Significant Statistical Heterogeneity Research Articles

Association Between Helicobacter pylori Colonization and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Various observational studies have examined a potential relationship between Helicobacter pylori colonization and inflammatory bowel diseases (IBDs); however, results are inconclusive. This systematic review evaluates articles reporting an association between human H. pylori colonization and IBD. A systematic search of studies was conducted to evaluate a possible relationship between H. pylori colonization and IBD. Seven databases and different types of gray literature were searched. After screening for relevant articles, selection and data extraction were done. After that, the data were analyzed, and pooled odds ratios (ORs) were calculated, using meta-analysis. Heterogeneity, sensitivity, and subgroups analyses were conducted. Funnel plots followed by Begg and Egger tests were done to assess the publication bias. Among 58 studies, including 13,549 patients with IBD and 506,554 controls, the prevalence of H. pylori colonization was 22.74% and 36.30%, respectively. A significant negative association was observed between H. pylori colonization and IBD (pooled OR: 0.45, 95% confidence interval 0.39-0.53, P≤0.001). The random-effect model showed significant statistical heterogeneity in the included studies (I2=79%). No publication bias was observed. Among subgroups, ORs were notably different when the data were stratified by the age difference between patient and control group, and by study regions and/or continent. Finally, the meta-regression analysis showed significant results, in terms of the age difference and region variables. In this meta-analysis, all statistical data support the theory that H. pylori has a protective role in IBD. However, more primary studies using proper methodology are needed to confirm this association.

Evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates.

In this commentary, we summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates. Our recently completed systematic review includes 12 randomized controlled trials performed all over the world. Our meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections. There were no adverse effects. There was no statistically significant decrease in necrotizing enterocolitis, mortality or neurodevelopmental impairment in lactoferrin supplemented preterm infants. There was significant statistical heterogeneity in the effects of lactoferrin on late-onset sepsis between larger and smaller studies, which may reflect either small study biases, differences in the effectiveness, dose or duration of supplemental lactoferrin products, or differences in underlying population risk, or any or all of these.

Association between maternal cadmium exposure and preterm birth: a meta-analysis

ABSTRACT The association between Cadmium and the risk of preterm birth (PTB) has remained controversial. A number of studies found a positive correlation between maternal Cd exposure and PTB; however, there are conflicting reports about this correlation. Therefore, herein we performed this meta-analysis to examine the association between maternal Cd exposure and the risk of PTB. A systematic search was conducted through PubMed, Scopus, Embase and OpenGrey from inception to May 2020 to find all eligible studies. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to examine this correlation. A random-effects model was applied in this meta-analysis due to significant statistical heterogeneity among included studies. Overall, 10 eligible studies met the inclusion criteria and were included in our analysis, and results of the present meta-analysis indicated that maternal cadmium exposure is associated with the risk of PTB (OR = 1.32; 95% CI = 1.08–1.61). This meta-analysis suggests that maternal Cd exposure might be associated with the risk of PTB. Yet, large prospective studies from different ethnic populations which consider other influencing parameters are still required to confirm this finding.

Complications of peripherally inserted central catheters in pregnancy: a systematic review and meta-analysis

Introduction Complication rates associated with peripherally inserted central catheters (PICCs) in the general population are variable, and rates specific to pregnant women are unclear. We conducted a systematic review and meta-analysis to estimate the rate of PICC-associated complications in pregnant women. Methods We searched published literature for records discussing PICC use in pregnant or postpartum women. We included studies with primary data regarding rates of maternal complications from PICC use. The primary outcomes were maternal infection (cellulitis, sepsis), venous thromboembolism (VTE), or combined major complication rate. Secondary outcomes were superficial thrombophlebitis or mechanical failure. Meta-analysis was performed using STATA 12 with the METAN and METAPROP software routines. Pooled estimates with 95%CI were calculated using random-effects models. Results After the removal of duplicates, the primary search yielded 318 articles, with 5 being included for final analysis. The pooled rate of combined infectious and thromboembolic complications was 26% (95%CI = 6–53%). For secondary outcomes the pooled rate of infectious complications was 18% (95%CI = 4–39%), VTE 6% (95%CI = 0–18%), mechanical failure 7% (95%CI = 3–12%), and superficial thrombophlebitis 1% (95%CI = 0–3%). There was significant statistical heterogeneity between studies for all outcomes calculated. Conclusion There are limited data regarding complication rates due to PICC use in pregnancy, with a high level of heterogeneity among existing studies. The risk of VTE appears comparable to PICC-associated VTE in the non-pregnant hospitalized population. The risk of infection associated with PICC use was the most variable, with rates ranging from 4% to 37%. This suggests that infection risk may be modifiable and further studies are needed to assess interventions that may lower this risk.

The effect of dexmedetomidine on postoperative and intensive care unit delirium: A meta‐analysis of randomized controlled trials

BackgroundThe present meta‐analysis aimed to assess the efficacy of dexmedetomidine on the occurrence of delirium among critically ill patients in the postoperative and intensive care unit.MethodsPubmed, Embase, Cochrane Library (Central), Web of Science and Clinical Trails databases for randomized controlled trials (RCTs) were searched to compare the effect of dexmedetomidine administration in comparison with control group (normal saline or other anesthetic drugs) on the incidence of delirium in adult patients until April 4, 2019. The sensitivity and subgroup analyses were adopted. Statistical analysis was performed with RevMan software version 5.3 and Stata 12.0. The primary endpoint was the incidence of delirium. The secondary outcome included the occurrence of hypotension, hypertension, bradycardia and tachycardia.Results20 RCTs were finally included in the analysis, with a total of 4,242 adult patients. The results of meta‐analysis showed that dexmedetomidine (odds ratio [OR]=0.47, 95% confidence interval [CI]: 0.35 to 0.64, p < 0.01) could significantly reduce the rate of delirium for the entire patients in the postoperative and intensive care unit when compared with control group. The subgroup analysis indicated that dexmedetomidine reduced the incidence of delirium between groups in cardiac surgery (OR=0.55, 95% CI: 0.30 to 0.98) and non‐cardiac surgery (OR=0.44, 95% CI: 0.31 to 0.64), normal saline (OR=0.47, 95% CI: 0.31 to 0.71) and anesthetic drugs (OR=0.50, 95% CI: 0.30 to 0.81), age ≥ 60 years old (OR=0.50, 95% CI: 0.36 to 0.68) and age < 60 years old (OR=0.34, 95% CI: 0.13 to 0.91), with loading dose (OR=0.38, 95% CI: 0.29 to 0.50) and without loading dose (OR=0.54, 95% CI: 0.44 to 0.67). However, there were no significant difference in delirium among mechanical ventilated patients (OR=0.30, 95% CI: 0.07 to 1.22) and in cardiac surgery patients with age ≥ 60 years old (OR=0.73, 95% CI: 0.44 to 1.22). Additionally, this analysis found that dexmedetomidine administration was associated with an increased incidence of hypertension (OR=0.54, 95% CI: 0.41 to 0.71) and bradycardia (OR=1.59, 95% CI: 1.25 to 2.03), while the incidence of hypotension (OR=0.90, 95% CI: 0.62 to 1.31) and tachycardia (OR=0.73, 95% CI: 0.37 to 1.45) did not differ significantly between dexmedetomidine treated and control groups..ConclusionThe present limited evidence suggests that dexmedetomidine can reduce the incidence of delirium in the postoperative and intensive care unit except in cardiac surgery patients with age ≥ 60. However, the pooled results should be interpreted with more caution due to significant statistical heterogeneity existed. Therefore, future high‐quality, large RCTs should further verify this findings among this population.

A159 ARE MOBILE HEALTH TECHNOLOGIES SUPPORTING COLONOSCOPY PREPARATION ASSOCIATED WITH BETTER PATIENT OUTCOMES: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS

Abstract Background Mobile health technologies are innovative solutions for delivering instructions to patients preparing for their colonoscopy appointments. Aims To systematically review the literature of the effect of smartphone-based technologies supporting colonoscopy appointment preparation on patient outcomes. Methods With the assistance of a librarian, one author searched MEDLINE, EMBASE, CINAHL and CENTRAL for randomized controlled trials (RCTs) that evaluated the effect of smartphone-based technologies for colonoscopy preparation on bowel cleanliness and user satisfaction. Two independent reviewers extracted data on patient and intervention characteristics and study outcomes, and appraised study quality using the Cochrane Risk-of-Bias tool. Summary statistics were generated using random effects models for the trials that used either the Boston Bowel Preparation Scale (BPPS) or the Ottawa Bowel Preparation Scale (OBPS). Statistical heterogeneity was assessed using I2. Results Ten RCTs met our inclusion criteria. Smartphone-based interventions included apps, SMS text messages, video clips, camera apps, and social media apps. Most studies showed smartphone-based interventions were associated with better quality bowel cleanliness scores and higher user satisfaction compared to usual care. Standardized mean differences for the BBPS and OBPS differed between the intervention and control groups [SMD 0.57, 95%CI 0.18, 0.95] and [SMD -0.39, 95%CI -0.59, -0.19], respectively. Statistically significant statistical heterogeneity was found for the meta-analyses for the trials employing the BBPS (I2=80%, p=0.03) but not for the trials using the OBPS (I2=45%, p=0.16). All RCTs were at high risk of bias from non-blinded participants, and most studies were at high or unclear risk of bias due to lack of allocation concealment. Funnel plots to evaluate publication bias were not generated as there were too few studies with sufficient data to analyze. Conclusions This systematic review found that smartphone-based technology users had better bowel cleanliness quality scores and higher satisfaction with the method of delivering instructions compared to patients given usual care. Given that all RCTs were at high risk of bias, high-quality RCTs that blind participants and conceal study group allocation are needed. Funding Agencies CIHRDepartment of Medicine, McGill University and the Research Institute of the McGill University Health Centre

Thrombotic risk following video-assisted thoracoscopic surgery versus open thoracotomy: a systematic review and meta-analysis.

There is no consensus on the risk of thrombotic events following video-assisted thoracoscopic surgery (VATS) versus open thoracotomy (OT), despite multiple studies. In fact, the estimates for the overall thrombotic risk for VATS versus OT are inconclusive. In this systematic review and meta-analysis, we endeavoured to ascertain the best estimate of thrombotic risk in VATS versus OT. Relevant studies were searched through PubMed and Cochrane Library database. Outcomes of interests were myocardial infarction (MI), pulmonary embolism (PE) and deep vein thrombosis (DVT). Data were pooled using random-effects model. The results were presented as odds ratio (OR) with the corresponding 95% confidence interval (CI). Nineteen studies were meta-analysed: 17 observational studies and 2 randomized controlled trials. Using propensity-matched data, in comparison with OT, VATS was associated with a statistically significant, postoperative reduction in MI (OR 0.60, 95% CI 0.39-0.91; P = 0.017), DVT/PE (OR 0.52, 95% CI 0.44-0.61; P < 0.001), PE (OR 0.59, 95% CI 0.43-0.82; P = 0.001) and DVT (OR 0.47, 95% CI 0.35-0.64; P < 0.001). Unadjusted data showed no statistical differences for all outcomes. The risk of DVT/PE (OR 0.55, 95% CI 0.42-0.72; P < 0.001), but not the other outcomes, remained significantly lower following the exclusion of the sole large study. There is no significant statistical heterogeneity between the included studies. Overall, the postoperative thrombotic risk following VATS is significantly lower than OT. Further prospective randomized controlled trials with large sample sizes are warranted to corroborate our findings.

Association Between Obesity and Sarcoidosis: A Systematic Review and Meta-analysis

<i>Background</i>: Sarcoidosis is a systemic inflammatory disease characterized by epithelioid granuloma formation in various organs. The etiology of sarcoidosis is unknown. Several studies report an increased risk of sarcoidosis in obese patients. The purpose of this study is to conduct a systematic review to assess the risk of sarcoidosis in obese or overweight patients, and to provide a population-based estimate of the risk of sarcoidosis in obese and overweight individuals. <i>Methods</i>: Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) guidelines, we conducted a comprehensive search of studies (Randomized control trial (RCT), cohort or case-control) studies that estimated the risk of sarcoidosis with body mass index (BMI) between 2009-2019 using keywords and MESH terms related to obesity and sarcoidosis. The search was conducted in MEDLINE, EBSCO, and CINAHL. Three independent investigators reviewed each article and assessed for bias. Data was extracted from each study that met inclusion criteria. Quantitative analysis was performed using Review Manager 5.3 software. <i>Results</i>: An initial search yielded 77 potential articles; 73 articles did not meet inclusion criteria and 4 were included in the final analysis. The pooled risk estimate for the incidence of sarcoidosis in obese and overweight individuals was 1.68 [95% confidence interval 1.5-1.87] with a significant statistical heterogeneity, I² of 92%. <i>Conclusion</i>: From our systematic review, obese and overweight individuals have a 68% (RR 1.68, 95% CI 1.50 to 1.87) increased risk of developing sarcoidosis in comparison with normal or underweight individuals. More studies are needed to further evaluate the role of obesity in the etiopathogenesis of sarcoidosis.

Association between MTHFR C677T polymorphism and non-traumatic osteonecrosis of the femoral head: An update meta-analysis

Abstract Objective To investigate the correlation between MTHFR C677T polymorphism and non-traumatic osteonecrosis of the femoral head. Methods Open published studies relevant to MTHFR C677T polymorphism and non-traumatic osteonecrosis of the femoral head were electronic systematic searched in the databases of cochrane central register of controlled trials, EMBSE and CNKI. The correlation between MTHFR C677T polymorphism and non-traumatic osteonecrosis of the femoral head was calculated by odds ratio (OR) and corresponding 95% confidence interval (95%CI). The publication bias for the included studies were assessed by Begg’s funnel plot and Egger’s line regression text. Results After systematic searching the electronic databases, 11 original studies were finally included the present work. The I2 test indicated significant statistical heterogeneity (I2=53.5%, P=0.018) across the included 11 publications. The polled results indicated that subjects of Caucasians with CC genotype had decreased risk of developing non-traumatic osteonecrosis of the femoral head (OR=0.65,95%CI: 0.44-0.96, P=0.031). However, there was no correlations between MTHFR C677T polymorphism and non-traumatic osteonecrosis of the femoral head in American Jewish and East Asian races(p&gt;0.05). Sensitivity analysis indicated the pooled ORs were not sensitive to any included single study. The Begg’s funnel plot was generally left and right symmetrical which indicated no obviously publications. The Egger’s line regression test also demonstrated no statistical publication bias (t=1.57, P=0.15). Conclusion According to the present evidence, MTHFR C677T polymorphism was correlated with non-traumatic osteonecrosis of the femoral head especially for Caucasians race. Subjects of Caucasians race with CC genotype had decreased risk of developing non-traumatic osteonecrosis of the femoral head.

Prophylactic Negative Pressure Wound Therapy for Closed Laparotomy Incisions: A Meta-analysis of Randomized Controlled Trials.

The aim of this study was to determine whether negative pressure wound therapy (NPWT) applied to primarily closed incisions decreases surgical site infections (SSIs) following open abdominal surgery. SSIs are a common cause of morbidity following open abdominal surgery. Prophylactic NPWT has shown promise for SSI reduction. However, the results of randomized controlled trials (RCTs) conducted among patients undergoing laparotomy have been inconsistent. We performed a meta-analysis of English language RCTs comparing the use of prophylactic NPWT to standard dressings on primarily closed laparotomy incisions following open abdominal surgery. Medline, EMBASE, Cochrane Library, and CINAHL databases were searched from inception to December 31, 2018, for relevant studies. A random-effects model was used for statistical analysis. Five RCTs totaling 792 patients were included in our meta-analysis after application of our exclusion and inclusion criteria. There was no significant difference in the risk of SSIs identified among those patients who had NPWT compared to standard dressings; relative risk (RR) 0.56 (95% confidence interval 0.30-1.03, P = 0.064). There was significant statistical heterogeneity across studies (I = 67.4%; P = 0.015). The adoption of NPWT for routine SSI prophylaxis following laparotomy is currently not supported and should be used primarily in the context of a clinical trial.

A meta-analysis of serum Hcy in diagnosis of diabetic nephropathy

Abstract Objective This meta-analysis aims to investigate the diagnostic performance of serum homocysteine (Hcy) as a biomarker for diabetic nephropathy (DN). Methods Clinical publications relevant to serum Hcy level and DN were systematic searched in the electronic databases of; Pubmed, Cochrane Library, Embase, Web of science, CNKI and CBM. The diagnostic data from each included original study was extracted and pooled by the effect size of diagnostic sensitivity, specificity, positive likely hood ratio (+LR), negative likely hood ratio (-LR), diagnostic odds ratio (DOR) and area under the symmetric ROC curve (AUC). Results 18 publications relevant to serum Hcy and DN were included in the meta-analysis. The I2 test demonstrated significant statistical heterogeneity across the 18 studies for the effect size of diagnostic. The pooled diagnostic sensitivity, specificity, +LR, -L, DOR, AUC were 0.76 (95%CI: 0.74-0.78), 0.84 (95%CI:0.82-0.86), 5.05 (95%CI:3.52-7.24), 0.27 (95%CI:0.19-0.39), 21.68 (95% CI:11.15to 42.14) and 0.90 respectively in the random effect model. Conclusion Based on the present publications, serum Hcy is a promising serological marker for DN diagnosis.

Early Aortic Valve Replacement versus Watchful Waiting in Asymptomatic Severe Aortic Stenosis: A Study-Level Meta-Analysis

ABSTRACT Background: The management of patients with asymptomatic, severe aortic stenosis (AS) is controversial. We performed a meta-analysis to examine the impact on outcomes of early aortic valve replacement (AVR) in patients with severe asymptomatic AS versus a watchful-waiting (WW) approach. Methods: Databases were searched for studies published until April 2019. Main outcome of interest was death during follow-up. Results: The search yielded 1,889 studies for inclusion. Of these, seven articles were analyzed and their data extracted. The total number of patients included was 3,839. The overall HR (95% CI) for death showed a statistically significant difference between the groups, with lower risk in the “early AVR” group (random effect model: HR 0.280; 95% CI 0.159–0.494, P < 0.001). There was evidence of significant statistical heterogeneity of treatment effect among the studies for death. Funnel plot analysis disclosed no asymmetry around the axis for the outcome of interest, which means that we have low risk of publication bias related to this outcome. Sensitivity analysis showed that none of the studies had a particular impact on the results. The meta-regression coefficients for the modulating factors age, male sex, presence of hypertension and presence of diabetes were significant for mortality, showing that the early intervention becomes even more protective in comparison with the conservative approach when we take these factors into consideration. Conclusion: Early AVR seems to be a better approach than WW in the treatment of asymptomatic patients with severe AS, but we would still advocate a case-by-case decision-making process.

Impact of alcohol consumption on the risk of developing bladder cancer: a systematic review and meta-analysis.

Epidemiologic studies that investigated alcohol consumption in relation to the risk of bladder cancer (BCa) have demonstrated inconsistent results. We conducted a systematic review and meta-analysis of the literature to investigate the association of alcohol including different types of alcoholic beverages consumption with the risk of BCa. A systematic search of Web of Science, Medline/PubMed and Cochrane library was performed in May 2018. Studies were considered eligible if they assessed the risk of BCa due to alcohol consumption (moderate or heavy dose) and different types of alcoholic beverages (moderate or heavy dose) in multivariable analysis in the general population (all genders, males or females) or compared with a control group of individuals without BCa. observational cohorts or case-control. Sixteen studies were included in this meta-analysis. Moderate and heavy alcohol consumption did not increase the risk of BCa in the entire population. Sub-group and sensitivity analyses revealed that heavy alcohol consumption increased significantly the risk of BCa in the Japanese population, RR 1.31 (95% CI 1.08-1.58, P < 0.01) in the multivariable analysis, and in males RR of 1.50 (95% CI 1.18-1.92, P < 0.01), with no significant statistical heterogeneity. Moreover, heavy consumption of spirits drinks increased the risk of BCa in males, RR 1.42 (95% CI 1.15-1.75, P < 0.01). In this meta-analysis, moderate and heavy alcohol consumption did not increase the risk of bladder cancer significantly. However, heavy consumption of alcohol might increase the risk of BCa in males and in some specific populations.

Efficacy of Probiotics and Prebiotics in Prevention of Infectious Complications Following Hepatic Resections: Systematic Review and Meta-Analysis.

Infections occurring after hepatic resection cause significant morbidity, mortality, and prolonged hospitalization. Probiotics and prebiotics are considered to offer protection against post-operative infections. We aimed to determine the effect of probiotics and prebiotics on the post-operative infection rate after hepatic resection by conducting a systematic review and a meta-analysis. We searched various databases, namely, the PubMed, Medline, Embase, and Cochrane Controlled Trials Registry (CENTRAL), for randomized controlled trials evaluating the effect of probiotics and/or prebiotics on the infection rate following hepatic resection. Extracted data were pooled and subsequently used in a meta-analysis with a random-effects model. Review was reported following the PRISMA guidelines. A total of 4 studies comprising 205 patients were included for our meta-analysis. The infection rates in the probiotic group and placebo group were 11.7% and 30.3%, respectively (p<0.001). The pooled risk ratio (RR) was 0.41 (95% confidence interval [CI]: 0.128-0.730). Subgroup analysis indicated that the wound infection rate in the probiotic group (5.3%) was significantly lower than that in the placebo group (RR: 0.387, 95% CI: 0.155-0.970, p=0.043). Furthermore, probiotics/prebiotics decreased the duration of hospital stay (-0.57 days; 95% CI: -0.861 to -0.274; p<0.001) and antibiotic use (mean difference: -3.89 days, 95% CI: -4.17 to -3.60; p<0.001). There was no significant statistical heterogeneity. Our findings show that administration of probiotics and/or prebiotics prior to operation day decreases the infection rate post-liver resection and could shorten the duration of hospitalization and antibiotics use.

Systematic review of depression and anxiety in psoriatic arthritis.

To investigate the point prevalence of depression and anxiety in psoriatic arthritis and putative reductions in these comorbidities with the treatment of psoriatic arthritis. We performed a systematic review in accordance with PRISMA guidelines examining point prevalence of depression and anxiety in psoriatic arthritis as well as effects of treatment for psoriatic arthritis on these psychiatric comorbidities. MEDLINE, EMBASE, EBM Reviews and Cochrane, and PsycINFO were searched from inception to October 2017. Quality of studies was assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. Study and population characteristics were extracted and entered into an electronic database for subsequent descriptive and meta-analysis of point prevalence. Three studies matched inclusion criteria with significant statistical heterogeneity. The prevalence of depression ranged between 9%-22% and anxiety between 15%-30% in patients with psoriatic arthritis. One study matched inclusion criteria for treatment effect analysis, albeit with a high risk of bias and illustrated a benefit of etanercept on the prevalence of depression (9% vs 16%) and anxiety (14% vs 30%) after 24weeks of treatment. This is the first systematic review of point prevalence of depression and anxiety in patients with psoriatic arthritis. There is a moderate point prevalence of both depression and anxiety in patients with psoriatic arthritis, which is similar or slightly higher than the general population and comparable to that seen in other rheumatic diseases. The effects of treatment for psoriatic arthritis on comorbid depression and anxiety remain unclear.

Effects of tumor size on prognosis in differentiated thyroid carcinoma smaller than 2 cm.

Benefits of subdividing small-differentiated thyroid carcinoma (sDTC) by tumor size are controversial. We conducted a meta-analysis to investigate whether tumor size is associated with prognosis of sDTC. PubMed and Web of Science databases were searched from their inception to September 2018. The identified studies according to the inclusion/exclusion criteria were analyzed using fixed/random-effects models. Data were calculated and results of the meta-analysis were expressed as odd ratio (OR). sDTC was classified as S1 (≤1 cm) and S2 (>1 cm and ≤2 cm). A systematic analysis was performed to compare the difference of recurrence, survival and clinicopathological factors between the two subgroups of sDTC (S1 vs. S2). A total of 21 studies published between 2004 and 2017 enrolling 219,291 patients were included. Findings showed that, S2 was associated with higher recurrence risk compared with S1 (OR=1.575, 95% CI=1.428–1.738; P<0.05). There was no statistical difference in survival between S1 and S2, but significant statistical heterogeneity (OR=1.160, 95% CI=0.810–1.662; P=0.448; I2=75.8%). Meta-regression analysis revealed publication year potentially caused the heterogeneity (P<0.05). Comparison of small papillary thyroid carcinoma alone agreed with the results of sDTC. T1b increased the risk of recurrence (OR=1.520; 95% CI=1.072–2.155; P<0.05) and death (OR=1.504; 95% CI 1.353–1.672; P<0.05) compared with T1a. S2 associated with extrathyroidal extension (OR=2.575; 95% CI=1.603–4.135; P<0.05), bilaterality (OR=2.278; 95% CI=1.905–2.723; P<0.05), vascular invasion (OR=4.494; 95% CI=2.812–7.183; P<0.05) and lymph node metastases (OR=1.12; 95% CI=1.10–1.14; P<0.05). Our analysis suggested it is necessary to subdivide sDTC into S1 and S2 owing to their different effects on prognosis, especially recurrence.

Clinical Outcomes of Transcatheter Aortic Valve Replacement in Nonagenarians: A Systematic Review and Meta-Analysis.

Objectives To compare the incidence of mortality and complications between nonagenarians and younger patients undergoing transcatheter aortic valve replacement (TAVR). Background TAVR has become an alternative treatment for nonagenarian patients with severe aortic stenosis. Previous studies have reported conflicting results regarding the clinical outcomes between nonagenarians and younger patients who underwent TAVR. Methods We searched PubMed, EMBASE, and Cochrane Library databases with predefined criteria from the inception dates to July 8, 2018. The primary clinical endpoint was 30-day and 1-year all-cause mortalities. Secondary outcomes were considered the rates of stroke, myocardial infarction, any bleeding, any acute kidney injury, any vascular complications, new pacemaker implantation, and conversion to surgical aortic valve replacement. Results A total of 5 eligible studies with 25,371 patients were included in this meta-analysis. Compared with younger patients who underwent TAVR, nonagenarians had a significantly higher mean Society of Thoracic Surgeons score (STS score) (MD, 2.80; 95%CI: 2.58, 3.30; P<0.00001) and logistic European System for Cardiac Operative Risk Evaluation (logistic EuroSCORE) (MD, 2.72; 95%CI: 1.01, 4.43; P=0.002). Nonagenarians were associated with significantly higher 30-day mortality (6.2% vs. 3.7%; OR, 1.73; 95%CI: 1.49, 2.00) and 1-year mortality (15.5% vs. 11.8%; OR, 1.39; 95%CI: 1.26, 1.53), without significant statistical heterogeneity. Nonagenarians were associated with significantly increased rates of major or life-threatening bleeding, vascular complications and stroke of 20%, 35%, and 32%, respectively. There were no significant differences in the rate of myocardial infarction, stage 2 or 3 acute kidney injury, new pacemaker implantation, or conversion to surgical aortic valve replacement. Conclusions Nonagenarians showed worse clinical outcomes than younger patients after TAVR, while the incidence of mortality was acceptable. TAVR remains an option for nonagenarian patients with severe aortic stenosis and should be comprehensively evaluated by the heart valve team.

The Magnitude of Improvement in Progression-Free Survival with Targeted Therapy in Relapsed/Refractory Chronic Lymphocytic Leukemia Based on Genetic Risk: A Systematic Review and Meta-Analysis

Background Currently, only genetic testing, del(17p) or TP53, determines choices of therapy in chronic lymphocytic leukemia (CLL) whereas mutational status of IGHV and 11q deletion are not recognized as reliable parameters for treatment selection (with exception for fludarabine, cyclophosphamide and rituximab [FCR] in mutated IGHV).To increase understanding of the predictive value of prognostic parameters in the novel therapy era, we conducted a systematic review and meta-analysis assessing the magnitude of improvement in progression-free survival (PFS) with B-cell receptor (BCR) or BCL2 pathway inhibitors based on the presence or absence of 17p deletion/TP53 mutations, 11q deletion and IGHV mutational status in relapsed refractory (R/R) CLL patients.Methods Randomized trials comparing BCR or BCL2 inhibitors to other treatment regimens were considered eligible for this analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was utilized as a reporting guideline. The search strategy yielded 1184 records for screening with 97 full-text articles assessed for eligibility. Finally, seven randomized trials were included in the quantitative meta-analysis, all of which compared BCR or BCL2 inhibitors to a different comparator.Results Meta-analysis of seven randomized trials comprising 2415 patients with R/R CLL revealed that treatment with BCR or BCL2 pathway inhibitors improved OS compared with the combined comparator treatments [Hazard ratio (HR) 0.555;95% confidence interval (CI): 0.452-0.680;P=0.000]. Of note, the I2 statistic for heterogeneity (i.e.,8.8% [P=0.36] ) and Q values (i.e., 6.583) indicated a high level of homogeneity of results across studies. Similar results were obtained with PFS (HR, 0.196; 95% CI: 0.144-0.268; P=0.000) although significant statistical heterogeneity existed across the studies (I2 = 78.6%, P<0.00001;Q=28.08).Next, we evaluated the magnitude of improvement in PFS obtained with BCR or BCL2 pathway inhibitors in R/R CLL patients with high-risk genetic features (Fig 1). The risk of progression was lower for 17p deleted patients (n= 450) treated with BCR or BCL2 inhibitors in comparison to combined comparator treatments (HR, 0.206; 95% CI, 0.108-0.392; P = .000; I2 = 76%; P=0.001;Q=20.853). The same applied with the analysis of TP53 which included five studies enrolling 582 R/R CLL patients with mutated TP53 (HR, 0.231 (95% CI:0.1370.390;P=0.000;I2=75.8%,P=0.0002;Q=16.513).Data for PFS by 11q deletion status, restricted to 4 studies (3 of ibrutinib and one of venetoclax) including 433 patients , revealed a significantly higher risk of progression for 11q deleted patients treated with comparator treatments [HR,0.081; 95% CI: 0.054-0.121; I2= 0.0% (P=0.56), Q =2.06]. Finally, data for PFS by IGHV mutational status that relied on 6 studies including 1580 IGHV unmutated patients favoured treatment with BCR or BCL2 inhibitors ( HR, 0.172; 95% CI, 0.109-0.272; P=0.000; I2= 84.8%, P<0.0001; Q= 32.98).An additional pooled meta-analysis restricted to patients with low risk genetic features revealed that the benefit observed with BCR or BCL2 inhibitors in patients with high-risk genetic features may extend to former (data not shown). Of note, the interaction analysis comparing the magnitude of PFS improvement in patients with and without high risk genetic features, respectively, showed that the benefit was independent of mutational status of IGHV (HR,1.39; 95% CI,0.77-2.40;P=0.26), mutational status of TP53 (HR,1.06; 95% CI,0.56-2.00;P=0.43) and 17p deletion (HR,1.10;95% CI,1.10;95%CI, 0.52-2.35;P=0.40). Interestingly, R/R CLL patients who carried 11q deletion treated with BCR or BCL2 inhibitor fared significantly better in terms of the improvement of PFS than patients without 11q deletion (HR,0.39; 95% CI,0.25-0.62;P<0.0001) indicating the particular value of novel therapies in patients with this genetic defect.Conclusions The important information provided by present meta-analysis is that the improvement over traditional treatments observed with BCR or BCL2 pathway inhibitors is common to all patients with R/R CLL, including those patients with unfavorable and favourable prognostic parameters. BCR signal transduction and BCL2 inhibitors have broad utility and overcome many but not all of the traditional poor risk molecular features in CLL. DisclosuresMolica:Gilead: Other: Advisory board; AbbVie: Other: Advisory board; Roche: Other: Advisory board; Jansen: Other: Advisory board. Levato:Novartis: Other: Advisory board. Shanafelt:Genentech: Research Funding; GlaxoSmithKline: Research Funding; Jansen: Research Funding; Pharmacyclics: Research Funding.

Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis.

BackgroundOverall reduction of antibiotic use is a widely adopted public health goal. Given evidence that consuming probiotics reduce the incidence, duration and/or severity of certain types of common acute infections, we hypothesized that probiotics are associated with reduced antibiotic use. This systematic review of randomized controlled trials (RCTs) assessed the impact of probiotic supplementation (any strain, dose or duration), compared to placebo, on antibiotic utilization for common, acute infections in otherwise healthy people of all ages.MethodsWe searched 13 electronic databases including MEDLINE, Embase and CENTRAL from inception to 17th January 2017. Backward and forward citation searches were also conducted. Two reviewers independently selected studies for inclusion and extracted study data. We assessed risk of bias for individual studies using criteria adapted from the Centre for Reviews and Dissemination, and the quality of evidence for each outcome was assessed using the GRADE system. Studies that evaluated similar outcomes were pooled statistically in meta-analyses using a random-effects model.ResultsWe screened 1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All 17 were conducted in infants and/or children with a primary aim of preventing acute respiratory tract infections, acute lower digestive tract infections or acute otitis media. Included studies used 13 probiotic formulations, all comprising single or combination Lactobacillus and Bifidobacterium delivered in a range of food or supplement products. Mean duration of probiotic supplementation ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis demonstrated that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54–0.94). When restricted to five studies with a low risk of bias, the pooled relative risk was 0.46 (95% CI: 0.23–0.97). Significant statistical heterogeneity was present in effect size estimates, which appeared to be due to one trial which could partly be considered as an outlier.ConclusionsProbiotics, provided to reduce the risk for common acute infections, may be associated with reduced antibiotic use in infants and children. Additional well-designed studies are needed to substantiate these findings in children and explore similar findings in other population groups.

Does hypermethylation of CpG island in the promoter region of the E-cadherin gene increase the risk of lung cancer? A meta-analysis.

BackgroundHypermethylation of the CpG island in the promoter regions of tumor suppressor genes is common in the cancer tissue of non‐small cell lung cancer (NSCLC) patients. Epithelial cadherin (E‐cadherin) is a classic tumor suppressor gene of the cadherin superfamily and its promoter region is usually hypermethylated in malignant carcinomas. However, whether hypermethylation of the CpG island in the promoter region of E‐cadherin increases the risk of lung cancer is unknown. We conducted a meta‐analysis of E‐cadherin gene promoter methylation status in cancer tissue (CT) and autologous controls (AC).MethodsElectronic databases were searched for E‐cadherin gene promoter methylation and NSCLC. The hypermethylation status between CT and AC of NSCLC patients were compared and pooled by random or fixed effect models according to statistical heterogeneity across the included studies.ResultsEleven publications relevant to E‐cadherin gene promoter hypermethylation and lung cancer risk were identified and included. E‐cadherin gene promoter hypermethylation frequency in CT and AC was 0.32 (95% confidence interval [CI] 0.22–0.41) and 0.12 (95% CI 0.04–0.20), respectively, with statistical difference (P < 0.05). Significant statistical heterogeneity was found across the 11 studies (I2 = 54.5, P < 0.05). The data was pooled through a random effect model with an odds ratio of 4.21 (95% CI 2.33–7.58) in CT compared to AC.ConclusionThe frequency of E‐cadherin promoter hypermethylation in CT is significantly higher than in AC, indicating that promoter hypermethylation of E‐cadherin plays an important role in NSCLC carcinogenesis.