-
Frontiers in Aging Neuroscience 2023Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk...
INTRODUCTION
Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.
METHODS
Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies.
RESULTS
Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16-1.64, < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20-2.25, = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92-1.54, = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64-0.95, = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70-0.94, = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77-0.95, = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775-1.069, = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513-0.915, = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474-1.266, = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979-1.789, = 0.069; ET: RR = 1.066, 95% C.I. 0.996-1.140, = 0.066].
DISCUSSION
These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.
PubMed: 37937120
DOI: 10.3389/fnagi.2023.1260427 -
Frontiers in Pharmacology 2023Ginseng consumption has been associated with various health outcomes. However, there are no review articles summarizing these reports. PubMed, Embase, the Cochrane...
Ginseng consumption has been associated with various health outcomes. However, there are no review articles summarizing these reports. PubMed, Embase, the Cochrane Library of Systematic Reviews, Scopus, CNKI and Wanfang databases were searched from inception to 31 July 2022. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence in each meta-analysis, and the results were summarized in a narrative form. Nineteen meta-analyses that met the eligibility criteria were identified from among 1,233 papers. The overall methodological quality was relatively poor, with only five studies being low-quality, and 14 critically low-quality. When compared with control treatments (mainly placebo), ginseng was beneficial for improving fatigue and physical function, sexual function, menopausal symptoms, metabolic indicators, inflammatory markers, unstable angina and respiratory diseases. Adverse events included gastrointestinal symptoms and potential bleeding; however, no serious adverse events were reported. This umbrella review suggests that ginseng intake has beneficial therapeutic effects for diverse diseases. However, the methodological quality of studies needs to be improved considerably. In addition, it is imperative to establish the clinical efficacy of ginseng through high-quality randomized controlled trials.
PubMed: 37465522
DOI: 10.3389/fphar.2023.1069268 -
Canadian Journal of Psychiatry. Revue... Jul 2023Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.
OBJECTIVES
We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.
METHODS
We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.
RESULTS
Forty-nine clinical trials (placebo group = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias ( = 0.029).
CONCLUSION
Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42019125979.
Topics: Adult; Humans; Placebo Effect; Obsessive-Compulsive Disorder; Anxiety Disorders
PubMed: 35876317
DOI: 10.1177/07067437221115029 -
Cureus Aug 2023This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for... (Review)
Review
This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for original studies comparing topical anesthetic agents with placebo in patients with premature ejaculation. After selecting relevant articles, we extracted data on baseline characteristics and predetermined endpoints. Intravaginal ejaculatory latency time (IELT) was the primary outcome for efficacy. Mean differences and corresponding 95% confidence intervals were used to present continuous data. A random-effects model was used to pool the data, and subgroup analysis was performed based on the type of anesthetic agent used. Eleven randomized controlled trials were examined, involving a total of 2008 participants. After analyzing the combined results, it was found that Severance Secret (SS) cream (CJ CheilJedang Corporation, Seoul, South Korea) demonstrated significantly higher effectiveness than a placebo in increasing IELT (P = 0.001). Similarly, the topical eutectic mixture for premature ejaculation (TEMPE), lidocaine, and the eutectic mixture of local anesthetics (EMLA) were significantly more efficient than a placebo (P<0.00001; P = 0.0001; P<0.00001). Additionally, it was found that lidocaine gel was more efficient than paroxetine or sildenafil (P = 0.04; P<0.00001). In conclusion, topical anesthetics increase IELT in men with premature ejaculation more effectively than placebo, sildenafil, tadalafil, paroxetine, and dapoxetine.
PubMed: 37664322
DOI: 10.7759/cureus.42913 -
The Cochrane Database of Systematic... Jul 2023Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.
OBJECTIVES
To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.
Topics: Humans; Adult; Crohn Disease; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Inflammatory Bowel Diseases; Remission Induction
PubMed: 37458279
DOI: 10.1002/14651858.CD013611.pub2 -
Journal of Clinical Hypertension... Aug 2023Studies have shown that angiotensin converting enzyme inhibitors (ACEIs) are superior in primary and secondary prevention for cardiac mortality and morbidity to... (Meta-Analysis)
Meta-Analysis
Studies have shown that angiotensin converting enzyme inhibitors (ACEIs) are superior in primary and secondary prevention for cardiac mortality and morbidity to angiotensin receptor blocker (ARBs). One of the common side effects from ACEI is dry cough. The aims of this systematic review, and network meta-analysis are to rank the risk of cough induced by different ACEIs and between ACEI and placebo, ARB or calcium channel blockers (CCB). We performed a systematic review, and network meta-analysis of randomized controlled trials to rank the risk of cough induced by each ACEI and between ACEI and placebo, ARB or CCB. A total of 135 RCTs with 45,420 patients treated with eleven ACEIs were included in the analyses. The pooled estimated relative risk (RR) between ACEI and placebo was 2.21 (95% CI: 2.05-2.39). ACEI had more incidences of cough than ARB (RR 3.2; 95% CI: 2.91, 3.51), and pooled estimated of RR between ACEI and CCB was 5.30 (95% CI: 4.32-6.50) Moexipril ranked as number one for inducing cough (SUCRA 80.4%) and spirapril ranked the least (SUCRA 12.3%). The order for the rest of the ACEIs are as follows: ramipril (SUCRA 76.4%), fosinopril (SUCRA 72.5%), lisinopril (SUCRA 64.7%), benazepril (SUCRA 58.6%), quinapril (SUCRA 56.5%), perindopril (SUCRA 54.1%), enalapril (SUCRA 49.7%), trandolapril (SUCRA 44.6%) and, captopril (SUCRA 13.7%). All ACEI has the similar risk of developing a cough. ACEI should be avoided in patients who have risk of developing cough, and an ARB or CCB is an alternative based on the patient's comorbidity.
Topics: Humans; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Network Meta-Analysis; Cough; Hypertension; Calcium Channel Blockers
PubMed: 37417783
DOI: 10.1111/jch.14695 -
Diabetes Research and Clinical Practice Aug 2023The effect of fecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome remains unclear. This systematic review employed a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The effect of fecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome remains unclear. This systematic review employed a meta-analysis of RCTs for assessment on the role of FMT in treating obesity and metabolic syndrome, and its impact on clinically relevant parameters.
METHOD
Major databases and grey literatures were searched identifying RCTs comparing FMT of lean donors with placebo in obese/metabolic syndrome patients. Studies using any form of placebo were included. Variations in the parameters before and after treatment were calculated followed by meta-analyses.
RESULT
Ten studies met the inclusion criteria and a total of 334 patients were included for further analysis. Clinically significant parameters associated with obesity and metabolic syndrome were explored and FMT was identified significantly and negatively associated with most indices of abdominal adiposity including caloric intake, fasting glucose, HOMA-IR, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides and CRP, Obesity parameters including fasting glucose and acetic acid were increased following FMT.
CONCLUSION
FMT is more advantageous for obese patients with elevated blood pressure, disordered glucose and insulin metabolism, and elevated blood lipids. The study of metabolic factors in obese patients will be our starting point in the future.
Topics: Humans; Fecal Microbiota Transplantation; Metabolic Syndrome; Obesity; Glucose; Lipids
PubMed: 37356723
DOI: 10.1016/j.diabres.2023.110803 -
Translational Psychiatry Sep 2023Depression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and... (Meta-Analysis)
Meta-Analysis
Depression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and network meta-analysis aimed to compare the efficacy at the same follow-up time points of psychological interventions in depression. We searched PubMed, Embase, and PsycINFO via OVID, and the Cochrane Library published up to December 12, 2021, and PubMed up to July 1, 2022. The primary outcome was depression relapse, considering the same time points that were extracted on survival curves or relapse curves. The study protocol was registered with PROSPERO, CRD42022343327. A total of 2,871 patients were included from 25 RCTs. Mindfulness-based cognitive therapy (MBCT) was significantly better than placebo at the 3 months, the 6 months, and the 9 months at follow-up. Cognitive behavioral therapy (CBT) was significantly better than treatment as usual at the 3 months, the 9 months, the 12 months, and the 15 months at follow-up. CBT was significantly better than placebo at the 21 months and the 24 months at follow-up. Behavioral activation therapy was significantly better than placebo at the 21 months and the 24 months at follow-up. Interpersonal psychotherapy was significantly better than placebo at the 24-month follow-up. All psychological interventions included in the study were significantly better than supportive counseling most of the time. The results were robust in various sensitivity and subgroup analyses. In conclusion, MBCT had a continuous effect in preventing relapse of depression. CBT had the longest but not continuous effect in preventing relapse of depression. The effects of behavioral activation therapy and interpersonal therapy for the prevention of depression appeared late. All psychological interventions included in the study were more effective than supportive counseling. More evidence is needed from large comparative trials that provide long-term follow-up data.
Topics: Humans; Network Meta-Analysis; Psychosocial Intervention; Depression; Behavior Therapy; Chronic Disease; Recurrence
PubMed: 37770471
DOI: 10.1038/s41398-023-02604-1 -
Nutrients Sep 2023Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to... (Meta-Analysis)
Meta-Analysis Review
Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to prevent GDM. The present systematic review and meta-analysis aimed to investigate the effect of inositol supplementation in preventing GDM and related outcomes. Systematic search was performed in CENTRAL, MEDLINE, and Embase until 13 September 2023. Eligible randomized controlled trials (RCTs) compared the efficacy of inositols to placebo in pregnant women at high risk for GDM. Our primary outcome was the incidence of GDM, whereas secondary outcomes were oral glucose tolerance test (OGTT) and maternal and fetal complications. (PROSPERO registration number: CRD42021284939). Eight eligible RCTs were identified, including the data of 1795 patients. The incidence of GDM was halved by inositols compared to placebo (RR = 0.42, CI: 0.26-0.67). Fasting, 1-h, and 2-h OGTT glucose levels were significantly decreased by inositols. The stereoisomer myoinositol also reduced the risk of insulin need (RR = 0.29, CI: 0.13-0.68), preeclampsia or gestational hypertension (RR = 0.38, CI: 0.2-0.71), preterm birth (RR = 0.44, CI: 0.22-0.88), and neonatal hypoglycemia (RR = 0.12, CI: 0.03-0.55). Myoinositol decrease the incidence of GDM in pregnancies high-risk for GDM. Moreover, myoinositol supplementation reduces the risk of insulin need, preeclampsia or gestational hypertension, preterm birth, and neonatal hypoglycemia. Based on the present study 2-4 g myoinositol canbe suggested from the first trimester to prevent GDM and related outcomes.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Diabetes, Gestational; Premature Birth; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Randomized Controlled Trials as Topic; Hypoglycemia; Insulin; Inositol
PubMed: 37836508
DOI: 10.3390/nu15194224 -
Frontiers in Immunology 2023A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG.
METHODS
PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86).
CONCLUSION
While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/?s=202370112, identifier 202370112.
Topics: Adult; Humans; Antibodies, Monoclonal; Activities of Daily Living; Bayes Theorem; Myasthenia Gravis
PubMed: 38022544
DOI: 10.3389/fimmu.2023.1280226