Meta-analysis Of Observational Studies In Epidemiology Research Articles

Sodium-Glucose Co-Transporter2 Inhibitors (SGLT2i) Exposure and Outcomes in Type2 Diabetes: A Systematic Review of Population-Based Observational Studies.

IntroductionSodium–glucose co-transporter 2 inhibitors (SGLT2is) are licensed for the treatment of type 2 diabetes (T2D) and more recently for heart failure with or without diabetes. They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, in reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs to broader populations and explore safety, for which RCTs are not usually powered, in more detail.MethodsA pre-planned and registered ((International PROSPEctive Register Of Systematic Reviews) PROSPERO registration CRD42019160792) systematic review of population-based studies investigating SGLT2i effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines was conducted.ResultsA total of 37 studies were identified (total n = 1,300,184 adults; total follow-up 910,577 person-years; exposures: SGLT2i class, canagliflozin, dapagliflozin and empagliflozin) exploring CV disease (CVD) outcomes, acute kidney injury (AKI), lower limb amputation (LLA), diabetic ketoacidosis (DKA), bone fracture, urinary tract infection (UTI), genital mycotic infection (GMI), hypoglycaemia, pancreatitis and venous thromboembolism. For CV and mortality outcomes, studies confirmed the associated safety of these drugs and correlated closely with the findings from RCTs, which may extend to primary CVD prevention (major adverse cardiovascular events point estimate range (PER) hazard ratio (HR) 0.78–0.94; hospitalised heart failure PER HR 0.48–0.79). For safety outcomes, SGLT2i exposure was not associated with an increased risk of AKI (PER HR 0.40–0.96), fractures (PER HR 0.87–1.11), hypoglycaemia (PER HR 0.76–2.49) or UTI (PER HR 0.72–0.98). There was a signal for increased association for GMIs (PER HR 2.08–3.15), and possibly for LLA (PER HR 0.74–2.79) and DKA (PER HR 0.96–2.14), but with considerable uncertainty.ConclusionIn T2D, SGLT2is appear safe from the CV perspective and may have associated benefit in primary as well as secondary CVD prevention. For safety, they may be associated with an increased risk of GMI, LLA and DKA, although longer follow-up studies are needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01004-2.

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

IntroductionIron profiles in patients with type 2 diabetes (T2D) are inconsistent. In this study, we assessed the levels of hepcidin, a regulatory protein involved in iron homoeostasis, in patients with T2D. We further evaluated the surrogate markers of hepcidin action, particularly those associated with erythropoiesis. MethodsThis systematic review and meta-analysis was reported following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched for relevant studies in electronic databases from inception until 31 October 2020 without any language restriction. The random effects model was used to calculate effect estimates, and outcomes were reported as either standardised mean difference (SMD) or mean differences (MD), 95 percent confidence interval (95% CI). ResultsEleven studies involving 2 620 participants were included in this study. Patients with T2D had a slight increase in hepcidin levels when compared to controls SMD: 0.07 [95% CI: -0.30, 0.44]. The subgroup analysis showed that studies involving patients with T2D who were overweight reported elevated hepcidin levels SMD: 0.35 [95% CI: 0.07, 0.62] whilst those with grade I obesity described reduced levels SMD: -0.42 [95% CI: -1.21, 0.38]. All T2D patients had low levels of haemoglobin MD: -0.23 g/dl [95% CI: -0.46, -0.01] irrespective of body weight. ConclusionThe levels of hepcidin are altered in patients with T2D and are disproportionately influenced by weight. Moreover, patients with T2D present with subclinical anaemia despite elevated iron stores. The regulation of hepcidin in patients with T2D is dependent on several factors and vary greatly, thus its sole use in clinical settings may be less beneficial.

Glucagon-Like Peptide1 Receptor Agonist (GLP1RA) Exposure and Outcomes in Type2 Diabetes: A Systematic Review of Population-Based Observational Studies.

IntroductionGlucagon-like peptide 1 receptor agonists (GLP1RAs) are licensed for the treatment of type 2 diabetes (T2D). They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs findings to broader populations and explore safety, for which RCTs are not usually powered, in more detail.MethodWe did a pre-planned and registered (PROSPERO registration CRD42020165720) systematic review of population-based studies investigating GLP1RA effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.ResultsA total of 22 studies were identified (including 200,148 participants and 396,457 person-years of follow-up) exploring exposure to GLP1RA class, exenatide and liraglutide (the only individual drugs with treatment effect estimates identified) on mortality, cardiovascular disease (CVD), acute pancreatitis (AP), pancreatic cancer (PC), thyroid cancer (TC), acute renal failure (ARF), diabetic retinopathy (DR), breast cancer (BC) and hypoglycaemia. For CV and mortality outcomes, studies confirmed the associated safety of these drugs. For liraglutide, point estimate (PE) range (PER) major adverse cardiovascular events (MACE) (0.53–0.95) and PER heart failure (0.34–1.22) were similar in direction to the beneficial effect observed in RCTs for MACE but varied widely for heart failure. For safety outcomes, exposure was not associated with AP (PER 0.50–1.17), PC (PER 0.40–1.54), BC (PER 0.90–1.51) or hypoglycaemia (PER 0.59–1.06). Only one study was identified exploring each of TC (no evidence of association, hazard ratio (HR) 1.46, 95% confidence interval (CI) 0.98–2.19), renal outcomes (no evidence of association, HR 0.77, 95% CI 0.42–1.41) and DR (no evidence of association, HR 0.67, 95% CI 0.51–0.90).ConclusionIn T2D, GLP1RAs appear safe from the CV perspective and (for liraglutide) may have associated benefit in primary as well as secondary CVD prevention. For non-CV safety, GLP1RA exposure was not associated with an increased risk of AP, PC, BC or hypoglycaemia; the other outcomes had too few studies to draw firm conclusions and should be explored further.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01021-1.

Association of Attention-Deficit/Hyperactivity Disorder in Childhood and Adolescence With the Risk of Subsequent Psychotic Disorder

Growing evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) in childhood and subsequent psychotic disorders. Both disorders share physiopathological features such as attention deficits, dopaminergic imbalance, and genetic susceptibility. However, the results of epidemiologic studies have been conflicting. To provide a quantitative synthesis of studies exploring the association between ADHD and the risk of subsequent psychotic disorder. A systematic literature search of the MEDLINE, Scopus, PsycInfo, and Web of Science databases was performed from inception until the final analysis on July 7, 2020. No restriction of language was applied. Cohort and case-control studies examining the relative risk of developing a psychotic disorder in people diagnosed with ADHD at younger than 18 years compared with control individuals without ADHD. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in reporting results. Two independent reviewers extracted the data and assessed the risk of bias of individual studies using the Newcastle-Ottawa Scale. Preferably adjusted odds ratios (aORs) or hazard ratios from the identified studies were extracted, and ORs were computed when they were not adjusted. A random-effects model was used to calculate the pooled relative effect using the meta package in R. An association between ADHD (exposure) and psychotic disorder (outcomes); both diagnoses were based on international classification. A total of 15 studies were included in the review. Twelve studies were pooled in the meta-analysis, representing 1.85 million participants. A diagnosis of ADHD in childhood was associated with a significant increase in the risk of subsequent psychotic disorder, with a pooled relative effect of 4.74 (95% CI, 4.11-5.46; I2 = 43% [95% CI, 0%-70%]). No significant between-group differences were found for subgroup analyses according to psychotic disorder (odds ratio [OR], 5.04; 95% CI, 4.36-5.83) or schizophrenia (OR, 4.59; 95% CI, 3.83-5.50) outcomes, cohort (OR, 4.64; 95% CI, 4.04-5.34) or case-control (OR, 6.81; 95% CI, 4.21-11.03) study design, and adjusted (OR, 4.72; 95% CI, 4.11-5.46) or unadjusted (OR, 3.81; 95% CI, 1.39-10.49) estimates. Meta-regressions were not significant when sex and bias score were used as covariates. No evidence of publication bias was found. These findings suggest that childhood ADHD is associated with an increased risk of a subsequent psychotic disorder. Further studies are required to determine the mechanisms linking these common conditions and whether early intervention for ADHD might reduce the risk of subsequent psychotic disorder.

The effect of coagulation factors in 2019 novel coronavirus patients: A systematic review and meta-analysis.

Background:The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19.Methods:We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity.Results:Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization.Conclusion:Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed.Trial registration:PROSPERO (CRD42020183514).

COVID-19 Outcomes Amongst Patients With Pre-existing Cardiovascular Disease and Hypertension.

Introduction: Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN.Methods: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models.Results: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1).Conclusion: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Protocol: A systematic review and meta-analysis of the role of fetal and infantile environmental exposure in etiopathogenesis of infantile hypertrophic pyloric stenosis.

Infantile hypertrophic pyloric stenosis (IHPS) is one of the hallmark pediatric surgical diseases. However, its etiology remains incompletely understood. By systematically reviewing the literature, we aim to clarify the effect of the effect of occupational and environmental factors and role of nitric oxide (NO) metabolism in the etiopathogenesis of IHPS. The systematic review is drafted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). Systematic literature search will be performed for the period 2000 (Jan) to 2020 (Dec) in the databases: MEDLINE, EMBASE, PubMed. The systematic search will cover the literature in English and Turkish language and will be limited to studies on human subjects. Four investigators will independently search the databases (MEDLINE, EMBASE, PubMed) according to the defined search strategy. The full-text of the selected articles will be screened independently by four reviewers, against the inclusion criteria. Descriptive data will be extracted from each study regarding: study details, methods, participants, outcomes and calculations of association for potential further statistical analysis. If meta-analysis could not be undertaken, systematic approach to analyzing the findings of included multiple studies will be described. Heterogeneity will be assessed by quantifying the inconsistency across studies using I2 statistic. Statistical analysis will be performed using Comprehensive Meta-Analysis Version 3.0 software. The p values lower than 0.05 will be considered statistically significant for all analyses.

Obstetrics outcomes after complete and partial molar pregnancy: Review of the literature and meta-analysis

The hydatidiform mole is a rare gynecological disease rising from the trophoblastic. Post-molar pregnancies have an extremely variable course, varying from repeated abortions, stillbirths, preterm births, live births, or recurring in further molar pregnancies. Literature on obstetric outcomes following molar pregnancy is poor, often including monocentric studies, and with data collected from national databases. This review and meta-analysis aim to analyze the obstetric outcomes after conservative management of complete (CHM) and partial (PHM) molar pregnancies. The meta-analysis was performed following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Six studies met the inclusion. Of the total 25,222 patients, 13,129 complete (52.1 %) and 12,093 partial (47.9 %) molar pregnancies were included. Live births rate after CHM was statistically higher (p = 0.002) compared to the live births after PHM (53.6 % vs. 51.0 %, 3266 vs. 1807 cases, respectively). Studies showed heterogeneity I2 = 57.7 %, pooled proportion = 0.2 %, and 95 % Confidence Interval (CI) 0.6 to 0.9. No statistically significant difference was demonstrated for ectopic pregnancies (p = 0.633), miscarriage (p = 0.637), preterm birth (p = 0.865), stillbirth (p = 0.911), termination of pregnancy (p = 0.572), and complete molar recurrence (p = 0.580) after CHM and PHM. Partial molar recurrence occurred more frequently after PHM than CHM (0.4 % vs. 0.3 %, 52 vs. 37 cases, respectively, p = 0.002). Careful counseling on the obstetric subsequent pregnancies outcomes should be provided to patients eager for further pregnancy and further studies are needed to confirm these results.

Changes in fasting bile acid profiles after Roux-en-Y gastric bypass and sleeve gastrectomy.

Bile acid is an essential factor that plays a role in metabolic regulation, but how bile acid is regulated after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remains unclear. This meta-analysis aimed to investigate changes in the levels of fasting bile acids following RYGB and SG. A systematic literature search of the PubMed, EMBASE, Cochrane Library and Web of Science databases through July 2020 was performed in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The concentrations of bile acids were evaluated. Thirteen studies with 289 patients were included. Our results showed that patients who underwent RYGB had increased levels of fasting total bile acids, primary bile acids, secondary bile acids, conjugated bile acids, and unconjugated bile acids, but no significant differences in all these bile acid levels were observed in patients who underwent SG. Furthermore, 12a-hydroxylated bile acid levels and the 12a-hydroxylated/non-12a-hydroxylated bile acid ratio also increased following RYGB. In this study, we found that fasting bile acid levels, especially 12a-hydroxylated bile acids levels, were increased after RYGB. However, no differences in fasting bile acid levels were observed following SG.

Cost-effectiveness of photobiomodulation therapy for the prevention and management of cancer treatment toxicities: a systematic review.

To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3-4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Minimally Invasive Approach in Boerhaave's Syndrome: Case Series and Systematic Review.

Introduction: Boerhaave's syndrome is a life-threatening spontaneous perforation of the esophagus associated with significant morbidity and mortality. Historically, thoracotomy has been the mainstay of treatment, but is associated with high morbidity and pain. Minimally invasive approaches provide alternative treatment possibilities. This systematic review together with inclusion of a case series from a tertiary esophagogastric unit assesses current evidence focused on minimally invasive surgical management of this condition. Methods: A systematic review was conducted in line with MOOSE (Meta-analyses Of Observational Studies in Epidemiology) guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles focusing on the minimally invasive management of Boerhaave's syndrome were identified and scrutinized. We also report demographics and outcomes for a consecutive case series of patients with acute Boerhaave's syndrome managed via thoracoscopy. Results: Fifteen studies were included comprising 5 retrospective cohort studies and 10 case reports. Management strategies were divided into three categories: thoracoscopic, endoscopic, and laparoscopic. Overall mortality rates for each treatment modality were 2%, 13%, and 33%, and treatment success rates 98%, 38%, and 67%, respectively. Postoperative infective complications were seen in 79% of patients, with only 2 patients requiring salvage thoracotomy. In our local case series, we report 4 consecutive patients managed with thoracoscopy, with a 100% treatment success rate. Conclusion: Minimally invasive approaches in the management of Boerhaave's syndrome are safe and effective. We propose a selective management algorithm involving a minimally invasive approach to management of this life-threatening condition. Registered with local clinical outcomes team as service evaluation. (Approval number sev/0171).

Chest computed tomography scan findings of coronavirus disease 2019 (COVID-19) patients: a comprehensive systematic review and meta-analysis.

IntroductionNumerous cases of pneumonia caused by coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. Chest computed tomography (CT) scan is highly important in the diagnosis and follow-up of lung disease treatment. The present meta-analysis was performed to evaluate chest CT scan findings in COVID-19 patients.Material and methodsAll research steps were taken according to the Meta-Analysis of Observational Studies In Epidemiology (MOOSE) protocol and the final report was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered this review at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42019127858).ResultsForty eligible studies including 4598 patients with COVID-19 were used for meta-analysis. The rate of positive chest CT scan in patients with COVID-19 was 94.5% (95% CI: 91.7-96.3). Bilateral lung involvement, pure ground-glass opacity (GGO), mixed (GGO pulse consolidation or reticular), consolidation, reticular, and presence of nodule findings in chest CT scan of COVID-19 pneumonia patients were respectively estimated to be 79.1% (95% CI: 70.8-85.5), 64.9% (95% CI: 54.1-74.4), 49.2% (95% CI: 35.7-62.8), 30.3% (95% CI: 19.6-43.6), 17.0% (95% CI: 3.9-50.9) and 16.6% (95% CI: 13.6-20.2). The distribution of lung lesions in patients with COVID-19 pneumonia was peripheral (70.0% [95% CI: 57.8-79.9]), central (3.9% [95% CI: 1.4-10.6]), and peripheral and central (31.1% [95% CI: 19.5-45.8]). The pulmonary lobes most commonly involved were the right lower lobe (86.5% [95% CI:57.7-96.8]) and left lower lobe (81.0% [95% CI: 50.5-94.7]).ConclusionsThe most important outcomes in chest CT scan of patients with COVID-19 pneumonia were bilateral lung involvement, GGO or mixed (GGO pulse consolidation or reticular) patterns, thickened interlobular septa, vascular enlargement, air bronchogram sign, peripheral distribution, and left and right lower lobes involvement. Our study showed that chest CT scan has high sensitivity in the diagnosis of COVID-19, and may therefore serve as a standard method for diagnosis of COVID-19.

Urinary Volatile Organic Compound Analysis for the Diagnosis of Cancer: A Systematic Literature Review and Quality Assessment.

The analysis of urinary volatile organic compounds (VOCs) is a promising field of research with the potential to discover new biomarkers for cancer early detection. This systematic review aims to summarise the published literature concerning cancer-associated urinary VOCs. A systematic online literature search was conducted to identify studies reporting urinary VOC biomarkers of cancers in accordance with the recommendations of the Cochrane Library and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Thirteen studies comprising 1266 participants in total were included in the review. Studies reported urinary VOC profiles of five cancer subtypes: prostate cancer, gastrointestinal cancer, leukaemia/lymphoma, lung cancer, and bladder cancer. Forty-eight urinary VOCs belonging to eleven chemical classes were identified with high diagnostic performance. VOC profiles were distinctive for each cancer type with limited cross-over. The metabolic analysis suggested distinctive phenotypes for prostate and gastrointestinal cancers. The heterogenicity of study design, methodological and reporting quality may have contributed to inconsistencies between studies. Urinary VOC analysis has shown promising performance for non-invasive diagnosis of cancer. However, limitations in study design have resulted in inconsistencies between studies. These limitations are summarised and discussed in order to support future studies.

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We performed a systematic review and meta-analysis to identify all prognostic factors for advanced colorectal neoplasia (aCRN, high-grade dysplasia, or CRC) in patients with IBD. A systematic literature search was conducted according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk of bias was assessed using the Quality in Prognostic Studies tool. Random-effects models were created separately for odds and hazard ratios, different study designs, and univariable or multivariable data. The evidence for all prognostic factors was categorized as "weak", "moderate", or "strong", based on estimate of effect sizes, heterogeneity, and risk of bias. A total of 164 studies were included, allowing pooled analysis of 31 potential prognostic factors. In the univariable analysis, the evidence for extensive disease was classified as strong while evidence for low-grade dysplasia, strictures, primary sclerosing cholangitis, post-inflammatory polyps, family history of CRC, and ulcerative colitis versus Crohn's disease was considered moderate. Evidence for any dysplasia, colon segment resection, aneuploidy, male sex, and age was classified as weak. In addition, histologic inflammation was identified as a risk factor in multivariable analysis (weak evidence). The evidence for the protective factors colonoscopic surveillance, 5-Aminosalicylic Acid, thiopurines, and smoking was moderate in univariable analysis. Multivariable analysis provided weak evidence for statin use. In this systematic review and meta-analysis, we identified 13 risk factors and 5 protective factors for aCRN in IBD patients, based on univariable and/or multivariable pooled analyses. These findings might lay the groundwork for an improved CRC risk stratification-based surveillance in IBD.

Epidemiology of streptomycin resistant Salmonella from humans and animals in Ethiopia: A systematic review and meta-analysis.

BackgroundStreptomycin is used as an epidemiological marker in monitoring programs for antimicrobial resistance in Salmonella serovars and indicates the presence of pentaresistance. However, comprehensive data on streptomycin resistant Salmonella among human, animal, and animal products is lacking in Ethiopia. In this review, we aimed to assess heterogeneity and pooled proportion of Salmonella serovars to streptomycin resistance among human, animal and animal products in Ethiopia.MethodsWe conducted a systematic review and meta-analysis of published literature from Ethiopia. We used the MEDLINE/ PubMed, Embase, Cochrane Library, and Google Scholar databases to identify genetic and phenotypic data on Salmonella isolates. To determine the heterogeneity and pooled proportion, we used metaprop commands and the random-effects model. Relative and cumulative frequencies were calculated to describe the overall preponderance of streptomycin resistance isolates after arcsine-transformed data. Metan funnel and meta-bias using a begg test were performed to check for publication bias.ResultsOverall, we included 1475 Salmonella serovars in this meta-analysis. The pooled proportion of streptomycin resistance was 47% (95% CI: 35–60%). Sub-group analysis by target population showed that the proportion of streptomycin resistance in Salmonella serovars was 54% (95% CI: 35–73%) in animal, 44% (95% Cl: 33–59%) in humans and 39% (95% CI: 24–55%) in animals products. The streptomycin resistant Salmonella serovars were statistically increasing from 0.35(95% CI: 0.12–0.58) in 2003 to 0.77(95% CI: 0.64–0.89) in 2018. The level of multidrug-resistant (MDR) Salmonella serovars was 50.1% in the meta-analysis.ConclusionWe found a high level of streptomycin resistance, including multidrug, Salmonella serovars among human, animals, and animal products. This resistance was significantly increasing in the last three decades (1985–2018). The resistance to streptomycin among Salmonella serovars isolated from animals was higher than humans. This mandates the continuous monitoring of streptomycin use and practicing one health approach to preventing further development of resistance in Ethiopia.RegistrationWe conducted a systematic review and meta-analysis after registration of the protocol in PROSPERO (CRD42019135116) following the MOOSE (Meta-Analysis of Observational Studies in Epidemiology).

Biological fluid levels of iron and iron‐related proteins in Parkinson’s disease: Review and meta‐analysis

Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD. However, the results on cerebrospinal (CSF) and serum/plasma iron levels in PD patients have been controversial. The aim of this systematic review and meta-analysis was to establish the CSF and serum/plasma levels of iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, and hepcidine) levels, and the urine levels of iron, in patients with PD. Four databases (PubMed, EMBASE, MedLine, and Web of Science - Core Collection) were reviewed for studies published from 1966 to October 5, 2020. References of interest were identified. A meta-analysis of eligible studies was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, using the R software package meta. A non-significant trend towards higher CSF iron levels and marginally significantly lower serum/plasma iron levels was observed in patients with PD compared with age- and sex-matched controls. CSF and serum/plasma ferritin and transferrin concentrations, and serum/plasma lactoferrin and haptoglobin concentrations did not differ significantly between PD patients and controls. The findings of this study suggest an association between decreased serum/plasma iron levels and, possibly, higher CSF iron levels with risk of PD.

Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure

Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization. To quantify the difference in the antipsychotic and antidepressant exposure among patients with genetically associated CYP2C19 and CYP2D6 poor (PM), intermediate (IM), and normal (NM) metabolizers. PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to June 30, 2020, with no language restrictions. Two independent reviewers performed study screening and assessed the following inclusion criteria: (1) appropriate CYP2C19 or CYP2D6 genotyping was performed, (2) genotype-based classification into CYP2C19 or CYP2D6 NM, IM, and PM categories was possible, and (3) 3 patients per metabolizer category were available. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for extracting data and quality, validity, and risk of bias assessments. A fixed-effects model was used for pooling the effect sizes of the included studies. Drug exposure was measured as (1) dose-normalized area under the plasma level (time) curve, (2) dose-normalized steady-state plasma level, or (3) reciprocal apparent total drug clearance. The ratio of means (RoM) was calculated by dividing the mean drug exposure for PM, IM, or pooled PM plus IM categories by the mean drug exposure for the NM category. Based on the data derived from 94 unique studies and 8379 unique individuals, the most profound differences were observed in the patients treated with aripiprazole (CYP2D6 PM plus IM vs NM RoM, 1.48; 95% CI, 1.41-1.57; 12 studies; 1038 patients), haloperidol lactate (CYP2D6 PM vs NM RoM, 1.68; 95% CI, 1.40-2.02; 9 studies; 423 patients), risperidone (CYP2D6 PM plus IM vs NM RoM, 1.36; 95% CI, 1.28-1.44; 23 studies; 1492 patients), escitalopram oxalate (CYP2C19 PM vs NM, RoM, 2.63; 95% CI, 2.40-2.89; 4 studies; 1262 patients), and sertraline hydrochloride (CYP2C19 IM vs NM RoM, 1.38; 95% CI, 1.27-1.51; 3 studies; 917 patients). Exposure differences were also observed for clozapine, quetiapine fumarate, amitriptyline hydrochloride, mirtazapine, nortriptyline hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, paroxetine hydrochloride, and venlafaxine hydrochloride; however, these differences were marginal, ambiguous, or based on less than 3 independent studies. In this systematic review and meta-analysis, the association between CYP2C19/CYP2D6 genotype and drug levels of several psychiatric drugs was quantified with sufficient precision as to be useful as a scientific foundation for CYP2D6/CYP2C19 genotype-based dosing recommendations.

Suggestibility in functional neurological disorder: a meta-analysis

ObjectiveResponsiveness to direct verbal suggestions (suggestibility) has long been hypothesised to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of...

Association of Circulating Tumor DNA With Disease-Free Survival in Breast Cancer

Fragmented DNA is continuously released into the circulation following apoptosis and necrosis of both cancerous and noncancerous cells; when it is released by cancer cells, it is specifically known as circulating tumor DNA (ctDNA). Previous studies have suggested that ctDNA can reflect tumor burden and guide potential therapeutic targets. To determine the association of ctDNA with breast cancer disease-free survival (DFS) and progression-free survival in early, locally advanced, and metastatic breast cancer. An electronic search was conducted using the Cochrane Library, ScienceDirect, PubMed, and Embase from July 30, 2019, to October 31, 2019; all languages were included. The following search terms were used: ctDNA OR circulating tumor DNA OR liquid biopsy AND breast cancer OR breast carcinoma OR breast tumor AND prognosis OR survival. All titles were screened, and the appropriate abstracts were reviewed. If any data were missing, the authors contacted the study authors for permission to access data and extrapolate hazard ratios (HRs). To be included in the analysis, the studies had to meet the following prespecified inclusion criteria: (1) a ctDNA blood sample was measured; (2) DFS, progression-free survival, or relapse-free survival was reported as an HR; and (3) the patient population only had breast cancer. Retrospective and prospective observational cohort studies were included. Two authors (C.C. and C.F.) independently reviewed the literature. All data were recorded independently by both authors and were compared at the end of the reviewing process to limit selection bias. Duplicates were removed and any disparities were clarified. Data were pooled using a fixed-effects or random-effects model according to the study heterogeneity. This study adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE). The primary outcome was the association of ctDNA with DFS or relapse-free survival in breast cancer. Secondary outcomes focused on subgroup analysis in the setting of early breast cancer and metastatic breast cancer. From a total of 263 publications found using the predefined search terms, data from 8 studies (3.0%) reporting on 739 patients in total were suitable for inclusion. Circulating tumor DNA gene variation detection (both before and after treatment) was statistically significantly associated with shorter DFS (HR, 4.44; 95% CI, 2.29-8.61; P < .001). Detection of ctDNA was statistically significantly associated with a reduction in DFS in both the early breast cancer subgroup (HR, 8.32; 95% CI, 3.01-22.99; P < .001) and the metastatic or locally advanced subgroup (HR, 1.91; 95% CI, 1.35-2.71; P < .001). Pretreatment and posttreatment plasma sample collection was analyzed in both early and metastatic groups. The posttreatment group encompassed both surgical and oncologic therapy. Pretreatment plasma detection of ctDNA was statistically significantly associated with reduced DFS (HR, 3.30; 95% CI, 1.98-5.52; P < .001). Posttreatment sampling of ctDNA failed to achieve statistical significance (HR, 8.17; 95% CI, 1.01-65.89; P = .05). In this systematic review and meta-analysis, elevated plasma ctDNA was associated with a high risk of relapse. This finding suggests that plasma ctDNA may provide an excellent method to stratify risk and personalize patient follow-up.

Abstract 13322: Association Between Allergic Diseases and Development of Kawasaki Disease Among Children: A Systematic Review and Meta-analysis

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It is the leading cause of pediatric acquired heart disease in developed countries. Growing evidence points to the role of immunoregulatory abnormalities for its causation. Hypothesis: It is hypothesized that a history of allergic diseases is associated with the development of KD in children. Methods: A systematic review and meta-analysis of observational studies was performed to ascertain the association between history of allergic diseases and KD. Major electronic databases were searched from inception through March 2020 using pre-defined index terms such as “allergic disease”, “Kawasaki disease” and “children”. Random effects model was used to derive pooled estimates of odds ratios (OR) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale was used for qualitative assessment. This study was reported according to MOOSE (Meta-analyses Of Observational Studies in Epidemiology). Results: Of 854 articles identified, 8 studies were considered eligible. History of allergic diseases was significantly associated with the development of KD (OR 1.99; 95% CI 1.26-2.73). On subgroup analysis of case-control studies (n=6), allergic diseases remained significantly associated with KD (OR 1.61; 95% CI 1.10-2.12). However, subgroup analysis with allergic diseases limited to asthma (n=5) revealed no significant association with KD (OR 1.17; 95% CI 0.45-1.90). Qualitative assessment found minimal concerns for bias. Conclusions: The available evidence suggests a strong association between history of allergic diseases and development of Kawasaki disease among children.