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Trends in Cardiovascular Medicine Feb 2024Treatment strategies that modulate autonomic tone through interventional and device-based therapies have been studied as an adjunct to pharmacological treatment of heart... (Meta-Analysis)
Meta-Analysis Review
Treatment strategies that modulate autonomic tone through interventional and device-based therapies have been studied as an adjunct to pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). The main objective of this study was to perform a meta-analysis of randomized controlled trials which evaluated the efficacy of device-based autonomic modulation for treatment of HFrEF. All randomized-controlled trials testing autonomic neuromodulation device therapy in HFrEF were included in this trial-level analysis. Autonomic neuromodulation techniques included vagal nerve stimulation (VNS), baroreflex activation (BRA), spinal cord stimulator (SCS), and renal denervation (RD). The prespecified primary endpoints included mean change and 95% confidence intervals (CI) of left ventricular ejection fraction (LVEF), NT pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QOL) measures including 6-minute hall walk distance (6-MHWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ). New York Heart Association (NYHA) functional class improvement was reported as odds ratios and 95% CI of improvement by at least 1 functional class. Eight studies were identified that included 1037 participants (2 VNS, 2 BRA, 1 SCS, and 3 RD trials). This included 6 open-label, 1 single-blind, and 1 sham-controlled, double-blind study. The mean age (±SD) was 61 (±9.3) years. The mean follow-up time was 7.9 months. Twenty percent of the total patients were female, and the mean BMI (±SD) was 29.86 (±4.12). Autonomic neuromodulation device therapy showed a statistically significant improvement in LVEF (4.02%; 95% CI 0.24,7.79), NT-proBNP (-219.80 pg/ml; 95% CI -386.56, -53.03), NYHA functional class (OR 2.32; 95% CI 1.76, 3.07), 6-MHWD (48.39 m; 95% CI 35.49, 61.30), and MLHFQ (-12.20; 95% CI -19.24, -5.16) compared to control. In patients with HFrEF, the use of autonomic neuromodulation device therapy is associated with improvement in LVEF, reduction in NT-proBNP, and improvement in patient-centered QOL outcomes in mostly small open-label trials. Large, double-blind, sham-controlled trials designed to detect differences in hard cardiovascular outcomes are needed before widespread use and adoption of autonomic neuromodulation device therapies in HFrEF.
Topics: Humans; Female; Middle Aged; Aged; Male; Heart Failure; Stroke Volume; Ventricular Function, Left; Quality of Life; Single-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36202286
DOI: 10.1016/j.tcm.2022.09.007 -
Frontiers in Pharmacology 2022The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in...
The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings. EMBASE, PUBMED, Cochrane, and www.clinicaltrials.gov databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included. This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17-1.41; I = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74-0.90; I = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62-0.81; I = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08-1.62, I = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting. This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings.
PubMed: 36188589
DOI: 10.3389/fphar.2022.960323 -
Journal of Palliative Medicine Jan 2023The use of inhaled isopropyl alcohol (IPA) has been proposed as a therapeutic intervention for the relief of nausea in various settings. The objective of this...
The use of inhaled isopropyl alcohol (IPA) has been proposed as a therapeutic intervention for the relief of nausea in various settings. The objective of this systematic review was to evaluate the existing evidence for the use of inhaled IPA in the management of nausea and vomiting. We performed a literature search on Medline, EMBASE, Web of Science, Scopus, CINAHL, PsycInfo, and Cochrane Library databases before November 2021. The following concepts were searched using subject headings and keywords as needed "aromatherapy," "alcohol," "ethylic alcohol," "ethanol," "isopropyl alcohol," "emesis," "chemotherapy-induced," "pregnancy," "hyperemesis gravidarum," "motion sickness," "emetics," "antiemetics," "inhalation," and "inhale." Searches were not limited to a specific language. The bibliographies of identified articles were also manually searched. Two authors independently assessed the included studies for risk of bias. Thirteen randomized controlled trials out of 158 studies identified met the inclusion criteria, with a total of 1253 participants. Twelve studies were conducted in the postoperative anesthesia care unit and two studies were performed in the emergency department setting. Four studies were double blinded, one was single blind, and eight were open label. Three studies assessed the use of inhaled IPA for prevention, whereas 10 studies evaluated its use in the treatment of nausea and vomiting. Seven studies reported IPA to be more effective, four studies reported no difference, and two studies reported IPA to be ineffective. Participant satisfaction was high overall, regardless of intervention received. No adverse effects were reported. The overall quality of evidence was low. There is a lack of strong evidence to support the use of inhaled IPA in the management of nausea and vomiting. Additional trials are warranted to confirm this finding and to further explore the use of inhaled IPA in various populations and settings.
Topics: Pregnancy; Female; Humans; 2-Propanol; Single-Blind Method; Nausea; Antiemetics; Vomiting
PubMed: 36178929
DOI: 10.1089/jpm.2022.0332 -
Multiple Sclerosis and Related Disorders Dec 2022Cognitive impairment is a common manifestation of multiple sclerosis (MS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairment is a common manifestation of multiple sclerosis (MS).
OBJECTIVE
To assess by systematic review and meta-analysis available evidence regarding the impact of nabiximols oromucosal spray on cognition in patients with MS.
METHODS
A systematic literature search of clinical studies (all types, any comparator) that measured cognitive function in patients with MS spasticity treated with nabiximols. Meta-analysis for cognitive endpoints was not possible due to heterogenous measurement instruments and outcomes. Meta-analysis was performed for adverse events (AEs) of special interest (cognition disorders) reported in randomized controlled trials (RCTs) of nabiximols versus placebo in patients with MS (with or without spasticity). Certainty of evidence and risk of bias were assessed.
RESULTS
Seven clinical studies (three RCTs) directly assessing cognitive function were included in the qualitative analysis. There was no consistent evidence to suggest that nabiximols causes cognitive impairment as assessed by a range of specific psychometric instruments across cognitive domains. Thirteen double-blind, placebo-controlled RCTs (nabiximols, n = 964; placebo, n = 904) were included in the meta-analysis of cognitive AEs. Most cognitive AEs (30 of 32 events, 93.8%) reported with nabiximols in MS patients occurred with not in-label use, i.e., dosage >12 sprays per day and/or not administered primarily for treatment of spasticity.
CONCLUSIONS
Within the limitations of the review, we can conclude that no detrimental effects of nabiximols on cognitive function were observed in patients with MS spasticity during up to 12 months follow-up and that cognitive AEs were rare and occurred only when nabiximols was not used according to its approved label.
Topics: Humans; Treatment Outcome; Cannabidiol; Dronabinol; Muscle Spasticity; Multiple Sclerosis; Drug Combinations; Cognition; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36174323
DOI: 10.1016/j.msard.2022.104173 -
Frontiers in Pharmacology 2022In China, Franch. (Chinese name: Huanglian) prescriptions (HLPs) are prominent hypoglycemic agents used in glycemic control. However, the curative effect of HLPs as...
In China, Franch. (Chinese name: Huanglian) prescriptions (HLPs) are prominent hypoglycemic agents used in glycemic control. However, the curative effect of HLPs as adjunctive therapies for type 2 diabetes mellitus (T2DM) has not been evaluated. Based on a systematic review and a meta-analysis, this study was conducted to assess the effects of HLPs combined with metformin as a reinforcing agent for T2DM. A total of 33 randomized controlled trials (RCTs) reporting on 2,846 cases concerning the use of HLPs in the treatment of T2DM were identified from the China National Knowledge Infrastructure (CNKI), Weipu (VIP), Wanfang, PubMed, Cochrane Library, and EMBASE databases. Primary outcomes included fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin, type A1c (HbA1c), fasting serum insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and gastrointestinal dysfunction (GD). Continuous data were expressed as mean differences (MDs) with 95% confidence intervals (CIs). The methodological quality of the included RCTs was assessed by Cochrane evidence-based medicine systematic evaluation. Statistical analysis was performed using the Review Manager and Stata software. The required information size and treatment benefits were evaluated by trial sequential analysis (TSA). The quality of evidence was rated using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The results revealed that HLPs are beneficial to improve the following: FBG (MD = -1.16%, 95% CI: -1.24 to -1.07), 2hPG (MD = -1.64%, 95% CI: -1.84 to -1.43), HbA1c (MD = -0.78%, 95% CI:-0.96 to -0.60), FINS (MD = -1.94%, 95% CI: -2.68 to -1.20), HOMA-IR (MD = -0.77%, 95% CI: -1.28 to -0.27), TC (MD = -0.70%, 95% CI: -1.00 to -0.39), TG (MD = -0.57%, 95% CI: -0.74 to -0.40), LDL-c (MD = -0.70%, 95% CI: -0.97 to -0.43), and HDL-c (MD = -0.21%, 95% CI: -0.32 to -0.10) for patients with T2DM. The funnel plot, Egger's test, and trim-and-fill method indicated a moderate publication bias in the results. The TSA showed that the required sample size of HLPs in improving FBG, 2hPG, HbA1c, FINS, HOMA-IR, TC, TG, LDL-c, and HDL-c could sufficiently draw reliable conclusions. GRADE assessment revealed that the quality of the evidence for the effectiveness of HLPs in improving FBG was moderate, but the quality of evidence for 2hPG, HbA1c, FINS, HOMA-IR, TC, TG, LDL-c, and HDL-c was low, and for GD was very low. The systematic review and meta-analysis suggested that HLPs were beneficial for achieving glycemic control. However, HLPs recommended for T2DM patients have yet to be confirmed because of the poor methodological quality of some trials. Therefore, more RCTs with multicenter and double-blind designs are needed to assess the efficacy of HLPs for patients with T2DM.
PubMed: 36160405
DOI: 10.3389/fphar.2022.956313 -
Frontiers in Pharmacology 2022Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA)...
Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS. A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075). Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MD = -0.42, 95% CI (-0.47, -0.37), five trials, < 0.00001; GEDM + CM for AIS on NIHSS: MD = -1.02, 95% CI (-1.51, -0.52), four trials, < 0.0001]; GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MD = -0.40, 95% CI (-0.54, -0.26), < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MD = -3.93, 95%CI (-7.72, -0.14), = 0.04]; GBDP in patients treated with CM; GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs. This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.
PubMed: 36120362
DOI: 10.3389/fphar.2022.933140 -
Journal of the American Heart... Sep 2022Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular... (Meta-Analysis)
Meta-Analysis
Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.
Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.
Topics: Anticholesteremic Agents; Apolipoproteins; Cholesterol; Cholesterol, LDL; Dicarboxylic Acids; Double-Blind Method; Ezetimibe; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36073669
DOI: 10.1161/JAHA.122.025551 -
International Journal of Sport... Nov 2022The aim of this study was to conduct a systematic review and meta-analysis of the effects of short-term creatine supplementation on repeated sprint ability. Fourteen... (Meta-Analysis)
Meta-Analysis
The aim of this study was to conduct a systematic review and meta-analysis of the effects of short-term creatine supplementation on repeated sprint ability. Fourteen studies met the inclusion criteria of adopting double-blind randomized placebo-controlled designs in which participants (age: 18-60 years) completed a repeated sprint test (number of sprints: 4 < n ≤ 20; sprint duration: ≤10 s; recovery duration: ≤90 s) before and after supplementing with creatine or placebo for 3-7 days in a dose of ∼20 g/day. No exclusion restrictions were placed on the mode of exercise. Meta-analyses were completed using random-effects models, with effects on measures of peak power output, mean power output, and fatigue (performance decline) during each repeated sprint test presented as standardized mean difference (δ), and with effects on body mass and posttest blood lactate concentration presented as raw mean difference (D). Relative to placebo, creatine resulted in a significant increase in body mass (D = 0.79 kg; p < .00001) and mean power output (δ = 0.61; p = .002). However, there was no effect of creatine on measures of peak power (δ = 0.41; p = .10), fatigue (δ = 0.08; p = .61), or posttest blood lactate concentration (D = 0.22 L/min; p = .60). In conclusion, creatine supplementation may increase mean power output during repeated sprint tests, although the absence of corresponding effects on peak power and fatigue means that more research, with measurements of intramuscular creatine content, is necessary to confirm.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Creatine; Exercise Test; Lactic Acid; Fatigue; Dietary Supplements; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36041731
DOI: 10.1123/ijsnem.2022-0072 -
Gynecological Endocrinology : the... Oct 2022Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including... (Meta-Analysis)
Meta-Analysis
Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including PubMed, EMBASE, Medline, Web of science, China national knowledge internet and Wanfang database up to 31 October 2021 were searched, and randomized controlled trials (RCTs) of BZA/CE for menopausal symptoms were included. Seven RCTs involving 5431 patients were included in this study. Compared with placebo group, there were significantly reduce in daily number of hot flushes, daily number of moderate or severe hot flushes, the percentages of parabasal cells and the time to fall sleep when patients treated with BZA/CE. Besides, there were significant improvement in sleep disturbance and total MENQOL. However, no significant improvements in sleep adequacy were observed in the three groups. Furthermore, BZA 20 mg/CE 0.625 mg was more effective than BZA 20 mg/CE 0.45 mg in improving the menopausal symptoms. Therefore, both bazedoxifene 20 mg plus conjugated estrogens 0.45 mg and bazedoxifene 20 mg plus conjugated estrogens 0.625 mg could significantly improve the menopause-related symptoms and MENQOL in postmenopausal women, and the curative effects of BZA 20 mg/CE 0.625 mg were better than that of BZA 20 mg/CE 0.45 mg. These findings need to be further confirmed by more high-quality RCTs.
Topics: Female; Humans; Estrogens, Conjugated (USP); Postmenopause; Selective Estrogen Receptor Modulators; Quality of Life; Double-Blind Method; Hot Flashes; Estrogens
PubMed: 36036169
DOI: 10.1080/09513590.2022.2117294 -
The International Journal of... Dec 2022Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.
METHODS
We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.
RESULTS
Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.
CONCLUSIONS
Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Piperazines; Sulfides; Randomized Controlled Trials as Topic; Cognitive Dysfunction; Treatment Outcome; Double-Blind Method
PubMed: 35981958
DOI: 10.1093/ijnp/pyac054