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Abstract Background The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin. Methods We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia. Results The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association. Conclusions Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.

Abstract Background Focal adhesion (FA) family genes have been studied as candidate genes for osteoporosis, but the results of genetic association studies (GASs) are controversial. To clarify these data, a systematic assessment of GASs for FA genes in osteoporosis was conducted. Methods We developed Cumulative Meta-Analysis of GAS-OSTEOporosis (CUMAGAS-OSTEOporosis), a web-based information system that allows the retrieval, analysis and meta-analysis (for allele contrast, recessive, dominant, additive and codominant models) of data from GASs on osteoporosis with the capability of update. GASs were identified by searching the PubMed and HuGE PubLit databases. Results Data from 72 studies involving 13 variants of 6 genes were analyzed and catalogued in CUMAGAS-OSTEOporosis. Twenty-two studies produced significant associations with osteoporosis risk under any genetic model. All studies were underpowered (1 (COL1A1) G2046T (all genetic models), COL1A1 G-1997T (allele contrast and dominant model) and integrin β-chain β3 (ITGB3) T176C (recessive and additive models). In COL1A1 G2046T, subgroup analysis has shown significant associations for Caucasians, adults, females, males and postmenopausal women. A differential magnitude of effect in large versus small studies (that is, indication of publication bias) was detected for the variant COL1A1 G2046T. Conclusion There is evidence of an implication of FA family genes in osteoporosis. CUMAGAS-OSTEOporosis could be a useful tool for current genomic epidemiology research in the field of osteoporosis.

Background: Endovascular aortic repair (EVAR) has conferred an early survival advantage compared to an open surgical repair (OSR) in patients with ruptured abdominal aortic aneurysms (rAAA). However, the long-term survival benefit after EVAR was not displayed among randomized controlled trials (RCTs), whereas many non-RCTs have provided conflicting results. We conducted a time-to-event individual patient data (IPD) meta-analysis on long-term rAAA data., Methods: All studies comparing mortality after EVAR versus OSR for rAAA were included. We used restricted mean survival times (RMSTs) as a measure of life expectancy for EVAR and OSR., Results: A total of 21 studies, including 12,187 patients (4952 EVAR and 7235 OSR) were finally deemed eligible. A secondary IPD analysis included 725 (372 EVAR and 353 OSR) patients only from the 3 RCTs (Immediate Management of the Patient With Rupture : Open Versus Endovascular Repair, Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus and Amsterdam Acute Aneurysm Trial trials). Among all studies, the median survival was 4.20 (95% confidence interval [CI]: 3.70-4.58) years for EVAR and 1.91 (95% CI: 1.57-2.39) years for OSR. Although EVAR presented with increased hazard risk from 4 to 7 years, which peaked at 6 years after the operation, the RMST difference was 0.54 (95% CI: 0.35-0.73; P < 0.001) years gained with EVAR at the end of the 10-year follow-up. IPD meta-analysis of RCTs did not demonstrate significant differences., Conclusions: At 10-years follow-up, EVAR was associated with a 6.5 month increase in life expectancy when compared to OSR after analyzing all eligible studies. Evidence from our study suggests that a strict follow-up program would be desirable, especially for patients with long-life expectancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background-Purpose: Randomized controlled trials (RCTs) are the cornerstone of evidence-based medicine, yet their quality is often suboptimal. The Consolidated Standards of Reporting Trials (CONSORT) statement is a list of advice to upgrade the quality of RCTs. The aim of this study was the assessment of the quality of RCTs for vitamin D supplements in thyroid autoimmunity according to the revised CONSORT 2010 checklist., Methods: Databases were searched for RCTs involving patients with autoimmune thyroid disorders (AITDs) who received vitamin D supplements published from 2011 to 2021. A list of 37-items was used and adherence ≥75% was considered of optimal quality. The primary outcome was the mean CONSORT adherence of studies. Secondary outcomes were the estimation of compliance per CONSORT item and the examination for possible determinants of the reporting quality., Results: Thirteen eligible trials were finally included. The mean compliance was 61.15% ± 14.86%. Only threeof the studies (23%) achieved a good reporting quality (≥75%), while ten (77%) were presented with inadequate reporting (<75%). Randomization and blinding were mainly poorly reported. Impact Factor (IF) of journal was associated with the reporting quality in the univariate analysis [p = 0.033, OR = 1.65, 95%CI = (1316, 1773)]. Sample size (p = 0.067), number of authors (p = 0.118) and number of citations (p = 0.125) were marginally not significant. None of the factors showed significant results in multivariate analysis. Reporting quality and IF were strongly positively correlated [Pearson's r = 0.740, p = 0.04]., Conclusion: This study shows that mean CONSORT adherence of RCTs for Vitamin D supplementation in AITDs is moderate, reflecting that study quality and transparency could be improved with better adherence to CONSORT rules., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: COVID-19 vaccine mandates are considered a controversial public health policy both in public debate and among healthcare workers (HCWs). Thus, the objective of this systematic review is to give a deep insight into HCWs' views and attitudes towards COVID-19 vaccination mandates amid the ongoing COVID-19 pandemic., Methods: A systematic literature search of five databases (PubMed, Scopus, Embase, CINAHL, and Web of Science) was conducted between July 2022 and November 2022. Original quantitative studies that addressed the attitudes of HCWs regarding COVID-19 vaccine mandates were considered eligible for this systematic review. All the included studies (n = 57) were critically appraised and assessed for risk of systematic bias. Meta-analyses were performed, providing a pooled estimate of HCWs' acceptance towards COVID-19 vaccine mandates for: 1. HCWs and 2. the general population., Results: In total, 64% (95% CI: 55%, 72%) of HCWs favored COVID-19 vaccine mandates for HCWs, while 50% (95% CI: 38%, 61%) supported mandating COVID-19 vaccines for the general population., Conclusions: Our findings indicate that mandatory vaccination against COVID-19 is a highly controversial issue among HCWs. The present study provides stakeholders and policy makers with useful evidence related to the compulsory or non-compulsory nature of COVID-19 vaccinations for HCWs and the general population. Other: The protocol used in this review is registered on PROSPERO with the ID number: CRD42022350275.

Background: Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent., Objective: The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD)., Methods: A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed., Results: A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p < .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs)., Conclusions: In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs., (© 2022 Wiley Periodicals LLC.)

Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease., Competing Interests: The authors have no conflict of interest.

Although fresh frozen plasma (FFP) transfusions are common practice in neonatology, robust evidence on their use is lacking. The aim of this study was to systematically review the literature for data on the practice of FFP transfusions in neonates and their association with neonatal morbidity and mortality. The authors identified 40 studies, which met the inclusion criteria for this review. It was demonstrated that the practice of FFP transfusions significantly varies throughout the world. The majority of FFP transfusions are administered "prophylactically", without evidence of active bleeding. Although FFP transfusions may restore coagulation tests results, they do not alter the clinical outcome of the neonates. Reactions following transfusions are probably underestimated in neonates, often undiagnosed and thus, underreported. High quality RCTs aiming to evaluate the effectiveness of FFP in specific clinical conditions are urgently needed, as they could change long-standing FFP transfusion practices, and help reduce neonatal morbidity and mortality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: We aimed at investigating the preventive role of exercise intervention during pregnancy, in high-risk women for gestational diabetes mellitus (GDM)., Materials and Methods: We searched PubMed, CENTRAL, and Scopus for randomized controlled trials (RCTs) that evaluated exercise interventions during pregnancy on women at high risk for GDM. Data were combined with random effects models. Between study heterogeneity (Cochran's Q statistic) and the extent of study effects variability [I2 with 95% confidence interval (CI)] were estimated. Sensitivity analyses examined the effect of population, intervention, and study characteristics. We also evaluated the potential for publication bias., Results: Among the 1,508 high-risk women who were analyzed in 9 RCTs, 374 (24.8%) [160 (21.4%) in intervention, and 214 (28.1%) in control group] developed GDM. Women who received exercise intervention during pregnancy were less likely to develop GDM compared to those who followed the standard prenatal care (OR 0.70, 95%CI 0.52, 0.93; P-value 0.02) [Q 10.08, P-value 0.26; I2 21% (95%CI 0, 62%]. Studies with low attrition bias also showed a similar result (OR 0.70, 95%CI 0.51, 0.97; P-value 0.03). A protective effect was also supported when analysis was limited to studies including women with low education level (OR 0.55; 95%CI 0.40, 0.74; P-value 0.0001); studies with exercise intervention duration more than 20 weeks (OR 0.54; 95%CI 0.40, 0.74; P-value 0.0007); and studies with a motivation component in the intervention (OR 0.69, 95%CI 0.50, 0.96; P-value 0.03). We could not exclude large variability in study effects because the upper limit of I2 confidence interval was higher than 50% for all analyses. There was no conclusive evidence for small study effects (P-value 0.31)., Conclusions: Our study might support a protective effect of exercise intervention during pregnancy for high-risk women to prevent GDM. The protective result should be corroborated by large, high quality RCTs., Competing Interests: The authors have declared that no competing interests exist.

Aim: Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA., Methods: We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta-analysed the available data., Results: There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69-1.26, P-value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20-3.02, P-value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82-1.66, P-value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58-2.15, P-value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding., Conclusion: There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects., (© 2022 British Pharmacological Society.)

Zoonotic diseases represent a significant health and economic burden in countries that rely on small ruminant milk production, such as Greece. Greece is endemic for many zoonotic diseases, some of which have occupational determinants. Our aim was to evaluate knowledge, attitude, and practices of livestock ruminant farmers concerning zoonoses. This study was performed as a cross-sectional study, using a questionnaire. We interviewed ruminant farmers ( n = 204) from 33 settlements of an area with intense agrarian activity. Three index variables, namely knowledge score, attitude score, and practice score, were constructed. The relations between the explanatory variables and the three indexes were assessed based on linear regression analyses. Regarding practices, 23 (11.3%) consume unpasteurized milk or products from unpasteurized milk and no one takes precautionary measures when assisting animals in parturition or during handling birth material. Education level was positively associated with better knowledge and practices, while close veterinary supervision of the farm was associated with better practices regarding the zoonoses prevention. The results indicate the need for continuous awareness and education actions. Close contact with a veterinarian can be utilized as a key tool both with the current brucellosis vaccination program and in the design of awareness campaigns regarding zoonoses in collaboration with other public health personnel.

Background: Diabetic retinopathy is a leading cause of visual loss in the working population. Pars plana vitrectomy has become the mainstream treatment option for severe proliferative diabetic retinopathy (PDR) associated with significant vitreous haemorrhage and/or tractional retinal detachment. Despite the advances in surgical equipment, diabetic vitrectomy remains a challenging operation, requiring advanced microsurgical skills, especially in the presence of tractional retinal detachment. Preoperative intravitreal bevacizumab has been widely employed as an adjuvant to ease surgical difficulty and improve postoperative prognosis.Aims: This study aims to assess the effectiveness of preoperative intravitreal bevacizumab in reducing intraoperative complications and improving postoperative outcomes in patients undergoing vitrectomy for the complications of PDR., Methods: A literature search was conducted using the PubMed, Cochrane, and ClinicalTrials.gov databases to identify all related studies published before 31/10/2020. Prespecified outcome measures were operation time, intraoperative iatrogenic retinal breaks, best-corrected visual acuity in the last follow-up visit, the presence of any postoperative vitreous haemorrhage and the need to re-operate. Evidence synthesis was performed using Fixed or Random Effects models, depending on the heterogeneity of the included studies. Heterogeneity was assessed using Q-statistic and I 2 . Additional meta-regression models, subgroup analyses and sensitivity analyses were performed as appropriate., Results: Thirteen randomized control trials, with a total of 688 eyes were included in this review. Comparison of the intraoperative data showed that bevacizumab reduced operation time ( p  < 0.001), minimized iatrogenic retinal breaks ( p  < 0.001), provided better long-term visual acuity outcomes ( p  = 0.005), and prevented vitreous haemorrhage ( p  < 0.001) and the need for reoperation ( p  = 0.001 < 0.05). Findings were strongly corroborated by additional sensitivity and subgroup analyses., Conclusion: Preoperative administration of bevacizumab is effective in reducing intraoperative complications and improving the postoperative prognosis of diabetic vitrectomy. PROSPERO registration number: CRD42021219280., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Professor David Steel (all unrelated to current work): Alcon – Grant funding, consultancy Roche – Consultancy Bayer – Grant funding Gyroscope – Consultancy Novartis – Consultancy, (© The Author(s), 2021.)

This study aims to provide an up-to-date meta-analysis of data from studies investigating the risk of bearing a child with autism spectrum disorder (ASD) after being conceived by assisted reproductive technology (ART). The study was conducted according to the PRISMA Statement. PubMed and Scopus databases were searched up to August 2, 2020. Observational studies using a type of conception of assisted reproductive technology and examined as outcome offspring with ASD were included. A random effect model was applied due to the heterogeneity of the studies. Statistical analysis was performed with Stata 13 software. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies. The search strategy identified 587 potentially relevant studies. A total of 15 studies provided adequate data for statistical comparisons and, therefore, were included in the meta-analysis. Analysis of the subset of studies that examined all offspring and controlled for confounder factors revealed that the use of ART is associated with a higher risk of ASD (RR = 1.11, 95% CI = 1.03-1.19, p < 0.009), while in the case of studies that focused on singletons, a statistically significant association between ART and ASD was not observed (RR = 0.96, 95% CI = 0.82-1.13, p = 0.654).Conclusion: The present meta-analysis confirmed the existing positive correlation between ART and ASD in offspring, suggesting that ART is correlated with a higher risk for bearing a child with ASD. In contrast, this relationship is not confirmed in singletons. High quality prospective studies with a larger number of participants are still required. What is Known: • Studies that investigated the association between ART and ASD in offspring have shown conflicting results. • A previous meta-analysis showed that offspring conceived by ART are 1.35 times more likely to develop ASD than offspring spontaneously conceived. What is New: • This investigation separately considered studies with and without adjustment for confounders. • The findings from the two analyses were similar., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Randomized controlled trials (RCTs) are the gold standard research in evaluating healthcare interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement improves the quality of RCTs in an evidence-based approach. To evaluate the reporting quality of published RCTs concerning the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis according to the CONSORT statement. Electronic databases were searched for English-language RCTs involving patients who received either anticoagulant or antiplatelet medication for prophylaxis of deep vein thrombosis and pulmonary embolism published from 2000 to 2019. Trials were considered eligible when the included patients received either anticoagulant or antiplatelet medication for primary and secondary prevention of deep vein thrombosis or pulmonary embolism and were randomly assigned to at least two treatment arms. Quality of reporting was assessed using a 37-item questionnaire based on the CONSORT 2010 checklist. Reporting was assessed in 2 publication periods (2000-2009) and (2010-2019). The effect of CONSORT statement in high- and low-ranked medical journals, according to their impact factor, has also been evaluated. The search identified 13 eligible articles for analysis. Only 12 of the 37 items of the checklist were addressed in 75% or more of the studies. Most items concerning the methodological issues were reported by fewer than 50% of the studies. Improvements over time were seen for items that assessed the methodological quality with no statistically significant difference. RCTs published in high-ranked journals showed better quality of reporting. Quality of reporting in RCTs focusing on the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Introduction: Cognitive functions are defined as the mental processes through which information is received, processed, stored, and retrieved. Oxidation is considered as an important factor that affects negatively the brain function. The aim: To assess the impact of oxidative stress, as it is measured by oxidative markers or by the presence of anti-oxidants, on cognitive decline., Patients and Methods: Materials and methods: A systematic review of published observational studies in PubMed and in Scopus was performed. During the review process the keywords were used as follows: ("oxidative stress") AND ("cognitive decline" OR "cognitive dysfunction" OR "cognitive impairment" OR "cognitive deficiency") AND ("observational study" OR "cross sectional study" OR "prospective study" OR "retrospective study" OR "cohort study"). The search was conducted for the years from 2016 to 2020., Conclusion: Conclusions: Seventy-four eligible studies were identified. Thirteen studies met the inclusion and quality criteria and were included in the systematic review. The studies conducted in ten different countries. Information about oxidative stress biomarkers is available in eight studies, while information about antioxidant factors is in ten studies. In all the thirteen studies the cognitive function was assessed with specific tools - scales. In the majority of studies, the presence of high scores in oxidative markers was positively associated with cognitive decline, while higher levels of antioxidant markers were associated with better cognitive function. Our results indicate that oxidative stress may be significantly associated with cognitive decline. The presence of the antioxidants glutathione, uric acid, melatonin, cysteine and peroxide dismutase has a positive effect on cognitive function.

Objectives: We assessed the proportion of primary health care (PHC) randomized controlled trial (RCT) protocols published in peer-reviewed journals that published results in subsequent papers in peer-reviewed journals; and whether this proportion changed over time., Study Design and Setting: We searched (last update June 2019) for RCTs published in peer-reviewed journals reporting primary outcome results for 620 protocols that were published up to 2014 and were retrieved in PubMed. We recorded the absolute number and the proportion of protocols with published results per year; and estimated whether the proportion changed over time., Results: Of the 620 published protocols, 525 (85%) disseminated their results through a published RCT by June 2019. The number of published protocols was increasing over time especially after 2001. However, the proportion of protocols per year with published results in subsequent papers was decreasing over time after 2002. Specifically, the proportion ranged from 86% to 96% for protocols published until 2010 while for those published from 2011 onward ranged from 76% to 86%. Mean time from protocol to results publication was 39 months (95% CI 37, 41)., Conclusion: Almost one-sixth of PHC trial protocols published in peer-reviewed journals did not publish their results in subsequent papers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Osteotomy of nasal bones in rhinoplasty is associated with postsurgical morbidities. Recent evidence has suggested that a surgical method applying piezoelectric ultrasound waves for nasal osteotomies in rhinoplasty reduces soft tissue damage and causes less postsurgical morbidities compared to conventional methods. The purpose of this study is to compare clinical outcomes of piezoelectric and conventional lateral nasal osteotomies in rhinoplasty., Methods: We searched PubMed, CENTRAL, and Web of Science up to 17 August 2019 for studies comparing postoperative outcomes of piezoelectric and conventional lateral osteotomies in rhinoplasty. We included studies comparing results of patients subjected to piezoelectric or conventional lateral nasal osteotomies in rhinoplasty. For outcomes, we considered postoperative pain, eyelid edema, periorbital ecchymosis, and intraoperative mucosal injury., Results: For eyelid edema, a statistically significant difference in favor of piezoelectric osteotomy was documented within the first 3 postoperative days (standardized mean difference [SMD] = -0.65; 95% CI = -1.18, -0.12, p = 0.02; I2 = 69%) and on postoperative day 7 (SMD = -0.69; 95% CI = -1.47, -0.09; p = 0.08; I2 = 85%). This was also the case for periorbital ecchymosis within the first 3 postoperative days (SMD = -0.85; 95% CI = -1.42, -0.28; p = 0.004; I2 = 72%) and on postoperative day 7 (SMD = -0.52; 95% CI = -0.79, -0.24; p = 0.0003; I2 = 71%). Intraoperative mucosal injury (OR = 0.06; 95% CI = 0.01, 0.53; p = 0.01; Ι2 = 0%) and postoperative pain (SMD = -0.99; 95% CI = -1.78, -0.11; p = 0.01; I2 = 49%) were also statistically lower during piezoelectric osteotomies., Conclusions: This study shows that lateral piezoelectric osteotomy in rhinoplasty decreases postoperative pain, edema, ecchymosis, and intraoperative mucosa injuries compared to the conventional osteotomy technique with a chisel. Piezoelectric osteotomies are especially associated with less postoperative edema and ecchymosis in osteotomies not executed under direct vision., (© 2020 S. Karger AG, Basel.)

Background: The presence of an intracranial aneurysm (IA) is thought to have a genetic origin. The genetic association studies (GAS) that investigated the association between IA and elastin gene (ELN) variants have produced contradictory or inconclusive results., Materials and Methods: In order to decrease the uncertainty of estimated genetic risk effects, a meta-analysis of published GAS-related variants in the ELN gene (ELN INT20 1315T > C, EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A) with susceptibility to IA was conducted using a genetic model-free approach. The risk effects were estimated using the generalized odds ratio (ORG) metric., Results: The analysis showed significant association for the INT20 1315T > C variant [ORG = 0.66 (0.45-0.95)], indicating a protection effect. For the variants EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A, no statistically significant association with IAs was found., Conclusion: There is evidence that the ELN variant INT20 1315T > C is implicated in the development of IA; however, the results should be interpreted with caution since the number of published studies is limited.

Purpose: The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM., Methods: We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs., Findings: Eight treatments (glucagon-like peptide-1 [GLP-1] agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 [DPP-4] inhibitors] plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable)., Implications: Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)

Background: The combination of Cisplatin plus Etoposide (EP) is currently the standard treatment for small cell lung cancer (SCLC). However, a large number of alternative treatments (monotherapies and combinations) have been studied in randomized controlled trials (RCTs) to identify more effective treatments. Aim of the present study was to assess the relative effectiveness and tolerability of these treatments., Methods: PubMed, EMBASE and Cochrane Central Register of Controlled Trials were systematically searched to identify all RCTs that compared treatments for SCLC. Then, effectiveness of the treatments relative to the combination of Cisplatin plus Etoposide, reference treatment) was estimated by performing a network of treatments analysis. The analysis evaluated two efficacy outcomes (complete response - CR and objective response rate - ORR) and two tolerability outcomes (neutropenia and febrile neutropenia). All RCTs that provided data for calculating the odds ratios (OR) for the selected outcomes were considered. The network analysis involved direct and indirect analyses., Results: We identified 71 articles eligible for inclusion, involving 91 different treatments. In total, 16,026 patients were included in the analysis. In the direct analysis the combination of Cisplatin plus Cyclophosphamide plus Etoposide plus Epirubicin showed better response than EP for the ORR outcome, but with worse tolerability (presence of neutropenia). The indirect analysis revealed that the combination of Cisplatin plus Doxorubicin plus Etoposide (plus Vincrisitine) showed better response that EP for the ORR outcome., Conclusions: No therapy shows better response for the two efficacy outcomes (CR and ORR); though, Cisplatin plus Doxorubicin plus Etoposide plus Vincrisitine might be a promising therapy for SCLC. The results should be interpreted with caution because the network was dominated by indirect comparisons. Large scale head-to-head RCTs are needed to confirm the present findings., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Data from 30 pharmacogenomic studies that investigated MDR1 mRNA expression or gene variants (C3435T, G2677TA, C1236T) and response to therapy in acute myeloid leukaemia (AML) were synthesized. Anthracycline-based regimens were mainly used. MDR1 mRNA overexpression was associated with poor response to therapy [odds ratio (OR) = 2.49 95% confidence interval (CI) 1.38-4.50]. The gene variants were not associated with response to treatment; the generalized ORs, a genetic model-free approach, for the variants C3435T, G2677TA and C1236T were ORG = 0.86 (95% CI 0.55-1.37), ORG = 0.97 (95% CI 0.58-1.64) and ORG = 1.17 (95% CI 0.75--1.83), respectively. There is indication that MDR1 mRNA expression may be considered as a potential marker for response to chemotherapy in AML patients.

Context: Scanty reports have focused on FDG-PET after radiofrequency ablation (RFA), for recurrence of hepatic metastases., Objective: To assess FDG-PET diagnostic accuracy on detection of recurrent hepatic lesions., Methods: After a comprehensive search of PubMed and EMBASE, we performed a patient-based diagnostic meta-analysis of post-RFA FDG-PET., Results: Across nine included articles, independent, random-effects sensitivity and specificity were 0.73(0.50-0.88) and 0.85(0.72-0.93), respectively. A symmetrical SROC curve was produced with no significant heterogeneity. Specificity was optimal for surgical RFA and colorectal origin of metastases., Conclusion: Synthesis of published evidence suggests PET/CT as an appropriate tool for optimizing post-ablation follow-up.

Background: The optimal treatment of multiple sclerosis (MS) is not yet well-defined., Objective: To estimate the relative effectiveness of treatments in MS, we performed a network of multiple-treatments meta-analysis of randomized controlled trials (RCTs) for relapsing MS using three main efficacy outcomes: relapse-free patients, patients without disease progression, and patients without magnetic resonance imaging progression., Methods: We systematically searched PubMed and the Cochrane Central Register of Controlled Trials to identify English-language articles with RCTs that compared pharmaceutical treatments using the terms multiple sclerosis and randomized controlled trial. All RCTs that involved patients with definite relapsing MS and provided data for calculating the odds ratios for the main outcomes were considered. First, comparative effectiveness relative to placebo was assessed using direct analysis. Then, each therapy was compared with interferon beta-1b (250 μg)* in direct and indirect analyses. Effect sizes were estimated by applying a random-effects model., Results: We identified 4165 titles; after screening, 109 articles were eligible for inclusion. In total, 26,828 patients were included. The network consisted of 145 treatments involving 59 direct comparisons with placebo and 8 direct comparisons with interferon beta-1b (250 μg). Two treatments showed better response compared with placebo (direct analysis) for all three efficacy outcomes: natalizumab (300 mg)(†) and fingolimod (0.5 mg). In comparing treatments with interferon beta-1b (250 μg), the network analysis revealed that no therapy shows better response for all 3 efficacy outcomes and alemtuzumab, 12 and 24 mg, have better response for 2 of the outcomes (relapse-free patients and patients without disease progression)., Conclusions: Although some treatments seem to have better efficacy, the results should be interpreted with caution because the network was dominated by indirect comparisons. Data from the selected studies included in the network cannot be extrapolated beyond them. Large RCTs that make head-to-head comparisons between treatments are needed to draw safe conclusions for the optimal treatment of MS., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a candidate gene for breast cancer (BC). However, the specific role of MTHFR polymorphisms and haplotypes has not been fully clarified and replicated. We examined the association of two common MTHFR polymorphisms (C677T and A1298C) and their haplotypes in a candidate-gene association study, involving 300 female patients with BC and 283 healthy women. The single locus analysis for the two polymorphisms revealed an association only for the C677T polymorphism [odds ratio (95% confidence interval), OR=2.05 (1.21-3.48)], but adjustment for age diminished this association [OR=1.76 (0.92-3.42)]. The menopausal status showed no significant effect in the association between the MTHFR polymorphisms and BC. The analysis of haplotypes showed an association for the C677-A1298 haplotypes (p=0.04). The available evidence from our study may support a contributory role of MTHFR polymorphisms in BC development. Future larger studies may help in elucidating the genetics of BC further.

The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways and their genes are implicated in the pathogenesis of low BMD. Data from 211 studies that investigated the association between BMD and gene variants involved in these pathways were catalogued in a web-based information system and analyzed. In individual studies, significant association was found for 16 variants in lumbar spine, 11 in femoral neck and 5 in hip. In meta-analysis, significant results were shown for the variants COL1A1 rs1800012 (in lumbar spine and femoral neck), COL1A1 rs1107946 (in lumbar spine), TGFB1 rs1982073 (in femoral neck and hip) and TGFB1 rs1800469 (in lumbar spine).

The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for breast cancer (BC), however, the specific role of variants and haplotypes has not been clarified. We examined the association of two polymorphisms (4b/a and G894T) and their haplotypes in a case-control sample of 306 patients with BC and in 131 healthy females. In addition, a meta-analysis of studies investigating association between NOS3 polymorphisms and BC was conducted. The single locus analysis for the two polymorphisms revealed an association only for the 4b/a polymorphism, but adjustment for age diminished this association (odds ratio (OR) (95% confidence interval)=0.98 (0.34-2.81)). The analysis of haplotypes showed an association for two haplotypes involving the 894T allele (bT and aT) (P<0.05). The meta-analysis for both polymorphisms produced nonsignificant associations without significant heterogeneity. A positive association was detected for the promoter T786C polymorphism (pooled OR=1.51 (1.07-2.12)), but this comparison was based on few studies. The available evidence from our study and the meta-analysis cannot support a major contributory role of these common NOS3 polymorphisms in BC, although future larger studies may help in drawing safer conclusions about the genetics of BC.