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Journal of Sleep Research Dec 2023Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.
Topics: Humans; Adult; Sleep Initiation and Maintenance Disorders; Sleep; Melatonin; Indenes
PubMed: 37434463
DOI: 10.1111/jsr.13939 -
Otology & Neurotology : Official... Apr 2024To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment.
DATA SOURCES
CINAHL, PubMed, and Scopus were searched for articles from conception to October 2022. MESH and key terms such as "tinnitus," "placebo," and "medication" were used to find randomized, placebo-controlled trials. The search was limited to articles in English.
METHODS
Randomized controlled trials with adult subjects evaluating tinnitus pretreatment and posttreatment with an oral or intratympanic medication versus a placebo arm were included. Crossover studies, studies involving middle/inner ear operations or devices, and studies that exclusively included nonidiopathic etiologies of tinnitus were excluded. Mean tinnitus symptom survey scores for the Tinnitus Handicap Inventory (THI), Tinnitus Severity Index, Tinnitus Functional Index, Tinnitus Handicap Questionnaire, and Visual Analog Scales for tinnitus Intensity/Loudness (VAS-L), Annoyance (VAS-An), and Awareness (VAS-Aw) were extracted for both placebo and experimental groups.
RESULTS
953 studies were screened with 23 studies being included in the final analysis. Meta-analysis of mean difference (MD) was calculated using RevMan 5.4. MD between pretreatment and posttreatment THI scores of the placebo arms was 5.6 (95% confidence interval, 3.3-8.0; p < 0.001). MD between pretreatment and posttreatment VAS scores of the placebo groups for Loudness, Annoyance, and Awareness were 0.8 (0.0 to 1.6, p = 0.05), 0.2 (-0.2 to 0.5, p = 0.34), and 0.3 (-0.0 to 0.7, p = 0.08), respectively.
CONCLUSIONS
Placebo treatment has shown effectiveness in improving patient-reported evaluations of tinnitus when using some standardized metrics such as THI and VAS-L; however, the improvement is not as substantial as nonplacebo treatment.
Topics: Adult; Humans; Tinnitus; Placebo Effect; Randomized Controlled Trials as Topic; Surveys and Questionnaires
PubMed: 38361332
DOI: 10.1097/MAO.0000000000004139 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
Alimentary Pharmacology & Therapeutics Oct 2023Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat.
AIM
To assess the efficacy of medical treatments for UP.
METHODS
We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome.
RESULTS
We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32).
CONCLUSIONS
Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
Topics: Adult; Humans; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Mesalamine; Proctitis; Remission Induction; Tacrolimus
PubMed: 37589498
DOI: 10.1111/apt.17666 -
The Journal of Pain Nov 2023Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of TBUP compared to other analgesics or placebo for acute postoperative pain. A systematic search was conducted using Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) until December 26, 2022. The search included randomized controlled trials comparing TBUP versus other analgesics or placebo for acute postoperative pain. A certainty assessment was conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The protocol for this review was registered on Prospective Register of Systematic Reviews (CRD42022318601). In total, 15 studies involving 1,205 participants were included that compared TBUP versus fentanyl (n = 2), celecoxib (n = 3), placebo (n = 2), tramadol (n = 5), diclofenac (n = 3), parecoxib (n = 1), and flurbiprofen (n = 1). Meta-analyses were conducted for 3 comparators that involved 2 studies each. There was no significant difference in pain between TBUP 10 mcg/h versus fentanyl 25 mcg/h (standardized mean difference [SMD] -.03, 95% confidence interval [CI] -.86 to .81, P = .95, I = 85%). TBUP 10 mcg/h was associated with less pain compared to celecoxib 200 mg twice daily (SMD -.32, 95% CI -.58 to -.05, P = .02, I = 0%) and placebo (SMD -2.29, 95% CI -4.32 to -.27, P = .03, I = 94%). The GRADE assessment showed a very low certainty of evidence for all comparisons. There is insufficient evidence that TBUP improves pain control compared to other analgesics for acute postoperative pain. PERSPECTIVE: This systematic review and meta-analysis compared the use of TBUP to other analgesics for postoperative pain. The results showed that there is insufficient evidence to recommend the use of TBUP in this setting. The findings will help clinicians select the most appropriate opioid regimens for postoperative pain.
Topics: Humans; Celecoxib; Analgesics, Opioid; Pain, Postoperative; Fentanyl; Buprenorphine
PubMed: 37442403
DOI: 10.1016/j.jpain.2023.07.001 -
The Journal of Allergy and Clinical... Apr 2024There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR).
BACKGROUND
There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR).
OBJECTIVES
We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR.
METHODS
The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.
RESULTS
This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses.
CONCLUSIONS
Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.
PubMed: 38685482
DOI: 10.1016/j.jaci.2024.04.016 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
PeerJ 2023To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis
Comparison of nutritional supplements in improving glycolipid metabolism and endocrine function in polycystic ovary syndrome: a systematic review and network meta-analysis.
OBJECTIVE
To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome (PCOS).
METHOD
Randomized controlled clinical trials on the effects of nutritional supplements in PCOS patients were searched in PubMed, Embase, Cochrane Library, and Web of Science from their establishments to March 15, 2023. Then, literature screening, data extraction, and network meta-analysis were performed. This study was registered at PROSPERO (registration number CRD 42023441257).
RESULT
Forty-one articles involving 2,362 patients were included in this study. The network meta-analysis showed that carnitine, inositol, and probiotics reduced body weight and body mass index (BMI) compared to placebo, and carnitine outperformed the other supplements (SUCRAs: 96.04%, 97.73%, respectively). Omega-3 lowered fasting blood glucose (FBG) (SUCRAs: 93.53%), and chromium reduced fasting insulin (FINS) (SUCRAs: 72.90%); both were superior to placebo in improving insulin resistance index (HOMA-IR), and chromium was more effective than Omega-3 (SUCRAs: 79.99%). Selenium was potent in raising the quantitative insulin sensitivity index (QUICKI) (SUCRAs: 87.92%). Coenzyme Q10 was the most effective in reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (SUCRAs: 87.71%, 98.78%, and 98.70%, respectively). Chromium and probiotics decreased TG levels, while chromium and vitamin D decreased TC levels. No significant differences were observed in high-density lipoprotein cholesterol (HDL-C), total testosterone (TT), sex-hormone binding globulin (SHBG), and C-reactive protein (CRP) between nutritional supplements and placebo.
CONCLUSION
Carnitine was relatively effective in reducing body mass, while chromium, Omega-3, and selenium were beneficial for improving glucose metabolism. Meanwhile, coenzyme Q10 was more efficacious for improving lipid metabolism. However, publication bias may exist, and more high-quality clinical randomized controlled trials are needed.
Topics: Female; Humans; Polycystic Ovary Syndrome; Network Meta-Analysis; Selenium; Carnitine; Cholesterol, HDL; Lipid Metabolism; Chromium; Glycolipids; Randomized Controlled Trials as Topic
PubMed: 38025704
DOI: 10.7717/peerj.16410 -
Scientific Reports Sep 2023The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic
PubMed: 37741858
DOI: 10.1038/s41598-023-42989-z -
Journal of Affective Disorders Mar 2024The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents.
METHOD
We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455).
RESULTS
Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ = 0.0072, I = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio.
LIMITATIONS
Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered.
CONCLUSIONS
Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.
Topics: Humans; Adolescent; Adult; Child; Risperidone; Olanzapine; Aripiprazole; Bipolar Disorder; Quetiapine Fumarate; Mania; Network Meta-Analysis; Antipsychotic Agents; Dibenzocycloheptenes
PubMed: 38211745
DOI: 10.1016/j.jad.2024.01.067