The Current Status of Clinical Research Involving Microneedles: A Systematic Review

In recent years, a number of clinical trials have been published on the efficacy and safety of drug delivery using microneedles (MNs). This review aims to systematically summarize and analyze the current evidence including the clinical effect and safety of MNs. Three electronic databases, including PubMed, were used to search the literature for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that evaluated the therapeutic efficacy of MNs from their inception to 28 June 2018. Data were extracted according to the characteristics of study subjects; disorder, types, and details of the intervention (MNs) and control groups; outcome measurements; effectiveness; and incidence of adverse events (AEs). Overall, 31 RCTs and seven CCTs met the inclusion criteria. Although MNs were commonly used in skin-related studies, evaluating the effects of MNs was difficult because many studies did not provide adequate comparison values between groups. For osteoporosis treatment, vaccine, and insulin delivery studies, MNs were comparable to or more effective than the gold standard. Regarding the safety of MNs, most AEs reported in each study were minor (grade 1 or 2). A well-designed RCT is necessary to clearly evaluate the effectiveness of MNs in the future.

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Novel Tetracyclines Versus Alternative Antibiotics for Treating Acute Bacterial Infection: A Meta-Analysis of Randomized Controlled Trials

Antibiotics ◽

10.3390/antibiotics8040233 ◽

2019 ◽

Vol 8 (4) ◽

pp. 233 ◽

Cited By ~ 1

Author(s):

Shao-Huan Lan ◽

Wei-Ting Lin ◽

Shen-Peng Chang ◽

Li-Chin Lu ◽

Chih-Cheng Lai ◽

...

Keyword(s):

Adverse Events ◽

Bacterial Infections ◽

Meta Analysis ◽

Controlled Trials ◽

Efficacy And Safety ◽

Control Groups ◽

Randomized Controlled ◽

Significant Difference ◽

Acute Bacterial Infections ◽

And Control

This meta-analysis assessed the efficacy and safety of novel tetracyclines for treating acute bacterial infections. Data from PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, and Embase databases were accessed until 11 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of novel tetracyclines with that of other antibiotics for treating acute bacterial infections were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of eight RCTs were included, involving 2283 and 2197 patients who received novel tetracyclines and comparators, respectively. Overall, no significant difference was observed in the clinical response rate at test of cure between the experimental and control groups (for modified intent-to-treat [MITT] population, risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.99–1.05; for clinically evaluable [CE] population, RR: 1.02, 95% CI: 1.00–1.04; and for microbiological evaluable [ME] population, RR: 1.01, 95% CI: 0.99–1.04). No significant difference in the microbiological response at the end of treatment was observed between the experimental and control groups (for ME population, RR: 1.01, 95% CI: 0.99–1.03; for microbiological MITT population, RR: 1.01, 95% CI: 0.96–1.07). No difference was observed concerning the risk of treatment-emergent adverse events (TEAEs), serious adverse events, and discontinuation of treatment due to TEAEs and all-cause mortality between the two groups. In conclusion, clinical efficacy and safety profile for novel tetracyclines in the treatment of acute bacterial infections were found to be similar to those for other available antibiotics.

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The Effectiveness of Tocilizumab in the Treatment of COVID-19 in Adults: A Meta-Analysis of Randomized Controlled Trials.

10.21203/rs.3.rs-551091/v1 ◽

2021 ◽

Author(s):

Chun Chen ◽

ZeMei Zhou ◽

Jing Zhang

Keyword(s):

Randomized Controlled Trials ◽

Hospital Discharge ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Composite Outcome ◽

Control Groups ◽

Randomized Controlled ◽

Serious Infection ◽

And Control

Abstract Background: Since December 2019, COVID-19 has spread to the world which leads to a global health threat. We aimed to investigate the effectiveness of tocilizumab on COVID-19 patients.Methods: We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and WHO international Clinical Trials Registry Platform (ICTRP) from their inception to March 10, 2021 for randomized controlled trials (RCTs) on tocilizumab supplementation in adults with COVID-19 disease. The primary outcomes were mortality at 28-30 day and 60-day, incidence of mechanical ventilation (MV), composite outcome of death or MV, time to hospital discharge, and intensive care unit (ICU) admissions. A random-effects meta-analysis model was used to pool studies. Results: Eleven studies with a total of 6,579 patients were included in our meta-analysis, of which 3,406 and 3,173 were respectively assigned to the tocilizumab and control groups. Tocilizumab could significantly reduce 28-30 day mortality (RR = 0.89, 95% CI 0.80-0.99, P = 0.04), incidence of MV (RR= 0.79, 95% CI 0.71-0.89, P = 0.0001), composition outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P = 0.0002), time to hospital discharge (HR = 1.30, 95% CI 1.16-1.45, P ＜ 0.00001 ), ICU admissions (RR = 0.64, 95% CI 0.47-0.88, P = 0.006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = 0.02) and events of serious adverse advents (RR = 0.64, 95% CI 0.47-0.86, P = 0.004). There was no significant difference between tocilizumab and control groups in 60-day mortality and adverse events (AEs).Conclusions: Tocilizumab could reduce the short-term mortality, incidence of MV, composite outcome of death or MV, ICU admissions, serious infection and events of serious adverse advents, and shorten the time to hospital discharge in hospitalized patients with COVID-19. The optimal effective dose needs to be confirmed by further studies.

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Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Stroke ◽

10.1161/str.43.suppl_1.a2211 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

James S McKinney ◽

William J Kostis ◽

John B Kostis

Keyword(s):

Statin Therapy ◽

Meta Analysis ◽

Active Group ◽

Controlled Trials ◽

Control Groups ◽

Randomized Controlled ◽

All Cause Mortality ◽

Group A ◽

The Difference ◽

And Control

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.

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Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years

Interventional Neurology ◽

10.1159/000442355 ◽

2016 ◽

Vol 5 (1-2) ◽

pp. 39-50 ◽

Cited By ~ 10

Author(s):

Mohammed Hussain ◽

Mohammad Moussavi ◽

Daniel Korya ◽

Siddhart Mehta ◽

Jaskiran Brar ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Randomized Controlled Trials ◽

Endovascular Therapy ◽

Standard Of Care ◽

Controlled Trials ◽

Control Groups ◽

Randomized Controlled ◽

And Control ◽

Iv Tpa

Background: Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). Objectives: Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). Results: A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. Conclusions: Endovascular therapy combined with IV tPA (in appropriately selected patients) for LVO-related AIS is superior to IV tPA alone. These results support establishing an endovascular therapy in addition to IV tPA as the standard of care for AIS secondary to LVO.

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Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review of Randomized Controlled Trials

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/890950 ◽

2014 ◽

Vol 2014 ◽

pp. 1-16

Author(s):

Ai-ju Liu ◽

Hui-qin Li ◽

Ji-huang Li ◽

Yuan-yuan Wang ◽

Dong Chen ◽

...

Keyword(s):

Systematic Review ◽

Herbal Medicine ◽

Randomized Controlled Trials ◽

Chinese Herbal Medicine ◽

Aspirin Resistance ◽

Current Evidence ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Chinese Herbal

Aspirin resistance (AR) is a prevalent phenomenon and leads to significant clinical consequences, but the current evidence for effective interventional strategy is insufficient. The objective of this systematic review is thus to assess the efficacy and safety of Chinese herbal medicine (CHM) for AR. A systematical literature search was conducted in 6 databases until December 2012 to identify randomized controlled trials (RCTs) of CHM for AR. As a result, sixteen RCTs with a total of 1011 subjects were identified, suggesting that the interests of the medical profession and the public in the use of CHM for AR have grown considerably in the recent years. Tongxinluo capsule and Danshen-based prescriptions were the most frequently used herbal prescriptions, while danshen root, milkvetch root, Leech, and Rosewood were the most frequently used single herbs. Despite the apparent reported positive findings, it is premature to determine the efficacy and safety of CHM for the treatment of AR due to poor methodological quality and insufficient safety data. However, CHMs appeared to be well tolerated in all included studies. Thus, CHM as a promising candidate is worthy of improvement and development for further clinical AR trials. Large sample-size and well-designed rigorous RCTs are needed.

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Music Interventions for Anxiety in Pregnant Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm8111884 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1884 ◽

Cited By ~ 1

Author(s):

Chien-Ju Lin ◽

Yu-Chen Chang ◽

Yu-Han Chang ◽

Yu-Hsuan Hsiao ◽

Hsin-Hui Lin ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Pregnant Women ◽

Meta Analysis ◽

Anxiety Reduction ◽

Controlled Trials ◽

Medical Patients ◽

Music Intervention ◽

Control Groups ◽

Randomized Controlled ◽

And Control

Prenatal anxiety is extremely common and may result in adverse effects on both the mother and the baby. Music interventions have been used to reduce anxiety in various medical patients and in pregnant women during childbirth. This study aims to assess the clinical efficacy of music interventions in women during pregnancy rather than during labor. Seven databases were searched from inception to September 2019 without language restrictions. We included only randomized controlled trials that compared music intervention and control groups for anxiety reduction in pregnant women. We used the revised Cochrane risk-of-bias tool (RoB 2.0) for quality assessment. Finally, 11 studies with 1482 participants were included. The pooled meta-analysis results showed that music interventions significantly decreased anxiety levels (standardized mean difference (SMD), −0.42; 95% confidence interval (CI), −0.83 to −0.02; I2 = 91%). Moreover, subgroup analysis showed that listening to music at home had significant anxiolytic benefits (SMD, −0.28; 95% CI, −0.47 to −0.08; I2 = 0%). However, meta-regression revealed a nonsignificant trend for increase in the anxiety-reducing effects of music interventions with increasing maternal age. In conclusion, music interventions may be beneficial in reducing anxiety and may be applied in pregnant women.

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N-acetylcysteine for radiocontrast-induced nephropathy: Potential role in the emergency department?

CJEM ◽

10.1017/s1481803500009210 ◽

2004 ◽

Vol 6 (04) ◽

pp. 253-258

Author(s):

Elaine Chong ◽

Peter J. Zed

Keyword(s):

Emergency Department ◽

Contrast Media ◽

English Language ◽

Potential Role ◽

Current Evidence ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Search Terms ◽

Adequate Hydration

ABSTRACT Objective: To systematically review the efficacy and safety of N-acetylcysteine (NAC) for the prevention of radiocontrast-induced nephropathy (RIN), and to discuss its potential role in the emergency department. Methodology: We conducted a search of MEDLINE (from 1966 to December 2003), PubMed (1966 to December 2003) and EMBASE (1988 to December 2003) for English-language, prospective, randomized, controlled trials in humans using the search terms N-acetylcysteine, acetylcysteine, radiopharmaceuticals, contrast media, and kidney failure (acute). Results: Five trials support and 4 trials refute the hypothesis that NAC helps prevent RIN. In 7 of 9 trials, oral NAC was administered twice daily for 2 days, on the day before and on the day of the radiocontrast study — a regime not feasible for emergent situations. More recent trials suggest that adequate hydration and lower volumes of radiocontrast, rather than NAC, are more effective ways to prevent RIN. Conclusion: Although further study may be indicated, current evidence does not suggest that NAC has a role in the emergency prevention of RIN.

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Phenoxymethylpenicillin Versus Amoxicillin for Infections in Ambulatory Care: A Systematic Review

Antibiotics ◽

10.3390/antibiotics7030081 ◽

2018 ◽

Vol 7 (3) ◽

pp. 81

Author(s):

Philip Skarpeid ◽

Sigurd Høye

Keyword(s):

Systematic Review ◽

Ambulatory Care ◽

Respiratory Tract Infections ◽

Clinical Effect ◽

Community Acquired Pneumonia ◽

Risk Of Bias ◽

Controlled Trials ◽

Inclusion Criteria ◽

Randomized Controlled ◽

Tract Infections

Most antibiotics are prescribed in primary care, and commonly for respiratory tract infections (RTIs). Narrow-spectrum phenoxymethylpenicillin is the antibiotic of choice for RTIs in the Scandinavian countries, while broader spectrum amoxicillin is used in most other European countries. This review summarizes the knowledge of the effect of phenoxymethylpenicillin versus amoxicillin for infections treated in ambulatory care. We searched PubMed/Medline and Embase for trials comparing the clinical effect of phenoxymethylpenicillin and amoxicillin. The Norwegian Knowledge Centre for the Health Services’ checklist was used to assess risk of bias. In total, 1687 studies were identified, and 18 of these fulfilled the inclusion criteria. One additional study was found as a reference. The randomized controlled trials revealed no significant differences in clinical effect in acute sinusitis (three RCTs), GAS tonsillitis (11 RCTs) and Lyme borreliosis (two RCTs). One RCT on community-acquired pneumonia found amoxicillin to be superior, while the results were conflicting in the two RCTs on acute otitis. The results suggest that non-Scandinavian countries should consider phenoxymethylpenicillin as the treatment of choice for RTIs because of its narrower spectrum. More studies should be conducted on the clinical effect of phenoxymethylpenicillin versus amoxicillin for acute otitis and lower RTIs.

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Erythropoiesis Stimulating Agents (ESA) for the Treatment of Chemotherapy Induced Anemia in Patients with Hemoglobin Levels (Hb) <11g/Dl- a Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood.v112.11.1305.1305 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1305-1305 ◽

Cited By ~ 4

Author(s):

Luciano Paladini ◽

Otavio Clark ◽

Luciana Clark ◽

Tobias Engel ◽

Eneas Faleiros

Keyword(s):

Systematic Review ◽

Relative Risk ◽

Meta Analysis ◽

Mortality Rates ◽

Regulatory Agencies ◽

Controlled Trials ◽

Inclusion Criteria ◽

Control Groups ◽

Randomized Controlled

Abstract Background: Anemia is a frequent condition in patients receiving chemotherapy. ESA are effective to control this condition, but a recently published meta-analysis and warnings from regulatory agencies have pointed to a possible increase in mortality in these patients. Objective: Our aim was to evaluate the safety of ESA when used according to label indications, that is, for patients with chemotherapy induced anemia (rather than cancer induced anemia) with Hb<11g/dl. Methods: We performed a systematic review and meta-analysis of all randomized controlled trials comparing the use of ESA versus placebo (or no treatment) in patients with chemotherapy induced anemia, for whom ESAs where indicated if Hb dropped below 11g/dl. The primary end-point was mortality. We searched several databases, including MEDLINE, EMBASE, LILACS and CENTRAL, among others. All suitable papers were retrived and data regarding the quality of the studies and mortality rates were extracted. Then, we performed a meta-analysis of these trials, using RevMan 5.0 software. Results: □There were 17 studies, with 3788 patients, meeting our inclusion criteria. There were 566 deaths among the 2208 patients that received ESA and 488 among the 1580 on control groups. The meta-analysis showed no increase in mortality rates associated with the use of ESA (Relative risk (RR) = 0.95; IC 95% 0.88 to 1.03; P=0.22). Also, there was no heterogeneity in the analysis (I2=0%), showing that the results were consistent among the studies. When we analised the Hb cut-off point in 10g/dl, the meta-analysis results were similar (RR=0.97; IC 95% 0.87 to 1.07; P 0.52; I2=0%). Conclusion: When used as indicated on label, that is, for patients with chemotherapy induced anemia with Hb<11g/dl ESA are NOT associated with higher mortality rates and remain a safe option for these patients.

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Comparative Efficacy and Safety of Oral P2Y 12 Inhibitors in Acute Coronary Syndrome

Circulation ◽

10.1161/circulationaha.120.046786 ◽

2020 ◽

Vol 142 (2) ◽

pp. 150-160 ◽

Cited By ~ 7

Author(s):

Eliano P. Navarese ◽

Safi U. Khan ◽

Michalina Kołodziejczak ◽

Jacek Kubica ◽

Sergio Buccheri ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Current Evidence ◽

Controlled Trials ◽

Mortality Reduction ◽

Efficacy And Safety ◽

Coronary Syndrome ◽

Randomized Controlled ◽

Significant Mortality

Background: New randomized, controlled trials have become available on oral P2Y 12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. Methods: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. Results: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72–0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75–0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80–1.01] and HR, 0.92 [95% CI, 0.84–1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94–1.29] and 1.12 [95% CI, 0.98–1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67–0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78–1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%–50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01–1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04–1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. Conclusions: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42019155648.

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