Safety Of Different Types Research Articles

Retrospective analysis of carcinogenicity assessments within FDA-notified GRAS determinations.

Frameworks have been developed to standardize the assessment of carcinogenic potential in the pharmaceutical and agrochemical industries, building upon decades of research. Carcinogenicity is also evaluated during the safety evaluation of food substances, using a comprehensive approach unique to each substance. To better understand these approaches, a retrospective assessment was conducted on the publicly available database of substances notified to the United States Food and Drug Administration (US FDA) as being Generally Recognized As Safe (GRAS). The data contained within these GRAS notifications (GRNs) were reviewed for the methods used to evaluate carcinogenic potential (genotoxicity studies, 2-year bioassays, other pre-clinical animal studies) to identify patterns that could provide an understanding of how this assessment has been conducted for different categories of food substances. While different approaches to the safety evaluation were required to adapt to the unique food substances, the data in all notifications supported the conclusion of safety. The evaluation of food substances for carcinogenic potential must consider all available data, including identifying the need for when more data must be generated to support an evaluation. Due to the complexity of substances used in food, ranging from defined chemical entities to minimally processed agricultural commodities to live microorganisms, the approach to conducting the safety evaluation of food substances must be able to adapt to the most relevant scientifically supported approach. This paper illustrates the data commonly used to support the safety of different types of food substances and proposes an approach familiar to other product sectors.

Outcomes of Oral Anticoagulation in Atrial Fibrillation Patients With or Without Comorbid Vascular Disease: Insights From the GARFIELD-AF Registry

BackgroundMany patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. MethodsAdults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. ResultsOf 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. ConclusionsAtrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.

Prognosis of coronary heart disease after percutaneous coronary intervention: a bibliometric analysis over the period 2004–2022

BackgroundAs the complexity and diversity of the percutaneous coronary intervention (PCI) are being explored and reported, burgeoning research has progressed in this field. However, there is no comprehensive analysis available on PCI-related studies published in the literature. This study aimed to analyze and visualize the changes of scientific output regarding prognosis of coronary heart disease (CHD) after PCI over the past 20 years and to reveal the knowledge domain and development trends in this field by using CiteSpace software.MethodsRelevant articles published over the period 2004–2022 were retrieved from the Web of Science Core Collection database. After manual selection, qualified documents were included and recorded with the information of their title, abstract, keyword, author, descriptor, citation, identifier, publishing year and publishing organization. We transferred the data to CiteSpace V5.8.R2 (Version 5.8.R2) to draw knowledge maps and to conduct co-occurrence analysis, cluster analysis, timeline analysis, burst term detection and citation analysis.ResultsA total of 14,699 literature records were found relating prognosis of CHD after PCI in the past 20 years (2004–2022), including 14,212 original articles and reviews, and they were published in 153 different journals. Publication production has increased annually and a total of 1182 authors, 796 institutes and 147 countries have contributed to these publications. Moreover, the most representative author was Gregg W Stone from the CardioVascular Research Foundation (CVRF) with 368 publications, whose team mainly focused on exploring the efficacy and safety of revascularization and the characteristics of susceptible population. The global productivity ranking was led by the USA with 3326 published papers, followed by Italy (n = 1355), Japan (n = 1080), China (n = 1075) and Germany (n = 937). And the keywords of these publications were “percutaneous coronary intervention” (n = 2271), “outcome” (n = 1756), “mortality” (n = 1730) and “impact” (n = 1334). Other commonly-used words were “predictor” (n = 1324), “intervention” (n = 1310), “angioplasty” (n = 1299), “risk” (n = 1144), “acute myocardial infarction” (n = 1136) and “artery disease” (n = 1098). Cluster analysis showed that 15 high connected clusters were generated with a modularity Q of 0.831 and a weighted mean silhouette of 0.9388 by applying the log-likelihood ratio algorithm, and the top 5 clusters were #0 optical coherence tomography, #1 dual antiplatelet therapy, #2 bleeding, #3 clopidogrel and #4 thrombus aspiration. Furthermore, the frontiers in the field of prognosis of CHD after PCI mainly involved “decision making”, “reperfusion”, “angioplasty”, “balloon”, “unstable angina”, “dual antiplatelet therapy”, “cardiac surgical score”, “restenosis”, “reperfusion”, “thrombolytic therapy”, etc.ConclusionsTo sum up, efficacy and safety of different types of stents, the risk factors of restenosis and thrombotic events after PCI, early risk assessment, and secondary prevention and complications of patients with CHD after PCI were research hotspots and frontier topics in the area by bibliometric analysis. The results could provide a comprehensive overview of the research hotspots and frontier topics relating prognosis of CHD after PCI, promoting a better understanding of the knowledge domain and development trends in this field during the past 20 years.

Postauricular versus systemic use of steroids for sudden hearing loss: A systematic review and meta-analysis of randomized controlled trials.

Sudden sensorineural hearing loss (SSNHL) can be debilitating and is one of the most common otological diseases. Steroids play an important role in its treatment. There are many ways to administer steroids, and the efficacy and safety of different administration routes remain unclear. This meta-analysis aimed to investigate the effect and safety of different types of steroid delivery administration for the treatment of SSNHL. We searched the Weipu, Wanfang, Chinese Biomedical Literature, National Knowledge Infrastructure, Web of Science, Embase and PubMed databases for randomized controlled trials (RCTs) on glucocorticoid treatments for SSNHL to compare the efficacy of postauricular injection and systemic steroid administration. Review Manager 5.4 software was used for data synthesis, which included the recovery rate (RR) of reported hearing improvement and change level in pure-tone audiometry (PTA). Subgroup analyses were performed based on different drugs, basic treatment, initial PTA, drug administration methods, onset time, and treatment course. Stata 15.1 software was used for analyses of publication bias and sensitivity. Our meta-analysis included 38 studies involving 3609 patients with SSNHL. In all included studies, the risk difference (RD) using reported improvement as an outcome measure was 0.12 for postauricular injection administration compared with systemic therapy (95% confidence interval [CI] = 0.008, 0.16, P < .00001, I2 = 59%). When examining PTA changes as an outcome measure (19 studies), the mean difference was 6.06 (95% CI = 3.96, 8.16, P < .00001, I2 = 70%). The RD for hearing improvement was compared among different factors, and the results showed that postauricular injection is superior to systemic steroid administration. Postauricular injection may be safer and more effective treatment than systemic therapy as a treatment for SSNHL.

Network meta-analysis for comparative effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy: A protocol and Bayesian network meta-analysis

Chemotherapy-induced peripheral neuropathy (CIPN) reduces the quality-of-life, affects recovery, and increases the risk of chemotherapeutic failure. Acupuncture may be effective in treating CIPN. This study aims to evaluate the effectiveness and safety of different types of acupuncture through a systematic review and a network meta-analysis. Therefore, the objective of this study is to indicate the relative efficacy and safety among various types of acupuncture for CIPN via a network meta-analysis (NMA) and systematic review. Six electronic databases, namely, Excerpta Medica Database [Embase], PubMed, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, and Wanfang Med Online will be searched for publications from 2010 to 2022. All relevant randomized controlled trials (RCTs) meeting the eligible criteria will be included. The primary outcome is the brief pain inventory score, including a brief pain inventory-short form, and autonomic nerve symptoms. Secondary outcomes include the quality-of-life assessment of anxiety, depression, and sleep of people with CIPN and adverse events. Reviewers will conduct processes for study selection, data extraction, and risk-of-bias assessment. Stata version 15.0 will be used to perform pairwise and Bayesian network NMA. Each included study will be assessed for bias using the Revised Cochrane risk-of-bias tool for randomized trials. A funnel plot will show publication bias. We assess the benefits and drawbacks of various acupuncture-related therapies, rank the efficacy of various acupuncture-related therapies for treating CIPN, and describe the best approaches or combinations of acupuncture interventions based on available data. This study will contribute to data on the safety and efficacy of acupuncture-related therapies for treating CIPN and will help clinicians better select acupuncture treatment types to deal with the different clinical problems of CIPN. There is no need for ethics approval for this systematic review and meta-analysis. The results will be published in a peer-reviewed journal. CRD42020198388

Savolitinib versus crizotinib for treating MET positive non-small cell lung cancer.

The c-MET protein, encoded by the mesenchymal-epithelial transition factor (MET) gene, can regulate cell proliferation, migration and invasion. Studies have shown that it is one of the essential driver genes for non-small cell lung cancer (NSCLC). Currently, several clinical studies have carried out objective assessments on the efficacy and safety of different types of MET tyrosine kinase inhibitors (TKIs). However, direct cross-sectional comparisons between different agents are still not available. Our study was a single-center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. We explored the efficacy and safety of crizotinib versus savolitinib in patients with METex14 skipping and MET amplification, separately. Patients with METex14 skipping (median PFS=10.7months) had a better clinical response to MET TKIs than MET amplification patients (median PFS=4.1months). In the METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib (p > 0.05). In the MET amplification subgroup, savolitinib (median PFS=7.1months) demonstrated a better progression-free survival benefit than crizotinib (median PFS=1.4months), p=0.05. The most common adverse effects of both MET TKIs were peripheral edema (41.2%), gastrointestinal reactions (23.5%), and liver injury (14.7%). The incidence rate of peripheral edema was higher in savolitinib than crizotinib. In METex14 skipping NSCLC patients,the efficacy of savolitinib and crizotinib did not show significant difference. In MET amplification patients, savolitinib showed better efficacy than crizotinib.

Antiplatelet therapy in patients with myocardial infarction with non-obstructive coronary arteries: A clinical perspective.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous group of diseases with different pathological mechanisms, and it is uncertain whether the classical secondary prevention and treatment strategies for myocardial infarction in obstructive coronary artery disease (MI-CAD) are appropriate for patients with MINOCA. Therefore the choice of antiplatelet agents and the therapeutic effect may vary depending on the etiology and pathophysiological mechanisms of MINOCA. This requires our clinical and scientific researchers to properly design prospective studies to explore the pathophysiology of MINOCA and its corresponding etiology in greater depth, so as to understand the effectiveness and safety of medical therapies for different etiologies of MINOCA. Although the current observational studies do not show an obvious beneficial effect of antiplatelet therapy on MINOCA. We are eager to conduct specific prospective randomized controlled trials of antiplatelet agents to assess the specificity, efficacy and safety of different types of antiplatelet agents in patients with MINOCA of different etiologies.

Efficacy and Safety of COVID-19 Vaccination in Older Adults: A Systematic Review and Meta-Analysis.

Objective: To analyze the differences in efficacy and safety of different types of novel coronavirus pneumonia (COVID-19) vaccines in different age groups (young adults and elderly). Methods: Randomized controlled trials (RCTs) on COVID-19 vaccine in PubMed, Embase, Web of Science, and Cochrane library were searched by computer, and eight eligible studies were analyzed. Meta-analysis was performed using Stata 16.0 and RevMan5.4 software. Results: The mean geometric titer (GMT) of the virus in the elderly was significantly higher than that in the placebo group (SMD = 0.91, 95% CI (0.68, 1.15), p < 0.01), presenting no obvious difference compared with the young adults (SMD = 0.19, 95% CI (0.38, 0.01), p = 0.06). Meanwhile, the effect of multiple vaccinations was better than that of single vaccination (SMD = 0.83, 95% CI (0.33, 1.34), p < 0.01). However, the number of adverse events (AEs) in the elderly was lower than that in the young adults (OR = 0.35, 95% CI (0.29, 0.42), p < 0.01). Conclusions: The immunization effect of COVID-19 vaccine in the elderly is obvious, especially after multiple vaccinations, and the incidence of AEs in the elderly is low, which proves that the vaccination of the elderly is safe and effective.

Comparison of Different Types of Drug-Eluting Stents for De Novo Long Coronary Artery Lesions.

Outcomes of percutaneous coronary intervention for diffuse long lesions remain relatively unfavorable. Prior clinical trials investigated the relative efficacy and safety of different types of drug-eluting stents (DES) in long lesions. This study sought to compare the relative performance of different types of DES for de novo long (≥25mm) coronary artery lesions. Using a pooled analysis of individual data of 1,450 patients from 3 randomized clinical trials, we compared angiographic and clinical outcomes of 5 different types of DES: 224 patients with cobalt-chromium everolimus-eluting stents (EES), 255 with platinum-chromium EES, 250 with Resolute zotarolimus-eluting stents, 245 with biodegradable polymer biolimus-eluting stents, and 476 with first-generation sirolimus-eluting stents (SES). The primary endpoint was in-segment late lumen loss at 9months. The primary endpoint was not significantly different between 4 second-generation DES and 1 first-generation SES (0.17 ± 0.41mm in cobalt-chromium EES; 0.11 ± 0.37 in platinum-chromium EES: 0.14 ± 0.38 in Resolute zotarolimus-eluting stents; 0.14 ± 0.38 in biodegradable polymer biolimus-eluting stents; or 0.10 ± 0.37 in SES, respectively, overall P = 0.38). Also, there were no significant between-group differences with respect to death, myocardial infarction, target-vessel revascularization, or stent thrombosis at 12months. In the multiple treatment propensity-score analysis, the risk of angiographic and clinical outcomes was also similar among several types of DES. In this patient-level pooled analysis, several second-generation DES showed similar angiographic and clinical outcomes in patients with de novo long coronary lesions. (Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-III [LONG-DES-III]; NCT01078038; Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV [LONG-DES-IV]; NCT01186094; and Everolimus-eluting [PROMUS-ELEMENT] vs. Biolimus A9-Eluting [NOBORI] Stents for Long-Coronary Lesions [LONG-DES-V]; NCT01186120).

Breast cancer recurrence after immediate and delayed postmastectomy breast reconstruction-A systematic review and meta-analysis.

BackgroundOncological safety of different types and timings of PMBR after breast cancer remains controversial. Lack of stratified risk assessment in literature makes current clinical and shared decision‐making complex. This is the first systematic review and meta‐analysis to evaluate differences in oncological outcomes after immediate versus delayed postmastectomy breast reconstruction (PMBR) for autologous and implant‐based PMBR separately.MethodsA systematic literature search was performed in MEDLINE, Cochrane Library, and Embase. The Cochrane Collaboration Handbook and Meta‐analysis Of Observational Studies in Epidemiology checklist were followed for data abstraction. Variability in point estimates attributable to heterogeneity was assessed using I 2‐statistic. (Loco)regional breast cancer recurrence rates, distant metastasis rates, and overall breast cancer recurrence rates were pooled in generalized linear mixed models using random effects.ResultsFifty‐five studies, evaluating 14,217 patients, were included. When comparing immediate versus delayed autologous PMBR, weighted average proportions were: 0.03 (95% confidence interval [CI], 0.02–0.03) versus 0.02 (95% CI, 0.01–0.04), respectively, for local recurrences, 0.02 (95% CI, 0.01–0.03) versus 0.02 (95% CI, 0.01–0.03) for regional recurrences, and 0.04 (95% CI, 0.03–0.06) versus 0.01 (95% CI, 0.00–0.03) for locoregional recurrences. No statistically significant differences in weighted average proportions for local, regional and locoregional recurrence rates were observed between immediate and delayed autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrences after autologous PMBR, and of all outcome measures after implant‐based PMBR.ConclusionsDelayed autologous PMBR leads to similar (loco)regional breast cancer recurrence rates compared to immediate autologous PMBR. This study highlights the paucity of strong evidence on breast cancer recurrence after specific types and timings of PMBR.Lay summery Oncologic safety of different types and timings of postmastectomy breast reconstruction (PMBR) remains controversial.Lack of stratified risk assessment in literature makes clinical and shared decision‐making complex.This meta‐analysis showed that delayed autologous PMBR leads to similar (loco)regional recurrence rates as immediate autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrence after autologous PMBR, and of all outcome measures after implant‐based PMBR.Based on current evidence, oncological concerns do not seem a valid reason to withhold patients from certain reconstructive timings or techniques, and patients should equally be offered all reconstructive options they technically qualify for.

PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis

BackgroundThe Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors.MethodsSeveral databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events.ResultsOverall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72–0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04–1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90–0.99).ConclusionsIn consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.

Incidence of adverse reactions to COVID-19 vaccination

Objective: To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019 (COVID-19) vaccination. Methods: We systematically searched PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP Database from the inception of each database to August 31, 2021. Randomized controlled clinical trials (RCTs) on the safety of different types of COVID-19 vaccines were retrieved and analyzed. A random or fixed-effects model was used with an odds ratio as the effect size. The quality of each reference was evaluated. The incidence of the adverse reactions of the placebo group and the vaccination group was compared. Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses. Results: A total of 13 articles were included, with 81 287 subjects. Compared with the placebo group, the vaccination group showed a higher combined risk ratio (RR) of total adverse reactions (RR=1.67, 95% CI: 1.46-1.91, P&lt;0.01), local adverse reactions (RR=2.86, 95% CI: 2.11-3.87, P&lt;0.01), systemic adverse reactions (RR=1.25, 95% CI: 0.92-1.72, P=0.16), pain (RR=2.55, 95% CI: 1.75-3.70, P&lt;0.01), swelling (RR=4.16, 95% CI: 1.71-10.17, P=0.002, fever (RR=2.34, 95% CI: 1.84-2.97, P&lt;0.01), fatigue (RR=1.36, 95% CI: 1.32-1.41, P&lt;0.01) and headache (RR=1.22, 95% CI: 1.18-1.26, P&lt;0.01). The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines (inactivated viral vaccines, mRNA vaccines and adenovirus vector vaccines) was higher than that of the placebo group, and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant (P&lt;0.01). The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group (P&lt;0.01). Conclusions: COVID-19 vaccines have a good safety, among which adenovirus vector vaccine has the highest incidence of adverse reactions. Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions, but the symptoms are mild and can be relieved by themselves. Our meta-analysis can help boost global awareness of vaccine safety, promote mass vaccination, help build regional and global immune barriers and effectively curb the recurrency of COVID-19.

Comparison of different embolic particles for superior rectal arterial embolization of chronic hemorrhoidal bleeding: gelfoam versus microparticle

BackgroundWhether different embolic particles with comparable diameter lead to similar beneficial effects in endovascular embolization of hemorrhoidal disease remains to be established. We sought to evaluate the efficacy and safety of different types of agents for superior rectal arterial embolization (SRAE) in patients with bleeding hemorrhoids.MethodsPatients with recurrent episodes of internal hemorrhoidal bleeding and chronic anemia treated by SRAE in three tertiary hospitals between March 2017 and June 2020 were retrospectively evaluated. The patients were divided into two study groups based on the embolic materials: embolization with coils (2–3 mm) + gelfoam particles at 350–560 μm (Group A, n = 23), embolization with coils (2–3 mm) + microparticles at 300–500 μm (Group B, n = 18). The technical success, preliminary clinical efficacy (percentage of patients without hematochezia), postoperative complications and short-term follow-up outcomes were analysed.ResultsA total of 41 patients (27 males) with symptomatic hemorrhoids were included in the study, mean age was 47 ± 12 years (range 25–72). 39% (16) patients with grade II hemorrhoids while 61% (25) patients with grade III. The technical success rate of the embolization procedure was 100%, and the preliminary clinical efficacy (87.0% vs 88.9%) showed no significant difference between the 2 groups (p = 0.098). No patients reported post-procedural and short-term serious complications, such as infection, intestinal ischemia or massive hemorrhage during the follow-up period (range 6–15 months).ConclusionsBoth gelfoam particles and microparticles with comparable diameter in the endovascular treatment of hemorrhoidal bleeding demonstrated similarly good short-term efficacy and safety profile.

Variability of CYP2C8 Polymorphisms in Three Jordanian Populations: Circassians, Chechens and Jordanian-Arabs.

CYP2C8 is a member of Cytochrome P450 enzymes system. It plays an important role in metabolizing a wide range of exogenous and endogenous compounds. CYP2C8 is involved in the metabolism of more than 100 drugs, typical substrates include: anticancer agents, antidiabetic agents, antimalarial agents, lipid lowering drugs and many others that constitute 20% of clinically prescribed drugs. Genetic variations of CYP2C8 have been reported with different frequencies in different populations. These genetic polymorphisms can lead to differences in the efficacy and safety of different types of medications metabolized by CYP2C8. The aim of this study was to investigate the allele frequencies of CYP2C8*3 (rs10509681 and rs11572080) and CYP2C8*4 (rs1058930) polymorphisms in three populations living in Jordan; Circassians and Chechens and Jordanian-Arabs and compare those frequencies with other populations. A total of 200 healthy Jordanians, 93 Circassians and 88 Chechens were included in this study. Genotyping of CYP2C8*3 and CYP2C8*4 polymorphisms was done by using polymerase chain reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP). Using the Chi-square test, we found that the prevalence of CYP2C8*3 and *4 among the three populations were significantly different. Moreover, the mutant allele CYP2C8*3 (416A) was only detected in the Jordanian-Arab population with an allele frequency of 0.082, while the mutant allele CYP2C8*4 (792G) was detected with frequencies of 0.065, 0.122, 0.017 in Jordanian-Arabs, Circassians and Chechens, respectively. As our results show, CYP2C8*3 was undetectable in our Circassians and Chechens samples, on the other hand, Circassians had the highest allele frequency of CYP2C8*4 compared to Chechens and Jordanian-Arabs. These genetic variations of the gene encoding the CYP2C8 drug metabolizing enzymes can lead to clinical differences in drug metabolism and ultimately variations in drug effectiveness and toxicities. This study provides evidence for the importance of personalized medicine in these populations and can be the foundation for future clinical studies.

Complementary and Alternative Therapies for Pregnant Women Suffering from Constipation: A Systematic review

Background: Constipation is one of the most common gastrointestinal symptoms in pregnant women.&#x0D; Purpose: This study was aimed at determining the effects of complementary and alternative therapy methods on the symptoms of pregnancy-related constipation.&#x0D; Search strategy: The authors performed a systematic search according to PRISMA&#x0D; guidelines. The database Web of Science, Scopus, EMBASE, CENTRAL, national databases were screened to reach studies published from January 2010 to March 2020 with restriction to human studies in English or Turkish language. The quality of the studies included in the study was assessed with the measurement tool proposed in the JADAD, JBI, and Observational Open-Label Studies scales.&#x0D; İnclusion criteria: Electronic searches were conducted in PubMed using the keywords constipation “pregnancy” or pregnant woman and “acupuncture” or “acupressure” or&#x0D; “massage” or “herbal medicine” or “aromatherapy” or “music therapy” or “homeopathy” or&#x0D; “hypnosis” or “meditation” or “feflexology” or “moxibustion” or “ayurvedic Medicine” or “ayurveda” or “Traditional Iranian Medicine&#x0D; Data extraction and analysis: Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors.&#x0D; Findings: 14536 studies were selected and 706 studies were screened based on their titles and abstracts. Seventy-three studies were analyzed in detail to assess whether they were suitable. In order to find a larger number of original articles, of the studies in the reference lists of these studies, those found in the electronical environment were screened, but no studies were found to meet the inclusion criteria. Finally, 3 studies were included in the study.&#x0D; Conclusions: The results demonstrated that herbal medicine and foot reflexology reduced constipation complaints during pregnancy without any side effects. Because the number of studies conducted to investigate the efficacy and safety of different types of complementary and alternative medicine methods in pregnant women with constipation is very few, more studies should be carried out on the issue.

The effectiveness of different acupuncture therapies for neck pain: A protocol for systematic review and/or network meta-analysis.

Background:Neck pain is common musculoskeletal disorders in adult population. Acupuncture treatment has been widely used for treating neck pain. Nevertheless, previous systematic reviews (SRs) on acupuncture for neck pain remain controversial, and there is no SR for the comparative efficacy and safety of various types of acupuncture. Therefore, this study aims to evaluate and rank the effectiveness and safety of different types of acupuncture for neck pain by SR and network meta-analysis.Methods:Nine databases will be searched, including Ovid-MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure (CNKI), KoreaMed, Korean medical database (KMBASE), Korean Studies Information Service System (KISS), ScienceON, and Oriental Medicine Advanced Searching Integrated System (OASIS) from their inception to July 2021. The primary outcome is the change of pain intensity. A frequentist network meta-analysis will be performed to compare all relative outcomes of different acupuncture methods, using R software. The quality of included randomized controlled trials will be assessed by Cochrane Collaboration “risk of bias” tools and the evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation instrument.Results:The final findings of this network meta-analysis will be published in a recognized journal.Conclusions:Our study will evaluate and compare the effectiveness of various types of acupuncture for neck pain and provide clinicians with best option for what types of acupuncture treatments are effective.Trial registration number:INPLASY202120041

Hematopoietic stem cell transplantation for people with β-thalassaemia.

Thalassaemia is anautosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting ina reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review. To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021. Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review. No relevant trials were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Comparison of clinical outcomes of multiple plastic stents and covered metal stent in refractory pancreatic ductal strictures in chronic pancreatitis- a systematic review and meta-analysis

BackgroundSymptomatic pancreatic duct (PD) strictures in chronic pancreatitis refractory to single plastic stenting are usually managed by placement of multiple plastic stents (MPS). Fully covered self-expanding metallic stents (FCSEMS) have also been used in the management of these patients. However, the overall efficacy and safety of different types of stents is unclear from the currently available studies. We performed this meta-analysis to assess the efficacy and complications from MPS and FCSEMS in patients with PD strictures refractory to treatment with single plastic stents. MethodsSeveral electronic databases were searched for all the studies evaluating the outcome of placement of multiple plastic stents and fully covered metal stents in patients with PD strictures refractory to single plastic stenting. We calculated the Weighted Pooled Ratio (WPR) with Confidence Interval (CI) between the MPS and FCSEMS. ResultsA total of 13 studies (including 2 abstracts) were included in the analysis. MPS were placed in 106 patients and FCSEMS in 192 patients. Improvement in pain after stenting (P = 0.794), risk of recurrence of pain after removal of stent (P = 0.48) and stricture recurrence after stent removal (P = 0.52) were comparable between MPS and FCSEMS. Risk of endoscopic re-intervention was also comparable between metal stents and MPS. However, FCSEMS was associated with overall higher risk of adverse events (P < 0.0001). ConclusionFCSEMS are comparable to multiple plastic stents in the treatment of symptomatic refractory PD strictures. However, use of FCSEMS is associated with increased risk of adverse events.

A comparison of the efficacy and safety of traditional Chinese medicine external treatment for the knee osteoarthritis: A protocol for systematic review and network meta-analysis.

Background:Knee osteoarthritis (KOA), also known as degenerative osteoarthritis, is a common and frequently occurring disease in orthopedics with cartilage degeneration as the pathogenic cause and articular bone hyperplasia as the sign. Many studies have confirmed that KOA can be effectively treated by traditional Chinese medicine (TCM) external treatment. So we take advantage of the method of network meta-analysis to systematically compare the efficacy and safety of different types of TCM external treatment for the KOA.Methods:We will research on external treatment of KOA by traditional Chinese medicine using randomized controlled trials (RCTs) in search database (EMBASE, PubMed, Web of Science, Chinese National Knowledge Infrastructure [CNKI], Weipu database [VIP], Wanfang, and China BioMedical Literature [CBM]). The data and evidence obtained will be processed using Stata 15.0 and WinBUGS 1.4.3.Results:We will evaluate the efficacy and safety of traditional Chinese medicine external treatment for the knee osteoarthritis in this study.Conclusion:This study will provide a new regimen for KOA treatment. It has extremely high reference value.INPLASY registration number:INPLASY2020120001.DOI number: 10.37766/inplasy2020.12.0001.

Safety of COVID-19 vaccine: A meta-analysis

Objective To systematically review the safety of different types of COVID-19 vaccines in the population. Methods Web of Science, PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and CBM databases were electronically searched to collect randomized controlled trials (RCTs) which reported safety of COVID-19 vaccines in population. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 5 RCTs involving 2 431 subjects were included. The results of the meta-analysis showed that COVID-19 vaccines developed more fever symptoms than placebo (RR=2.21, 95%CI 1.38 to 3.54, P=0.000 9). However, there was no significant difference in the incidence of adverse reactions (RR=1.28, 95%CI 0.96 to 1.70, P=0.10), injection site adverse reactions (RR=1.47, 95%CI 0.65 to 3.36, P=0.36) and systemic adverse reactions (RR=0.96, 95%CI 0.78 to 1.17, P=0.66) between two groups. Conclusions Current evidence shows that COVID-19 vaccines are sufficiently safe. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions. © 2021 West China University of Medical Science. All rights reserved.