-
Journal of Controlled Release :... Aug 2022Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome... (Review)
Review
Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.
Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Drug Delivery Systems; Lipids; Polymers; Solubility
PubMed: 35654170
DOI: 10.1016/j.jconrel.2022.05.048 -
CNS Drugs Aug 2023Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia.... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.
BACKGROUND
Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use.
METHODS
We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis.
RESULTS
Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported.
CONCLUSION
Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Recurrence; Chronic Disease
PubMed: 37490267
DOI: 10.1007/s40263-023-01028-1 -
The Lancet. Global Health Jan 2020About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than... (Meta-Analysis)
Meta-Analysis
BACKGROUND
About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than current human doses, ivermectin is a known teratogen in mammals. During these campaigns with recommended doses, pregnant women might be inadvertently exposed. We therefore aimed to evaluate the existing evidence for serious and non-serious adverse events after ivermectin exposure in pregnant women.
METHODS
For this systematic review and meta-analysis, we searched relevant databases and trial registry platforms on July 15, 2018, for randomised controlled trials (RCTs) and observational studies that reported adverse events in pregnant women. We did not use language or date restrictions. Outcomes of interest were spontaneous abortions, stillbirths, congenital anomalies, and neonatal death (serious adverse events), as well as maternal morbidity, preterm births, and low birthweight (adverse events). The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias Tool for RCTs. We did the meta-analysis of observational studies and RCTs separately. The quality of evidence was assessed using the GRADE approach. The study protocol is registered with PROSPERO, protocol CRD42016046914.
FINDINGS
We identified 147 records, of which only five observational studies and one RCT were included for quantitative analysis; these studies were published between 1990 and 2008, and were done in six African countries. 893 women with 899 pregancy outcomes were included, of whom 496 pregnant women (500 pregnancy outcomes) received ivermectin inadvertently during MDA campaigns in the observational studies and 397 pregnant women (399 pregnancy outcomes) purposely received ivermectin as part of the open-label RCT. No study reported neonatal deaths, maternal morbidity, preterm births, or low birthweight. It is unclear whether exposure to ivermectin during pregnancy increases the risk of spontaneous abortions and stillbirths (odds ratio [OR] 1·15 [95% CI 0·75-1·78] with very low certainty of evidence for the four observational studies and 0·62 [0·18-2·14] with very low certainty of evidence for the RCT) or congenital anomalies (OR 1·69 [95% CI 0·83-3·41] with very low certainty of evidence for the five observational studies and 1·10 [0·07-17·65] with very low certainty of evidence for the RCT).
INTERPRETATION
There is insufficient evidence to conclude on the safety profile of ivermectin during pregnancy. Treatment campaigns should focus additional efforts on preventing inadvertent treatment of pregnant women.
FUNDING
Unitaid.
Topics: Administration, Oral; Adult; Female; Humans; Ivermectin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Teratogens
PubMed: 31839144
DOI: 10.1016/S2214-109X(19)30453-X -
Europace : European Pacing,... Jan 2021Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains... (Meta-Analysis)
Meta-Analysis
AIMS
Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk.
METHODS AND RESULTS
PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian-Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75-0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71-0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60-0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74-1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs.
CONCLUSION
This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Vitamin K
PubMed: 33085751
DOI: 10.1093/europace/euaa242 -
Systematic Reviews Oct 2022This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral...
BACKGROUND
This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs.
METHODS
We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews.
RESULTS
We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients' choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin.
CONCLUSIONS
For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017084263-one deviation; efficacy and safety were from one review.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Genotype; Stroke; Venous Thromboembolism; Warfarin; Review Literature as Topic
PubMed: 36303235
DOI: 10.1186/s13643-022-02098-w -
Rheumatology (Oxford, England) Oct 2021The objective of this study was to identify and summarize the efficacy and safety of systemic glucocorticoids (GCs) and local injections of GC in SpA.
OBJECTIVE
The objective of this study was to identify and summarize the efficacy and safety of systemic glucocorticoids (GCs) and local injections of GC in SpA.
METHODS
PubMed (Medline) and EMBASE were searched with pre-defined keywords for relevant articles in English reporting randomized controlled trials (RCTs), non-randomized interventional studies and non-randomized observational studies of the efficacy of GC in SpA, with five or more patients, for inclusion in a systematic literature review. Local injections of GC included IA and entheseal injections, but excluded SI joint injections.
RESULTS
Out of 9657 records identified, there were 14 studies on the use of systemic GCs in SpA (364 patients), including two RCTs of oral prednisolone. On pooling data from two placebo-controlled RCTs (≤24 weeks), BASDAI 50 was 4.2 times more likely (95% CI: 1.5, 11.5) and Ankylosing Spondylitis Assessment Group (ASAS) 20 was twice more likely (95% CI: 1.1, 3.64) to occur in patients on high-dose oral prednisolone (± taper). Pulsed GCs led to dramatic improvements that lasted a few weeks to a few months. There were no deaths or major adverse events. There were 10 studies (560 patients) on local GCs in SpA. IA injection was effective in achieving a sustained response in 51.5-90% of joints at 6 months. Entheseal injections led to reduced pain and improved US parameters.
CONCLUSION
There were limited studies on either systemic or local injections of GCs in SpA. However, there was good evidence of efficacy with the use of high-dose systemic GCs in the short term (≤6 months) in SpA. Both IA and entheseal injections seemed safe and effective.
Topics: Administration, Oral; Adolescent; Adult; Clinical Trials as Topic; Female; Glucocorticoids; Humans; Injections, Intra-Articular; Male; Middle Aged; Observational Studies as Topic; Prednisolone; Spondylarthritis; Treatment Outcome; Young Adult
PubMed: 33748829
DOI: 10.1093/rheumatology/keab275 -
The Journal of Clinical Pediatric... Sep 2023Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This... (Meta-Analysis)
Meta-Analysis
Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This systematic review and meta-analysis aimed to evaluate the association between JIA and periodontal diseases to facilitate oral health management and periodontal disease prevention in JIA patients. We conducted a comprehensive search of Web of Science, Cochrane Library, PubMed, Embase, Chinese Scientific and Technological Journal (VIP) database, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) up to 30 September 2022, without publication dates or language restrictions. Two authors independently evaluated observational studies for inclusion, and the quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). Continuous variables are presented as mean difference (MD) and 95% confidence interval (CI). Parameters of the simplified oral hygiene index (OHI-S), plaque index (PI), gingival index (GI), clinical attachment loss (CAL), and probing depth (PD) were considered as outcome measures and were compared between JIA patients and healthy controls. The initial search comprised 15 studies with a total of 1537 individuals. The meta-analysis showed the parameters of OHI-S (MD = 0.12, 95% CI: 0.04-0.19, = 0.002), PI (MD = 2.08, 95% CI: 1.67-2.50, < 0.00001), GI (MD = 0.50, 95% CI: 0.17-0.82, = 0.003), CAL (MD = 0.22, 95% CI: 0.01-0.43, = 0.04), and PD (MD = 1.42, 95% CI: 0.08-2.77, = 0.04) in JIA patients were significantly higher than those of healthy controls. All of the included studies were of high quality. This systematic review and meta-analysis showed a possible association between JIA and periodontal diseases. Therefore, it is recommended to continuously pay attention to the periodontal health of JIA patients and fully explore the underlying mechanism.
Topics: United States; Humans; Arthritis, Juvenile; Periodontal Diseases; Administration, Oral; Databases, Factual; Oral Health
PubMed: 37732432
DOI: 10.22514/jocpd.2023.050 -
Therapeutic Advances in Cardiovascular... 2022Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF)... (Meta-Analysis)
Meta-Analysis
AIMS
Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF) undergoing bioprosthetic heart valve replacement or valve repair.
METHODS AND RESULTS
The aim of this meta-analysis was to review the safety and efficacy of DOAC in patients with surgical implanted bioprosthetic heart valves or valve repairs and AF including data from six clinical trials with a total of 1,857 patients. The efficacy and safety data of DOAC and VKA were pooled to perform random-effects meta-analyses using the Mantel-Haenszel method with pooled risk ratios (RR) and 95% confidence interval (CI). A trial sequential analysis (TSA) was performed to assess statistical robustness. Death caused by cardiovascular cause or thromboembolic events were comparable (RR 0.67, 95% CI: 0.42-1.08; = 0.10) as DOAC significantly reduced the risk for major bleeding (RR 0.55, 95% CI: 0.35-0.88; = 0.01) and thromboembolic stroke or systemic embolism rates (RR 0.54, 95% CI: 0.32-0.90; = 0.02). Rates for intracranial bleeding and hemorrhagic stroke (RR 0.27, 95% CI: 0.07-0.99; = 0.05) show a trend toward fewer events in the DOAC group. Outcomes for major or minor bleeding events and all-cause mortality were comparable for DOAC and VKA.
CONCLUSION
Cumulative data analysis reveals that DOAC may provide an effective and safe alternative to VKA in patients with AF after surgically implanted bioprosthetic heart valves or repair with AF. Within a relatively heterogeneous study population, this meta-analysis shows a risk reduction of major bleedings and thromboembolic stroke or systemic embolisms for DOAC.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Thromboembolism
PubMed: 35481366
DOI: 10.1177/17539447221093963 -
International Journal of Cardiology May 2023A systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation electrical cardioversion: An update systematic review and meta-analysis.
BACKGROUND
A systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has not been previously performed. In this setting, we conducted a meta-analysis of studies evaluating DOACs vs vitamin K antagonists (VKA) as common comparator.
METHODS
We searched Cochrane Library, Pubmed, Web Of Science and Scopus databases for all English-only articles concerning studies that have estimated the effect of DOACs and VKA on stroke, transient ischemic attack or systemic embolism (SSE) and major bleeding (MB) events in AF patients undergoing electrical cardioversion. We selected 22 articles comprising 66 cohorts and 24,322 procedures (12,612 with VKA).
RESULTS
During follow-up (studies' median 42 days), 135 SSE (52 DOACs and 83 VKA) and 165 MB (60 DOACs and 105 VKA) were recorded. The overall pooled effects, DOACs vs VKA, was estimated by an univariate Odds Ratio of 0.92 (0.63-1.33; p = 0.645) for SSE and 0.58 (0.41-0.82; p = 0.002) for MB; at bivariate evaluation, adjusting for study type, were respectively 0.94 (0.55-1.63; p = 0.834) and 0.63 (0.43-0.92, p = 0.016). Each single DOAC showed similar and non statistically different results in outcome occurrence compared to VKA as well as when Apixaban, Dabigatran, Edoxaban and Rivaroxaban were indirectly compared to each other.
CONCLUSIONS
In patients undergoing electrical cardioversion, compared to VKA, DOACs have similar thromboembolic protection with lower major bleeding incidence. Single molecule does not show difference in event rate compared to each other. Our findings, provide useful information about safety and efficacy profile of DOACs and VKA.
Topics: Humans; Atrial Fibrillation; Electric Countershock; Anticoagulants; Hemorrhage; Stroke; Embolism; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 36907451
DOI: 10.1016/j.ijcard.2023.03.023 -
Annals of Vascular Surgery Mar 2022PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. Current guidelines recommend at least a single antiplatelet or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. Current guidelines recommend at least a single antiplatelet or anticoagulant agent in symptomatic PAD and lifelong antithrombotic treatment after a revascularization procedure. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with peripheral artery disease (PAD). PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide.
METHODS
The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk ratios (RR) were calculated using the random effects model.
RESULTS
Overall, 10 studies were included in this systematic review and meta-analysis. In 4 studies, 14,257 patients with PAD were enrolled and they were assigned to receive either aspirin (ASA)+/- clopidogrel (N = 5,894) or DOAC+/- anti-platelet (e.g., ASA, clopidogrel) (n = 8,363). Non DOAC users were found to have higher reintervention rates (RR 1.12; 95% CI 1.01-1.24; P = 0.025) compared to DOAC users. No statistically significant difference was observed between the 2 groups, in terms of major bleeding (RR 0.78; 95% CI 0.50-1.23; P = 0.285), all-cause mortality (RR 0.98; 95% CI: 0.83-1.16; P = 0.818) and cardiovascular mortality (RR: 0.99; 95% CI: 0.73-1.333; P = 0.946) mortality. In addition, two real-world studies comparing DOAC with warfarin showed decreased rates of major cardiovascular events in the DOAC group.
CONCLUSION
DOAC use alone or combined with an anti-platelet agent could be associated with lower re-intervention rates, without increasing the risk for adverse bleeding events. However, this study failed to detect any difference in terms of all-cause mortality, MACEs and MALEs between DOAC users and DOAC naïve patients. Future studies are needed to better determine the efficacy and safety of DOACs in patients with PAD.
Topics: Administration, Oral; Anticoagulants; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors
PubMed: 34644644
DOI: 10.1016/j.avsg.2021.07.028