced serum phosphorus level in hemodialysis patients.
Topics: Humans; Hyperphosphatemia; Double-Blind Method; Renal Dialysis; Diarrhea; Phosphorus; Randomized Controlled Trials as Topic
PubMed: 37349983
DOI: 10.1111/1744-9987.14028 -
Advances in Therapy Jul 2023Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC).... (Review)
Review
INTRODUCTION
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
METHODS
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
RESULTS
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
CONCLUSION
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
Topics: Humans; Eosinophils; Anti-Asthmatic Agents; Biological Products; Asthma; Leukocyte Count; Eosinophilia; Double-Blind Method
PubMed: 37233876
DOI: 10.1007/s12325-023-02514-0 -
Clinical Drug Investigation Jun 2023Many randomized clinical trials (RCTs) for antidepressants in children and adolescents have failed to demonstrate efficacy due to a high placebo response. The aim of...
BACKGROUND AND OBJECTIVE
Many randomized clinical trials (RCTs) for antidepressants in children and adolescents have failed to demonstrate efficacy due to a high placebo response. The aim of this study was to identify the potential factors affecting placebo response using meta-regression analysis of RCTs for antidepressants in children and adolescents using the Children's Depressive Rating Scale-Revised (CDRS-R) as the outcome.
METHODS
PubMed and ClinicalTrials.gov were searched for randomized, double-blind, placebo-controlled trials of antidepressants for the acute treatment of major depressive disorder in children and adolescents. The outcome used in the present study was the mean change of the CDRS-R total score from baseline to the last assessment for the primary efficacy in the placebo arm. Potential factors related to the placebo response, such as study design, operational, and patient factors, were explored using meta-regression.
RESULTS
The analyses included 23 trials. On multivariable meta-regression, setting up a placebo lead-in period was significantly associated with a smaller placebo response in the CDRS-R.
CONCLUSION
Setting up a placebo lead-in period should be considered in future clinical trials of antidepressants in adolescents and children.
Topics: Humans; Adolescent; Child; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Placebo Effect; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37222973
DOI: 10.1007/s40261-023-01273-8 -
Asian Journal of Psychiatry Jul 2023We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive... (Meta-Analysis)
Meta-Analysis
We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive disorder (MDD) or bipolar depression (BD). A random-effects model was adopted to analyze the primary and secondary outcomes using the Review Manager, Version 5.3 software. This meta-analysis (MA) identified five double-blind randomized controlled trials (RCTs) comprising 239 MDD or BD patients with a major depressive episode. Active aiTBS overperformed sham stimulation in the study-defined response. This MA found preliminary evidence that active aiTBS resulted in a greater response in treating major depressive episodes in MDD or BD patients than sham stimulation.
Topics: Humans; Depressive Disorder, Major; Bipolar Disorder; Transcranial Magnetic Stimulation; Treatment Outcome; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 37201381
DOI: 10.1016/j.ajp.2023.103618 -
The Journal of Headache and Pain May 2023Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression.
METHODS
We conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥ 50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders.
RESULTS
A total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho = 0.32, p = 0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho = 0.08, p = 0.596). Placebo response also varied by route of administration.
CONCLUSION
Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.
Topics: Adult; Humans; Migraine Disorders; Treatment Outcome; Double-Blind Method; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 37193973
DOI: 10.1186/s10194-023-01587-0 -
European Archives of Psychiatry and... Oct 2023The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials....
UNLABELLED
The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials. This is due to its positive safety profile, cost-effectiveness, and potential scalability for a wide outreach in clinical practice. Here, we provide a systematic review of the available studies and also a report on the results of a randomized controlled trial (RCT) on tDCS at home for the treatment of MDD. This trial had to be prematurely terminated due to safety concerns. The HomeDC trial is a double-blinded, placebo-controlled, parallel-group study. Patients with MDD (DSM-5) were randomized to active or sham tDCS. Patients conducted tDCS at home for 6 weeks with 5 sessions/week (30 min at 2 mA) anode over F3, cathode over F4. Sham tDCS resembled active tDCS, with ramp-in and ramp-out periods, but without intermittent stimulation. The study was prematurely terminated due to an accumulation of adverse events (AEs, skin lesions), so that only 11 patients were included. Feasibility was good. Safety monitoring was not sufficient enough to detect or prevent AEs within an appropriate timeframe. Regarding antidepressant effects, the reduction in depression scales over time was significant. However, active tDCS was not superior to sham tDCS in this regard. Both the conclusions from this review and the HomeDC trial show that there are several critical issues with the use of tDCS at home that need to be addressed. Nevertheless the array of transcranial electric simulation (TES) methods that this mode of application offers, including tDCS, is highly interesting and warrants further investigation in high quality RCTs.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov .
TRIAL REGISTRATION NUMBER
NCT05172505. Registration date: 12/13/2021, https://clinicaltrials.gov/ct2/show/NCT05172505 . *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers) **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71 . For more information, visit: http://www.prisma-statement.org/.
Topics: Humans; Transcranial Direct Current Stimulation; Pilot Projects; Treatment Outcome; Depressive Disorder, Major; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 37191697
DOI: 10.1007/s00406-023-01620-y -
The Journal of Obstetrics and... Jul 2023The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine,... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section.
METHODS
The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores.
RESULTS
About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 μg norepinephrine and 81-120 mg phenylephrine; 121-150 μg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 μg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 μg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 μg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores.
CONCLUSIONS
Based on this study, 5-10 mg ephedrine and 13-16 μg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Phenylephrine; Ephedrine; Norepinephrine; Vasoconstrictor Agents; Cesarean Section; Bradycardia; Network Meta-Analysis; Bayes Theorem; Anesthesia, Spinal; Hypotension; Hypertension; Anesthesia, Obstetrical; Double-Blind Method
PubMed: 37170779
DOI: 10.1111/jog.15671 -
Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis.Archives of Osteoporosis May 2023Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment.
METHODS
We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms "osteoporosis" and "odanacatib." The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN.
RESULTS
Ten articles-all double-blinded, randomized, placebo-controlled trials-were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups.
CONCLUSION
ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.
Topics: Aged; Female; Middle Aged; Humans; Bone Density Conservation Agents; Osteoporosis, Postmenopausal; Double-Blind Method; Osteoporosis; Bone Density; Fractures, Bone; Stroke
PubMed: 37169994
DOI: 10.1007/s11657-023-01261-7 -
PloS One 2023Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line... (Meta-Analysis)
Meta-Analysis
Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear.
METHOD
We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al.
RESULTS
Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy.
CONCLUSIONS
The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Network Meta-Analysis; Lung Neoplasms; Bevacizumab; Mutation; Randomized Controlled Trials as Topic
PubMed: 37071610
DOI: 10.1371/journal.pone.0283719 -
International Urogynecology Journal Sep 2023The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD). (Meta-Analysis)
Meta-Analysis
The efficacy and safety of medication for treating overactive bladder in patients with Parkinson's disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials.
INTRODUCTION AND HYPOTHESIS
The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD).
METHODS
Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis.
RESULTS
We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy.
CONCLUSIONS
Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.
Topics: Humans; Urinary Bladder, Overactive; Parkinson Disease; Quality of Life; Acetanilides; Double-Blind Method; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37052644
DOI: 10.1007/s00192-023-05528-y