Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials

PubMed Central

2014-01-01

Background It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs. Methods Pooled analyses were performed of 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin + metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method). Results In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12). Conclusions Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk. PMID:24490835

Use of Sugammadex in Patients With Obesity: A Pooled Analysis.

PubMed

Monk, Terri G; Rietbergen, Henk; Woo, Tiffany; Fennema, Hein

A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis.

PubMed

Juo, Y Y; Johnston, F M; Zhang, D Y; Juo, H H; Wang, H; Pappou, E P; Yu, T; Easwaran, H; Baylin, S; van Engeland, M; Ahuja, N

2014-12-01

Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published studies in order to examine the association between CIMP and CRC prognosis. A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics. Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07-1.97, Q = 3.95, I(2) = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18-1.73, Q = 4.03, I(2) = 0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12-1.68, Q = 4.45, I(2) = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy. CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival benefit to CRC patients remained to be determined through future prospective randomized studies. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis

PubMed Central

Juo, Y. Y.; Johnston, F. M.; Zhang, D. Y.; Juo, H. H.; Wang, H.; Pappou, E. P.; Yu, T.; Easwaran, H.; Baylin, S.; van Engeland, M.; Ahuja, N.

2014-01-01

Background Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published studies in order to examine the association between CIMP and CRC prognosis. Materials and methods A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics. Results Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07–1.97, Q = 3.95, I2 = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18–1.73, Q = 4.03, I2 = 0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12–1.68, Q = 4.45, I2 = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy. Conclusion CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival benefit to CRC patients remained to be determined through future prospective randomized studies. PMID:24718889

Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis.

PubMed

Wijarnpreecha, Karn; Thongprayoon, Charat; Chesdachai, Supavit; Panjawatanana, Panadeekarn; Ungprasert, Patompong; Cheungpasitporn, Wisit

2017-10-01

The aim of this meta-analysis was to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton-pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs). Comprehensive literature review was conducted utilizing MEDLINE and EMBASE databases through April 2017 to identify all studies that investigated the risks of CKD or ESRD in patients taking PPIs/H2RAs versus those without PPIs/H2RAs. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067252). Five studies with 536,902 participants were patients were identified and included in the data analysis. When compared with non-PPIs users, the pooled risk ratio (RR) of CKD or ESRD in patients with PPI use was 1.33 (95% CI 1.18-1.51). Pre-specified subgroup analysis (stratified by CKD or ESRD status) demonstrated pooled RRs of 1.22 (95% CI 1.14-1.30) for association between PPI use and CKD and 1.88 (95% CI 1.71-2.06) for association between PPI use and ESRD, respectively. However, there was no association between the use of H2RAs and CKD with a pooled RR of 1.02 (95% CI 0.83-1.25). When compared with the use of H2RAs, the pooled RR of CKD in patients with PPI use was 1.29 (95% CI 1.22-1.36). Our study demonstrates statistically significant 1.3-fold increased risks of CKD and ESRD in patients using PPIs, but not in patients using H2RAs.

Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis.

PubMed

Passiglia, Francesco; Rizzo, Sergio; Rolfo, Christian; Galvano, Antonio; Bronte, Enrico; Incorvaia, Lorena; Listi, Angela; Barraco, Nadia; Castiglia, Marta; Calo, Valentina; Bazan, Viviana; Russo, Antonio

2018-03-08

Recent studies evaluated the diagnostic accuracy of circulating tumor DNA (ctDNA) in the detection of epidermal growth factor receptor (EGFR) mutations from plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue genotyping. However it is less clear if the location of metastatic site may influence the ability to identify EGFR mutations in plasma. This pooled analysis aims to evaluate the association between the metastatic site location and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients. Data from all published studies, evaluating the sensitivity of plasma-based EGFR-mutation testing, stratified by metastatic site location (extrathoracic (M1b) vs intrathoracic (M1a)) were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the ctDNA analysis sensitivity, according to metastatic site location. A total of ten studies, with 1425 patients, were eligible. Pooled analysis showed that the sensitivity of ctDNA-based EGFR-mutation testing is significantly higher in patients with M1b vs M1a disease (OR: 5.09; 95% CIs: 2.93 - 8.84). A significant association was observed for both EGFR-activating (OR: 4.30, 95% CI: 2.35-7.88) and resistant T790M mutations (OR: 11.89, 95% CI: 1.45-97.22), regardless of the use of digital-PCR (OR: 5.85, 95% CI: 3.56-9.60) or non-digital PCR technologies (OR: 2.96, 95% CI: 2.24-3.91). These data suggest that the location of metastatic sites significantly influences the diagnostic accuracy of ctDNA analysis in detecting EGFR mutations in NSCLC patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cardiothoracic ratio for prediction of left ventricular dilation: a systematic review and pooled analysis.

PubMed

Loomba, Rohit S; Shah, Parinda H; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit

2015-03-01

Increased cardiothoracic ratio noted on chest radiographs often prompts concern and further evaluation with additional imaging. This study pools available data assessing the utility of cardiothoracic ratio in predicting left ventricular dilation. A systematic review of the literature was conducted to identify studies comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by echocardiography. Electronic databases were used to identify studies which were then assessed for quality and bias, with those with adequate quality and minimal bias ultimately being included in the pooled analysis. The pooled data were used to determine the sensitivity, specificity, positive predictive value and negative predictive value of cardiomegaly in predicting left ventricular dilation. A total of six studies consisting of 466 patients were included in this analysis. Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive predictive value and 82.7% negative predictive value. When a secondary analysis was conducted with a pediatric study excluded, a total of five studies consisting of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2% specificity, 42.5% positive predictive value and 74.0% negative predictive value. Cardiothoracic ratio as determined by chest radiograph is sensitive but not specific for identifying left ventricular dilation. Cardiothoracic ratio also has a strong negative predictive value for identifying left ventricular dilation.

Assessing Tuberculosis Case Fatality Ratio: A Meta-Analysis

PubMed Central

Straetemans, Masja; Glaziou, Philippe; Bierrenbach, Ana L.; Sismanidis, Charalambos; van der Werf, Marieke J.

2011-01-01

Background Recently, the tuberculosis (TB) Task Force Impact Measurement acknowledged the need to review the assumptions underlying the TB mortality estimates published annually by the World Health Organization (WHO). TB mortality is indirectly measured by multiplying estimated TB incidence with estimated case fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case fatality ratio in TB patients having initiated TB treatment. Methods We searched for eligible studies in the PubMed and Embase databases through March 4th 2011 and by reference listing of relevant review articles. Main analyses included the estimation of the pooled percentages of: a) TB patients dying due to TB after having initiated TB treatment and b) TB patients dying during TB treatment. Pooled percentages were estimated using random effects regression models on the combined patient population from all studies. Main Results We identified 69 relevant studies of which 22 provided data on mortality due to TB and 59 provided data on mortality during TB treatment. Among HIV infected persons the pooled percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI): 3.7%–14.7%) and among HIV uninfected persons 3.0% (95% CI: −1.2%–7.4%) based on the results of eight and three studies respectively providing data for this analyses. The pooled percentage of TB patients dying during TB treatment was 18.8% (95% CI: 14.8%–22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%–4.92%) among HIV uninfected patients based on the results of 27 and 19 studies respectively. Conclusion The results of the literature review are useful in generating prior distributions of CFR in countries with vital registration systems and have contributed towards revised estimates of TB mortality This literature review did not provide us with all data needed for a valid estimation of TB CFR in TB patients initiating TB treatment. PMID:21738585

Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

PubMed

Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

2016-11-25

Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

Deep-learning-based classification of FDG-PET data for Alzheimer's disease categories

NASA Astrophysics Data System (ADS)

Singh, Shibani; Srivastava, Anant; Mi, Liang; Caselli, Richard J.; Chen, Kewei; Goradia, Dhruman; Reiman, Eric M.; Wang, Yalin

2017-11-01

Fluorodeoxyglucose (FDG) positron emission tomography (PET) measures the decline in the regional cerebral metabolic rate for glucose, offering a reliable metabolic biomarker even on presymptomatic Alzheimer's disease (AD) patients. PET scans provide functional information that is unique and unavailable using other types of imaging. However, the computational efficacy of FDG-PET data alone, for the classification of various Alzheimers Diagnostic categories, has not been well studied. This motivates us to correctly discriminate various AD Diagnostic categories using FDG-PET data. Deep learning has improved state-of-the-art classification accuracies in the areas of speech, signal, image, video, text mining and recognition. We propose novel methods that involve probabilistic principal component analysis on max-pooled data and mean-pooled data for dimensionality reduction, and multilayer feed forward neural network which performs binary classification. Our experimental dataset consists of baseline data of subjects including 186 cognitively unimpaired (CU) subjects, 336 mild cognitive impairment (MCI) subjects with 158 Late MCI and 178 Early MCI, and 146 AD patients from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We measured F1-measure, precision, recall, negative and positive predictive values with a 10-fold cross validation scheme. Our results indicate that our designed classifiers achieve competitive results while max pooling achieves better classification performance compared to mean-pooled features. Our deep model based research may advance FDG-PET analysis by demonstrating their potential as an effective imaging biomarker of AD.

Unilateral vocal fold paralysis after congenital cardiothoracic surgery: a meta-analysis.

PubMed

Strychowsky, Julie E; Rukholm, Gavin; Gupta, Michael K; Reid, Diane

2014-06-01

There is variation in the literature in regard to the occurrence of unilateral vocal fold paralysis (UVFP) after congenital cardiothoracic surgery. The objective of this study was to identify and appraise the evidence for the occurrence of UVFP after congenital cardiothoracic surgery in a meta-analysis. A comprehensive search strategy in Medline, Embase, and the Cochrane Library was conducted, limited to English publications. Two independent reviewers screened studies for eligibility criteria. Of the 162 identified studies, 32 (20%) met the inclusion criteria. Using the Oxford Centre for Evidence-Based Medicine guidelines, 2 reviewers appraised the level of evidence, extracted data, and resolved discrepancies by consensus. Weighted pooled proportion and 95% confidence intervals (CIs) are reported. Thirty-two studies (n = 5625 patients) were included. Levels of evidence varied from level 3 to 4. Among all studies, the weighted pooled proportion of UVFP was 9.3% (95% CI, 6.6% to 12.5%), and among 11 studies (n = 584 patients) that postoperatively evaluated patients with flexible nasopharyngolaryngoscopy to document presence of UVFP, the weighted pooled proportion of UVFP was 29.8% (95% CI, 18.5% to 42.5%). Twenty-one studies (n = 2748 patients) evaluated patients undergoing patent ductus arteriosus ligation surgery, and the weighted pooled proportion of UVFP was 8.7% (95% CI, 5.4% to 12.6%). Six of these (n = 274 patients) assessed all patients postoperatively, and the weighted pooled proportion of UVFP was 39% (95% CI, 18% to 63%). Pooled analyses of risk factors and comorbidities are reported. Heterogeneity and publication bias were detected. UVFP is a demonstrated risk of congenital cardiothoracic surgery. Routine postoperative nasopharyngolaryngoscopy for vocal fold assessment by an otolaryngologist is suggested. Copyright © 2014 by the American Academy of Pediatrics.

The risk of kidney stones following bariatric surgery: a systematic review and meta-analysis.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Vijayvargiya, Priya; Anthanont, Pimjai; Erickson, Stephen B

2016-01-01

With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney stones following bariatric surgery. A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85). Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery.

Smoking and EGFR status may predict outcomes of advanced NSCLC treated with PD-(L)1 inhibitors beyond first line: A meta-analysis.

PubMed

Abdel-Rahman, Omar

2017-11-08

The aim of this study was to assess the potential clinical and biological predictive markers of survival in pretreated advanced NSCLC patients treated with the three PD-(L)1 inhibitors (nivolumab, pembrolizumab and atezolizumab). PubMed database has been searched. The review author extracted relevant information on participant characteristics and study outcomes for this review and assessed risk of bias of the included trials. Data analysis was conducted through RevMan v.5.3. Five randomized controlled trials with 3013 patients were included. There was no predictive value for the age of the patients (taking 65 years as a cutoff value), the histology (squamous vs nonsquamous) or performance score (score 0 vs score 1); while there appears to be a value for smoking history and EGFR status. The pooled HR for death for patients with EGFR mutant disease was 1.11 [95% CI: 0.80, 1.53; P = 0.54]; while pooled HR for death for patients with EGFR wild type disease was 0.67 [95% CI: 0.60, 0.75; P < 0.00001]. The pooled HR for death for patients with current/former smokers was 0.71 [95% CI: 0.63, 0.82; P < 0.00001]; while pooled HR for death for patients with never smokers was 0.79 [95% CI: 0.60, 1.06; P = 0.11]. However, because of the low-to-moderate quality of data, these conclusions may change with publication of other ongoing trials. Smoking history and EGFR status may help predict the performance of PD-(L)1 inhibitors vs docetaxel in previously treated NSCLC patients. © 2017 John Wiley & Sons Ltd.

Sensory impairments of the lower limb after stroke: a pooled analysis of individual patient data.

PubMed

Tyson, Sarah F; Crow, J Lesley; Connell, Louise; Winward, Charlotte; Hillier, Susan

2013-01-01

To obtain more generalizable information on the frequency and factors influencing sensory impairment after stroke and their relationship to mobility and function. A pooled analysis of individual data of stroke survivors (N = 459); mean (SD) age = 67.2 (14.8) years, 54% male, mean (SD) time since stroke = 22.33 (63.1) days, 50% left-sided weakness. Where different measurement tools were used, data were recorded. Descriptive statistics described frequency of sensory impairments, kappa coefficients investigated relationships between sensory modalities, binary logistic regression explored the factors influencing sensory impairments, and linear regression assessed the impact of sensory impairments on activity limitations. Most patients' sensation was intact (55%), and individual sensory modalities were highly associated (κ = 0.60, P < .001). Weakness and neglect influenced sensory impairment (P < .001), but demographics, stroke pathology, and spasticity did not. Sensation influenced independence in activities of daily living, mobility, and balance but less strongly than weakness. Pooled individual data analysis showed sensation of the lower limb is grossly preserved in most stroke survivors but, when present, it affects function. Sensory modalities are highly interrelated; interventions that treat the motor system during functional tasks may be as effective at treating the sensory system as sensory retraining alone.

Can Imaging Parameters Provide Information Regarding Histopathology in Head and Neck Squamous Cell Carcinoma? A Meta-Analysis.

PubMed

Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

2018-04-01

Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. Associations between 18 F-FDG positron emission tomography (PET) and KI 67 were reported in 8 studies (236 patients). The pooled correlation coefficient was 0.20 (95% CI = [-0.04; 0.44]). Furthermore, in 4 studies (64 patients), associations between 18 F-fluorothymidine PET and KI 67 were analyzed. The pooled correlation coefficient between SUV max and KI 67 was 0.28 (95% CI = [-0.06; 0.94]). In 2 studies (23 patients), relationships between KI 67 and dynamic contrast-enhanced magnetic resonance imaging were reported. The pooled correlation coefficient between K trans and KI 67 was -0.68 (95% CI = [-0.91; -0.44]). Two studies (31 patients) investigated correlation between apparent diffusion coefficient (ADC) and KI 67. The pooled correlation coefficient was -0.61 (95% CI = [-0.84; -0.38]). In 2 studies (117 patients), relationships between 18 F-FDG PET and p53 were analyzed. The pooled correlation coefficient was 0.0 (95% CI = [-0.87; 0.88]). There were 3 studies (48 patients) that investigated associations between ADC and tumor cell count in HNSCC. The pooled correlation coefficient was -0.53 (95% CI = [-0.74; -0.32]). Associations between 18 F-FDG PET and HIF-1α were investigated in 3 studies (72 patients). The pooled correlation coefficient was 0.44 (95% CI = [-0.20; 1.08]). ADC may predict cell count and proliferation activity, and SUV max may predict expression of HIF-1α in HNSCC. SUV max cannot be used as surrogate marker for expression of KI 67 and p53. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Pemphigus and smoking- insights from a big data analysis.

PubMed

Kridin, Khalaf; Comaneshter, Doron; Batat, Erez; Cohen, Arnon D

2018-04-28

We have read with great interest the manuscript written by Lai et al.(1). The authors performed a systematic review and pooled-analysis aiming to summarize the current knowledge regarding the prevalence of smoking among patients with pemphigus relative to control subjects. By summarizing the findings of 13 observational studies comprising 3046 pemphigus patients, a pooled OR of 0.9 (95% CI, 0.82-0.99; P<0.05) was revealed indicating that smoking may exert a protective effect against the development of pemphigus(1). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis

PubMed Central

Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9–8.4 and pooled HR = 8.7, 95% CI 6.6–11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4–2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1–1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1–2.4 and HR = 2.4, 95% CI 1.5–3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0–1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0–2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers. PMID:27806057

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis.

PubMed

Bachelet, Delphine; Hässler, Signe; Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.

A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.

PubMed

Li, Yang; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

PubMed Central

Schweizer, Anja; Dejager, Sylvie; Foley, James E; Kothny, Wolfgang

2011-01-01

Aim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies. PMID:21415917

Esophageal dilation in head and neck cancer patients: A systematic review and meta-analysis.

PubMed

Moss, William J; Pang, John; Orosco, Ryan K; Weissbrod, Philip A; Brumund, Kevin T; Weisman, Robert A; Brigger, Matthew T; Coffey, Charles S

2018-01-01

To characterize the safety profile and effectiveness of esophageal dilation in head and neck cancer patients. A systematic review was undertaken for articles reporting outcomes of esophageal dilation in head and neck cancer patients. The Medline, Scopus, Web of Science, and Cochrane databases were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Complications related to esophageal dilation in head and neck cancer patients was the primary outcome of interest. Success rates, demographic data, cancer staging, and treatment data were assessed secondarily. Statistical analyses included both qualitative and quantitative assessments. A limited meta-analysis and pooling of the data was performed using a random effects model. Of the collective 8,243 initial candidate articles, 15 retrospective studies containing data for a collective 449 patients were ultimately included in the analysis. There was significant heterogeneity in the outcomes data. With an overall complication rate of 10.6% (95% confidence interval [CI]: 4.1%,17%) and a pooled success rate of 72.9% (95% CI: 65.7%,80.1%) per patient, the articles generally supported the use of dilation. Head and neck cancer patients experience a higher rate of complications following dilation compared to patients with other causes of benign stricture. Esophageal dilation is effective in improving dysphagia, but these benefits are often transient and thus necessitate repeat interventions. Laryngoscope, 128:111-117, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Prognostic value of angiopoietin-2 in non-small cell lung cancer patients: a meta-analysis.

PubMed

Xuan, Zi-Xue; Zhang, Su; Yuan, Shou-Jun; Wang, Wei; Yu, Jia

2016-09-02

Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer deaths worldwide. The targeted therapy had made important progress in recent years, but few potential predictive biomarkers for prognosis of NSCLC patients were identified. Angiopoietin-2 (Ang-2), a cytokine upregulated in tumor endothelial cells and some tumor cells including NSCLC, is a partial agonist and antagonist of angiopoietin-1 (Ang-1). Ang-1 is another ligand for the tyrosine kinase receptor Tie2; it promotes recruitment of pericytes and smooth muscle cells, stabilizing vascular networks by binding to Tie2. Although many studies mainly considered that Ang-2 correlated with progression and prognosis of NSCLC significantly, there are much conflicting and controversial data. Therefore, we conducted a meta-analysis to assess the relationship between Ang-2 and prognosis, a clinical outcome of NSCLC. The search was based on major databases from PubMed, Cochrane Library, EMBASE, and CNKI, and 20 eligible publications (range from 2002 to 2015) are included in our meta-analysis with 2011 NSCLC patients in total. These studies illuminated the correlation between the expression of Ang-2 and NSCLC, based on either prognostic factors or clinicopathological features. Pooled calculations were carried out on the odds ratio (OR) and the corresponding 95 % confidence interval (CI) to perform this meta-analysis, and all statistical analyses were carried out by STATA 12.0 and Review Manager 5.3. According to our results, the expression of Ang-2 in NSCLC tissues was significantly higher than that in normal lung tissues, indicating that Ang-2 over-expression may be a predictive marker (pooled OR = 5.09, corresponding 95 % confidence interval (95 % CI) 3.10-8.36, p = 0.000). In addition, our pooled data showed that Ang-2 expression was positively correlated with tumor stages (pooled OR = 3.58, 95 % CI 2.40-5.35, p = 0.000), differentiation (pooled OR = 0.65, 95 % CI 0.45-0.94, p = 0.02), lymphatic invasion (pooled OR = 3.15, 95 % CI 1.97-5.03, p = 0.000), and poor survival (pooled OR = 1.93, 95 % CI 1.47-2.52, p = 0.000) of NSCLC, but seems to have no significant impact on tumor size (pooled OR = 1.09, 95 % CI 0.59-2.00, p = 0.78). These results demonstrate that Ang-2 expression significantly correlated with poor prognosis for patients with NSCLC.

Coffee consumption and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Wijarnpreecha, Karn; Thongprayoon, Charat; Ungprasert, Patompong

2017-02-01

Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health concern. Coffee might have a protective effect against NAFLD. However, the results of previous reports are conflicting. Therefore, we carried out this meta-analysis to summarize all available data. This study consisted of two meta-analyses. The first meta-analysis included observational studies comparing the risk of NAFLD in patients who did and did not drink coffee. The second analysis included studies comparing the risk of liver fibrosis between NAFLD patients who did and did not drink coffee. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated. Out of 355 articles, five studies fulfilled our eligibility criteria and were included in the analysis. The risk of NAFLD in patients who drank coffee was significantly lower than that in patients who did not pooled RR 0.71 (95% CI, 0.60-0.85). We also found a significantly decreased risk of liver fibrosis among NAFLD patients who drank coffee compared with those who did not, with a pooled RR of 0.70 (95% CI, 0.60-0.82). However, it should be noted that the definition of regular coffee consumption varied between studies, which is the main limitation of this meta-analysis. Our study found a significantly decreased risk of NAFLD among coffee drinkers and significantly decreased risk of liver fibrosis among patients with NAFLD who drank coffee on a regular basis. Whether consumption of coffee could be considered a preventative measure against NAFLD needs further investigations.

Prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C: a systematic review and meta-analysis.

PubMed

Khan, Ajmal; Agarwal, Ritesh; Aggarwal, Ashutosh N; Gupta, Dheeraj

2010-07-01

Activated protein C reduces 28-day mortality in patients with severe sepsis, but its anticoagulant properties entail a risk of bleeding. The aim of this systematic review was to evaluate the prevalence of serious bleeding events in patients receiving activated protein C. We searched the MEDLINE and EMBASE databases for studies that described the prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C. We calculated the bleeding rates by calculating proportions and 95% CIs for each study, and then pooled the data to derive a pooled proportion and 95% CI. Our search yielded 17 studies, which included 10,679 patients. The occurrence of serious bleeding events in patients receiving activated protein C ranged from 0.5% to 9.6%, and the pooled prevalence was 3.3% (95% CI 2.4-4.4%) by the random effects model. The occurrence of intracranial hemorrhage ranged from 0% to 1.4%, and the pooled prevalence was 0.44% (95% CI 0.31-0.6%). Sensitivity analysis showed a higher prevalence of bleeding in the observational studies than in the randomized controlled trials. There was substantial clinical and statistical heterogeneity, but no evidence of publication bias. Activated protein C is associated with significant risk of bleeding, so strict inclusion and exclusion criteria should be set prior to administering activated protein C.

Analysis of Nausea in Clinical Studies of Lubiprostone for the Treatment of Constipation Disorders.

PubMed

Cryer, Byron; Drossman, Douglas A; Chey, William D; Webster, Lynn; Habibi, Sepideh; Wang, Martin

2017-12-01

Lubiprostone is a ClC-2 chloride channel activator approved for the treatment of chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) in adults and irritable bowel syndrome with constipation (IBS-C) in women. Lubiprostone is generally well tolerated, with nausea being the most common adverse event. To characterize nausea with lubiprostone using pooled results from clinical studies in patients with CIC, OIC, or IBS-C. Data from three 3- and 4-week placebo-controlled studies and three long-term open-label studies were pooled for the CIC analysis. The OIC and IBS-C analyses each used pooled data from three 12-week placebo-controlled studies and one 36-week open-label extension study. The populations included the following numbers of patients: CIC, 316 (placebo) and 1113 (lubiprostone 24 mcg twice daily [BID]); OIC, 652 (placebo) and 889 (lubiprostone 24 mcg BID); and IBS-C, 435 (placebo) and 1011 (lubiprostone 8 mcg BID). The incidence of nausea in lubiprostone-treated patients ranged from 11.4 to 31.1%, with the highest incidence in patients with CIC. Among patients with any nausea, most reported only mild or moderate severity (96.5-99.1% across indications) and only one event (83.6-88.7%); most events occurred within the first 5 days of treatment. Nausea was the most common adverse event following the treatment with lubiprostone. Event rates varied by indication and dose, and the majority of nausea adverse events were mild to moderate in severity. Nausea events predominantly occurred early in the treatment period in all of the pooled study populations.

Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis.

PubMed

Potkin, Steven G; Phiri, Phillip; Szegedi, Armin; Zhao, Jun; Alphs, Larry; Cazorla, Pilar

2013-11-01

A Phase 2 efficacy study suggested that asenapine (ASE) was superior to risperidone in decreasing negative symptoms in schizophrenia at 6 weeks, prompting design of two negative symptom studies. Two 26-week core studies with 26-week extensions compared asenapine (ASE: 5-10mg twice-daily] and olanzapine (OLA: 5-20mg once-daily) as monotherapies in reducing persistent negative symptoms (PNS). While neither study met the primary endpoint of superiority of ASE over OLA, ASE was statistically superior to OLA in one extension study. This prompted a pooled analysis of the treatment effects of both drugs. Data were pooled from two 26-week core studies and extensions. Efficacy endpoints: change in Negative Symptom Assessment scale-16 (NSA-16) total score at Week 26 (prespecified primary endpoint) and Week 52. Additional measures: change in Positive and Negative Syndrome Scale (PANSS)-total, Marder factors, negative subscale scores, Clinical Global Impression Severity of Illness score (CGI-S) assessments, NSA-16 factor domains, NSA global score, and individual items. Pooled data from the extension studies (n=502) showed no differences between ASE and OLA at Week 26. At Week 52, ASE showed superiority over OLA in NSA-16 total score, NSA global, PANSS Marder negative and PANSS negative subscales, some NSA-16 items, and four of five factor domains. In addition, pooled data for patients who entered the core trials (n=949) were analyzed over 52weeks (whether or not patients entered the extension). No significant differences between groups were observed in change in NSA-16 total score at 26-weeks. At Week 52, ASE was significantly superior over OLA in this measure, NSA global score and PANSS Marder negative factor. There were more early dropouts due to AEs, including worsening of the disease, in the ASE group. In this pooled analysis, ASE and OLA did not differ significantly over 26 weeks, but indicated a signal of superiority for ASE with continued treatment up to 52 weeks. © 2013.

Renin–angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta‐analysis

PubMed Central

Khan, Muhammad Shahzeb; Fonarow, Gregg C.; Khan, Hassan; Greene, Stephen J.; Anker, Stefan D.; Gheorghiade, Mihai

2017-01-01

Abstract Studies with angiotensin‐converting enzyme inhibitors (ACE‐Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction (HFpEF) have yielded inconsistent results. To conduct a systematic review and meta‐analysis of all evidence for ACE‐I and ARBs in patients with HFpEF, we searched PubMed, Ovid SP, Embase, and Cochrane database to identify randomized trials and observational studies that compared ACE‐I or ARBs against placebo or standard therapy in HFpEF patients. Random‐effect models were used to pool the data, and I 2 testing was performed to assess the heterogeneity of the included studies. A total of 13 studies (treatment arm = 8676 and control arm = 8608) were analysed. Pooled analysis of randomized trials for ACE‐I and ARBs (n = 6) did not show any effect on all‐cause mortality [relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.93–1.11, P = 0.68, I 2 = 0%], while results from observational studies showed a significant improvement (RR = 0.91, 95% CI = 0.87–0.95, P = 0.005, I 2 = 81.5%). In pooled analyses of all studies, ACE‐I showed a reduction of all‐cause mortality (RR = 0.91, 95% CI = 0.87–0.95, P = 0.01). There was no reduction in cardiovascular mortality seen, but in pooled analysis of randomized trials, there was a trend towards reduced HF hospitalization risk (RR = 0.91, 95% CI = 0.83–1.01, I 2 = 0%, P = 0.074). These data suggest that ACE‐I and ARBs may have a role in improving outcomes of patients with HFpEF, underscoring the need for future research with careful patient selection, and trial design and conduct. PMID:28869332

A meta-analysis of use of Prostate Imaging Reporting and Data System Version 2 (PI-RADS V2) with multiparametric MR imaging for the detection of prostate cancer.

PubMed

Zhang, Li; Tang, Min; Chen, Sipan; Lei, Xiaoyan; Zhang, Xiaoling; Huan, Yi

2017-12-01

This meta-analysis was undertaken to review the diagnostic accuracy of PI-RADS V2 for prostate cancer (PCa) detection with multiparametric MR (mp-MR). A comprehensive literature search of electronic databases was performed by two observers independently. Inclusion criteria were original research using the PI-RADS V2 system in reporting prostate MRI. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data necessary to complete 2 × 2 contingency tables were obtained from the included studies. Thirteen studies (2,049 patients) were analysed. This is an initial meta-analysis of PI-RADs V2 and the overall diagnostic accuracy in diagnosing PCa was as follows: pooled sensitivity, 0.85 (0.78-0.91); pooled specificity, 0.71 (0.60-0.80); pooled positive likelihood ratio (LR+), 2.92 (2.09-4.09); pooled negative likelihood ratio (LR-), 0.21 (0.14-0.31); pooled diagnostic odds ratio (DOR), 14.08 (7.93-25.01), respectively. Positive predictive values ranged from 0.54 to 0.97 and negative predictive values ranged from 0.26 to 0.92. Currently available evidence indicates that PI-RADS V2 appears to have good diagnostic accuracy in patients with PCa lesions with high sensitivity and moderate specificity. However, no recommendation regarding the best threshold can be provided because of heterogeneity. • PI-RADS V2 shows good diagnostic accuracy for PCa detection. • Initially pooled specificity of PI-RADS v2 remains moderate. • PCa detection is increased by experienced radiologists. • There is currently a high heterogeneity in prostate diagnostics with MRI.

Efficacy and complication of endoscopic submucosal dissection for superficial esophageal carcinoma: a systematic review and meta-analysis

PubMed Central

2014-01-01

Aim For patients with superficial esophageal carcinoma, ESD was one of treatment modalities to remove the lesion safely and effectively. We perform this meta-analysis to determine the efficacy and incidence of complication of ESD for patients with superficial esophageal carcinoma. Method Articles were searched in MEDLINE (PubMed and Ovid), Cochrane Database of Systemic Reviews, Google scholar, and Web of Science. Two reviewers independently searched and extracted data. Meta-analysis of the efficacy of ESD was analyzed by calculating pooled en bloc and R0 resection rate. Incidence of complications such as perforation, stenosis and mediastinal emphysema was also calculated. Pooling was conducted using either fixed-effects model or random-effects model depending on the heterogeneity across studies. Results 21 studies (1152 patients and 1240 lesions) were included in this analysis. The pooled en bloc resection rate was 99% (95% CI 99%-100%). Stratified by tumor size, en bloc resection rates did not show any significant difference. The pooled R0 resection rate was 90% (95% CI 87%-93%). The pooled R0 resection rate was 85% (95% CI, 80%-90%) for large tumor and 92% (95% CI, 87%-93%) for small tumor (p < 0.001). Stenosis served as the most common reported complication with pooled incidence of 5% (95% CI 3-8%), followed by perforation (1%, 95% CI 0-1%) and mediastinal emphysema (0% CI 0-1%). The incidence of postoperative stenosis decreased significantly after 2011 (2%, 95% CI 0-3%) compared with that before 2011 (9%, 95% CI 3-8%) (p < 0.001). Conclusion ESD was an efficient modality for treating superficial esophageal carcinoma, with perfect en bloc and R0 resection rate and low complication rate. The most common complication of ESD was stenosis. Although recurrence rate was low, patients should be maintained in a scheduled surveillance program. PMID:24885614

Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease: a systematic review and meta-analysis.

PubMed

Costa, João; Magro, Fernando; Caldeira, Daniel; Alarcão, Joana; Sousa, Rita; Vaz-Carneiro, António

2013-09-01

We systematically reviewed infliximab benefit in reducing hospitalizations and/or major surgery rates in patients with inflammatory bowel disease (IBD). A literature search to May 2012 was performed to identify all studies (experimental and observational) evaluating patients with IBD treated with infliximab and providing data on hospitalizations and/or major surgery rates. Three reviewers independently performed studies' selection, quality assessment, and data extraction. Analyses were carried according to study design (randomized clinical trials [RCTs] and observational studies) and IBD type (Crohn's disease [CD] and ulcerative colitis [UC]). Random-effects meta-analysis was used to derive pooled and 95% confidence intervals (CIs) estimates of odds ratios (OR). Heterogeneity was assessed with I test. Twenty-seven eligible studies were included (9 RCTs and 18 observational studies). Infliximab reduced hospitalization risk, both in pooled RCTs (OR, 0.51; 95% CI 0.40-0.65; I = 0%) and results of observational studies (OR, 0.29, 95% CI, 0.19-0.43; I = 87%), without differences between CD and UC. Infliximab reduced surgery risk in pooled RCTs results, both in CD (OR, 0.31; 95% CI, 0.15-0.64; I = 0%) and UC (OR, 0.57; 95% CI, 0.37-0.88; I = 0%). Pooled estimate from observational studies favored infliximab for patients with CD (OR, 0.32; 95% CI, 0.21-0.49; I = 77%), but not for patients with UC. The best evidence available points toward a reduction of the risk of hospitalization and major surgery requirement in patients with IBD treated with infliximab. This impact is clinically and economically relevant because hospitalization and surgery are considered to be markers of disease severity and significantly contribute to the total direct costs associated with IBD.

Prevalence of sleep-disordered breathing in acute coronary syndrome: a systemic review and meta-analysis.

PubMed

Huang, Zhuoshan; Zheng, Zhengda; Luo, Yanting; Li, Suhua; Zhu, Jieming; Liu, Jinlai

2017-03-01

This study aimed to review the literature on the prevalence of sleep-disordered breathing (SDB) in patients with acute coronary syndrome (ACS). Relevant studies were searched on PubMed, EMBASE, and Cochrane Library through December 2014. Data were extracted using standardized forms. Pooled prevalence of all SDB (apnea-hypopnea index (AHI) > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients was calculated using DerSimonian-Laird random-effects model. Sensitivity analysis was performed based on races and diagnostic methods of SDB. A total of 32 studies were included in the present meta-analysis, examining 3360 patients. The meta-analysis indicated that pooled prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients were 69 % (95 % confidence interval (CI) = 61, 77 %), 43 % (95 % CI = 36, 49 %), and 25 % (95 % CI = 17, 33 %), respectively. Sensitivity analysis indicated that the pooled prevalence of SDB in Western population was similar to that in Asian population. However, diagnostic methods of SDB seemed to have various impacts on the prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30). High prevalence of all SDB, moderate-to-severe SDB, and severe SDB was found in ACS patients. It is clinically important to screen for SDB in patients with ACS.

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials.

PubMed

Saha, S A; Molnar, J; Arora, R R

2008-01-01

The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques. Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated. Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death. Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.

Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data.

PubMed

Dadabhai, Alia S; Saberi, Behnam; Lobner, Katie; Shinohara, Russell T; Mullin, Gerard E

2017-02-18

To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.

Generic immunosuppression in solid organ transplantation: systematic review and meta-analysis

PubMed Central

Molnar, Amber O; Fergusson, Dean; Tsampalieros, Anne K; Bennett, Alexandria; Fergusson, Nicholas; Ramsay, Timothy

2015-01-01

Objective To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants. Design Systematic review and meta-analysis of all studies comparing generic with innovator immunosuppressive drugs. Data sources Medline and Embase from 1980 to September 2014. Review methods A literature search was performed for all studies comparing a generic to an innovator immunosuppressive drug in solid organ transplantation. Two reviewers independently extracted data and assessed quality of studies. Meta-analyses of prespecified outcomes were performed when deemed appropriate. Outcomes included patient survival, allograft survival, acute rejection, adverse events and bioequivalence. Results 1679 citations were screened, of which 50 studies met eligibility criteria (17 randomized trials, 15 non-randomized interventional studies, and 18 observational studies). Generics were compared with Neoral (cyclosporine) (32 studies), Prograf (tacrolimus) (12 studies), and Cellcept (mycophenolate mofetil) (six studies). Pooled analysis of randomized controlled trials in patients with kidney transplants that reported bioequivalence criteria showed that Neoral (two studies) and Prograf (three studies) were not bioequivalent with generic preparations according to criteria of the European Medicines Agency. The single Cellcept trial also did not meet bioequivalence. Acute rejection was rare but did not differ between groups. For Neoral, the pooled Peto odds ratio was 1.23 (95% confidence interval 0.64 to 2.36) for kidney randomized controlled trials and 0.66 (0.40 to 1.08) for observational studies. For kidney observational studies, the pooled Peto odds ratios were 0.98 (0.37 to 2.60) for Prograf and 0.49 (0.09 to 2.56) for Cellcept. Meta-analyses for non-renal solid organ transplants were not performed because of a lack of data.There were insufficient data reported on patient or graft survival. Pooling of results was limited by inconsistent study methods and reporting of outcomes. Many studies did not report standard criteria used to determine bioequivalence. While rates of acute rejection seemed similar and were relatively rare, few studies were designed to properly compare clinical outcomes. Most studies had short follow-up times and included stable patients without a history of rejection. Conclusions High quality data showing bioequivalence and clinical efficacy of generic immunosuppressive drugs in patients with transplants are lacking. Given the serious consequences of rejection and allograft failure, well designed studies on bioequivalence and safety of generic immunosuppression in transplant recipients are needed. PMID:26101226

Relationship Between Visual Acuity and Retinal Thickness During Anti-Vascular Endothelial Growth Factor Therapy for Retinal Diseases.

PubMed

Ou, William C; Brown, David M; Payne, John F; Wykoff, Charles C

2017-08-01

To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases. Retrospective analysis of clinical trial data. Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression. At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data. DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data.

PubMed

Zinkstok, Sanne M; Vergouwen, Mervyn D I; Engelter, Stefan T; Lyrer, Philippe A; Bonati, Leo H; Arnold, Marcel; Mattle, Heinrich P; Fischer, Urs; Sarikaya, Hakan; Baumgartner, Ralf W; Georgiadis, Dimitrios; Odier, Céline; Michel, Patrik; Putaala, Jukka; Griebe, Martin; Wahlgren, Nils; Ahmed, Niaz; van Geloven, Nan; de Haan, Rob J; Nederkoorn, Paul J

2011-09-01

The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease.

PubMed

Donohue, James F; Jones, Paul W; Bartels, Christian; Marvel, Jessica; D'Andrea, Peter; Banerji, Donald; Morris, David G; Patalano, Francesco; Fogel, Robert

2018-04-01

In clinical trials of inhaled bronchodilators, chronic obstructive pulmonary disease (COPD) guidelines recommend that patient-reported outcomes (PROs) are assessed alongside lung function. How these endpoints are related is unclear. Pooled longitudinal data from 23 randomised controlled COPD studies were analyzed (N = 23,213). Treatments included long-acting β 2 agonists, long-acting muscarinic antagonists (LABAs or LAMAs) and the LABA/LAMA combination QVA149. Outcome measures were Transition Dyspnoea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) scores, COPD exacerbation frequency and rescue medication use. Relationships between changes in trough forced expiratory volume in one second (ΔFEV 1 ) and outcomes following treatment were assessed using correlations of data summaries and model-based analysis: generalized linear mixed-effect regression modelling to determine if ΔFEV 1 could predict patient outcomes with different treatments. Mean age was 64 years, 73% were male, and most had moderate (45%) or severe (52%) disease. Statistically significant correlations were observed between ΔFEV 1 and each outcome measure (exacerbations Rs = 0.05; rescue medication, SGRQ, TDI, r = 0.11-0.16; all p < .001). Patients with greater improvements in trough FEV 1 had on average better SGRQ and TDI scores, fewer exacerbations, and used less rescue medication. For SGRQ and TDI scores, minimal clinically important differences were observed over the range of pooled ΔFEV 1 values. Model-based predictions confirmed the treatment effect was partly explained by changes in FEV 1 from baseline with improvements in PROs observed across all treatments when trough FEV 1 improved. Across all endpoints active treatments were better than placebo (p < .0001), and LABA/LAMA treatment resulted in numerically better treatment outcomes than either monocomponent. These data suggest that FEV 1 improvements post-bronchodilation correlate with PRO improvements. Further improvements in patient outcomes may be expected by maximizing lung function improvements. Registration details for the 23 randomised controlled studies used in this pooled analysis are supplied in Additional File 4. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targets of perioperative fluid therapy and their effects on postoperative outcome: a systematic review and meta-analysis.

PubMed

Berger, M M; Gradwohl-Matis, I; Brunauer, A; Ulmer, H; Dünser, M W

2015-07-01

Perioperative fluid management plays a fundamental role in maintaining organ perfusion, and is considered to affect morbidity and mortality. Targets according to which fluid therapy should be administered are poorly defined. This systematic review aimed to identify specific targets for perioperative fluid therapy. The PubMed database (January 1993-December 2013) and reference lists were searched to identify clinical trials which evaluated specific targets of perioperative fluid therapy and reported clinically relevant perioperative endpoints in adult patients. Only studies in which targeted fluid therapy was the sole intervention were included into the main data analysis. A pooled data analysis was used to compare mortality between goal-directed fluid therapy and control interventions. Thirty-six clinical studies were selected. Sixteen studies including 1224 patients specifically evaluated targeted fluid therapy and were included into the main data analysis. Three specific targets for perioperative fluid therapy were identified: a systolic or pulse pressure variation <10-12%, an increase in stroke volume <10%, and a corrected flow time of 0.35-0.4 s in combination with an increase in stroke volume <10%. Targeting any one of these goals resulted in less postoperative complications (pooled data analysis: OR 0.53; CI95, 0.34-0.83; P=0.005) and a shorter length of intensive care unit/hospital stay, but no difference in postoperative mortality (pooled data analysis: OR 0.61; CI95, 0.33-1.11; P=0.12). This systematic review identified three goals for perioperative fluid administration, targeting of which appeared to be associated with less postoperative complications and shorter intensive care unit/hospital lengths of stay. Perioperative mortality remained unaffected.

Diagnostic performance of FDG PET or PET/CT in prosthetic infection after arthroplasty: a meta-analysis.

PubMed

Jin, H; Yuan, L; Li, C; Kan, Y; Hao, R; Yang, J

2014-03-01

The purpose of this study was to systematically review and perform a meta-analysis of published data regarding the diagnostic performance of positron emission tomography (PET) or PET/computed tomography (PET/CT) in prosthetic infection after arthroplasty. A comprehensive computer literature search of studies published through May 31, 2012 regarding PET or PET/CT in patients suspicious of prosthetic infection was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of PET or PET/CT in patients suspicious of prosthetic infection on a per prosthesis-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of PET or PET/CT in patients with suspicious of prosthetic infection. Fourteen studies comprising 838 prosthesis with suspicious of prosthetic infection after arthroplasty were included in this meta-analysis. The pooled sensitivity of PET or PET/CT in detecting prosthetic infection was 86% (95% confidence interval [CI] 82-90%) on a per prosthesis-based analysis. The pooled specificity of PET or PET/CT in detecting prosthetic infection was 86% (95% CI 83-89%) on a per prosthesis-based analysis. The area under the ROC curve was 0.93 on a per prosthesis-based analysis. In patients suspicious of prosthetic infection, FDG PET or PET/CT demonstrated high sensitivity and specificity. FDG PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false positive results and influcing factors should kept in mind.

Noninvasive positive pressure ventilation for acute respiratory failure in delirious patients: understudied, underreported, or underappreciated? A systematic review and meta-analysis.

PubMed

Charlesworth, Michael; Elliott, Mark W; Holmes, John D

2012-12-01

We performed a systematic review and meta-analysis of the literature to determine the prevalence of delirium in patients receiving noninvasive positive pressure ventilation (NPPV) for acute respiratory failure and to quantify the prognostic impact of delirium with respect to NPPV failure. We searched the databases EMBASE (1996 to present), MEDLINE (1996 to present), PsycINFO(®) (2002 to present) and CINAHL (1992 to present). A Google™ search and hand searching of bibliographies or relevant articles were also performed. We searched for prospective observational studies conducted in a setting where patients with acute respiratory failure receiving NPPV were screened for delirium. All authors independently assessed references for inclusion and extracted data. Information was collated regarding study design, baseline characteristics of included patients, and the prevalence of delirium. Where prognostic information regarding NPPV failure was reported, a risk ratio for the association between delirium and NPPV failure was derived. These values were pooled in the meta-analysis. Three articles were retrieved by the search strategy. These included 239 patients receiving noninvasive ventilation who were assessed for delirium. The prevalence of delirium was recorded at between 33 and 38 % with a pooled prevalence of 37 %. Two studies reported prognostic data and the risk ratios for noninvasive ventilation failure in delirium were calculated as 1.79 (95 % CI 1.09-2.94) and 3.28 (95 % CI 1.60-6.73). A meta-analysis was performed and the pooled risk ratio was found to be 2.12 (95 % CI 1.41-3.18). The data in this context was scarce and of low quality. A diagnosis of delirium was made in 9 patients and inferred in 80. Despite the current lack of high-quality data and studies, the high reported prevalence of delirium and the association with noninvasive ventilation failure lends support for more awareness amongst health-care professionals and more routine screening. More focused primary research is necessary in this area. Adherence to NICE guidelines regarding delirium in these patients should be a standard of care.

Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis.

PubMed

Nadeem, Rashid; Singh, Mukesh; Nida, Mahwish; Waheed, Irfan; Khan, Adnan; Ahmed, Saeed; Naseem, Jawed; Champeau, Daniel

2014-05-15

Obstructive sleep apnea (OSA) is associated with obesity, metabolic syndrome, and dyslipidemia, which may be related to decrease androgen levels found in OSA patients. Dyslipidemia may contribute to atherosclerosis leading to increasing risk of heart disease. Systematic review was conducted using PubMed and Cochrane library by utilizing different combinations of key words; sleep apnea, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglyceride (TG). Inclusion criteria were: English articles, and studies with adult population in 2 groups of patients (patients with OSA and without OSA). A total 96 studies were reviewed for inclusion, with 25 studies pooled for analysis. Sixty-four studies were pooled for analysis; since some studies have more than one dataset, there were 107 datasets with 18,116 patients pooled for meta-analysis. All studies measured serum lipids. Total cholesterol pooled standardized difference in means was 0.267 (p = 0.001). LDL cholesterol pooled standardized difference in means was 0.296 (p = 0.001). HDL cholesterol pooled standardized difference in means was -0.433 (p = 0.001). Triglyceride pooled standardized difference in means was 0.603 (p = 0.001). Meta-regression for age, BMI, and AHI showed that age has significant effect for TC, LDL, and HDL. BMI had significant effect for LDL and HDL, while AHI had significant effect for LDL and TG. Patients with OSA appear to have increased dyslipidemia (high total cholesterol, LDL, TG, and low HDL).

Daily remote monitoring of implantable cardioverter-defibrillators: insights from the pooled patient-level data from three randomized controlled trials (IN-TIME, ECOST, TRUST).

PubMed

Hindricks, Gerhard; Varma, Niraj; Kacet, Salem; Lewalter, Thorsten; Søgaard, Peter; Guédon-Moreau, Laurence; Proff, Jochen; Gerds, Thomas A; Anker, Stefan D; Torp-Pedersen, Christian

2017-06-07

Remote monitoring of implantable cardioverter-defibrillators may improve clinical outcome. A recent meta-analysis of three randomized controlled trials (TRUST, ECOST, IN-TIME) using a specific remote monitoring system with daily transmissions [Biotronik Home Monitoring (HM)] demonstrated improved survival. We performed a patient-level analysis to verify this result with appropriate time-to-event statistics and to investigate further clinical endpoints. Individual data of the TRUST, ECOST, and IN-TIME patients were pooled to calculate absolute risks of endpoints at 1-year follow-up for HM vs. conventional follow-up. All-cause mortality analysis involved all three trials (2405 patients). Other endpoints involved two trials, ECOST and IN-TIME (1078 patients), in which an independent blinded endpoint committee adjudicated the underlying causes of hospitalizations and deaths. The absolute risk of death at 1 year was reduced by 1.9% in the HM group (95% CI: 0.1-3.8%; P = 0.037), equivalent to a risk ratio of 0.62. Also the combined endpoint of all-cause mortality or hospitalization for worsening heart failure (WHF) was significantly reduced (by 5.6%; P = 0.007; risk ratio 0.64). The composite endpoint of all-cause mortality or cardiovascular (CV) hospitalization tended to be reduced by a similar degree (4.1%; P = 0.13; risk ratio 0.85) but without statistical significance. In a pooled analysis of the three trials, HM reduced all-cause mortality and the composite endpoint of all-cause mortality or WHF hospitalization. The similar magnitudes of absolute risk reductions for WHF and CV endpoints suggest that the benefit of HM is driven by the prevention of heart failure exacerbation.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts.

PubMed

Rodriguez-Rodriguez, Luis; Ivorra-Cortes, Jose; Carmona, F David; Martín, Javier; Balsa, Alejandro; van Steenbergen, Hanna W; van der Helm-van Mil, Annette H M; González-Álvaro, Isidoro; Fernandez-Gutiérrez, Benjamín

2015-11-05

Prostaglandin E receptor 4 (PTGER4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze its role in radiological joint damage in rheumatoid arthritis (RA). Six independent cohorts of patients with RA of European or North American descent were included, comprising 1789 patients with 5083 sets of X-rays. The Hospital Clínico San Carlos Rheumatoid Arthritis, Princesa Early Arthritis Register Longitudinal study, and Hospital Universitario de La Paz early arthritis (Spain) cohorts were used as discovery cohorts, and the Leiden Early Arthritis Clinic (The Netherlands), Wichita (United States), and National Databank for Rheumatic Diseases (United States and Canada) cohorts as replication cohorts. First, the PTGER4 rs6896969 single-nucleotide polymorphism (SNP) was genotyped using TaqMan assays and available Illumina Immunochip data and studied in the discovery and replication cohorts. Second, the PTGER4 gene and adjacent regions were analyzed using Immunochip genotyping data in the discovery cohorts. On the basis of pooled p values, linkage disequilibrium structure of the region, and location in regions with transcriptional properties, SNPs were selected for replication. The results from discovery, replication, and overall cohorts were pooled using inverse-variance-weighted meta-analysis. Influence of the polymorphisms on the overall radiological damage (constant effect) and on damage progression over time (time-varying effect) was analyzed. The rs6896969 polymorphism showed a significant association with radiological damage in the constant effect pooled analysis of the discovery cohorts, although no significant association was observed in the replication cohorts or the overall pooled analysis. Regarding the analysis of the PTGER4 region, 976 variants were analyzed in the discovery cohorts. From the constant and time-varying effect analyses, 12 and 20 SNPs, respectively, were selected for replication. Only the rs76523431 variant showed a significant association with radiographic progression in the time-varying effect pooled analysis of the discovery, replication, and overall cohorts. The overall pooled effect size was 1.10 (95 % confidence interval 1.05-1.14, p = 2.10 × 10(-5)), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele. The PTGER4 gene is a candidate risk factor for radiological progression in RA.

Baseline severity but not gender modulates quantified Crataegus extract effects in early heart failure--a pooled analysis of clinical trials.

PubMed

Eggeling, Thomas; Regitz-Zagrosek, Vera; Zimmermann, Andrea; Burkart, Martin

2011-11-15

The efficacy of quantified Crataegus extract in chronic heart failure (CHF) has been assessed in numerous clinical studies. The present pooled analysis evaluates the impact of baseline severity and gender on objective and patient-reported endpoints and associations between both types of outcomes in patients with early CHF. Available data from 687 individual patients treated with quantified Crataegus extract or placebo in ten studies were pooled. Treatment effects on physiologic outcome parameters and on symptoms were analysed for their association with baseline severity and gender. Changes in symptom scores were investigated with respect to their relation to physiologic outcome parameters. Results were compared with observations in a 3-year cohort study. Physiologic outcome parameters maximal workload (MWL), left ventricular ejection fraction (LVEF) and pressure-heart rate product increase (PHRPI) at 50 W ergometric exercise improved more in active treatment than in placebo patients. Magnitude of improvement was independent from baseline for LVEF but increased for MWL and PHRPI with baseline severity. Improvement of typical symptoms like reduced exercise tolerance, exertional dyspnea, weakness, fatigue, and palpitations improved more with active treatment and in patients with more severe symptoms. A weak association between improvements in MWL, PRHP, and symptoms could be demonstrated. Gender differences in treatment effects could be explained by baseline differences. Results of the pooled analysis are in agreement with observations in the cohort study. Crataegus extract treatment effects on physiologic outcomes and typical symptoms were modulated by baseline severity. Taking baseline differences into account, benefits were comparable in male and female patients with impaired exercise-tolerance in early chronic heart-failure. Copyright © 2011 Elsevier GmbH. All rights reserved.

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

PubMed Central

Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

2015-01-01

Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (< 3 hours reference), had a pooled OR for mortality of 1.16 (0.92 to 1.46, p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hour reference) had a pooled OR for mortality of 1.46 (0.89 to 2.40, p = 0.13). There was no increased mortality in the pooled ORs for each hourly delay from <1 to >5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence. PMID:26121073

The hepatic safety and tolerability of the cyclooxygenase-2 selective NSAID celecoxib: pooled analysis of 41 randomized controlled trials.

PubMed

Soni, Paresh; Shell, Briton; Cawkwell, Gail; Li, Chunming; Ma, Hong

2009-08-01

To assess the hepatic safety and tolerability of celecoxib versus placebo and three commonly prescribed nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This was a retrospective, pooled analysis of a 41-study dataset involving patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic low back pain, and Alzheimer's disease. Criteria for selection of studies were: (1) Randomized, parallel-group design and planned treatment duration of > or =2 weeks (2) > or =1 placebo or NSAID comparator (3) > or =1 arm with celecoxib at total daily dose of > or =200 mg (4) Data available as of October 31, 2004 Data were pooled by treatment and subject from the safety analysis population of included studies. Treatment-emergent hepatobiliary adverse events (AEs) were compared for celecoxib <200 mg/day (943 patients), 200 mg/day (12 008 patients), 400 mg/day (7380 patients), and 800 mg/day (4602 patients); placebo (4057 patients); diclofenac 100-150 mg/day (7639 patients); naproxen 1000 mg/day (2953 patients); and ibuprofen 2400 mg/day (2484 patients). Hepatobiliary laboratory abnormalities were also analyzed. There were no cases of liver failure, treatment-related liver transplant, or treatment-related hepatobiliary death. Incidence of serious hepatic AEs was low, with 13 (0.05%) serious hepatic AEs among 24 933 celecoxib-treated patients, and 16 (0.21%) among 7639 diclofenac-treated patients. No patients receiving celecoxib or any nonselective NSAID met criteria for Hy's rule (alanine aminotransferase [ALT] > or =3 x upper limit of normal [ULN] with bilirubin > or =2 x ULN). The incidence of notable (> or =5 x ULN) and severe (> or =10 x ULN) ALT elevations was similar for all treatment groups except diclofenac. Significantly fewer hepatobiliary AEs were reported for celecoxib (any dose; 1.11%) than for diclofenac (vs. 4.24%, p < 0.0001); for ibuprofen (vs. 1.53%, p = 0.06) and placebo (vs. 0.89%, p = 0.21) the incidence of AEs was comparable to celecoxib. A number of limitations should be considered when evaluating the results: findings were limited by the quality and reporting of the studies selected; difficulty in estimating the incidence of AEs due to the low frequency of events; acetaminophen not included as an active comparator. In this pooled analysis, the incidence of hepatic AEs in patients treated with celecoxib was similar to that for both placebo-treated patients and patients treated with ibuprofen or naproxen, but lower than for diclofenac.

Esophagectomy in patients with liver cirrhosis: a systematic review and Bayesian meta-analysis.

PubMed

Asti, E; Sozzi, M; Bonitta, G; Bernardi, D; Bonavina, L

2018-04-10

Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the literature and meta-analysis to investigate postoperative outcomes in these patients. Studies reporting outcomes after esophagectomy in patients with liver cirrhosis were searched in Medline, Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017, matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal surgery". Extracted data included study characteristics, demographic and clinical patient characteristics, type of surgical procedure, and postoperative outcomes. A systematic review and Bayesian meta-analysis were performed. Five observational, retrospective and single-arm studies with a total of 157 patients were included. The main cause of death was liver failure followed by pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most frequent postoperative complications (pooled rates 36% and 34%, respectively). The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was 18% (95% HPD=17-27%). Study heterogeneity (τ2) was low, ranging from 0.046 to 0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of patients in one series. Five-year survival was similar between cirrhotic and non-cirrhotic patients but was statistically significantly higher in patients with MELD score<10. Sound scientific evidence with regard to efficacy and outcomes of esophagectomy in patients with concomitant liver cirrhosis is lacking. There is a need to properly select these frail patients to reduce postoperative morbidity and mortality rates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease: results of a pooled analysis of two randomized, double-blind, placebo-controlled trials in Japan

PubMed Central

Nakamura, Yu; Kitamura, Shin; Homma, Akira; Shiosakai, Kazuhito; Matsui, Daiju

2014-01-01

Background: With the increase in the aging population, there is a pressing need to provide effective treatment options for individuals with Alzheimer's disease (AD). Memantine is an N-methyl-D-aspartate receptor antagonist used to treat AD in > 80 countries worldwide, and studies in the USA and Europe have shown it to be effective in improving language deficits; however, there are currently no data on language improvements in Japanese patients treated with memantine. Objectives: To clarify the efficacy and safety of memantine in Japanese outpatients with moderate to severe AD, using a pooled analysis of two multicenter randomized placebo-controlled trials, a phase 2 dose-finding study and a phase 3 study. Results: The final analysis comprised 633 patients (318 receiving memantine and 315 placebo). Memantine produced better outcomes in terms of Severe Impairment Battery-Japanese version, Clinician's Interview-Based Impression of Change plus-Japanese version, Behavioral Pathology in AD Rating Scale, and language scores, versus placebo. The overall incidence of adverse events and adverse reactions was similar between groups. Conclusion: In this pooled analysis of Japanese patients, memantine achieved better outcomes than placebo in terms of cognition, including attention, praxis, visuospatial ability and language, and behavioral and psychological symptoms, including activity disturbances and aggressiveness. PMID:24673497

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review.

PubMed

Thiebaut, Mathilde; Launay, David; Rivière, Sébastien; Mahévas, Thibault; Bellakhal, Syrine; Hachulla, Eric; Fain, Olivier; Mekinian, Arsène

2018-06-01

To describe safety and efficacy of rituximab in patients with systemic sclerosis. We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8; 18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.

PubMed

Hughes, Dyfrig A; Vilar, F Javier; Ward, Charlotte C; Alfirevic, Ana; Park, B Kevin; Pirmohamed, Munir

2004-06-01

Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B*5701 would be a cost-effective use of healthcare resources. Patients with and without abacavir hypersensitivity were identified from a UK HIV clinic. Patients were genotyped for HLA B*5701, and pooled data used for calculation of test characteristics. The cost-effectiveness analysis incorporated the cost of testing, cost of treating abacavir hypersensitivity, and the cost and selection of alternative antiretroviral regimens. A probabilistic decision analytic model (comparing testing versus no testing) was formulated and Monte Carlo simulations performed. Of the abacavir hypersensitive patients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4-132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on the choice of comparator, routine testing for HLA B*5701 ranged from being a dominant strategy (less expensive and more beneficial than not testing) to an incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per hypersensitivity reaction avoided. Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.

Risk of iatrogenic injury to the infrapatellar branch of the saphenous nerve during hamstring tendon harvesting: A meta-analysis.

PubMed

Pękala, Przemysław A; Tomaszewski, Krzysztof A; Henry, Brandon Michael; Ramakrishnan, Piravin Kumar; Roy, Joyeeta; Mizia, Ewa; Walocha, Jerzy A

2017-11-01

Our goal was to conduct a comprehensive analysis of studies reporting data on the rate of injury to the infrapatellar branch of the saphenous nerve following hamstring tendon graft harvesting with respect to the type of incision over the pes anserinus. A broad search through all major electronic databases was conducted to identify articles eligible for inclusion. All available data were extracted and pooled into the analysis. Eleven studies (n = 1,050 patients) were included in the meta-analysis. The study revealed that a vertical incision during hamstring tendon harvesting over the pes anserinus was associated with the highest rate of injury with a pooled rate of 51.4% (95% confidence interval [CI], 34.6-67.2%). This was followed by oblique and horizontal incisions with pooled rates of 26.0% (95% CI,1.3-61.3%) and 22.4% (95% CI, 5.4-45.5%), respectively. We highly recommend the use of the shortest possible oblique incision during hamstring tendon harvesting over the pes anserinus. Muscle Nerve 56: 930-937, 2017. © 2017 Wiley Periodicals, Inc.

Addressing data privacy in matched studies via virtual pooling.

PubMed

Saha-Chaudhuri, P; Weinberg, C R

2017-09-07

Data confidentiality and shared use of research data are two desirable but sometimes conflicting goals in research with multi-center studies and distributed data. While ideal for straightforward analysis, confidentiality restrictions forbid creation of a single dataset that includes covariate information of all participants. Current approaches such as aggregate data sharing, distributed regression, meta-analysis and score-based methods can have important limitations. We propose a novel application of an existing epidemiologic tool, specimen pooling, to enable confidentiality-preserving analysis of data arising from a matched case-control, multi-center design. Instead of pooling specimens prior to assay, we apply the methodology to virtually pool (aggregate) covariates within nodes. Such virtual pooling retains most of the information used in an analysis with individual data and since individual participant data is not shared externally, within-node virtual pooling preserves data confidentiality. We show that aggregated covariate levels can be used in a conditional logistic regression model to estimate individual-level odds ratios of interest. The parameter estimates from the standard conditional logistic regression are compared to the estimates based on a conditional logistic regression model with aggregated data. The parameter estimates are shown to be similar to those without pooling and to have comparable standard errors and confidence interval coverage. Virtual data pooling can be used to maintain confidentiality of data from multi-center study and can be particularly useful in research with large-scale distributed data.

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis.

PubMed

Bronte, Giuseppe; Rolfo, Christian; Passiglia, Francesco; Rizzo, Sergio; Gil-Bazo, Ignacio; Fiorentino, Eugenio; Cajozzo, Massimo; Van Meerbeeck, Jan P; Lequaglie, Cosimo; Santini, Daniele; Pauwels, Patrick; Russo, Antonio

2015-09-01

Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (1y-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. Six eligible trials (741 patients) were selected. Pooled analysis showed a significant improvement in ORR (OR: 3.243; 95% CI: 1.883-5.583) and 1y-SR (OR: 1.743; 95% CI: 1.203-2.525) in favor of platinum-based doublets. G3-4 hematological toxicities were also more frequent in this group. This meta-analysis suggests that platinum-combination regimens are superior to singleagent both in terms of ORR and survival-rate with increase of severe hematological toxicities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of outcomes between off-pump versus on-pump coronary artery bypass surgery in elderly patients: a meta-analysis.

PubMed

Zhu, Z G; Xiong, W; Ding, J L; Chen, J; Li, Y; Zhou, J L; Xu, J J

2017-03-02

The aim of this study was to analyze if off-pump coronary artery bypass surgery (CABG) is associated with better treatment outcomes in elderly patients (>70 years of age) than on-pump CABG, using meta-analysis. Medline, PubMed, Cochrane and Google Scholar databases were searched until September 13, 2016. Sensitivity and quality assessment were performed. Twenty-two studies, three randomized control trials (RCTs) and 20 non-RCTs were included with 24,127 patients. The risk of death associated with on-pump or off-pump CABG in the RCTs were similar (pooled OR=0.945, 95%CI=0.652 to 1.371, P=0.766). However, in the non-RCTs, mortality risk was lower in patients treated with off-pump CABG than on-pump CABG (pooled OR=0.631, 95%CI=0.587 to 0.944, P=0.003). No differences were observed between the two treatment groups in terms of the occurrence of 30-day post-operative stroke or myocardial infarction (P≥0.147). In the non-RCTs, off-pump CABG treatment was associated with a shorter length of hospital stay (pooled standardized difference in means=-0.401, 95%CI=-0.621 to -0.181, P≤0.001). The meta-analysis with pooled data from non-RCTs, but not RCTs, found that mortality was lower with off-pump compared with on-pump CABG, and suggested that there may be some benefit of off-pump CABG compared with on-pump CABG in the risk of mortality and length of hospital stay.

Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosis--a pooled analysis of EVA-3S, SPACE and ICSS.

PubMed

Bonati, L H; Fraedrich, G

2011-02-01

Recent randomised controlled trials comparing carotid artery stenting (CAS) with endarterectomy (CEA) for the treatment of symptomatic carotid stenosis were not powered to investigate differences in risks in specific patient subgroups. We therefore performed a pooled analysis of individual patient data from the Symptomatic Severe Carotid Stenosis trial (EVA-3S), the Stent-Protected Angioplasty versus Carotid Endarterectomy trial (SPACE), and the International Carotid Stenting Study (ICSS). Individual data from all 3433 patients randomised and analysed in these trials were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. In the first 120 days after randomisation (ITT analysis), the primary outcome event occurred in 153/1725 patients in the CAS group (8.9%) compared with 99/1708 patients in the CEA group (5.8%, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20-1.95, p = 0.0006; absolute risk difference 3.2, 95% CI 1.4-4.9). Age was the only subgroup variable which significantly modified the treatment effect: in patients <70 years old (the median age), the 120-day stroke or death risk was 5.8% in CAS and 5.7% in CEA (RR 1.00, 0.68-1.47); in patients 70 years or older, there was an estimated two-fold increase in risk with CAS over CEA (12.0% vs. 5.9%, RR 2.04, 1.48-2.82, interaction p = 0.0053). Endarterectomy was safer in the short-term than stenting, because of an increased risk of stroke associated with stenting in patients over the age of 70 years. Stenting should be avoided in older patients, but may be as safe as endarterectomy in younger patients. Determination of the efficacy and ultimate balance between the two procedures requires further data on long-term stroke recurrence. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Voxel-based morphometric multisite collaborative study on schizophrenia.

PubMed

Segall, Judith M; Turner, Jessica A; van Erp, Theo G M; White, Tonya; Bockholt, H Jeremy; Gollub, Randy L; Ho, Beng C; Magnotta, Vince; Jung, Rex E; McCarley, Robert W; Schulz, S Charles; Lauriello, John; Clark, Vince P; Voyvodic, James T; Diaz, Michele T; Calhoun, Vince D

2009-01-01

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.

Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication: a systematic review and meta-analysis.

PubMed

Moojen, Wouter A; Arts, Mark P; Bartels, Ronald H M A; Jacobs, Wilco C H; Peul, Wilco C

2011-10-01

Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all systematic reviews, randomized clinical trials and prospective cohort series to quantify the effectiveness of IPDs and to evaluate the potential side-effects. Data from all studies prospectively describing clinical results based on validated outcome scales and reporting complications of treatment of patients with INC with IPD placement. We searched MEDLINE, EMBASE, Web of Science, Cochrane (CENTRAL), CINAHL, Academic Search Premier, Science Direct up to July 2010. Studies describing patients with INC caused by lumbar stenosis, reporting complication rate and reporting based on validated outcome scores, were eligible. Studies with only instrumented IPD results were excluded. Eleven studies eligible studies were identified. Two independently RCTs and eight prospective cohorts were available. In total 563 patients were treated with IPDs. All studies showed improvement in validated outcome scores after 6 weeks and 1 year. Pooled data based on the Zurich Claudication Questionnaire of the RCTs were more in favor of IPD treatment compared with conservative treatment (pooled estimate 23.2, SD 18.5-27.8). Statistical heterogeneity after pooled data was low (I-squared 0.0, p = 0.930). Overall complication rate was 7%. As the evidence is relatively low and the costs are high, more thorough (cost-) effectiveness studies should be performed before worldwide implementation is introduced.

Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤ 4.0 cm): A Meta-analysis.

PubMed

He, Qiqi; Wang, Hanzhang; Kenyon, Jonathan; Liu, Guiming; Yang, Li; Tian, Junqiang; Yue, Zhongjin; Wang, Zhiping

2015-01-01

To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs ≤ 4.0 cm). Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek's funnel plot was used to evaluate the publication bias. A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95 % CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95 % CI: 0.06-0.13), the pooled DOR was 296.52(95 % CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959 ± 0.0254. Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs ≤ 4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration.

Sensitivity and Specificity of CT and Its signs for Diagnosis of Strangulation in Patients with Acute Small Bowel Obstruction.

PubMed

Jha, Ashwini Kumar; Tang, Wen Hao; Bai, Zhi Bin; Xiao, Jia Quan

2014-01-01

To perform a meta-analysis to review the sensitivity and specificity of computed tomography and different known computed yomography signs for the diagnosis of strangulation in patients with acute small bowel obstruction. A comprehensive Pubmed search was performed for all reports that evaluated the use of CT and discussed different CT criteria for the diagnosis of acute SBO. Articles published in English language from January 1978 to June 2008 were included. Review articles, case reports, pictorial essays and articles without original data were excluded. The bivariate random effect model was used to obtain pooled sensitivity and pooled specificity. Summary receiver operating curve was calculated using Meta-Disc. Software Openbugs 3.0.3 was used to summarize the data. A total of 12 studies fulfilled the inclusion criteria. The pooled sensitivity and specificity of CT in the diagnosis of strangulation was 0.720 (95% CI 0.674 to 0.763) and 0.866 (95% CI 0.837 to 0.892) respectively. Among different CT signs, mesenteric edema had highest Pooled sensitivity of 0. 741 and lack of bowel wall enhancement had highest pooled specificity of 0.991. This review demonstrates that CT is highly sensitive as well as specific in the preoperative diagnosis of strangulation SBO which are in accordance with the published studies. Our analysis also shows that "presence of mesenteric fluid" is most sensitive, and "lack of bowel wall enhancement" is most specific CT sign of strangulation, and also justifies need of large scale prospective studies to validate the results obtained as well as to determine a clinical protocol.

FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis.

PubMed

Tomasello, Gianluca; Petrelli, Fausto; Ghidini, Michele; Russo, Alessandro; Passalacqua, Rodolfo; Barni, Sandro

2017-07-13

The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions. A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer). Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded. Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial. Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions. Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30.2 months (95% CI, 26.5-33.7 months) in 6 trials with data available, and progression-free survival was 12.4 months (95% CI, 10.0-14.3 months) in 9 trials with data available. In meta-regression analysis, variables significantly associated with conversion surgery were disease limited to the liver and a higher median number of cycles (close to 12). For patients with surgically unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant overall response rate. Such an effective regimen leads to a probability of surgical conversion of distant metastases approaching 40%, with more than one-fourth of patients having an R0 resection.

Automated vessel segmentation using cross-correlation and pooled covariance matrix analysis.

PubMed

Du, Jiang; Karimi, Afshin; Wu, Yijing; Korosec, Frank R; Grist, Thomas M; Mistretta, Charles A

2011-04-01

Time-resolved contrast-enhanced magnetic resonance angiography (CE-MRA) provides contrast dynamics in the vasculature and allows vessel segmentation based on temporal correlation analysis. Here we present an automated vessel segmentation algorithm including automated generation of regions of interest (ROIs), cross-correlation and pooled sample covariance matrix analysis. The dynamic images are divided into multiple equal-sized regions. In each region, ROIs for artery, vein and background are generated using an iterative thresholding algorithm based on the contrast arrival time map and contrast enhancement map. Region-specific multi-feature cross-correlation analysis and pooled covariance matrix analysis are performed to calculate the Mahalanobis distances (MDs), which are used to automatically separate arteries from veins. This segmentation algorithm is applied to a dual-phase dynamic imaging acquisition scheme where low-resolution time-resolved images are acquired during the dynamic phase followed by high-frequency data acquisition at the steady-state phase. The segmented low-resolution arterial and venous images are then combined with the high-frequency data in k-space and inverse Fourier transformed to form the final segmented arterial and venous images. Results from volunteer and patient studies demonstrate the advantages of this automated vessel segmentation and dual phase data acquisition technique. Copyright © 2011 Elsevier Inc. All rights reserved.

Perioperative Aspirin for Prevention of Venous Thromboembolism: The PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials.

PubMed

Eikelboom, John W; Kearon, Clive; Guyatt, Gordon; Sessler, Daniel I; Yusuf, Salim; Cook, Deborah; Douketis, James; Patel, Ameen; Kurz, Andrea; Allard, Rene; Jones, Philip M; Dennis, Rodolfo J; Painter, Thomas W; Bergese, Sergio D; Leslie, Kate; Wijeysundera, Duminda N; Balasubramanian, Kumar; Duceppe, Emmanuelle; Miller, Scott; Diedericks, Johan; Devereaux, P J

2016-12-01

The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.

Effects of self-management health information technology on glycaemic control for patients with diabetes: a meta-analysis of randomized controlled trials.

PubMed

Tao, Da; Or, Calvin Kl

2013-04-01

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) which had evaluated self-management health information technology (SMHIT) for glycaemic control in patients with diabetes. A total of 43 RCTs was identified, which reported on 52 control-intervention comparisons. The glycosylated haemoglobin (HbA 1c ) data were pooled using a random effects meta-analysis method, followed by a meta-regression and subgroup analyses to examine the effects of a set of moderators. The meta-analysis showed that use of SMHITs was associated with a significant reduction in HbA 1c compared to usual care, with a pooled standardized mean difference of -0.30% (95% CI -0.39 to -0.21, P < 0.001). Sample size, age, study setting, type of application and method of data entry significantly moderated the effects of SMHIT use. The review supports the use of SMHITs as a self-management approach to improve glycaemic control. The effect of SMHIT use is significantly greater when the technology is a web-based application, when a mechanism for patients' health data entry is provided (manual or automatic) and when the technology is operated in the home or without location restrictions. Integrating these variables into the design of SMHITs may augment the effectiveness of the interventions. © SAGE Publications Ltd, 2013.

Safety of Tofacitinib in the Treatment of Rheumatoid Arthritis in Latin America Compared With the Rest of the World Population.

PubMed

Castañeda, Oswaldo M; Romero, Felix J; Salinas, Ariel; Citera, Gustavo; Mysler, Eduardo; Rillo, Oscar; Radominski, Sebastiao C; Cardiel, Mario H; Jaller, Juan J; Alvarez-Moreno, Carlos; Ponce de Leon, Dario; Castelli, Graciela; García, Erika G; Kwok, Kenneth; Rojo, Ricardo

2017-06-01

Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint destruction. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post hoc analysis assessed the safety of tofacitinib in Latin American (LA) patients with RA versus the Rest of World (RoW) population. Data were pooled from 14 clinical studies of tofacitinib: six Phase 2, six Phase 3 and two long-term extension studies. Incidence rates (IRs; patients with events/100 patient-years of treatment exposure) were calculated for safety events of special interest combined across tofacitinib doses. 95% confidence intervals (CI) for IRs were calculated using the maximum likelihood method. Descriptive comparisons were made between LA and RoW (excluding LA) populations. This analysis included data from 984 LA patients and 4687 RoW patients. IRs for safety events of special interest were generally similar between LA and RoW populations, with overlapping 95% CIs. IRs for discontinuation due to adverse events, serious infections, tuberculosis, all herpes zoster (HZ), serious HZ, malignancies (excluding non-melanoma skin cancer) and major adverse cardiovascular events were numerically lower for LA versus RoW patients; IR for mortality was numerically higher. No lymphoma was reported in the LA population versus eight cases in the RoW population. Exposure (extent and length) was lower in the LA population (2148.33 patient-years [mean = 2.18 years]) versus RoW (10515.68 patient-years [mean = 2.24 years]). This analysis of pooled data from clinical studies of tofacitinib in patients with RA demonstrates that tofacitinib has a consistent safety profile across LA and RoW patient populations.

Multiplexed droplet single-cell RNA-sequencing using natural genetic variation.

PubMed

Kang, Hyun Min; Subramaniam, Meena; Targ, Sasha; Nguyen, Michelle; Maliskova, Lenka; McCarthy, Elizabeth; Wan, Eunice; Wong, Simon; Byrnes, Lauren; Lanata, Cristina M; Gate, Rachel E; Mostafavi, Sara; Marson, Alexander; Zaitlen, Noah; Criswell, Lindsey A; Ye, Chun Jimmie

2018-01-01

Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets). These capabilities enable multiplexed dscRNA-seq experiments in which cells from unrelated individuals are pooled and captured at higher throughput than in standard workflows. Using simulated data, we show that 50 single-nucleotide polymorphisms (SNPs) per cell are sufficient to assign 97% of singlets and identify 92% of doublets in pools of up to 64 individuals. Given genotyping data for each of eight pooled samples, demuxlet correctly recovers the sample identity of >99% of singlets and identifies doublets at rates consistent with previous estimates. We apply demuxlet to assess cell-type-specific changes in gene expression in 8 pooled lupus patient samples treated with interferon (IFN)-β and perform eQTL analysis on 23 pooled samples.

Reliability of muscle strength assessment in chronic post-stroke hemiparesis: a systematic review and meta-analysis.

PubMed

Rabelo, Michelle; Nunes, Guilherme S; da Costa Amante, Natália Menezes; de Noronha, Marcos; Fachin-Martins, Emerson

2016-02-01

Muscle weakness is the main cause of motor impairment among stroke survivors and is associated with reduced peak muscle torque. To systematically investigate and organize the evidence of the reliability of muscle strength evaluation measures in post-stroke survivors with chronic hemiparesis. Two assessors independently searched four electronic databases in January 2014 (Medline, Scielo, CINAHL, Embase). Inclusion criteria comprised studies on reliability on muscle strength assessment in adult post-stroke patients with chronic hemiparesis. We extracted outcomes from included studies about reliability data, measured by intraclass correlation coefficient (ICC) and/or similar. The meta-analyses were conducted only with isokinetic data. Of 450 articles, eight articles were included for this review. After quality analysis, two studies were considered of high quality. Five different joints were analyzed within the included studies (knee, hip, ankle, shoulder, and elbow). Their reliability results varying from low to very high reliability (ICCs from 0.48 to 0.99). Results of meta-analysis for knee extension varying from high to very high reliability (pooled ICCs from 0.89 to 0.97), for knee flexion varying from high to very high reliability (pooled ICCs from 0.84 to 0.91) and for ankle plantar flexion showed high reliability (pooled ICC = 0.85). Objective muscle strength assessment can be reliably used in lower and upper extremities in post-stroke patients with chronic hemiparesis.

Prevalence of rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease: a meta and meta-regression analysis.

PubMed

Zhang, Xiaona; Sun, Xiaoxuan; Wang, Junhong; Tang, Liou; Xie, Anmu

2017-01-01

Rapid eye movement sleep behavior disorder (RBD) is thought to be one of the most frequent preceding symptoms of Parkinson's disease (PD). However, the prevalence of RBD in PD stated in the published studies is still inconsistent. We conducted a meta and meta-regression analysis in this paper to estimate the pooled prevalence. We searched the electronic databases of PubMed, ScienceDirect, EMBASE and EBSCO up to June 2016 for related articles. STATA 12.0 statistics software was used to calculate the available data from each research. The prevalence of RBD in PD patients in each study was combined to a pooled prevalence with a 95 % confidence interval (CI). Subgroup analysis and meta-regression analysis were performed to search for the causes of the heterogeneity. A total of 28 studies with 6869 PD cases were deemed eligible and included in our meta-analysis based on the inclusion and exclusion criteria. The pooled prevalence of RBD in PD was 42.3 % (95 % CI 37.4-47.1 %). In subgroup analysis and meta-regression analysis, we found that the important causes of heterogeneity were the diagnosis criteria of RBD and age of PD patients (P = 0.016, P = 0.019, respectively). The results indicate that nearly half of the PD patients are suffering from RBD. Older age and longer duration are risk factors for RBD in PD. We can use the minimal diagnosis criteria for RBD according to the International Classification of Sleep Disorders to diagnose RBD patients in our daily work if polysomnography is not necessary.

Risk of hepatitis B virus reactivation with direct-acting antivirals against hepatitis C virus: A cohort study from Egypt and meta-analysis of published data.

PubMed

El Kassas, Mohamed; Shimakawa, Yusuke; Ali-Eldin, Zainab; Funk, Anna-Louise; Wifi, Mohamed Naguib; Zaky, Samy; El-Raey, Fathiya; Esmat, Gamal; Fontanet, Arnaud

2018-05-08

Hepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV. We prospectively followed HBV surface antigen (HBsAg)-positive Egyptians undergoing interferon-free DAAs, to estimate the risk of HBV reactivation and HBV-related hepatitis. We also conducted a meta-analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD). Of 4471 CHC patients, 35 HBsAg-positive patients started interferon-free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg-positive patients was 18.2% (95% CI: 7.9%-30.7%) without HBV therapy and 0.0% (95% CI: 0.0%-0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%-34.7%). The pooled reactivation risk in HBsAg-negative, antibody to HBV core antigen-positive (anti-HBc-positive) patients was negligible (0.1%, 95% CI: 0.0%-0.3%), irrespective of the presence of antibody to HBsAg (anti-HBs). We confirmed high HBV reactivation risk in HBsAg-positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg-negative anti-HBc-positive patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis.

PubMed

Chen, Lihua; Liu, Min; Bao, Jing; Xia, Yunbao; Zhang, Jiuquan; Zhang, Lin; Huang, Xuequan; Wang, Jian

2013-01-01

To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (P<0.001). After the sensitivity analysis, two studies were excluded, and the pooled r was -0.61 (95% CI: -0.66, -0.56) and was not significantly heterogeneous (P = 0.127). Regarding tumor type subgroup analysis, there were sufficient data to support a strong negative correlation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias. There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.

Patient satisfaction with intravenous acetaminophen: a pooled analysis of five randomized, placebo-controlled studies in the acute postoperative setting.

PubMed

Apfel, Christian C; Souza, Kimberly; Portillo, Juan; Dalal, Poorvi; Bergese, Sergio D

2015-01-01

Intravenous (IV) acetaminophen has been shown to reduce postoperative pain and opioid consumption, which may lead to increased patient satisfaction. To determine the effect IV acetaminophen has on patient satisfaction, a pooled analysis from methodologically homogenous studies was conducted. We obtained patient-level data from five randomized, placebo-controlled studies in adults undergoing elective surgery in which patient satisfaction was measured using a 4-point categorical rating scale. The primary endpoint was "excellent" satisfaction and the secondary endpoint was "good" or "excellent" satisfaction at 24 hr after first study drug administration. Bivariate analyses were conducted using the chi-square test and Student's t-test and multivariable analyses were conducted using logistic regression analysis. Patients receiving IV acetaminophen were more than twice as likely as those who received placebo to report "excellent" patient satisfaction ratings (32.3% vs. 15.9%, respectively). Of all variables that remained statistically significant in the multivariable analysis (i.e., type of surgery, duration of anesthesia, last pain rating, and opioid consumption), IV acetaminophen had the strongest positive effect on "excellent" patient satisfaction with an odds ratio of 2.76 (95% CI 1.81-4.23). Results for "excellent" or "good" satisfaction were similar. When given as part of a perioperative analgesic regimen, IV acetaminophen was associated with significantly improved patient satisfaction.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

PubMed Central

Pandit, Anil; Aryal, Madan Raj; Aryal Pandit, Aashrayata; Hakim, Fayaz Ahmad; Giri, Smith; Mainali, Naba Raj; Sharma, Prashant; Lee, Howard R; Fortuin, F David; Mookadam, Farouk

2014-01-01

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials. PMID:25332779

Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis.

PubMed

Qiu, Yun; Mao, Ren; Chen, Bai-Li; Zhang, Sheng-Hong; Guo, Jing; He, Yao; Zeng, Zhi-Rong; Ben-Horin, Shomron; Chen, Min-Hu

2017-09-01

It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59; P < .001). However, the pooled analysis did not demonstrate a significant difference in trough levels of anti-TNF agents between patients with versus without concurrent use of immunomodulators (standardized mean difference, 0.11; 95% confidence interval, 0.19-0.41; P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction); the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I 2  = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation of antibodies against TNF antagonists in patients with inflammatory bowel disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Meta-analysis of randomized and quasi-randomized clinical trials of topical antibiotics after primary closure for the prevention of surgical-site infection.

PubMed

Heal, C F; Banks, J L; Lepper, P; Kontopantelis, E; van Driel, M L

2017-08-01

Surgical-site infections (SSIs) increase patient morbidity and costs. The aim was to identify and synthesize all RCTs evaluating the effect of topical antibiotics on SSI in wounds healing by primary intention. The search included Ovid MEDLINE, Ovid Embase, the Cochrane Wounds Specialized Register, Central Register of Controlled Trials and EBSCO CINAHL from inception to May 2016. There was no restriction of language, date or setting. Two authors independently selected studies, extracted data and assessed risk of bias. When sufficient numbers of comparable trials were available, data were pooled in meta-analysis. Fourteen RCTs with 6466 participants met the inclusion criteria. Pooling of eight trials (5427 participants) showed that topical antibiotics probably reduced the risk of SSI compared with no topical antibiotic (risk ratio (RR) 0·61, 95 per cent c.i. 0·42 to 0·87; moderate-quality evidence), equating to 20 fewer SSIs per 1000 patients treated. Pooling of three trials (3012 participants) for risk of allergic contact dermatitis found no clear difference between antibiotics and no antibiotic (RR 3·94, 0·46 to 34·00; very low-quality evidence). Pooling of five trials (1299 participants) indicated that topical antibiotics probably reduce the risk of SSI compared with topical antiseptics (RR 0·49, 0·30 to 0·80; moderate-quality evidence); 43 fewer SSIs per 1000 patients treated. Pooling of two trials (541 participants) showed no clear difference in the risk of allergic contact dermatitis with antibiotics or antiseptic agents (RR 0·97, 0·52 to 1·82; very low-quality evidence). Topical antibiotics probably prevent SSI compared with no topical antibiotic or antiseptic. No conclusion can be drawn regarding whether they cause allergic contact dermatitis. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

PubMed

Rodríguez, Marta; Silva, Javier; López-Alfonso, Ana; López-Muñiz, María Belen; Peña, Cristina; Domínguez, Gemma; García, Jose Miguel; López-Gónzalez, Ana; Méndez, Miriam; Provencio, Mariano; García, Vanesa; Bonilla, Félix

2014-09-01

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content. © 2014 Wiley Periodicals, Inc.

Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: a pooled analysis of six randomized, double-blind, placebo-controlled studies.

PubMed

Papakostas, George I; Culpepper, Larry; Fayyad, Rana S; Musgnung, Jeff; Guico-Pabia, Christine J

2013-11-01

This study assessed the efficacy of desvenlafaxine 50 mg/day compared with placebo for treating moderate or severe major depressive disorder (MDD). Data were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day fixed-dose studies in adults with MDD. The primary endpoint was improvement in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at week 8. HAM-D17 changes were evaluated in patients with moderate (18

Reliability of abstracting performance measures: results of the cardiac rehabilitation referral and reliability (CR3) project.

PubMed

Thomas, Randal J; Chiu, Jensen S; Goff, David C; King, Marjorie; Lahr, Brian; Lichtman, Steven W; Lui, Karen; Pack, Quinn R; Shahriary, Melanie

2014-01-01

Assessment of the reliability of performance measure (PM) abstraction is an important step in PM validation. Reliability has not been previously assessed for abstracting PMs for the referral of patients to cardiac rehabilitation (CR) and secondary prevention (SP) programs. To help validate these PMs, we carried out a multicenter assessment of their reliability. Hospitals and clinical practices from around the United States were invited to participate in the Cardiac Rehabilitation Referral Reliability (CR3) Project. Twenty-nine hospitals and 23 outpatient centers expressed interest in participating. Seven hospitals and 6 outpatient centers met participation criteria and submitted completed data. Site coordinators identified 35 patients whose charts were reviewed by 2 site abstractors twice, 1 week apart. Percent agreement and the Cohen κ statistic were used to describe intra- and interabstractor reliability for patient eligibility for CR/SP, patient exceptions for CR/SP referral, and documented referral to CR/SP. Results were obtained from within-site data, as well as from pooled data of all inpatient and all outpatient sites. We found that intra-abstractor reliability reflected excellent repeatability (≥ 90% agreement; κ ≥ 0.75) for ratings of CR/SP eligibility, exceptions, and referral, both from pooled and site-specific analyses of inpatient and outpatient data. Similarly, the interabstractor agreement from pooled analysis ranged from good to excellent for the 3 items, although with slightly lower measures of reliability. Abstraction of PMs for CR/SP referral has high reliability, supporting the use of these PMs in quality improvement initiatives aimed at increasing CR/SP delivery to patients with cardiovascular disease.

Gastrografin may reduce time to oral diet in prolonged post-operative ileus: a pooled analysis of two randomized trials.

PubMed

Milne, Tony G E; Vather, Ryash; O'Grady, Gregory; Miquel, Jordi; Biondo, Sebastiano; Bissett, Ian

2018-03-06

Gastrografin has been suggested as a rescue therapy for prolonged post-operative ileus (PPOI) but trial data has been inconclusive. This study aimed to determine the benefit of gastrografin use in patients with PPOI by pooling the results of two recent randomized controlled trials assessing the efficacy of gastrografin compared to placebo given at time of PPOI diagnosis. Anonymized, individual patient data from patients undergoing elective bowel resection for any indication were included, stoma closure was excluded. The primary outcome was duration of PPOI. Secondary outcomes were time to tolerate oral diet, passage of flatus/stool, requirement and duration of nasogastric tube, length of post-operative stay and rate of post-operative complications. Individual patient data were pooled for analysis (53 gastrografin, 55 placebo). Gastrografin trended towards a reduction in PPOI duration compared to placebo, respectively, median 96 h (interquartile range, IQR, 78 h) versus median 120 h (IQR, 84 h), however, this result was non-significant (P = 0.11). In addition, no significant difference was detected between the two groups for time to passage of flatus/stool (P = 0.36) and overall length of stay (P = 0.35). Gastrografin conferred a significantly faster time to tolerate an oral diet compared to placebo (median 84 h versus median 107 h, P = 0.04). There was no difference in post-operative complications between the two interventions (P > 0.05). Gastrografin did not significantly reduce PPOI duration or length of stay after abdominal surgery, but did reduce time to tolerate a solid diet. Further studies are required to clarify the role of gastrografin in PPOI. © 2018 Royal Australasian College of Surgeons.

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

François, Clément; Rowse, Gerald J; Hewitt, L Arthur; Vo, Pamela; Hauser, Robert A

2016-08-18

Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

PubMed Central

Muhsen, Khitam; Levine, Myron M.

2012-01-01

We performed a systematic literature review and meta-analysis examining the association between diarrhea in young children in nonindustrialized settings and Giardia lamblia infection. Eligible were case/control and longitudinal studies that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly in stools) from diarrhea patients and controls without diarrhea were abstracted. Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric diarrhea studies met the meta-analysis inclusion criteria. Random-effects model meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls) yielded a pooled OR of 0.60 (95% CI, .38–.94; P = .03), indicating that G. lamblia was not associated with acute diarrhea. However, limited data suggest that initial Giardia infections in early infancy may be positively associated with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR of 3.18 (95% CI, 1.50–6.76; P < .001), positively linking Giardia with that syndrome. The well-powered Global Enteric Multicenter Study (GEMS) is prospectively addressing the association between G. lamblia infection and diarrhea in children in developing countries. PMID:23169940

Celiac disease and the risk of kidney diseases: A systematic review and meta-analysis.

PubMed

Wijarnpreecha, Karn; Thongprayoon, Charat; Panjawatanan, Panadeekarn; Thamcharoen, Natanong; Pachariyanon, Pavida; Nakkala, Kiran; Cheungpasitporn, Wisit

2016-12-01

Previous epidemiologic studies attempting to demonstrate the risk of kidney diseases among patients with celiac disease (CD) have yielded inconsistent results. This meta-analysis was conducted with the aims to summarize all available evidence. A literature search was performed using MEDLINE and EMBASE from inception to May 2016. Studies that provided relative risks, odd ratios, or hazard ratios examining the risk of kidney diseases among patients with CD versus individuals without CD were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Eight studies met our eligibility criteria and were included in our analysis. A pooled RR of overall kidney diseases in patients with CD was 2.01 (95% CI, 1.44-2.81, I 2 =76%). The pooled RR of end-stage renal disease in patients with CD was 2.57 (95% CI, 2.03-3.24). Subgroup analyses showed that significant risks were increased for diabetic nephropathy (pooled RR of 1.49, 95% CI, 1.09-2.02) and IgA nephropathy (pooled RR of 2.62, 95% CI, 1.27-5.42) in patients with CD. Our study demonstrates a significantly increased risk of kidney diseases among patients with CD. These findings may influence clinical management and primary prevention of kidney diseases in patients with CD. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis.

PubMed

Guo, Ya-Huan; Sun, Hai-Feng; Zhang, Yan-Bing; Liao, Zi-Jun; Zhao, Lei; Cui, Jie; Wu, Tao; Lu, Jian-Rong; Nan, Ke-Jun; Wang, Shu-Hong

2017-03-21

Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis. Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 - 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 - 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 - 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 - 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71- 0.94,p=0.005, I2=29%). Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.

A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer

PubMed Central

Wang, Cuihua; Yu, Xuetao; Wang, Wei

2016-01-01

Abstract Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC. Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC. Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies. Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61–0.75) and 0.83 (95% CI 0.75–0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41–2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69–1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57–0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28–0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14–0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of PD-1/PD-L1 inhibitors. Conclusion: The PD-1/PD-L1 therapy significantly prolonged the OS and improved the ORR, simultaneously lowering the treatment-related adverse effect events versus docetaxel. PMID:28033249

Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis.

PubMed

Chokesuwattanaskul, Ronpichai; Thongprayoon, Charat; Tanawuttiwat, Tanyanan; Kaewput, Wisit; Pachariyanon, Pavida; Cheungpasitporn, Wisit

2018-06-01

At the present, apixaban is the only nonvitamin K oral anticoagulant approved by the Food and Drug Administration for use with patients with creatinine clearance <15 mL/min or end-stage renal disease (ESRD). However, the recommendations are based on pharmacokinetic and pharmacodynamic data and there was lack of clinical trial evidence. We aimed to assess safety and efficacy of apixaban in patients with advanced chronic kidney disease (CKD) or ESRD. Databases were searched through November 2017. Studies that reported incidence or odd ratios of bleeding complications or thromboembolic events in the use of apixaban in patients with CKD stage 4-5 or ESRD on dialysis were included. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Five studies were included into the analysis consisting of 43,850 patients in observational cohort studies. The majority of patients (87%) used apixaban for atrial fibrillation. The pooled estimated incidence of any bleeding complications on apixaban was 17.4% (95% confidence interval [CI]: 13.0%-23.0%). Compared to warfarin, apixaban was significantly associated with reduced risk of major bleeding (pooled odds ratio [OR], 0.42; 95% CI, 0.28-0.61). In studies in ESRD patients on dialysis, the pooled OR of major bleeding was 0.27 (95% CI, 0.07-0.95). There was no significant difference in risk of thromboembolic events in advanced CKD or ESRD patients on apixaban versus vitamin K antagonists (pooled OR, 0.56; 95% CI, 0.23-1.39). Among patients with advanced CKD and ESRD, the use of apixaban was associated with lower risk of major bleeding compared to warfarin, and was found to be relatively effective with no excess risk of thromboembolic events. © 2018 Wiley Periodicals, Inc.

Tomographic phase analysis to detect the site of accessory conduction pathway in Wolff-Parkinson-White syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakajima, K.; Bunko, H.; Tada, A.

1984-01-01

Phase analysis has been applied to Wolff-Parkinson-White syndrome (WPW) to detect the site of accessory conduction pathway (ACP); however, there was a limitation to estimate the precise location of ACP by planar phase analysis. In this study, the authors applied phase analysis to gated blood pool tomography. Twelve patients with WPW who underwent epicardial mapping and surgical division of ACP were studied by both of gated emission computed tomography (GECT) and routine gated blood pool study (GBPS). The GBPS was performed with Tc-99m red blood cells in multiple projections; modified left anterior oblique, right anterior oblique and/or left lateral views.more » In GECT, short axial, horizontal and vertical long axial blood pool images were reconstructed. Phase analysis was performed using fundamental frequency of the Fourier transform in both GECT and GBPS images, and abnormal initial contractions on both the planar and tomographic phase analysis were compared with the location of surgically confirmed ACPs. In planar phase analysis, abnormal initial phase was identified in 7 out of 12 (58%) patients, while in tomographic phase analysis, the localization of ACP was predicted in 11 out of 12 (92%) patients. Tomographic phase analysis is superior to planar phase images in 8 out of 12 patients to estimate the location of ACP. Phase analysis by GECT can avoid overlap of blood pool in cardiac chambers and has advantage to identify the propagation of phase three-dimensionally. Tomographic phase analysis is a good adjunctive method for patients with WPW to estimate the site of ACP.« less

Long non-coding RNA AFAP1-AS1 is a novel biomarker in various cancers: a systematic review and meta-analysis based on the literature and GEO datasets.

PubMed

Wang, Yumin; Mo, Yongzhen; Yang, Xiang; Zhou, Ruoyu; Wu, Zeyu; He, Yuchen; Yang, Xue; Zhong, Yaxian; Du, Yajun; Zhou, Hang; Li, Xiaoling; Li, Yong; Li, Guiyuan; Zeng, Zhaoyang; Guo, Can; Xiong, Wei

2017-11-24

Growing evidence indicates that AFAP1-AS1 plays an important role in various cancers, suggesting that it might be a potential cancer biomarker. A meta-analysis was performed using microarray data obtained via the Affymetrix Human Genome U133 Plus 2.0 platform (found in the GEO database) and data obtained through a systematic search of PubMed and Web of Science. The pooled odds ratio (OR) and hazard ratio (HR) with 95% CI (confidence interval) were used to judge the value of biomarkers. A total of 30 studies were included in this meta-analysis, comprising a total of 3573 patients. AFAP1-AS1 was significantly linked with overall survival (OS) (HR = 1.58; 95% CI: 1.12-2.23) and recurrence-free survival (RFS) (HR = 2.32, 95% CI: 1.68-3.19). We found that AFAP1-AS1 was a risk factor in the prognoses of lung cancer (pooled HR: 1.54; 95% CI: 1.01-2.34), digestive system cancer (pooled HR: 1.87; 95% CI: 1.45-2.41) and nasopharyngeal carcinoma (HR: 11.82; 95% CI: 5.09-27.46). AFAP1-AS1 was also a risk factor for RFS in breast cancer (pooled HR = 2.90; 95% CI: 1.69-4.98), as well as TNM stage in both esophageal cancer (pooled OR = 1.90; 95% CI: 1.01-3.57) and colorectal cancer (OR = 6.72; 95% CI: 1.92-23.58). AFAP1-AS1 was significantly associated with lymph node metastasis in clear cell carcinoma (OR = 5.04; 95% CI: 2.36-10.78) and distant metastasis in pancreatic cancer (OR = 11.64; 95% CI: 2.13-63.78). AFAP1-AS1 can serve as a novel molecular marker predicting tumor progression, patient prognosis and lymph node metastasis in different types of cancers.

A meta-analysis of prehospital airway control techniques part II: alternative airway devices and cricothyrotomy success rates.

PubMed

Hubble, Michael W; Wilfong, Denise A; Brown, Lawrence H; Hertelendy, Attila; Benner, Randall W

2010-01-01

Airway management is a key component of prehospital care for seriously ill and injured patients. Oral endotracheal intubation (OETI) is the definitive airway of choice in most emergency medical services (EMS) systems. However, OETI may not be an approved skill for some clinicians or may prove problematic in certain patients because of anatomic abnormalities, trauma, or inadequate relaxation. In these situations alternative airways are frequently employed. However, the reported success rates for these devices vary widely, and established benchmarks are lacking. We sought to determine pooled estimates of the success rates of alternative airway devices (AADs) and needle cricothyrotomy (NCRIC) and surgical cricothyrotomy (SCRIC) placement through a meta-analysis of the literature. We performed a systematic literature search for all English-language articles reporting success rates for AADs, SCRIC, and NCRIC. Studies of field procedures performed by prehospital personnel from any nation were included. All titles were reviewed independently by two authors using prespecified inclusion criteria. Pooled estimates of success rates for each airway technique were calculated using a random-effects meta-analysis model. Of 2,005 prehospital airway titles identified, 35 unique studies were retained for analysis of AAD success rates, encompassing a total of 10,172 prehospital patients. The success rates for SCRIC and NCRIC were analyzed across an additional 21 studies totaling 512 patients. The pooled estimates (and 95% confidence intervals [CIs]) for intervention success across all clinicians and patients were as follows: esophageal obturator airway-esophageal gastric tube airway (EOA-EGTA) 92.6% (90.1%-94.5%); pharyngeotracheal lumen airway (PTLA) 82.1% (74.0%-88.0%); esophageal-tracheal Combitube (ETC) 85.4% (77.3%-91.0%); laryngeal mask airway (LMA) 87.4% (79.0%-92.8%); King Laryngeal Tube airway (King LT) 96.5% (71.2%-99.7%); NCRIC 65.8% (42.3%-83.59%); and SCRIC 90.5% (84.8%-94.2%). We provide pooled estimates for prehospital AAD, NCRIC, and SCRIC airway interventions. Of the AADs, the King LT demonstrated the highest insertion success rate (96.5%), although this estimate is based on limited data, and data regarding its ventilatory effectiveness are lacking; more data are available for the ETC and LMA. The ETC, LMA, and PTLA all had similar-but lower-success rates (82.1%-87.4%). NCRIC has a low rate of success (65.8%); SCRIC has a much higher success rate (90.5%) and should be considered the preferred percutaneous rescue airway.

Diagnostic value of C-reactive protein to rule out infectious complications after major abdominal surgery: a systematic review and meta-analysis.

PubMed

Gans, Sarah L; Atema, Jasper J; van Dieren, Susan; Groot Koerkamp, Bas; Boermeester, Marja A

2015-07-01

Infectious complications occur frequently after major abdominal surgery and have a major influence on patient outcome and hospital costs. A marker that can rule out postoperative infectious complications (PICs) could aid patient selection for safe and early hospital discharge. C-reactive protein (CRP) is a widely available, fast, and cheap marker that might be of value in detecting PIC. Present meta-analysis evaluates the diagnostic value of CRP to rule out PIC following major abdominal surgery, aiding patient selection for early discharge. A systematic literature search of Medline, PubMed, and Cochrane was performed identifying all prospective studies evaluating the diagnostic value of CRP after abdominal surgery. Meta-analysis was performed according to the PRISMA statement. Twenty-two studies were included for qualitative analysis of which 16 studies were eligible for meta-analysis, representing 2215 patients. Most studies analyzed the value of CRP in colorectal surgery (eight studies). The pooled negative predictive value (NPV) improved each day after surgery up to 90% at postoperative day (POD) 3 for a pooled CRP cutoff of 159 mg/L (range 92-200). Maximum predictive values for PICs were reached on POD 5 for a pooled CRP cutoff of 114 mg/L (range 48-150): a pooled sensitivity of 86% (95% confidence interval (CI) 79-91%), specificity of 86% (95% CI 75-92%), and a positive predictive value of 64% (95% CI 49-77%). The pooled sensitivity and specificity were significantly higher on POD 5 than on other PODs (p < 0.001). Infectious complications after major abdominal surgery are very unlikely in patients with a CRP below 159 mg/L on POD 3. This can aid patient selection for safe and early hospital discharge and prevent overuse of imaging.

Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase III controlled trials.

PubMed

Carreño, Mar; Benbadis, Selim; Rocha, Francisco; Blum, David; Cheng, Hailong

2017-12-01

To investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients. Post-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis. The modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period : Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period : Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering-off period : Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo. Treatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.

Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis.

PubMed

D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A; Lebbé, Celeste; Brady, Benjamin; Neyns, Bart; Schmidt, Henrik; Hassel, Jessica C; Hodi, F Stephen; Lorigan, Paul; Savage, Kerry J; Miller, Wilson H; Mohr, Peter; Marquez-Rodas, Ivan; Charles, Julie; Kaatz, Martin; Sznol, Mario; Weber, Jeffrey S; Shoushtari, Alexander N; Ruisi, Mary; Jiang, Joel; Wolchok, Jedd D

2017-01-10

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

PubMed Central

Larkin, James; Sosman, Jeffrey A.; Lebbé, Celeste; Brady, Benjamin; Neyns, Bart; Schmidt, Henrik; Hassel, Jessica C.; Hodi, F. Stephen; Lorigan, Paul; Savage, Kerry J.; Miller, Wilson H.; Mohr, Peter; Marquez-Rodas, Ivan; Charles, Julie; Kaatz, Martin; Sznol, Mario; Weber, Jeffrey S.; Shoushtari, Alexander N.; Ruisi, Mary; Jiang, Joel; Wolchok, Jedd D.

2017-01-01

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes. PMID:28056206

Incidence Proportion of Acute Cor Pulmonale in Patients with Acute Respiratory Distress Syndrome Subjected to Lung Protective Ventilation: A Systematic Review and Meta-analysis.

PubMed

Das, Saurabh Kumar; Choupoo, Nang Sujali; Saikia, Priyam; Lahkar, Amitabh

2017-06-01

Reported incidence of acute cor pulmonale (ACP) in patients with acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being subjected to lung protective ventilation according to the current guidelines. The objective of this review is to find pooled cumulative incidence of ACP in patients with ARDS undergoing lung protective ventilation. We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical Trial Registry. Cross-sectional or cohort studies were included if they reported or provided data that could be used to calculate the incidence proportion of ACP. Inverse variance heterogeneity (IVhet) and random effect model were used for the main outcome and measures. We included 16 studies encompassing 1661 patients. The cumulative incidence of ACP using IVhet analysis was 23% (95% confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation. Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP. Patients with ARDS have a 23% risk of developing ACP with lung protective ventilation. Findings of this review indicate the need of updating existing guidelines for ventilating ARDS patients to incorporate right ventricle protective strategy.

PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data.

PubMed

Fanti, Stefano; Minozzi, Silvia; Castellucci, Paolo; Balduzzi, Sara; Herrmann, Ken; Krause, Bernd Joachim; Oyen, Wim; Chiti, Arturo

2016-01-01

For the last decade PET and PET/CT with (11)C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of (11)C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of (11)C-choline PET, restaging of patients with biochemical relapse, following a rigorous methodological approach and including assessment of the risk of bias. We conducted a systematic review and meta-analysis of the literature assessing (11)C-choline PET/CT for its accuracy in the diagnosis and ability to detect the site of recurrence of PC in the restaging of patients with biochemical recurrence after initial treatment with curative intent. We performed a comprehensive literature search of PubMed and the Cochrane Library to determine the accuracy for the detection of the site of recurrence (prostate bed recurrences, metastatic spread to locoregional pelvic lymph nodes or distant metastases). Only studies with a reference standard (for prostatic bed histopathology, for histopathology or biopsy of distant metastases or a composite reference standard with clinical follow-up of at least 12 months, correlative imaging and clinical data) were included. Overall 425 studies were retrieved, of which 43 were judged as potentially relevant and 29 with 2,686 participants were finally included. Of these 29 studies, 18 reported results for any relapse, All 18 studies, with a total of 2,126 participants, reported detection rates. The pooled rate was 62 % (95 % CI 53 - 71 %). Of the 18 studies, 12 with 1,270 participants reported useful data to derive sensitivity and specificity. The pooled sensitivity was 89 % (95 % CI 83 - 93 %) and the pooled specificity was 89 % (95 % CI 73 - 96 %). Of 11 studies reporting results for local relapse, 9 with 993 participants reported detection rates. The pooled rate was 27 % (95 % CI 16 - 38 %). Six studies with 491 participants reported sensitivity and specificity. The pooled sensitivity was 61 % (95 % CI 40 - 80 %) and the pooled specificity was 97 % (95 % CI 87 - 99 %). Ten studies reported results for lymph nodes and distant metastases. For nodal disease, 7 studies with 752 participants reported detection rates. The pooled rate was 36 % (95 % CI 22 - 50 %). For bone metastases, 8 studies with 775 participants reported detection rates. The pooled rate was 25 % (95 % CI 16 - 34 %). There is a significant amount of (11)C-choline PET data published showing a high degree of consistency in inclusion criteria, acquisition protocols and scan interpretation criteria. Furthermore, the quality of the data derived limited to the same standard of reference was acceptable. Despite a high variability in the observed prevalence of any relapse, the diagnostic performance of (11)C-choline PET was in line with previous meta-analyses. Our data confirm the very good accuracy of (11)C-choline PET for detection of lymph node metastases and/or distant lesions in a single examination in patients with biochemical relapse.

Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis.

PubMed

Khan, Muhammad Ali; Baron, Todd H; Kamal, Faisal; Ali, Bilal; Nollan, Richard; Ismail, Mohammad Kashif; Tombazzi, Claudio; Artifon, Everson L A; Repici, Alessandro; Khashab, Mouen A

2017-07-01

Background and study aims  There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method  Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group.  Results  The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I 2  = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions  CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success. © Georg Thieme Verlag KG Stuttgart · New York.

Prognostic Value of MACC1 in Digestive System Neoplasms: A Systematic Review and Meta-Analysis

PubMed Central

Wu, Zhenzhen; Zhou, Rui; Su, Yuqi; Sun, Li; Liao, Yulin; Liao, Wangjun

2015-01-01

Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49–2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33–2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms. PMID:26090393

Prognostic Value of MACC1 in Digestive System Neoplasms: A Systematic Review and Meta-Analysis.

PubMed

Wu, Zhenzhen; Zhou, Rui; Su, Yuqi; Sun, Li; Liao, Yulin; Liao, Wangjun

2015-01-01

Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49-2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33-2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms.

Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies.

PubMed

Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

2016-10-01

To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of "very early" PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis

PubMed Central

Engel, S S; Williams-Herman, D E; Golm, G T; Clay, R J; Machotka, S V; Kaufman, K D; Goldstein, B J

2010-01-01

Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin. PMID:20412332

Gender Differences in Appropriate Shocks and Mortality among Patients with Primary Prophylactic Implantable Cardioverter-Defibrillators: Systematic Review and Meta-Analysis.

PubMed

Conen, David; Arendacká, Barbora; Röver, Christian; Bergau, Leonard; Munoz, Pascal; Wijers, Sofieke; Sticherling, Christian; Zabel, Markus; Friede, Tim

2016-01-01

Some but not all prior studies have shown that women receiving a primary prophylactic implantable cardioverter defibrillator (ICD) have a lower risk of death and appropriate shocks than men. To evaluate the effect of gender on the risk of appropriate shock, all-cause mortality and inappropriate shock in contemporary studies of patients receiving a primary prophylactic ICD. PubMed, LIVIVO, Cochrane CENTRAL between 2010 and 2016. Studies providing at least 1 gender-specific risk estimate for the outcomes of interest. Abstracts were screened independently for potentially eligible studies for inclusion. Thereby each abstract was reviewed by at least two authors. Out of 680 abstracts retained by our search strategy, 20 studies including 46'657 patients had gender-specific information on at least one of the relevant endpoints. Mean age across the individual studies varied between 58 and 69 years. The proportion of women enrolled ranged from 10% to 30%. Across 6 available studies, women had a significantly lower risk of first appropriate shock compared with men (pooled multivariable adjusted hazard ratio 0.62 (95% CI [0.44; 0.88]). Across 14 studies reporting multivariable adjusted gender-specific hazard ratio estimates for all-cause mortality, women had a lower risk of death than men (pooled hazard ratio 0.75 (95% CI [0.66; 0.86]). There was no statistically significant difference for the incidence of first inappropriate shocks (3 studies, pooled hazard ratio 0.99 (95% CI [0.56; 1.73]). Individual patient data were not available for most studies. In this large contemporary meta-analysis, women had a significantly lower risk of appropriate shocks and death than men, but a similar risk of inappropriate shocks. These data may help to select patients who benefit from primary prophylactic ICD implantation.

Simulated Patients in Physical Therapy Education: Systematic Review and Meta-Analysis.

PubMed

Pritchard, Shane A; Blackstock, Felicity C; Nestel, Debra; Keating, Jenny L

2016-09-01

Traditional models of physical therapy clinical education are experiencing unprecedented pressures. Simulation-based education with simulated (standardized) patients (SPs) is one alternative that has significant potential value, and implementation is increasing globally. However, no review evaluating the effects of SPs on professional (entry-level) physical therapy education is available. The purpose of this study was to synthesize and critically appraise the findings of empirical studies evaluating the contribution of SPs to entry-level physical therapy education, compared with no SP interaction or an alternative education strategy, on any outcome relevant to learning. A systematic search was conducted of Ovid MEDLINE, PubMed, AMED, ERIC, and CINAHL Plus databases and reference lists of included articles, relevant reviews, and gray literature up to May 2015. Articles reporting quantitative or qualitative data evaluating the contribution of SPs to entry-level physical therapy education were included. Two reviewers independently extracted study characteristics, intervention details, and quantitative and qualitative evaluation data from the 14 articles that met the eligibility criteria. Pooled random-effects meta-analysis indicated that replacing up to 25% of authentic patient-based physical therapist practice with SP-based education results in comparable competency (mean difference=1.55/100; 95% confidence interval=-1.08, 4.18; P=.25). Thematic analysis of qualitative data indicated that students value learning with SPs. Assumptions were made to enable pooling of data, and the search strategy was limited to English. Simulated patients appear to have an effect comparable to that of alternative educational strategies on development of physical therapy clinical practice competencies and serve a valuable role in entry-level physical therapy education. However, available research lacks the rigor required for confidence in findings. Given the potential advantages for students, high-quality studies that include an economic analysis should be conducted. © 2016 American Physical Therapy Association.

Method for data analysis in different institutions: example of image guidance of prostate cancer patients.

PubMed

Piotrowski, T; Rodrigues, G; Bajon, T; Yartsev, S

2014-03-01

Multi-institutional collaborations allow for more information to be analyzed but the data from different sources may vary in the subgroup sizes and/or conditions of measuring. Rigorous statistical analysis is required for pooling the data in a larger set. Careful comparison of all the components of the data acquisition is indispensable: identical conditions allow for enlargement of the database with improved statistical analysis, clearly defined differences provide opportunity for establishing a better practice. The optimal sequence of required normality, asymptotic normality, and independence tests is proposed. An example of analysis of six subgroups of position corrections in three directions obtained during image guidance procedures for 216 prostate cancer patients from two institutions is presented. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile infection in low- and middle-human development index countries: a systematic review.

PubMed

Forrester, Joseph D; Cai, Lawrence Z; Mbanje, Chenesa; Rinderknecht, Tanya N; Wren, Sherry M

2017-10-01

To describe the impact and epidemiology of Clostridium difficile infection (CDI) in low- and middle-human development index (LMHDI) countries. Prospectively registered, systematic literature review of existing literature in the PubMed, Ovid and Web of Science databases describing the epidemiology and management of C. difficile in LMHDI countries. Risk factors were compared between studies when available. Of the 218 abstracts identified after applying search criteria, 25 studies were reviewed in detail. The weighted pooled infection rate among symptomatic non-immunosuppressed inpatients was 15.8% (95% CI 12.1-19.5%) and was 10.1% (95% CI 3.0-17.2%) among symptomatic outpatients. Subgroup analysis of immunosuppressed patient populations revealed pooled infection rates similar to non-immunosuppressed patient populations. Risk factor analysis was infrequently performed. While the percentages of patients with CDI in LMHDI countries among the reviewed studies are lower than expected, there remains a paucity of epidemiologic data evaluating burden of C. difficile infection in these settings. © 2017 John Wiley & Sons Ltd.

The association between prostatitis and prostate cancer. Systematic review and meta-analysis.

PubMed

Perletti, Gianpaolo; Monti, Elena; Magri, Vittorio; Cai, Tommaso; Cleves, Anne; Trinchieri, Alberto; Montanari, Emanuele

2017-12-31

The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III) and a histologically confirmed diagnosis of prostate cancer. Crude odds ratios and 95% confidence intervals (CI) were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P < 0.00001). The total set of data showed considerable heterogeneity (I2 = 91%). Both the Egger's test and the Begg's test for funnel plot asymmetry did not reach statistical significance. The 'trim and fill' method applied to the funnel plot imputed 3 missing studies and the resulting adjusted estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

Item response theory analysis of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised in the Pooled Resource Open-Access ALS Clinical Trials Database.

PubMed

Bacci, Elizabeth D; Staniewska, Dorota; Coyne, Karin S; Boyer, Stacey; White, Leigh Ann; Zach, Neta; Cedarbaum, Jesse M

2016-01-01

Our objective was to examine dimensionality and item-level performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) across time using classical and modern test theory approaches. Confirmatory factor analysis (CFA) and Item Response Theory (IRT) analyses were conducted using data from patients with amyotrophic lateral sclerosis (ALS) Pooled Resources Open-Access ALS Clinical Trials (PRO-ACT) database with complete ALSFRS-R data (n = 888) at three time-points (Time 0, Time 1 (6-months), Time 2 (1-year)). Results demonstrated that in this population of 888 patients, mean age was 54.6 years, 64.4% were male, and 93.7% were Caucasian. The CFA supported a 4* individual-domain structure (bulbar, gross motor, fine motor, and respiratory domains). IRT analysis within each domain revealed misfitting items and overlapping item response category thresholds at all time-points, particularly in the gross motor and respiratory domain items. Results indicate that many of the items of the ALSFRS-R may sub-optimally distinguish among varying levels of disability assessed by each domain, particularly in patients with less severe disability. Measure performance improved across time as patient disability severity increased. In conclusion, modifications to select ALSFRS-R items may improve the instrument's specificity to disability level and sensitivity to treatment effects.

ViPAR: a software platform for the Virtual Pooling and Analysis of Research Data.

PubMed

Carter, Kim W; Francis, Richard W; Carter, K W; Francis, R W; Bresnahan, M; Gissler, M; Grønborg, T K; Gross, R; Gunnes, N; Hammond, G; Hornig, M; Hultman, C M; Huttunen, J; Langridge, A; Leonard, H; Newman, S; Parner, E T; Petersson, G; Reichenberg, A; Sandin, S; Schendel, D E; Schalkwyk, L; Sourander, A; Steadman, C; Stoltenberg, C; Suominen, A; Surén, P; Susser, E; Sylvester Vethanayagam, A; Yusof, Z

2016-04-01

Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations. Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates 'virtual pooling' where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage. Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory. ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/]. © The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

PubMed

Charidimou, Andreas; Karayiannis, Christopher; Song, Tae-Jin; Orken, Dilek Necioglu; Thijs, Vincent; Lemmens, Robin; Kim, Jinkwon; Goh, Su Mei; Phan, Thanh G; Soufan, Cathy; Chandra, Ronil V; Slater, Lee-Anne; Haji, Shamir; Mok, Vincent; Horstmann, Solveig; Leung, Kam Tat; Kawamura, Yuichiro; Sato, Nobuyuki; Hasebe, Naoyuki; Saito, Tsukasa; Wong, Lawrence K S; Soo, Yannie; Veltkamp, Roland; Flemming, Kelly D; Imaizumi, Toshio; Srikanth, Velandai; Heo, Ji Hoe

2017-12-05

To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( p = 0.001). There was no association between CMBs and recurrent ischemic stroke. The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies. © 2017 American Academy of Neurology.

Meta-analysis of association between mobile phone use and glioma risk.

PubMed

Wang, Yabo; Guo, Xiaqing

2016-12-01

The purpose of this study was to evaluate the association between mobile phone use and glioma risk through pooling the published data. By searching Medline, EMBSE, and CNKI databases, we screened the open published case-control or cohort studies about mobile phone use and glioma risk by systematic searching strategy. The pooled odds of mobile use in glioma patients versus healthy controls were calculated by meta-analysis method. The statistical analysis was done by Stata12.0 software (http://www.stata.com). After searching the Medline, EMBSE, and CNKI databases, we ultimately included 11 studies range from 2001 to 2008. For ≥1 year group, the data were pooled by random effects model. The combined data showed that there was no association between mobile phone use and glioma odds ratio (OR) =1.08 (95% confidence interval [CI]: 0.91-1.25,P > 0.05). However, a significant association was found between mobile phone use more than 5 years and glioma risk OR = 1.35 (95% CI: 1.09-1.62, P < 0.05). The publication bias of this study was evaluated by funnel plot and line regression test. The funnel plot and line regression test (t = 0.25,P = 0.81) did not indicate any publication bias. Long-term mobile phone use may increase the risk of developing glioma according to this meta-analysis.

Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

PubMed

Giridharan, Nisha; Horn, Paul S; Greiner, Hansel M; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2016-11-01

This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families. Copyright © 2016 Elsevier B.V. All rights reserved.

Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer.

PubMed

Yang, James Chih-Hsin; Ou, Sai-Hong Ignatius; De Petris, Luigi; Gadgeel, Shirish; Gandhi, Leena; Kim, Dong-Wan; Barlesi, Fabrice; Govindan, Ramaswamy; Dingemans, Anne-Marie C; Crino, Lucio; Lena, Herve; Popat, Sanjay; Ahn, Jin Seok; Dansin, Eric; Golding, Sophie; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Zeaiter, Ali; Shaw, Alice T

2017-10-01

Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety. The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification. This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data

PubMed Central

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-01

AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. CONCLUSION Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD. PMID:29399288

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data.

PubMed

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-27

To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

HTR1A Polymorphisms and Clinical Efficacy of Antipsychotic Drug Treatment in Schizophrenia: A Meta-Analysis

PubMed Central

Fabbri, Chiara; Kato, Masaki; Koshikawa, Yosuke; Tajika, Aran; Kinoshita, Toshihiko; Serretti, Alessandro

2016-01-01

Background: This meta-analysis was conducted to evaluate whether HTR1A gene polymorphisms impact the efficacy of antipsychotic drugs in patients with schizophrenia. Methods: Candidate gene studies that were published in English up to August 6, 2015 were identified by a literature search of PubMed, Web of Science, and Google scholar. Data were pooled from individual clinical trials considering overall symptoms, positive symptoms and negative symptoms, and standard mean differences were calculated by applying a random-effects model. Results: The present meta-analysis included a total of 1281 patients from 10 studies. Three polymorphisms of HTR1A (rs6295, rs878567, and rs1423691) were selected for the analysis. In the pooled data from all studies, none of these HTR1A polymorphisms correlated significantly with either overall symptoms or positive symptoms. However, C allele carriers of the rs6295 polymorphism showed a significantly greater negative symptoms improvement than G allele carriers (P=.04, standardized mean difference =-0.14, 95％CI = 0.01 to 0.28). Conclusions: The results of our present analysis indicate that the HTR1A rs6295 polymorphism may impact negative symptoms improvement but not on either overall symptoms or positive symptoms improvement. However, this meta-analysis was based on a small number of studies and patients, and the effect size on negative symptoms was small. Given this limitation, the results should be confirmed by further investigations. PMID:26568455

Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: a meta-analysis.

PubMed

Wanders, Linda K; Dekker, Evelien; Pullens, Bo; Bassett, Paul; Travis, Simon P L; East, James E

2014-05-01

American and European guidelines propose complete endoscopic resection of polypoid dysplasia (adenomas or adenoma-like masses) in patients with longstanding colitis, with close endoscopic follow-up. The incidence of cancer after detection of flat low-grade dysplasia or dysplasia-associated lesion or mass is estimated at 14 cases/1000 years of patient follow-up. However, the risk for polypoid dysplasia has not been determined with precision. We investigated the risk of cancer after endoscopic resection of polypoid dysplasia in patients with ulcerative colitis. MEDLINE, EMBASE, PubMed, and the Cochrane library were searched for studies of patients with colitis and resected polypoid dysplasia, with reports of colonoscopic follow-up and data on cancers detected. Outcomes from included articles were pooled to provide a single combined estimate of outcomes by using Poisson regression. Of 425 articles retrieved, we analyzed data from 10 studies, comprising 376 patients with colitis and polypoid dysplasia with a combined 1704 years of follow-up. A mean of 2.8 colonoscopies were performed for each patient after the index procedure (range, 0-15 colonoscopies). The pooled incidence of cancer was 5.3 cases (95% confidence interval, 2.7-10.1 cases)/1000 years of patient follow-up. There was no evidence of heterogeneity or publication bias. The pooled rate of any dysplasia was 65 cases (95% confidence interval, 54-78 cases)/1000 patient years. Patients with colitis have a low risk of colorectal cancer after resection of polypoid dysplasia; these findings support the current strategy of resection and surveillance. However, these patients have a 10-fold greater risk of developing any dysplasia than colorectal cancer and should undergo close endoscopic follow-up. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

PubMed Central

Qi, Xing-Shun

2017-01-01

Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients. PMID:28265583

Prevalence of irritable bowel syndrome-type symptoms in patients with celiac disease: a meta-analysis.

PubMed

Sainsbury, Anita; Sanders, David S; Ford, Alexander C

2013-04-01

Patients with celiac disease (CD) often report symptoms compatible with irritable bowel syndrome (IBS). However, the prevalence of these symptoms in patients with CD and their relation to adherence to a gluten-free diet (GFD) have not been assessed systematically. We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012) to identify cross-sectional surveys or case-control studies reporting prevalence of IBS-type symptoms in adult patients (≥ 16 years old) with established CD. The number of individuals with symptoms meeting criteria for IBS was extracted for each study, according to case or control status and adherence to a GFD. Pooled prevalence and odds ratios (ORs), with 95% confidence intervals (CIs), were calculated. We analyzed data from 7 studies with 3383 participants. The pooled prevalence of IBS-type symptoms in all patients with CD was 38.0% (95% CI, 27.0%-50.0%). The pooled OR for IBS-type symptoms was higher in patients with CD than in controls (5.60; 95% CI, 3.23-9.70). In patients who were nonadherent with a GFD, the pooled OR for IBS-type symptoms, compared with those who were strictly adherent, was 2.69 (95% CI, 0.75-9.56). There was also a trend toward a higher OR for IBS-type symptoms among patients who did not adhere to the GFD, compared with controls (12.42; 95% CI, 6.84-11.75), compared with that observed for adherent CD patients vs controls (4.28; 95% CI, 1.56-11.75). IBS-type symptoms occur frequently in patients with CD and are more common than among controls. Adherence to a GFD might be associated with a reduction in symptoms. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

PubMed

Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

2016-04-01

Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none). Across all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug. This retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS. NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348. F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Periodontitis and risk of psoriasis: a systematic review and meta-analysis.

PubMed

Ungprasert, P; Wijarnpreecha, K; Wetter, D A

2017-05-01

The association between periodontitis and systemic diseases has been increasingly recognized. However, the data on the association between periodontitis and psoriasis are still limited. To summarize all available data on the association between periodontitis and the risk of psoriasis. Two investigators independently searched published studies indexed in MEDLINE and EMBASE databases from inception to July 2016 using a search strategy that included terms for psoriasis and periodontitis. Studies were included if the following criteria were met: (i) case-control or cohort study comparing the risk of psoriasis in subjects with and without periodontitis; (ii) subjects without periodontitis were used as comparators in cohort studies while participants without psoriasis were used as controls in case-control studies; and (iii) effect estimates and 95% confidence intervals (CI) were provided. Point estimates and standard errors from each study were extracted and combined together using the generic inverse variance technique described by DerSimonian and Laird. Two cohort studies and three case-control studies met the inclusion criteria and were included in the meta-analysis. The pooled risk ratio of psoriasis in patients with periodontitis versus comparators was 1.55 (95% CI, 1.35-1.77). The statistical heterogeneity was insignificant with an I 2 of 18%. Subgroup analysis according to study design revealed a significantly higher risk among patients with periodontitis with a pooled RR of 1.50 (95% CI, 1.37-1.64) for cohort studies and a pooled RR of 2.33 (95% CI, 1.51-3.60) for case-control studies. Patients with periodontitis have a significantly elevated risk of psoriasis. © 2016 European Academy of Dermatology and Venereology.

Phenytoin versus Leviteracetam for Seizure Prophylaxis after brain injury – a meta analysis

PubMed Central

2012-01-01

Background Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury. Methods An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures. Results The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate’s Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79). Conclusions Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended. PMID:22642837

Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three Korean Observational Studies (the VICTORY Study).

PubMed

Suh, Sunghwan; Song, Sun Ok; Kim, Jae Hyeon; Cho, Hyungjin; Lee, Woo Je; Lee, Byung-Wan

2017-01-01

The present observational study aimed to evaluate the clinical effectiveness of vildagliptin with metformin in Korean patients with type 2 diabetes mellitus (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective observational study of vildagliptin/metformin (fixed DC or free DC). The effectiveness endpoint was the proportion of patients who achieved a glycemic target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the analysis; of these, 2087 patients were eligible. The mean patient age was 56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0% at 24 weeks. The glycemic target achievement rate was significantly greater in patients with baseline HbA1c < 7.5% versus ≥7.5% (84.64% versus 43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%). Multivariate logistic regression analysis indicated that disease duration ( P < 0.0001), baseline HbA1c ( P < 0.0001), and DC type ( P = 0.0103) had significant effects on drug effectiveness. Vildagliptin plus metformin appeared as an effective treatment option for patients with T2DM in clinical practice settings in Korea.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients: A systematic review and meta-analysis.

PubMed

Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-08-01

Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I) assessment was performed. Six randomized controlled trials comparing 253 pediatric patients (age range, 2-18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were -7.15 (95% CI: -10.77 to -3.54; I = 96%; P = 0.0001) and -17.32 (95% CI: -29.31 to -5.32; I = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was -6.00 (95% CI: -11.46 to -0.53; I = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27-1.71; I = 59%; P = 0.41). We suggest that sugammadex is fast and effective in reversing rocuronium-induced NMB in pediatric patients. Although there was no evidence of a higher incidence of adverse events with sugammadex compared to that with neostigmine or placebo, much more data regarding the safety of sugammadex in pediatric patients may be still required.

Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke.

PubMed

Iwamoto, J; Takeda, T; Matsumoto, H

2012-04-01

Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta-analysis) was performed. Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer's disease, 0.27 (0.08, 0.96) for Parkinson's disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. The present meta-analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke. © 2011 John Wiley & Sons A/S.

Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.

PubMed

Ng, Qin Xiang; Venkatanarayanan, Nandini; Ho, Collin Yih Xian

2017-03-01

St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available. Using the keywords [St John's Wort OR Hypericum perforatum OR hypericin OR hyperforin OR johanniskraut OR] AND [depression OR antidepressant OR SSRI], a preliminary search (without language restriction) on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group, Cochrane Field for Complementary Medicine, China National Knowledge Infrastructure and WanFang database yielded 5428 papers between 1-Jan-1960 and 1-May-2016. 27 clinical trials with a total of 3808 patients were reviewed, comparing the use of St John's wort and SSRI. In patients with depression, St John's wort demonstrated comparable response (pooled RR 0.983, 95% CI 0.924-1.042, p<0.001) and remission (pooled RR 1.013, 95% CI 0.892-1.134, p<0.001) rate, and significantly lower discontinuation/dropout (pooled OR 0.587, 95% CI 0.478-0.697, p<0.001) rate compared to standard SSRIs. The pooled SMD from baseline HAM-D scores (pooled SMD -0.068, 95% CI -0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms. Evidence on the long-term efficacy and safety of St. John's wort is limited as the duration of all available studies ranged from 4 to 12 weeks. It is also unclear if St John's wort would be beneficial for patients with severe depression, high suicidality or suicide risk. For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrative Analysis of “-Omics” Data Using Penalty Functions

PubMed Central

Zhao, Qing; Shi, Xingjie; Huang, Jian; Liu, Jin; Li, Yang; Ma, Shuangge

2014-01-01

In the analysis of omics data, integrative analysis provides an effective way of pooling information across multiple datasets or multiple correlated responses, and can be more effective than single-dataset (response) analysis. Multiple families of integrative analysis methods have been proposed in the literature. The current review focuses on the penalization methods. Special attention is paid to sparse meta-analysis methods that pool summary statistics across datasets, and integrative analysis methods that pool raw data across datasets. We discuss their formulation and rationale. Beyond “standard” penalized selection, we also review contrasted penalization and Laplacian penalization which accommodate finer data structures. The computational aspects, including computational algorithms and tuning parameter selection, are examined. This review concludes with possible limitations and extensions. PMID:25691921

Blood pressure and fasting lipid changes after 24 weeks' treatment with vildagliptin: a pooled analysis in >2,000 previously drug-naïve patients with type 2 diabetes mellitus.

PubMed

Evans, Marc; Schweizer, Anja; Foley, James E

2016-01-01

We have previously shown modest weight loss with vildagliptin treatment. Since body weight balance is associated with changes in blood pressure (BP) and fasting lipids, we have assessed these parameters following vildagliptin treatment. Data were pooled from all double-blind, randomized, controlled, vildagliptin mono-therapy trials on previously drug-naïve patients with type 2 diabetes mellitus who received vildagliptin 50 mg once daily (qd) or twice daily (bid; n=2,108) and wherein BP and fasting lipid data were obtained. Data from patients receiving vildagliptin 50 mg qd or bid showed reductions from baseline to week 24 in systolic BP (from 132.5±0.32 to 129.8±0.34 mmHg; P<0.0001), diastolic BP (from 81.2±0.18 to 79.6±0.19 mmHg; P<0.0001), fasting triglycerides (from 2.00±0.02 to 1.80±0.02 mmol/L; P<0.0001), very low density lipoprotein cholesterol (from 0.90±0.01 to 0.83±0.01 mmol/L; P<0.0001), and low density lipoprotein cholesterol (from 3.17±0.02 to 3.04±0.02 mmol/L; P<0.0001), whereas high density lipoprotein cholesterol increased (from 1.19±0.01 to 1.22±0.01 mmol/L; P<0.001). Weight decreased by 0.48±0.08 kg (P<0.001). This large pooled analysis demonstrated that vildagliptin shows a significant reduction in BP and a favorable fasting lipid profile that are associated with modest weight loss.

Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy.

PubMed

Saraiya, N; Yopp, A C; Rich, N E; Odewole, M; Parikh, N D; Singal, A G

2018-05-30

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response. Characterize HCC recurrence patterns after DAA therapy. Two reviewers searched MEDLINE and SCOPUS from January 2015 to December 2017 and identified studies evaluating HCC recurrence patterns following DAA therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with PRISMA guidelines. Among 24 studies (n = 1820 patients), the proportion of patients with HCC recurrence following DAA therapy ranged from 0% to 59% (pooled estimate 24.4%; 95% CI: 18.4%-30.4%). Among 11 full text manuscripts, pooled HCC recurrence was 21.9% (95% CI: 16.2%-28.3%). Factors associated with recurrence included history of prior HCC recurrence and a shorter interval between HCC complete response and DAA initiation. Nine studies comparing DAA-treated and interferon-treated or untreated patients found similar recurrence among DAA-treated patients. Most (77.8%) patients with HCC recurrence were detected at an early tumour stage, of whom 64.7% received curative treatment. Study limitations included heterogeneous cohorts, potential misclassification of HCC absence prior to DAA, ascertainment bias for recurrence, and short durations of follow-up. Current data suggest acceptable HCC recurrence rates after DAA therapy, particularly if DAA therapy is delayed at least 6 months after HCC complete response. However, data characterising HCC recurrence after DAA therapy are of limited quality, highlighting the need for high quality prospective studies. © 2018 John Wiley & Sons Ltd.

Prognostic indices for early mortality in ischaemic stroke - meta-analysis.

PubMed

Mattishent, K; Kwok, C S; Mahtani, A; Pelpola, K; Myint, P K; Loke, Y K

2016-01-01

Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores. We searched MEDLINE and EMBASE in February 2014 for prognostic models (published between 2003 and 2014) used in predicting early mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability of the tools through meta-analysis of the area under the curve receiver operating characteristic curve (AUROC) or c-statistic. We evaluated the following components of study validity: collection of prognostic variables, neuroimaging, treatment pathways and missing data. We identified 18 articles (involving 163 240 patients) reporting on the performance of prognostic models for mortality in ischaemic stroke, with 15 articles providing AUC for meta-analysis. Most studies were either retrospective, or post hoc analyses of prospectively collected data; all but three reported validation data. The iSCORE had the largest number of validation cohorts (five) within our systematic review and showed good performance in four different countries, pooled AUC 0.84 (95% CI 0.82-0.87). We identified other potentially useful prognostic tools that have yet to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72) and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). Our meta-analysis has identified and summarized the performance of several prognostic scores with modest to good predictive accuracy for early mortality in ischaemic stroke, with the iSCORE having the broadest evidence base. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Meta-analysis of randomized controlled trials comparing outcomes for stapled hemorrhoidopexy versus LigaSure hemorrhoidectomy for symptomatic hemorrhoids in adults.

PubMed

Lee, Ko-Chao; Chen, Hong-Hwa; Chung, Kuan-Chih; Hu, Wan-Hsiang; Chang, Chia-Lo; Lin, Shung-Eing; Tsai, Kai-Lung; Lu, Chien-Chang

2013-01-01

This purpose of the meta-analysis was to compare treatment outcomes for adult patients with symptomatic hemorrhoids treated by stapled hemorrhoidopexy or LigaSure hemorrhoidectomy. A search of public medical databases was made to identify randomized controlled trials (RCTs) comparing stapled hemorrhoidopexy (SH) with LigaSure hemorrhoidectomy (LH) for the treatment of adult patients with symptomatic grade 3 and grade 4 hemorrhoids. Postoperative pain as measured using a visual analog scale was the primary outcome, and rate of recurrent prolapse and postoperative bleeding were secondary outcome measures. Four RCTs were identified that met the inclusion criteria. Data for the pooled outcomes were analyzed using odds ratio (OR) analysis. None of the studies in the analysis indicated a significant difference between SH and LH for the outcomes VAS pain score, recurrence rate, or postoperative bleeding. Pooled analysis revealed a significant OR in favor of the SH method for recurrent prolapse (OR = 5.529, P = 0.016) for up to 2 years after surgery. No significant differences between the two methods were identified for VAS pain scores (OR = -1.060, P = 0.149) or postoperative bleeding OR = 1.188, P = 0.871). Pooled analysis of RCT results comparing SH to LH for symptomatic hemorrhoids revealed a significantly greater incidence of recurrent prolapse for SH. The two techniques were associated with similar levels of postoperative pain and postoperative bleeding. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Protective effects of methotrexate against ischemic cardiovascular disorders in patients treated for rheumatoid arthritis or psoriasis: novel therapeutic insights coming from a meta-analysis of the literature data

PubMed Central

Vecchis, Renato De; Baldi, Cesare; Palmisani, Leonardo

2016-01-01

Objective: The association between chronic use of methotrexate and decreased risk of ischemic cardiovascular events (CVE) among patients with psoriatic or rheumatoid arthritis (RA) was investigated using a systematic review and meta-analysis. Methods: The studies should have recruited adults receiving methotrexate, followed up for at least one year. Moreover, studies should have reported “hard” cardiovascular endpoints, by evaluating the cardiovascular outcomes of the habitual users of the drug or of new users compared with patients with the same disease who had never used methotrexate. The outcome of interest was the overall pooled odds ratio (OR) of major adverse cardiovascular events, i.e., a composite of new- onset angina, acute coronary syndrome, need for percutaneous or surgical coronary revascularization, stroke, and cardiovascular death. The study was performed according to the PRISMA statement. Results: Seven observational studies, mostly engaging patients with RA, were included in the meta-analysis. The pooled odds ratio (OR) was 0.73 (95% CI=0.70- 0.77 p<0.001). When stratified meta-analysis models were assessed, the pooled OR was 0.80 (95% CI=0.66-0.97; p=0.022) for studies adjusting for clinical severity of RA. Furthermore, the OR was even more significant after adjustment for concomitant use of other drugs specific for RA (OR=0.71, 95% CI=0.67-0.75, p<0.001). Conclusion: Methotrexate at low doses, such those used for maintenance therapy of RA, predicted a decreased risk of CVE. Since methotrexate doesn’t interfere with blood lipids, platelet aggregation or insulin resistance, the protective association may originate from mechanisms other than those exerted by antiplatelet drugs or statins. PMID:26467356

Accuracy of Presurgical Functional MR Imaging for Language Mapping of Brain Tumors: A Systematic Review and Meta-Analysis.

PubMed

Weng, Hsu-Huei; Noll, Kyle R; Johnson, Jason M; Prabhu, Sujit S; Tsai, Yuan-Hsiung; Chang, Sheng-Wei; Huang, Yen-Chu; Lee, Jiann-Der; Yang, Jen-Tsung; Yang, Cheng-Ta; Tsai, Ying-Huang; Yang, Chun-Yuh; Hazle, John D; Schomer, Donald F; Liu, Ho-Ling

2018-02-01

Purpose To compare functional magnetic resonance (MR) imaging for language mapping (hereafter, language functional MR imaging) with direct cortical stimulation (DCS) in patients with brain tumors and to assess factors associated with its accuracy. Materials and Methods PubMed/MEDLINE and related databases were searched for research articles published between January 2000 and September 2016. Findings were pooled by using bivariate random-effects and hierarchic summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, functional MR imaging paradigm, magnetic field strength, statistical threshold, and analysis software affected classification accuracy. Results Ten articles with a total of 214 patients were included in the analysis. On a per-patient basis, the pooled sensitivity and specificity of functional MR imaging was 44% (95% confidence interval [CI]: 14%, 78%) and 80% (95% CI: 54%, 93%), respectively. On a per-tag basis (ie, each DCS stimulation site or "tag" was considered a separate data point across all patients), the pooled sensitivity and specificity were 67% (95% CI: 51%, 80%) and 55% (95% CI: 25%, 82%), respectively. The per-tag analysis showed significantly higher sensitivity for studies with shorter functional MR imaging session times (P = .03) and relaxed statistical threshold (P = .05). Significantly higher specificity was found when expressive language task (P = .02), longer functional MR imaging session times (P < .01), visual presentation of stimuli (P = .04), and stringent statistical threshold (P = .01) were used. Conclusion Results of this study showed moderate accuracy of language functional MR imaging when compared with intraoperative DCS, and the included studies displayed significant methodologic heterogeneity. © RSNA, 2017 Online supplemental material is available for this article.

A comparison of the techniques of direct pars interarticularis repairs for spondylolysis and low-grade spondylolisthesis: a meta-analysis.

PubMed

Mohammed, Nasser; Patra, Devi Prasad; Narayan, Vinayak; Savardekar, Amey R; Dossani, Rimal Hanif; Bollam, Papireddy; Bir, Shyamal; Nanda, Anil

2018-01-01

OBJECTIVE Spondylosis with or without spondylolisthesis that does not respond to conservative management has an excellent outcome with direct pars interarticularis repair. Direct repair preserves the segmental spinal motion. A number of operative techniques for direct repair are practiced; however, the procedure of choice is not clearly defined. The present study aims to clarify the advantages and disadvantages of the different operative techniques and their outcomes. METHODS A meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following databases were searched: PubMed, Cochrane Library, Web of Science, and CINAHL ( Cumulative Index to Nursing and Allied Health Literature). Studies of patients with spondylolysis with or without low-grade spondylolisthesis who underwent direct repair were included. The patients were divided into 4 groups based on the operative technique used: the Buck repair group, Scott repair group, Morscher repair group, and pedicle screw-based repair group. The pooled data were analyzed using the DerSimonian and Laird random-effects model. Tests for bias and heterogeneity were performed. The I 2 statistic was calculated, and the results were analyzed. Statistical analysis was performed using StatsDirect version 2. RESULTS Forty-six studies consisting of 900 patients were included in the study. The majority of the patients were in their 2nd decade of life. The Buck group included 19 studies with 305 patients; the Scott group had 8 studies with 162 patients. The Morscher method included 5 studies with 193 patients, and the pedicle group included 14 studies with 240 patients. The overall pooled fusion, complication, and outcome rates were calculated. The pooled rates for fusion for the Buck, Scott, Morscher, and pedicle screw groups were 83.53%, 81.57%, 77.72%, and 90.21%, respectively. The pooled complication rates for the Buck, Scott, Morscher, and pedicle screw groups were 13.41%, 22.35%, 27.42%, and 12.8%, respectively, and the pooled positive outcome rates for the Buck, Scott, Morscher, and pedicle screw groups were 84.33%, 82.49%, 80.30%, and 80.1%, respectively. The pedicle group had the best fusion rate and lowest complication rate. CONCLUSIONS The pedicle screw-based direct pars repair for spondylolysis and low-grade spondylolisthesis is the best choice of procedure, with the highest fusion and lowest complication rates, followed by the Buck repair. The Morscher and Scott repairs were associated with a high rate of complication and lower rates of fusion.

Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Kimura, Naoko; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2013-11-01

Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies ('specificity (other)'). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies ('specificity (unknown and other)') using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Endostar combined with chemotherapy compared with chemotherapy alone in the treatment of nonsmall lung carcinoma: A meta-analysis based on Chinese patients.

PubMed

Wang, J; Gu, L J; Fu, C X; Cao, Z; Chen, Q Y

2014-03-01

Lung cancer is the leading cause of cancer-associated death world-wide. And the lung cancer is generally divided into small cell lung carcinoma and non-small cell lung cancer. For advanced NSCLC, the chemotherapy and target therapy were the important treatment modality. This meta-analysis was to evaluate the clinical efficacy and toxicity between endostar combined chemotherapy and chemotherapy alone in Chinese patients. We searched the PubMed, EMBASE, and CNKI databases to find the potential relevant articles reporting the endostar combined with chemotherapy regimen in the treatment of nonsmall cell lung cancer in Chinese patients. The tumor response and toxicity difference between the two groups were demonstrated by odds ratio (OR) and its 95% confidence interval (95% CI). All the data was pooled by Stata 11.0 (http://www.stata.com; Stata Corporation, College Station, TX) software. We included 14 studies published in Chinese or English studies. The pooled results showed adding endostar in the chemotherapy regimen can significant increase the objective response rate (OR = 2.42, 95% CI = 1.87-3.12, P = 0.00) and disease control rate (OR = 2.22, 95% CI = 1.68-2.94, P = 0.00). For toxicities, the pooled data showed no statistical difference for grade III-IV granulocytopenia risk (OR = 1.04, 95% CI = 0.74-1.44, P = 0.83). Nausea and vomiting (OR = 0.93 95% CI: 0.51-1.52, P = 0.78) and grade III-IV alopecia (OR = 0.99, 95% CI: 0.76-1.29, P = 0.95). The funnel plot showed no statistical publications. Combined treatment with endostar can improve the response rate for NSCLC patients without increasing the risk of developing severe adverse event.

Transcatheter Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Darmoch, Fahed; Al-Khadra, Yasser; Soud, Mohamad; Fanari, Zaher; Alraies, M Chadi

2018-01-01

Patent foramen ovale (PFO) with atrial septal aneurysm is suggested as an important potential source for cryptogenic strokes. Percutaneous PFO closure to reduce the recurrence of stroke compared to medical therapy has been intensely debated. The aim of this study is to assess whether PFO closure in patients with cryptogenic stroke is safe and effective compared with medical therapy. A search of PubMed, Medline, and Cochrane Central Register from January 2000 through September 2017 for randomized controlled trails (RCT), which compared PFO closure to medical therapy in patients with cryptogenic stroke was conducted. We used the items "PFO or patent foramen ovale", "paradoxical embolism", "PFO closure" and "stroke". Data were pooled for the primary outcome measure using the random-effects model as pooled rate ratio (RR). The primary outcome was reduction in recurrent strokes. Among 282 studies, 5 were selected. Our analysis included 3,440 patients (mean age 45 years, 55% men, mean follow-up 2.9 years), 1,829 in the PFO closure group and 1,611 in the medical therapy group. The I2 heterogeneity test was found to be 48%. A random effects model combining the results of the included studies demonstrated a statistically significant risk reduction in risk of recurrent stroke in the PFO closure group when compared with medical therapy (RR 0.42; 95% CI 0.20-0.91, p = 0.03). Pooled data from 5 large RCTs showed that PFO closure in patients with cryptogenic stroke is safe and effective intervention for prevention of stroke recurrence compared with medical therapy. © 2018 S. Karger AG, Basel.

Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy.

PubMed

Feng, E-S; Sui, C-B; Wang, T-X; Sun, G-L

2016-12-01

Stereotactic radiosurgery (RS) is a potential option for some patients with temporal lobe epilepsy (TLE). The aim of this meta-analysis was to determine the pooled seizure-free rate and the time interval to seizure cessation in patients with lesions in the mesial temporal lobe, and who were eligible for either stereotactic or gamma knife RS. We searched the Medline, Cochrane, EMBASE, and Google Scholar databases using combinations of the following terms: RS, stereotactic radiosurgery, gamma knife, and TLE. We screened 103 articles and selected 13 for inclusion in the meta-analysis. Significant study heterogeneity was detected; however, the included studies displayed an acceptable level of quality. We show that approximately half of the patients were seizure free over a follow-up period that ranged from 6 months to 9 years [pooled estimate: 50.9% (95% confidence interval: 0.381-0.636)], with an average of 14 months to seizure cessation [pooled estimate: 14.08 months (95% confidence interval: 11.95-12.22 months)]. Nine of 13 included studies reported data for adverse events (AEs), which included visual field deficits and headache (the two most common AEs), verbal memory impairment, psychosis, psychogenic non-epileptic seizures, and dysphasia. Patients in the individual studies experienced AEs at rates that ranged from 8%, for non-epileptic seizures, to 85%, for headache. Our findings indicate that RS may have similar or slightly less efficacy in some patients compared with invasive surgery. Randomized controlled trials of both treatment regimens should be undertaken to generate an evidence base for patient decision-making. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

PubMed Central

Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

2016-01-01

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

Prevalence and burden of chronic kidney disease among the general population and high-risk groups in Africa: a systematic review

PubMed Central

Abd ElHafeez, Samar; Bolignano, Davide; D’Arrigo, Graziella; Dounousi, Evangelia; Tripepi, Giovanni; Zoccali, Carmine

2018-01-01

Objectives While increasing attention is paid to the rising prevalence of chronic diseases in Africa, there is little focus on chronic kidney disease (CKD). This systematic review assesses CKD burden among the general population and high-risk groups on the entire African continent. Design, setting and participants We searched Medline and PubMed databases for articles published between 1 January 1995 and 7 April 2017 by sensitive search strategies focusing on CKD surveys at the community level and high-risk groups. In total, 7918 references were evaluated, of which 7766 articles were excluded because they did not meet the inclusion criteria. Thus, 152 studies were included in the final analysis. Outcome measurement The prevalence of CKD in each study group was expressed as a range and pooled prevalence rate of CKD was calculated as a point estimate and 95% CI. No meta-analysis was done. Data were presented for different populations. Results In the community-level studies, based on available medium-quality and high-quality studies, the prevalence of CKD ranged from 2% to 41% (pooled prevalence: 10.1%; 95% CI 9.8% to 10.5%). The prevalence of CKD in the high-risk groups ranged from 1% to 46% (pooled prevalence: 5.6%; 95% CI 5.4% to 5.8%) in patients with HIV (based on available medium-quality and high-quality studies), 11%–90% (pooled prevalence: 24.7%; 95% CI 23.6% to 25.7%) in patients with diabetes (based on all available studies which are of low quality except four of medium quality) and 13%–51% (pooled prevalence: 34.5%; 95 % CI 34.04% to 36%) in patients with hypertension (based on all available studies which are of low quality except two of medium quality). Conclusion In Africa, CKD is a public health problem, mainly attributed to high-risk conditions as hypertension and diabetes. The poor data quality restricts the validity of the findings and draws the attention to the importance of designing future robust studies. PMID:29326180

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

PubMed Central

Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

2016-01-01

AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients. PMID:28050240

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease.

PubMed

Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

2016-12-18

To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

Breast-specific gamma camera imaging with 99mTc-MIBI has better diagnostic performance than magnetic resonance imaging in breast cancer patients: A meta-analysis.

PubMed

Zhang, Aimi; Li, Panli; Liu, Qiufang; Song, Shaoli

2017-01-01

This study aimed to evaluate the diagnostic role of breast-specific gamma camera imaging (BSGI) with technetium-99m-methoxy isobutyl isonitrile ( 99m Tc-MIBI) and magnetic resonance imaging (MRI) in patients with breast cancer through a meta-analysis. Three reviewers searched articles published in medical journals before June 2016 in MEDLINE, EMBASE and Springer Databases; the references listed in original articles were also retrieved. We used the quality assessment of diagnostic accuracy studies (QUADAS) tool to assess the quality of the included studies. Heterogeneity, pooled sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves were calculated by Meta-DiSc software to estimate the diagnostic performance of BSGI and MRI. Ten studies with 517 patients were included after meeting the inclusion criteria. We did a subgroup analysis of the same data type. The pooled sensitivities of BSGI and MRI were: 0.84 (95% CI, 0.79-0.88) and 0.89 (95% CI, 0.84-0.92) respectively, and the pooled specificities of BSGI and MRI were: 0.82 (95% CI, 0.74-0.88) and 0.39 (95% CI, 0.30-0.49) respectively. The areas under the SROC curve of BSGI and MRI were 0.93 and 0.72 respectively. The results of our meta-analysis indicated that compared with MRI, BSGI has similar sensitivity, higher specificity, better diagnostic performance, and can be widely used in clinical practice.

Prognostic significance of positive circumferential resection margin in esophageal cancer: a systematic review and meta-analysis.

PubMed

Wu, Jie; Chen, Qi-Xun; Teng, Li-song; Krasna, Mark J

2014-02-01

To assess the prognostic significance of positive circumferential resection margin on overall survival in patients with esophageal cancer, a systematic review and meta-analysis was performed. Studies were identified from PubMed, EMBASE, and Web of Science. Survival data were extracted from eligible studies to compare overall survival in patients with a positive circumferential resection margin with patients having a negative circumferential resection margin according to the Royal College of Pathologists (RCP) criteria and the College of American Pathologists (CAP) criteria. Survival data were pooled with hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). A random-effects model meta-analysis on overall survival was performed. The pooled HRs for survival were 1.510 (95% CI, 1.329-1.717; p<0.001) and 2.053 (95% CI, 1.597-2.638; p<0.001) according to the RCP and CAP criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients with T3 stage disease according to the RCP (HR, 1.381; 95% CI, 1.028-1.584; p=0.001) and CAP (HR, 2.457; 95% CI, 1.902-3.175; p<0.001) criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients receiving neoadjuvant therapy according to the RCP (HR, 1.676; 95% CI, 1.023-2.744; p=0.040) and CAP (HR, 1.847; 95% CI, 1.226-2.78; p=0.003) criteria, respectively. Positive circumferential resection margin is associated with poor prognosis in patients with esophageal cancer, particularly in patients with T3 stage disease and patients receiving neoadjuvant therapy. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Assessment of the psychometrics of a PROMIS item bank: self-efficacy for managing daily activities

PubMed Central

Hong, Ickpyo; Li, Chih-Ying; Romero, Sergio; Gruber-Baldini, Ann L.; Shulman, Lisa M.

2017-01-01

Purpose The aim of this study is to investigate the psychometrics of the Patient-Reported Outcomes Measurement Information System self-efficacy for managing daily activities item bank. Methods The item pool was field tested on a sample of 1087 participants via internet (n = 250) and in-clinic (n = 837) surveys. All participants reported having at least one chronic health condition. The 35 item pool was investigated for dimensionality (confirmatory factor analyses, CFA and exploratory factor analysis, EFA), item-total correlations, local independence, precision, and differential item functioning (DIF) across gender, race, ethnicity, age groups, data collection modes, and neurological chronic conditions (McFadden Pseudo R2 less than 10 %). Results The item pool met two of the four CFA fit criteria (CFI = 0.952 and SRMR = 0.07). EFA analysis found a dominant first factor (eigenvalue = 24.34) and the ratio of first to second eigenvalue was 12.4. The item pool demonstrated good item-total correlations (0.59–0.85) and acceptable internal consistency (Cronbach’s alpha = 0.97). The item pool maintained its precision (reliability over 0.90) across a wide range of theta (3.70), and there was no significant DIF. Conclusion The findings indicated the item pool has sound psychometric properties and the test items are eligible for development of computerized adaptive testing and short forms. PMID:27048495

Assessment of the psychometrics of a PROMIS item bank: self-efficacy for managing daily activities.

PubMed

Hong, Ickpyo; Velozo, Craig A; Li, Chih-Ying; Romero, Sergio; Gruber-Baldini, Ann L; Shulman, Lisa M

2016-09-01

The aim of this study is to investigate the psychometrics of the Patient-Reported Outcomes Measurement Information System self-efficacy for managing daily activities item bank. The item pool was field tested on a sample of 1087 participants via internet (n = 250) and in-clinic (n = 837) surveys. All participants reported having at least one chronic health condition. The 35 item pool was investigated for dimensionality (confirmatory factor analyses, CFA and exploratory factor analysis, EFA), item-total correlations, local independence, precision, and differential item functioning (DIF) across gender, race, ethnicity, age groups, data collection modes, and neurological chronic conditions (McFadden Pseudo R (2) less than 10 %). The item pool met two of the four CFA fit criteria (CFI = 0.952 and SRMR = 0.07). EFA analysis found a dominant first factor (eigenvalue = 24.34) and the ratio of first to second eigenvalue was 12.4. The item pool demonstrated good item-total correlations (0.59-0.85) and acceptable internal consistency (Cronbach's alpha = 0.97). The item pool maintained its precision (reliability over 0.90) across a wide range of theta (3.70), and there was no significant DIF. The findings indicated the item pool has sound psychometric properties and the test items are eligible for development of computerized adaptive testing and short forms.

Performance of FLT-PET for pulmonary lesion diagnosis compared with traditional FDG-PET: A meta-analysis.

PubMed

Wang, Zixing; Wang, Yuyan; Sui, Xin; Zhang, Wei; Shi, Ruihong; Zhang, Yingqiang; Dang, Yonghong; Qiao, Zhen; Zhang, Biao; Song, Wei; Jiang, Jingmei

2015-07-01

Widely used (18)F 2'-deoxy-2'-fluoro-d-glucose (FDG) positron emission tomography (PET) can be problematic with false positives in cancer imaging. This study aims to investigate the diagnostic accuracy of a candidate PET tracer, (18)F 2',3'-dideoxy-3'-fluoro-2-thiothymidine (FLT), in diagnosing pulmonary lesions compared with FDG. After comprehensive search and study selection, a meta-analysis was performed on data from 548 patients pooled from 17 studies for evaluating FLT accuracy, in which data from 351 patients pooled from ten double-tracer studies was used for direct comparison with FDG. Weighted sensitivity and specificity were used as main indicators of test performance. Individual data was extracted and patient subgroup analyses were performed. Overall, direct comparisons showed lower sensitivity (0.80 vs. 0.89) yet higher specificity (0.82 vs. 0.66) for FLT compared with FDG (both p<0.01). Patient subgroup analysis showed FLT was less sensitive than FDG in detecting lung cancers staged as T1 or T2, and those ≤2.0 cm in diameter (0.81 vs. 0.93, and 0.53 vs. 0.78, respectively, both p<0.05), but was comparable for cancers staged as T3 or T4, and those >2.0 cm in diameter (0.95 vs. 1.00, 0.96 vs. 0.88, both p>0.05). For benignities, FLT performed better compared with FDG in ruling out inflammation-based lesions (0.57 vs. 0.32, p<0.05), and demonstrated greater specificity regardless of lesion sizes. Although FLT cannot replace FDG in detecting small and early lung cancers, it may help to prevent patients with larger or inflammatory lesions from cancer misdiagnosis or even over-treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

PubMed

Savaskan, Egemen; Mueller, Heiko; Hoerr, Robert; von Gunten, Armin; Gauthier, Serge

2018-03-01

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Return to Play in Elite Contact Athletes After Anterior Cervical Discectomy and Fusion: A Meta-Analysis

PubMed Central

McAnany, Steven J.; Overley, Samuel; Andelman, Steven; Patterson, Diana C.; Cho, Samuel K.; Qureshi, Sheeraz; Hsu, Wellington K.

2017-01-01

Study Design: Systematic literature review and meta-analysis of studies published in English language. Objective: Return to play after anterior cervical discectomy and fusion (ACDF) in contact athletes remains a controversial topic with no consensus opinion in the literature. Additional information is needed to properly advise and treat this population of patients. This study is a meta-analysis assessing return to competitive contact sports after undergoing an ACDF. Methods: A literature search of Medline, Embase, and Cochrane Reviews was performed to identify investigations reporting return to play following ACDF in professional contact athletes. The pooled results were performed by calculating the effect size based on the logic event rate. Studies were weighted by the inverse of the variance, which included both within and between-study error. Confidence intervals (CIs) were reported at 95%. Heterogeneity was assessed using the Q statistic and I 2. Sensitivity analysis and publication bias calculations were performed. Results: The initial literature search resulted in 166 articles, of which 5 were determined relevant. Overall, return to play data was provided for 48 patients. The pooled clinical success rate for return to play was 73.5% (CI = 56.7%, 85.8%). The logit event rate was calculated to be 1.036 (CI = 0.270, 1.802), which was statistically significant (P = .008). The studies included in this meta-analysis demonstrated minimal heterogeneity with Q value of 4.038 and I 2 value of 0.956. Conclusions: Elite contact athletes return to competition 73.5% of the time after undergoing ACDF. As this is the first study to pool results from existing studies, it provides strong evidence to guide decision making and expectations in this patient population. PMID:28894685

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

PubMed

Zakko, Salam F; Gordon, Glenn L; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-01-01

A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Creating a data exchange strategy for radiotherapy research: towards federated databases and anonymised public datasets.

PubMed

Skripcak, Tomas; Belka, Claus; Bosch, Walter; Brink, Carsten; Brunner, Thomas; Budach, Volker; Büttner, Daniel; Debus, Jürgen; Dekker, Andre; Grau, Cai; Gulliford, Sarah; Hurkmans, Coen; Just, Uwe; Krause, Mechthild; Lambin, Philippe; Langendijk, Johannes A; Lewensohn, Rolf; Lühr, Armin; Maingon, Philippe; Masucci, Michele; Niyazi, Maximilian; Poortmans, Philip; Simon, Monique; Schmidberger, Heinz; Spezi, Emiliano; Stuschke, Martin; Valentini, Vincenzo; Verheij, Marcel; Whitfield, Gillian; Zackrisson, Björn; Zips, Daniel; Baumann, Michael

2014-12-01

Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within "Big Data". Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis.

PubMed

Li, Ying; Ehiri, John; Tang, Shenglan; Li, Daikun; Bian, Yongqiao; Lin, Hui; Marshall, Caitlin; Cao, Jia

2013-07-02

Delay in seeking care is a major impediment to effective management of tuberculosis (TB) in China. To elucidate factors that underpin patient and diagnostic delays in TB management, we conducted a systematic review and meta-analysis of factors that are associated with delays in TB care-seeking and diagnosis in the country. This review was prepared following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. Relevant studies published up to November 2012 were identified from three major international and Chinese literature databases: Medline/PubMed, EMBASE and CNKI (China National Knowledge Infrastructure). We included 29 studies involving 38,947 patients from 17 provinces in China. Qualitative analysis showed that key individual level determinants of delays included socio-demographic and economic factors, mostly poverty, rural residence, lack of health insurance, lower educational attainment, stigma and poor knowledge of TB. Health facility determinants included limited availability of resources to perform prompt diagnosis, lack of qualified health workers and geographical barriers.Quantitative meta-analysis indicated that living in rural areas was a risk factor for patient delays (pooled odds ratio (OR) (95% confidence interval (CI)): 1.79 (1.62, 1.98)) and diagnostic delays (pooled OR (95% CI): 1.40 (1.23, 1.59)). Female patients had higher risk of patient delay (pooled OR (95% CI): 1.94 (1.13, 3.33)). Low educational attainment (primary school and below) was also a risk factor for patient delay (pooled OR (95% CI): 2.14 (1.03, 4.47)). The practice of seeking care first from Traditional Chinese Medicine (TMC) providers was also identified as a risk factor for diagnostic delay (pooled OR (95% CI): 5.75 (3.03, 10.94)). Patient and diagnostic delays in TB care are mediated by individual and health facility factors. Population-based interventions that seek to reduce TB stigma and raise awareness about the benefits of early diagnosis and prompt treatment are needed. Policies that remove patients' financial barriers in access to TB care, and integration of the informal care sector into TB control in urban and rural settings are central factors in TB control.

Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

PubMed

Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

2018-01-01

Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Efficacy of Enhanced External Counterpulsation in Patients With Chronic Refractory Angina on Canadian Cardiovascular Society (CCS) Angina Class: An Updated Meta-Analysis.

PubMed

Zhang, Chunmei; Liu, Xiangjuan; Wang, Xiaomeng; Wang, Qi; Zhang, Yun; Ge, Zhiming

2015-11-01

A growing number of patients with chronic artery disease suffer from angina, despite the optimal medical management (ie, β-blockers, calcium channel blockers, and long-acting nitrates) and revascularization. Currently, enhanced external counterpulsation (EECP) therapy has been verified as a noninvasive, safe therapy for refractory angina. The study was designed to evaluate the efficacy of EECP in patients with chronic refractory angina according to Canadian Cardiovascular Society (CCS) angina class.We identified systematic literature through MEDLINE, EMBASE, the Cochrane Clinical Trials Register Database, and the ClinicalTrials. gov Website from 1990 to 2015. Studies were considered eligible if they were prospective and reported data on CCS class before and after EECP treatment. Meta-analysis was performed to assess the efficacy of EECP therapy by at least 1 CCS angina class improvement, and proportion along with the 95% confidence interval (CI) was calculated. Statistical heterogeneity was calculated by I statistic and the Q statistic. Sensitivity analysis was addressed to test the influence of trials on the overall pooled results. Subgroup analysis was applied to explore potential reasons for heterogeneity.Eighteen studies were enrolled in our meta-analysis. Pooled analysis showed 85% of patients underwent EECP had a reduction by at least one CCS class (95%CI 0.81-0.88, I = 58.5%, P < 0.001). The proportion of patients enrolled at primarily different studies with chronic heart failure (CHF) improved by at least 1 CCS class was about 84% after EECP (95%CI 0.81-0.88, I = 32.7%, P = 0.1668). After 3 large studies were excluded, the pooled proportion was 82% (95%CI 0.79-0.86, I = 18%, P = 0.2528). Funnel plot indicated that some asymmetry while the Begg and Egger bias statistic showed no publication bias (P = 0.1495 and 0.2859, respectively).Our study confirmed that EECP provided an effective treatment for patients who were unresponsive to medical management and/or invasive therapy. However, the long-term benefits of EECP therapy needed further studies to evaluate in the management of chronic refractory angina.

Creating a data exchange strategy for radiotherapy research: Towards federated databases and anonymised public datasets

PubMed Central

Skripcak, Tomas; Belka, Claus; Bosch, Walter; Brink, Carsten; Brunner, Thomas; Budach, Volker; Büttner, Daniel; Debus, Jürgen; Dekker, Andre; Grau, Cai; Gulliford, Sarah; Hurkmans, Coen; Just, Uwe; Krause, Mechthild; Lambin, Philippe; Langendijk, Johannes A.; Lewensohn, Rolf; Lühr, Armin; Maingon, Philippe; Masucci, Michele; Niyazi, Maximilian; Poortmans, Philip; Simon, Monique; Schmidberger, Heinz; Spezi, Emiliano; Stuschke, Martin; Valentini, Vincenzo; Verheij, Marcel; Whitfield, Gillian; Zackrisson, Björn; Zips, Daniel; Baumann, Michael

2015-01-01

Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within “Big Data”. Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology. PMID:25458128

Comparing survival outcomes of gross total resection and subtotal resection with radiotherapy for craniopharyngioma: a meta-analysis.

PubMed

Wang, Guoqing; Zhang, Xiaoyang; Feng, Mengzhao; Guo, Fuyou

2018-06-01

Recent studies suggest that subtotal resection (STR) followed by radiation therapy (RT) is an appealing alternative to gross total resection (GTR) for craniopharyngioma, but it remains controversial. We conducted a meta-analysis to determine whether GTR is superior to STR with RT for craniopharyngioma. A systematic search was performed for articles published until October 2017 in the PubMed, Embase, and Cochrane Central databases. The endpoints of interest are overall survival and progression-free survival. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed or random-effects model. The data were analyzed using Review Manager 5.3 software. A total of 744 patients (seven cohort studies) were enrolled for analyses. There were no significant differences between the GTR and STR with RT groups when the authors compared the pooled HRs at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI: 0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI: 0.42-5.44, P = 0.52) were similar between the two groups. The current meta-analysis suggests that GTR and STR with RT have the similar survival outcomes for craniopharyngioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Delayed Breast Reconstruction on Patients With Upper Extremity Lymphedema: A Systematic Review of the Literature and Pooled Analysis.

PubMed

Siotos, Charalampos; Hassanein, Aladdin H; Bello, Ricardo J; Sebai, Mohamad E; Seal, Stella M; Manahan, Michele A; Cooney, Damon S; Cooney, Carisa M; Rosson, Gedge D

2018-06-26

Breast cancer-related lymphedema (BCRL) is a debilitating condition with morbidity, hindered quality of life, and increased health-related costs. Experimental studies support the use of musculocutaneous flaps for managing animal models with lymphedema. Although vascularized lymph node transfer (VLNT) and lymphovenous anastomosis are used to surgically treat patients with lymphedema, it is not known whether musculocutaneous or adipocutaneous flaps (eg, delayed autologous breast reconstruction) are effective for treating refractory upper extremity BCRL. We conducted a systematic review and pooled analysis to assess the impact of delayed breast reconstruction on developed BCRL. Following PRISMA guidelines, we systematically searched PubMed, Scopus, EMBASE, and Google Scholar databases for relevant studies published through November 11, 2016. We screened 934 unique articles. Of these, we conducted full-text and reference screening on 37 articles. We then performed a pooled and sensitivity analysis using random effects. Eight studies met our inclusion criteria. One study was a case report; 7 studies were case series with sample sizes ranging from 3 to 38 patients. According to our pooled analysis 58% of patients reported improvement after breast reconstruction with or without VLNT. Sensitivity analysis revealed that 84% (95% confidence interval, 0.74-0.95) of patients who underwent breast reconstruction and VLNT reported improvement, whereas only 22% (95% confidence interval, 0.12-0.32) of those who had breast reconstruction alone reported improvement. Our review summarizes the current evidence regarding the effect of delayed breast reconstruction on established lymphedema. The VLNT component of the autologous breast reconstruction procedures may be the largest contributing factor leading to lymphedema improvement.

Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma.

PubMed

Kumar, Shaji K; Laubach, Jacob P; Giove, Thomas J; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G

2017-09-01

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules. © 2017 John Wiley & Sons Ltd.

Efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis: 52-week pooled results from two phase 3 studies.

PubMed

Wei, James C-C; Baeten, Dominique; Sieper, Joachim; Deodhar, Atul; Bhosekar, Vaishali; Martin, Ruvie; Porter, Brian

2017-05-01

To evaluate efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis (AS) via a pooled subgroup analysis from two phase 3 studies, MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375). In MEASURE 1, patients were randomized to intravenous secukinumab 10 mg/kg or placebo at baseline, Weeks 2 and 4, followed by subcutaneous (s.c.) secukinumab 150 mg, 75 mg or placebo every 4 weeks (q4w) at Week 8. In MEASURE 2, patients were randomized to s.c. secukinumab 150 mg, 75 mg or placebo at baseline, Weeks 1, 2 and 3, and q4w starting at Week 4. Efficacy outcomes were SpondyloArthritis International Society (ASAS) 20/40, high-sensitivity C-reactive protein (hsCRP), ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form-36 physical component summary, AS quality of life (QoL), ASAS partial remission, and Ankylosing Spondylitis Disease Activity Score - CRP at Weeks 16 and 52. Due to lack of efficacy, the secukinumab 75 mg dose in MEASURE 2 was excluded from this pooled Asian subgroup analysis. Safety analysis included patients who received ≥ 1 dose of study treatment. Of 517 patients enrolled into the MEASURE studies, 69 (13.3%) were Asians: 46 in pooled secukinumab and 23 in placebo. At Week 16, ASAS20/40 responses in Asian patients were 69.6%/43.5% with pooled secukinumab versus 26.1%/17.4% with placebo, which were comparable with rates reported in the overall study population. Secukinumab improved predefined efficacy endpoints at Week 16, with responses sustained through Week 52. Secukinumab was well tolerated in Asian patients, with a safety profile consistent with that reported in the overall study population. Secukinumab improved signs and symptoms, physical function, and disease-specific QoL in Asian patients with active AS. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients.

PubMed

van Leeuwen, Nikki; Lingsma, Hester F; Perel, Pablo; Lecky, Fiona; Roozenbeek, Bob; Lu, Juan; Shakur, Haleema; Weir, James; Steyerberg, Ewout W; Maas, Andrew I R

2012-04-01

Major extracranial injury (MEI) is common in traumatic brain injury (TBI) patients, but the effect on outcome is controversial. To assess the prognostic value of MEI on mortality after TBI in an individual patient data meta-analysis of 3 observational TBI studies (International Mission on Prognosis and Clinical Trial Design in TBI [IMPACT]), a randomized controlled trial (Corticosteroid Randomization After Significant Head Injury [CRASH]), and a trauma registry (Trauma Audit and Research Network [TARN]). MEI (extracranial injury with an Abbreviated Injury Scale ≥ 3 or requiring hospital admission) was related to mortality with logistic regression analysis, adjusted for age, Glasgow Coma Scale motor score, and pupil reactivity and stratified by TBI severity. We pooled odds ratios (ORs) with random-effects meta-analysis. We included 39,274 patients. Mortality was 25%, and 32% had MEI. MEI was a strong predictor for mortality in TARN, with adjusted odds ratios of 2.81 (95% confidence interval [CI], 2.44-3.23) in mild, 2.18 (95% CI, 1.80-2.65) in moderate, and 2.14 (95% CI, 1.95-2.35) in severe TBI patients. The prognostic effect was smaller in IMPACT and CRASH, with pooled adjusted odds ratios of 2.14 (95% CI, 0.93-4.91) in mild, 1.46 (95% CI, 1.14-1.85) in moderate, and 1.18 (95% CI, 1.03-1.55) in severe TBI. When patients who died within 6 hours after injury were excluded from TARN, the effect of MEI was comparable with IMPACT and CRASH. MEI is an important prognostic factor for mortality in TBI patients. However, the effect varies by population, which explains the controversy in the literature. The strength of the effect is smaller in patients with more severe brain injury and depends on time of inclusion in a study.

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis.

PubMed

Plantinga, N L; de Smet, A M G A; Oostdijk, E A N; de Jonge, E; Camus, C; Krueger, W A; Bergmans, D; Reitsma, J B; Bonten, M J M

2018-05-01

Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis.

PubMed

Zehtabchi, Shahriar; Abdel Baki, Samah G; Falzon, Louise; Nishijima, Daniel K

2014-12-01

The antifibrinolytic agent tranexamic acid (TXA) has demonstrated clinical benefit in trauma patients with severe bleeding, but its effectiveness in patients with traumatic brain injury (TBI) is unclear. We conducted a systematic review to evaluate the following research question: In ED patients with or at risk of intracranial hemorrhage (ICH) secondary to TBI, does TXA compared to placebo improve patients' outcomes? MEDLINE, EMBASE, CINAHL, and other databases were searched for randomized controlled trial (RCT) or quasi-RCT studies that compared the effect of TXA to placebo on outcomes of TBI patients. The main outcomes of interest included mortality, neurologic function, hematoma expansion, and adverse effects. We used "Grading quality of evidence and strength of recommendations" to assess the quality of trials. Two authors independently abstracted data using a data collection form. Results from studies were pooled when appropriate. Of 1030 references identified through the search, 2 high-quality RCTs met inclusion criteria. The effect of TXA on mortality had a pooled relative risk of 0.64 (95% confidence interval [CI], 0.41-1.02); on unfavorable functional status, a relative risk of 0.77 (95% CI, 0.59-1.02); and on ICH progression, a relative risk of 0.76 (95% CI, 0.58-0.98). No serious adverse effects (such as thromboembolic events) associated with TXA group were reported in the included trials. Pooled results from the 2 RCTs demonstrated statistically significant reduction in ICH progression with TXA and a nonstatistically significant improvement of clinical outcomes in ED patients with TBI. Further evidence is required to support its routine use in patients with TBI. Copyright © 2014 Elsevier Inc. All rights reserved.

Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia.

PubMed

Meyer, Jonathan M; Mao, Yongcai; Pikalov, Andrei; Cucchiaro, Josephine; Loebel, Antony

2015-11-01

The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40-160 mg/day lurasidone; two studies included active comparators (2-6 mg/day risperidone or 200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N = 89 risperidone, N = 33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months.

Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three Korean Observational Studies (the VICTORY Study)

PubMed Central

Suh, Sunghwan; Song, Sun Ok; Kim, Jae Hyeon; Cho, Hyungjin

2017-01-01

The present observational study aimed to evaluate the clinical effectiveness of vildagliptin with metformin in Korean patients with type 2 diabetes mellitus (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective observational study of vildagliptin/metformin (fixed DC or free DC). The effectiveness endpoint was the proportion of patients who achieved a glycemic target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the analysis; of these, 2087 patients were eligible. The mean patient age was 56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0% at 24 weeks. The glycemic target achievement rate was significantly greater in patients with baseline HbA1c < 7.5% versus ≥7.5% (84.64% versus 43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%). Multivariate logistic regression analysis indicated that disease duration (P < 0.0001), baseline HbA1c (P < 0.0001), and DC type (P = 0.0103) had significant effects on drug effectiveness. Vildagliptin plus metformin appeared as an effective treatment option for patients with T2DM in clinical practice settings in Korea. PMID:29057274

Effects of exenatide twice daily, exenatide once weekly or insulin in patients with type 2 diabetes and baseline HbA1c ≥10.0%: Two pooled analyses including 20 randomised controlled trials.

PubMed

Busch, Robert S; Ruggles, James; Han, Jenny; Hardy, Elise

2017-12-01

Patients with advanced type 2 diabetes (T2D) and high glycated haemoglobin (HbA1c) values can be difficult to treat because of their severe metabolic disease. This pooled analysis examined the treatment effects of exenatide twice daily (BID), exenatide once weekly (QW) and insulin in patients with high baseline HbA1c (≥10.0%). This post hoc analysis used pooled data from 12 and 8 randomised controlled trials of exenatide BID and exenatide QW, respectively. Patients with T2D who completed at least 24 weeks of treatment with exenatide BID, exenatide QW or insulin (insulin glargine, insulin detemir or insulin aspart) were categorised by baseline HbA1c. Patients with HbA1c ≥10.0% were included in the analysis. Both exenatide and insulin reduced HbA1c (mean ± SE reduction: -2.0% ± 0.2% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide BID studies, and -2.6% ± 0.1% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide QW studies; all P < .001). Body weight decreased with exenatide and increased with insulin. Systolic blood pressure decreased with exenatide QW. Insulin dose increased over the course of treatment. The most common adverse events with exenatide were gastrointestinal. Insulin was associated with some hypoglycaemia risk. Hypoglycaemia events occurred infrequently with exenatide when given without sulphonylureas. For patients with high HbA1c, treatment with exenatide or insulin both improved glycaemic control. Given the associated weight loss and low risk of hypoglycaemia, exenatide may be a suitable alternative to treatment with insulin in certain patients with T2D and high HbA1c. © 2017 John Wiley & Sons Ltd.

Liposomal bupivacaine versus traditional bupivacaine for pain control after total hip arthroplasty: A meta-analysis.

PubMed

Ma, Ting-Ting; Wang, Yu-Hui; Jiang, Yun-Feng; Peng, Cong-Bin; Yan, Chao; Liu, Zi-Gui; Xu, Wei-Xing

2017-06-01

In the past, the efficacy of local infiltration of liposomal bupivacaine for total hip arthroplasty (THA) patients was in debate. Therefore, this meta-analysis was conducted to determine whether local infiltration of liposomal bupivacaine provides better pain relief after THA. We searched Web of Science, PubMed, Embase, and the Cochrane Library databases to the April 2017. Any studies comparing liposomal bupivacaine and traditional bupivacaine were included in our meta-analysis. The outcomes included visual analog scale (VAS) at 24, 48, and 72 hours, total morphine consumption at 24 hours, and the length of hospital stay. We assessed the pooled data using a random-effect model. Six studies were finally included in this meta-analysis. Our pooled data analysis demonstrated that liposomal bupivacaine was more effective than the traditional bupivacaine in terms of VAS at 24 hours (P  =  .018) and the length of hospital stay (P  =  .000). There was no significant difference in terms of the VAS at 48 and 72 hours and total morphine consumption at 24 hours (P >.05). Compared with the traditional bupivacaine, liposomal bupivacaine shows better pain control at 24 hours and reduces the length of hospital stay after THA. Its economic costs must be assessed in multimodal center randomized controlled trials when being recommended as a long-acting alternative analgesic agent for a THA patient.

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis

PubMed Central

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2015-01-01

Background No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, particularly delayed nausea. Objective To compare the efficacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Methods Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Results Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. Limitations This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be influenced by interindividual variability. Conclusion Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. PMID:25830233

Everolimus-Eluting Stents in Patients With Bare-Metal and Drug-Eluting In-Stent Restenosis: Results From a Patient-Level Pooled Analysis of the RIBS IV and V Trials.

PubMed

Alfonso, Fernando; Pérez-Vizcayno, María José; García Del Blanco, Bruno; García-Touchard, Arturo; López-Mínguez, José-Ramón; Masotti, Mónica; Zueco, Javier; Melgares, Rafael; Mainar, Vicente; Moreno, Raul; Domínguez, Antonio; Sanchís, Juan; Bethencourt, Armando; Moreu, José; Cequier, Angel; Martí, Vicens; Otaegui, Imanol; Bastante, Teresa; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Cárdenas, Alberto; Fernández, Cristina

2016-07-01

Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is more challenging than that of patients with bare-metal stent ISR. However, the results of everolimus-eluting stents (EES) in these distinct scenarios remain unsettled. A pooled analysis of the RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) and RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) randomized trials was performed using patient-level data to compare the efficacy of EES in bare-metal stent ISR and DES-ISR. Inclusion and exclusion criteria were identical in both trials. Results of 94 patients treated with EES for bare-metal stent ISR were compared with those of 155 patients treated with EES for DES-ISR. Baseline characteristics were more adverse in patients with DES-ISR, although they presented later and more frequently with a focal pattern. After intervention, minimal lumen diameter (2.22±0.5 versus 2.38±0.5 mm, P=0.01) was smaller in the DES-ISR group. Late angiographic findings (89.3% of eligible patients), including minimal lumen diameter (2.03±0.7 versus 2.36±0.6 mm, P<0.001) and diameter stenosis (23±22 versus 13±17%, P<0.001) were poorer in patients with DES-ISR. Results were consistent in the in-segment and in-lesion analyses. On multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR. Finally, at 1-year clinical follow-up (100% of patients), mortality (2.6 versus 0%, P<0.01) and need for target vessel revascularization (8 versus 2%, P=0.03) were higher in the DES-ISR group. This patient-level pooled analysis of the RIBS IV and RIBS V randomized clinical trials suggests that EES provide favorable outcomes in patients with ISR. However, the results of EES are less satisfactory in patients with DES-ISR than in those with bare-metal stent ISR. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01239953 and NCT01239940. © 2016 American Heart Association, Inc.

Effects of azilsartan medoxomil compared with olmesartan and valsartan on ambulatory and clinic blood pressure in patients with type 2 diabetes and prediabetes

PubMed Central

White, William B.; Cuadra, René H.; Lloyd, Eric; Bakris, George L.; Kupfer, Stuart

2016-01-01

Background: Angiotensin receptor blockers (ARBs) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus (T2DM). Azilsartan medoxomil (AZL-M) is a potent ARB for the treatment of stages 1-2 hypertension. We compared the efficacy, safety, and metabolic effects of AZL-M to both valsartan (VAL) and olmesartan (OLM), separately in patients with impaired fasting glucose (prediabetes mellitus) and T2DM. Methods: A pooled analysis of 3821 patients from three separate randomized placebo-controlled trials comparing the effects of AZL-M (40 and 80 mg), OLM (40 mg), VAL (320 mg), and placebo on changes in ambulatory and clinic blood pressure (BP) among patients with hypertension and prediabetes mellitus or T2DM was performed. Two analysis pools were created to facilitate comparisons: Pool A included patients who received placebo, AZL-M or OLM and Pool B included those who received AZL-M or VAL. Within each pool, patients were stratified by glycemic subgroups (normoglycemic, prediabetes mellitus, or T2DM) based on hemoglobin A1c values. Changes from baseline in both 24-h and clinic SBP were the primary efficacy assessments. Results: Baseline 24-h mean SBPs were approximately 145 and 146 mmHg in the prediabetes mellitus and T2DM subgroups, respectively; corresponding clinic SBPs were approximately 158 and 159 mmHg. Baseline hemoglobin A1c values for each subgroup (both pools) were normoglycemic, 5.3%; prediabetes mellitus, 6.0%; and T2DM, 6.9%. Changes from baseline in 24-h or clinic SBP were significantly greater with AZL-M, 80 mg compared with either OLM 40 mg or VAL 320 mg in all subgroups in each pool. Safety and tolerability were similar among the active treatment and placebo subgroups. Conclusion: These analyses indicate that AZL-M, 80 mg/day lowers SBP by a greater magnitude than OLM or VAL at maximally approved doses in patients with prediabetes mellitus and T2DM. These findings have important clinical implications for this high-risk patient group. PMID:26766564

Effects of azilsartan medoxomil compared with olmesartan and valsartan on ambulatory and clinic blood pressure in patients with type 2 diabetes and prediabetes.

PubMed

White, William B; Cuadra, René H; Lloyd, Eric; Bakris, George L; Kupfer, Stuart

2016-04-01

Angiotensin receptor blockers (ARBs) are preferred antihypertensive therapies in patients with type 2 diabetes mellitus (T2DM). Azilsartan medoxomil (AZL-M) is a potent ARB for the treatment of stages 1-2 hypertension. We compared the efficacy, safety, and metabolic effects of AZL-M to both valsartan (VAL) and olmesartan (OLM), separately in patients with impaired fasting glucose (prediabetes mellitus) and T2DM. A pooled analysis of 3821 patients from three separate randomized placebo-controlled trials comparing the effects of AZL-M (40 and 80 mg), OLM (40 mg), VAL (320 mg), and placebo on changes in ambulatory and clinic blood pressure (BP) among patients with hypertension and prediabetes mellitus or T2DM was performed. Two analysis pools were created to facilitate comparisons: Pool A included patients who received placebo, AZL-M or OLM and Pool B included those who received AZL-M or VAL. Within each pool, patients were stratified by glycemic subgroups (normoglycemic, prediabetes mellitus, or T2DM) based on hemoglobin A1c values. Changes from baseline in both 24-h and clinic SBP were the primary efficacy assessments. Baseline 24-h mean SBPs were approximately 145 and 146 mmHg in the prediabetes mellitus and T2DM subgroups, respectively; corresponding clinic SBPs were approximately 158 and 159 mmHg. Baseline hemoglobin A1c values for each subgroup (both pools) were normoglycemic, 5.3%; prediabetes mellitus, 6.0%; and T2DM, 6.9%. Changes from baseline in 24-h or clinic SBP were significantly greater with AZL-M, 80 mg compared with either OLM 40 mg or VAL 320 mg in all subgroups in each pool. Safety and tolerability were similar among the active treatment and placebo subgroups. These analyses indicate that AZL-M, 80 mg/day lowers SBP by a greater magnitude than OLM or VAL at maximally approved doses in patients with prediabetes mellitus and T2DM. These findings have important clinical implications for this high-risk patient group.

DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis.

PubMed

Steffensen, Charlotte; Pereira, Alberto M; Dekkers, Olaf M; Jørgensen, Jens Otto L

2016-12-01

Type 2 diabetes (T2D) and Cushing's syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. Systematic review and meta-analysis of the literature. A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications. © 2016 European Society of Endocrinology.

Comparison of digital tomosynthesis and chest radiography for the detection of pulmonary nodules: systematic review and meta-analysis.

PubMed

Kim, Jun H; Lee, Kyung H; Kim, Kyoung-Tae; Kim, Hyun J; Ahn, Hyeong S; Kim, Yeo J; Lee, Ha Y; Jeon, Yong S

2016-12-01

To compare the diagnostic accuracy of digital tomosynthesis (DTS) with that of chest radiography for the detection of pulmonary nodules by meta-analysis. A systematic literature search was performed to identify relevant original studies from 1 January 1 1976 to 31 August 31 2016. The quality of included studies was assessed by quality assessment of diagnostic accuracy studies-2. Per-patient data were used to calculate the sensitivity and specificity and per-lesion data were used to calculate the detection rate. Summary receiver-operating characteristic curves were drawn for pulmonary nodule detection. 16 studies met the inclusion criteria. 1017 patients on a per-patient basis and 2159 lesions on a per-lesion basis from 16 eligible studies were evaluated. The pooled patient-based sensitivity of DTS was 0.85 [95% confidence interval (CI) 0.83-0.88] and the specificity was 0.95 (0.93-0.96). The pooled sensitivity and specificity of chest radiography were 0.47 (0.44-0.51) and 0.37 (0.34-0.40), respectively. The per-lesion detection rate was 2.90 (95% CI 2.63-3.19). DTS has higher diagnostic accuracy than chest radiography for detection of pulmonary nodules. Chest radiography has low sensitivity but similar specificity, comparable with that of DTS. Advances in knowledge: DTS has higher diagnostic accuracy than chest radiography for the detection of pulmonary nodules.

Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew; Puli, Srinivas R

2016-07-11

In patients requiring surgical resection for malignant biliary jaundice, it is unclear if preoperative biliary drainage (PBD) would improve mortality and morbidity by restoration of biliary flow prior to operation. This is a meta-analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice. The primary outcome is comparing mortality outcomes in patients with malignant obstructive jaundice undergoing direct surgery (DS) versus PBD. The secondary outcomes include major adverse events and length of hospital stay in both the groups. Studies using PBD in patients with malignant obstructive jaundice were included in this study. For the data collection and extraction, articles were searched in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, etc. Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). Initial search identified 2230 reference articles, of which 204 were selected and reviewed. Twenty-six studies (N = 3532) for PBD in malignant obstructive jaundice which met the inclusion criteria were included in this analysis. The odds ratio for mortality in PBD group versus DS group was 0.96 (95 % CI = 0.71 to 1.29). Pooled number of major adverse effects was lower in the PBD group at 10.40 (95 % CI = 9.96 to 10.83) compared to 15.56 (95 % CI = 15.06 to 16.05) in the DS group. Subgroup analysis comparing internal PBD to DS group showed lower odds for major adverse events (odds ratio, 0.48 with 95 % CI = 0.32 to 0.74). In patients with malignant biliary jaundice requiring surgery, PBD group had significantly less major adverse effects than DS group. Length of hospital stay and mortality rate were comparable in both the groups.

(131)I-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta-analysis.

PubMed

van Hulsteijn, L T; Niemeijer, N D; Dekkers, O M; Corssmit, E P M

2014-04-01

(131)I-MIBG therapy can be used for palliative treatment of malignant paraganglioma and phaeochromocytoma. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of (131)I-MIBG therapy on tumour volume in patients with malignant paraganglioma/phaeochromocytoma. A literature search was performed in December 2012 to identify potentially relevant studies. Main outcomes were the pooled proportions of complete response, partial response and stable disease after radionuclide therapy. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. Seventeen studies concerning a total of 243 patients with malignant paraganglioma/phaeochromocytoma were treated with (131)I-MIBG therapy. The mean follow-up ranged from 24 to 62 months. A meta-analysis of the effect of (131)I-MIBG therapy on tumour volume showed pooled proportions of complete response, partial response and stable disease of, respectively, 0·03 (95% CI: 0·06-0·15), 0·27 (95% CI: 0·19-0·37) and 0·52 (95% CI: 0·41-0·62) and for hormonal response 0·11 (95% CI: 0·05-0·22), 0·40 (95% CI: 0·28-0·53) and 0·21 (95% CI: 0·10-0·40), respectively. Separate analyses resulted in better results in hormonal response for patients with paraganglioma than for patients with phaeochromocytoma. Data on the effects of (131)I-MIBG therapy on malignant paraganglioma/phaeochromocytoma suggest that stable disease concerning tumour volume and a partial hormonal response can be achieved in over 50% and 40% of patients, respectively, treated with (131)I-MIBG therapy. It cannot be ruled out that stable disease reflects not only the effect of MIBG therapy, but also (partly) the natural course of the disease. © 2013 John Wiley & Sons Ltd.

Multivariate modelling and personality organization: a comparative study of the Defense Mechanism Test and linguistic expressions.

PubMed

Sundbom, E; Jeanneau, M

1996-03-01

The main aim of the study is to establish an empirical connection between perceptual defences as measured by the Defense Mechanism Test (DMT)--a projective percept-genetic method--and manifest linguistic expressions based on word pattern analyses. The subjects were 25 psychiatric patients with the diagnoses neurotic personality organization (NPO), borderline personality organization (BPO) and psychotic personality organization (PPO) in accordance with Kernberg's theory. A set of 130 DMT variables and 40 linguistic variables were analyzed by means of partial least squares (PLS) discriminant analysis separately and then pooled together. The overall hypothesis was that it would be possible to define the personality organization of the patients in terms of an amalgam of perceptual defences and word patterns, and that these two kinds of data would confirm each other. The result of the combined PLS analysis revealed a very good separation between the diagnostic groups as measured by the pooled variable sets. Among other things, it was shown that NPO patients are principally characterized by linguistic variables, whereas BPO and PPO patients are better defined by perceptual defences as measured by the DMT method.

Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis.

PubMed

Wang, Jin; Xu, Lijuan; Shi, Ruihua; Huang, Xiayue; Li, Simon Wing Heng; Huang, Zuhu; Zhang, Guoxin

2011-01-01

Whether gastric atrophy (GA) and intestinal metaplasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-analysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradication. English-language articles in the medical literature containing information about the association between infection with H. pylori and gastric premalignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis. Twelve studies containing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histological alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00-0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09-0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (-0.12-0.16), p = 0.76, and for corpus IM, the pooled WMD was -0.02 (-0.05-0.02), p = 0.42. Our study shows that eradication of H. pylori results in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori-positive patients in those with GA in corpus. Copyright © 2011 S. Karger AG, Basel.

Effect of chorionic villus sampling on the occurrence of preeclampsia and gestational hypertension: An updated systematic review and meta-analysis.

PubMed

Başaran, Ahmet; Başaran, Mustafa; Topatan, Betül; Martin, James N

2016-01-01

To perform a meta-analysis for an assessment of the risk of preeclampsia or gestational hypertension following chorionic villus sampling (CVS). PubMed was systematically searched from its inception through January 2016. Nine reports were identified. A pre-specified scale was used to assess their quality. We performed pooling into three subgroups with respect to the control group: A) Patients with no invasive prenatal diagnostic procedure served as a control group for comparison. The odds ratios for gestational hypertension (0.76, 95% CI 0.46-1.26), preeclampsia (0.83, 95% CI 0.42-1.67), and severe preeclampsia (0.49, 95% CI 0.04-5.78) or when hypertension categories were pooled (0.80, 95% CI 0.46-1.41) were not significantly different. B) Patients with midtrimester diagnostic amniocentesis and patients with no invasive prenatal diagnostic procedure were combined as a control group for comparison. The odds ratios for preeclampsia (1, 95% CI 0.46-2.18), severe preeclampsia (0.83, 95% CI 0.14-4.85), and pooled hypertension categories (1.07, 95% CI 0.63-1.84) were not significantly different. C) Patients with midtrimester diagnostic amniocentesis served as a control group. There was a significant difference in the odds ratio for preeclampsia between the CVS and amniocentesis groups (2.47, 95% CI 1.14-5.33). There was a marginal difference in the odds ratio for combined pregnancy-induced hypertension categories between the CVS and amniocentesis groups (1.61, 95% CI 1.02-2.53). The available data do not indicate an increased risk of preeclampsia or gestational hypertension following first trimester CVS. The heterogeneity and retrospective design of existing studies are limiting factors for our analysis and findings.

Aidi injection combined with radiation in the treatment of non-small cell lung cancer: A meta-analysis evaluation the efficacy and side effects.

PubMed

Zhang, Hongzhi; Jiang, Huijuan; Hu, Xigang; Jia, Zongling

2015-08-01

The purpose of this meta-analysis was to assess the clinical efficacy and side effects of Aidi injection combined with radiation in the treatment of non-small cell lung cancer (NSCLC). By searching PubMed, the Cochrane central register of controlled trials, EMBSE and CNKI databases, the efficacy and side effect data of Aidi injection combined with radiation in the treatment of NSCLC from the published clinical studies were collected. The data were pooled using Stata version 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX). Ten clinical studies with 1084 subjects were included in this meta-analysis. The combined data showed the clinical efficacy in experiment group was higher than that of control group (risk ratio [RR] = 1.72, 95% confidence interval [CI]: 1.52-1.96, P = 0.00); four articles reported the life quality improvement. The pooled data showed that the use of Aidi can significantly improve the quality of life in the procedure of radiation (RR = 2.29, 95% CI: 1.76-2.98, P = 0.00); six studies reported the radiation toxicities. The pooled data showed that Aidi injection can significant decrease the radiation pneumonia (OR = 0.46, 95% CI: 0. 34-0.63), radiation esophagitis (OR = 0.53, 95% CI: 0.40-0.71), and marrow suppression (OR = 0.50, 95% CI: 0.42-0.59). Aidi injection can improve the clinical efficacy, quality of life, and decrease the radiation-related toxicities in NSCLC patients who received radiation.

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies.

PubMed

Sanyal, A J; Boyer, T D; Frederick, R T; Wong, F; Rossaro, L; Araya, V; Vargas, H E; Reddy, K R; Pappas, S C; Teuber, P; Escalante, S; Jamil, K

2017-06-01

The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246). © 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis.

PubMed

Ley, Brett; Swigris, Jeffrey; Day, Bann-Mo; Stauffer, John L; Raimundo, Karina; Chou, Willis; Collard, Harold R

2017-09-15

Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up. In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.

Impact of Community-Based DOT on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis

PubMed Central

Zhang, HaiYang; Ehiri, John; Yang, Huan; Tang, Shenglan; Li, Ying

2016-01-01

Background Poor adherence to tuberculosis (TB) treatment can lead to prolonged infectivity and poor treatment outcomes. Directly observed treatment (DOT) seeks to improve adherence to TB treatment by observing patients while they take their anti-TB medication. Although community-based DOT (CB-DOT) programs have been widely studied and promoted, their effectiveness has been inconsistent. The aim of this study was to critical appraise and summarize evidence of the effects of CB-DOT on TB treatment outcomes. Methods Studies published up to the end of February 2015 were identified from three major international literature databases: Medline/PubMed, EBSCO, and EMBASE. Unpublished data from the grey literature were identified through Google and Google Scholar searches. Results Seventeen studies involving 12,839 pulmonary TB patients (PTB) in eight randomized controlled trials (RCTs) and nine cohort studies from 12 countries met the criteria for inclusion in this review and 14 studies were included in meta-analysis. Compared with clinic-based DOT, pooled results of RCTs for all PTB cases (including smear-negative or -positive, new or retreated TB cases) and smear-positive PTB cases indicated that CB-DOT promoted successful treatment [pooled RRs (95%CIs): 1.11 (1.02–1.19) for all PTB cases and 1.11 (1.02–1.19) for smear-positive PTB cases], and completed treatment [pooled RRs (95%CIs): 1.74(1.05, 2.90) for all PTB cases and 2.22(1.16, 4.23) for smear-positive PTB cases], reduced death [pooled RRs (95%CIs): 0.44 (0.26–0.72) for all PTB cases and 0.39 (0.23–0.66) for smear-positive PTB cases], and transfer out [pooled RRs (95%CIs): 0.37 (0.23–0.61) for all PTB cases and 0.42 (0.25–0.70) for smear-positive PTB cases]. Pooled results of all studies (RCTs and cohort studies) with all PTB cases demonstrated that CB-DOT promoted successful treatment [pooled RR (95%CI): 1.13 (1.03–1.24)] and curative treatment [pooled RR (95%CI): 1.24 (1.04–1.48)] compared with self-administered treatment. Conclusions CB-DOT did improved TB treatment outcomes according to the pooled results of included studies in this review. Studies on strategies for implementation of patient-centered and community-centered CB-DOT deserve further attention. PMID:26849656

Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials.

PubMed

Damman, Peter; Clayton, Tim; Wallentin, Lars; Lagerqvist, Bo; Fox, Keith A A; Hirsch, Alexander; Windhausen, Fons; Swahn, Eva; Pocock, Stuart J; Tijssen, Jan G P; de Winter, Robbert J

2012-02-01

To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome. A meta-analysis was performed of patient-pooled data from the FRISC II-ICTUS-RITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management. Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged <65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients <65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar. The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged <65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy. Trial registration http://www.controlled-trials.com/ISRCTN82153174 (ICTUS), http://www.controlled-trials.com/ISRCTN07752711 (RITA-3).

A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma.

PubMed

Stenner, Frank; Chastonay, Rahel; Liewen, Heike; Haile, Sarah R; Cathomas, Richard; Rothermundt, Christian; Siciliano, Raffaele D; Stoll, Susanna; Knuth, Alexander; Buchler, Tomas; Porta, Camillo; Renner, Christoph; Samaras, Panagiotis

2012-01-01

To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use. Copyright © 2012 S. Karger AG, Basel.

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.

PubMed

Powell, J T; Sweeting, M J; Ulug, P; Blankensteijn, J D; Lederle, F A; Becquemin, J-P; Greenhalgh, R M

2017-02-01

The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575. © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Citalopram and escitalopram in the treatment of major depressive disorder: a pooled analysis of 3 clinical trials.

PubMed

Li, Huafang; Li, Ting; Li, Guanjun; Luo, Jianfeng

2014-11-01

Pooled analysis is a powerful technique that is increasingly used to detect differences in efficacy between pharmacologic agents. Some studies have compared the efficacy and tolerability of citalopram and escitalopram, with contradictory results. The aim of this study was to compare the efficacy and tolerability of citalopram and escitalopram in the treatment of major depressive disorder (MDD) using pooled analyses. Data from 3 randomized, double-blind studies that compared citalopram (20 to 40 mg/d) and escitalopram (10 to 20 mg/d) were pooled and analyzed. The primary efficacy parameter was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Efficacy assessments were made at weeks 0 (baseline), 1, 2, 4, and 6. Based on the mean change from baseline in the HAM-D-17 at weeks 1, 2, 4, and 6, the efficacy of citalopram, 20 to 40 mg/d, was equivalent to escitalopram, 10 to 20 mg/d (P > .05). Similar results were seen for severely depressed patients, with a mean treatment difference of 13.9 (SE = 7.6) vs 15.9 (SE = 7.5). Response and remission rates at week 6 were similar (response, 72.4% for citalopram, compared with 73.5% for escitalopram; remission, 52.6% vs 54.5%, respectively). The pooled analysis showed that over a 6-week treatment period, citalopram, 20 to 40 mg/d, is equivalent to escitalopram, 10 to 20 mg/d, in both efficacy and tolerability.

Effect of patient education in the management of coronary heart disease: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Brown, James P R; Clark, Alexander M; Dalal, Hasnain; Welch, Karen; Taylor, Rod S

2013-08-01

To assess the effects of patient education on mortality, morbidity, health-related quality of life (HRQoL), and healthcare costs in people with coronary heart disease (CHD). Systematic review and meta-analysis. Data sources were Cochrane Library, Medline, Embase, PsycINFO, CINAHL, and ongoing trial registries until August 2010. We also checked study references. The study selection was based on design (randomized controlled trials with follow up of at least 6 months, published from 1990 onwards), population (adults with CHD), intervention (patient education stated to be the primary intervention), and comparators (usual care or no educational intervention). Thirteen studies (68,556 people with CHD) were included. Educational interventions ranged from two visits to a 4-week residential stay with 11 months of reinforcement sessions. Compared to no educational intervention, there was weak evidence that education reduced all-cause mortality (pooled relative risk (RR) 0.79, 95% CI 0.55 to 1.13) and cardiac morbidity outcomes: myocardial infarction (pooled RR 0.63, 95% CI 0.26 to 1.48), revascularization (pooled RR 0.58, 95% CI 0.19 to 1.71), and hospitalization (pooled RR 0.83, 95% CI 0.65 to 1.07) at median 18-months follow up. There was evidence to suggest that education can improve HRQoL and decrease healthcare costs by reductions in downstream healthcare utilization. Our review had insufficient power to exclude clinically important effects of education on mortality and morbidity. Nevertheless it supports the practice of CHD secondary prevention and rehabilitation programmes including education as an intervention. Further research is needed to determine the most effective and cost-effective format, duration, timing, and methods of education delivery.

Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials.

PubMed

Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M

2013-02-01

Renal impairment increases mortality among patients with spontaneous bacterial peritonitis (SBP), despite administration of non-nephrotoxic antibiotics. Albumin infusion has been reported to reduce renal impairment and mortality in patients with SBP. We performed a meta-analysis of randomized controlled trials (RCTs) to quantify the effect of albumin infusion on renal impairment and mortality in patients with SBP. We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov for RCTs that evaluated albumin treatment for patients with SBP; we also performed searches by additional methods. Four trials of 288 total patients were included in our analysis. Data were quantitatively combined under a fixed-effects model. We found no evidence of statistically significant heterogeneity or publication bias among the studies analyzed. Albumin was compared with no albumin in 3 trials and with artificial colloid in 1 trial. All patients received antibiotics. The incidence of renal impairment in control groups was 44 of 144 (30.6%), compared with 12 of 144 (8.3%) in groups given albumin. The pooled odds ratio for a reduction in renal impairment after albumin infusion was 0.21 (95% confidence interval, 0.11-0.42). Odds ratios for renal impairment after albumin therapy ranged from 0.19-0.30 among the individual studies. Mortality among controls was 51 of 144 (35.4%), compared with 23 of 144 (16.0%) among patients who received albumin. The pooled odds ratio for decreased mortality after infusion of albumin was 0.34 (95% confidence interval, 0.19-0.60). Odds ratios for mortality in individual RCTs ranged from 0.16-0.55. In a meta-analysis of 4 RCTs (288 patients), albumin infusion prevented renal impairment and reduced mortality among patients with SBP. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Suprapubic compared with transurethral bladder catheterization for gynecologic surgery: a systematic review and meta-analysis.

PubMed

Healy, Eibhlín F; Walsh, Colin A; Cotter, Amanda M; Walsh, Stewart R

2012-09-01

Suprapubic catheterization is commonly used for postoperative bladder drainage after gynecologic procedures. However, recent studies have suggested an increased rate of complications compared with urethral catheterization. We undertook a systematic review and meta-analysis of randomized controlled trials comparing suprapubic catheterization and urethral catheterization in gynecologic populations. PubMed, EMBASE, CINAHL, Google Scholar, and trial registries were searched from 1966 to March 2012 for eligible randomized controlled trials comparing postoperative suprapubic catheterization and urethral catheterization in gynecologic patients. We used these search terms: "catheter," "supra(-)pubic catheter," "urinary catheter," "gyn(a)ecological," "catheterization techniques gyn(a)ecological surgery," "transurethral catheter," and "bladder drainage." No language restrictions were applied. METHODS AND STUDY SELECTION: The primary outcome was urinary tract infection. Secondary outcomes were the need for recatheterization, duration of catheterization, catheter-related complications, and duration of hospital stay. Pooled effect size estimates were calculated using the random effects model from DerSimonian and Laird. In total, 12 eligible randomized controlled trials were included in the analysis (N=1,300 patients). Suprapubic catheterization was associated with a significant reduction in postoperative urinary tract infections (20% compared with 31%, pooled odds ratio [OR] 0.31, 95% confidence interval [CI] 0.185-0.512, P<.01) but an increased risk of complications (29% compared with 11%, pooled OR 4.14, 95% CI 1.327-12.9, P=.01). Complications were mostly related to catheter tube malfunction with no visceral injuries reported. No differences in the rate of recatheterization or hospital stay were demonstrated. Robust patient satisfaction and cost-effectiveness data are lacking. Based on the best available evidence, no route for bladder drainage in gynecologic patients is clearly superior. The reduced rate of infective morbidity with suprapubic catheterization is offset by a higher rate of catheter-related complications and crucially does not translate into reduced hospital stay. As yet, there are insufficient data to determine which route is most appropriate for catheterization; therefore, cost and patient-specific factors should be paramount in the decision. Minimally invasive surgery may alter the requirement for prolonged postoperative catheterization.

Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.

PubMed

Broersen, Leonie H A; Jha, Meghna; Biermasz, Nienke R; Pereira, Alberto M; Dekkers, Olaf M

2018-05-31

To systematically review the effectiveness of medical treatment for Cushing's syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies. Eight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing's syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals. We included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing's disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing's disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data. This meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing's disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.

Prevalence of oropharyngeal dysphagia in Parkinson's disease: a meta-analysis.

PubMed

Kalf, J G; de Swart, B J M; Bloem, B R; Munneke, M

2012-05-01

Dysphagia is a potentially harmful feature, also in Parkinson's disease (PD). As published prevalence rates vary widely, we aimed to estimate the prevalence of oropharyngeal dysphagia in PD in a meta-analysis. We conducted a systematic literature search in February 2011 and two independent reviewers selected the papers. We computed the estimates of the pooled prevalence weighted by sample size. Twelve studies were suitable for calculating prevalence rates. Ten studies provided an estimate based on subjective outcomes, which proved statistically heterogeneous (p < 0.001), with a pooled prevalence estimate with random effect analysis of 35% (95% CI 28-41). Four studies provided an estimate based on objective measurements, which were statistically homogeneous (p = 0.23), with a pooled prevalence estimate of 82% (95% CI 77-87). In controls the pooled subjective prevalence was 9% (95% CI 2-17), while the pooled objective prevalence was 23% (95% CI 13-32). The pooled relative risk was 3.2 for both subjective outcomes (95% CI 2.32-4.41) and objective outcomes (95% CI 2.08-4.98). Clinical heterogeneity between studies was chiefly explained by differences in disease severity. Subjective dysphagia occurs in one third of community-dwelling PD patients. Objectively measured dysphagia rates were much higher, with 4 out of 5 patients being affected. This suggests that dysphagia is common in PD, but patients do not always report swallowing difficulties unless asked. This underreporting calls for a proactive clinical approach to dysphagia, particularly in light of the serious clinical consequences. Copyright © 2011 Elsevier Ltd. All rights reserved.

Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis.

PubMed

Sankaran, Sharanya J; Xiao, Amy Y; Wu, Landy M; Windsor, John A; Forsmark, Christopher E; Petrov, Maxim S

2015-11-01

Acute pancreatitis (AP) and chronic pancreatitis (CP) traditionally have been thought to be distinct diseases, but there is evidence that AP can progress to CP. Little is known about the mechanisms of pancreatitis progression. We performed a meta-analysis to quantify the frequency of transition of AP to CP and identify risk factors for progression. We searched PubMed, Scopus, and Embase for studies of patients with AP who developed CP, published from 1966 through November 2014. Pooled prevalence and 95% confidence intervals (CIs) were calculated for these outcomes, and sensitivity, subgroup, and meta-regression analyses were conducted. We analyzed 14 studies, which included a total of 8492 patients. The pooled prevalence of recurrent AP was 22% (95% CI, 18%-26%), and the pooled prevalence of CP was 10% (95% CI, 6%-15%). Sensitivity analyses yielded a pooled prevalence of CP of 10% (95% CI, 4%-19%) and 36% (95% CI, 20%-53%) in patients after the first occurrence and recurrent AP, respectively. Subgroup analyses found alcohol use and smoking to be the largest risk factors for the development of CP, with pooled prevalence values of 65% (95% CI, 48%-56%) and 61% (95% CI, 47%-73%), respectively. Meta-regression analysis found that men were more likely than women to transition from AP to CP. Ten percent of patients with a first episode of AP and 36% of patients with recurrent AP develop CP; the risk is higher among smokers, alcoholics, and men. Prospective clinical studies are needed to study pancreatitis progression. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of Pilates-based exercises on pain and disability in individuals with persistent nonspecific low back pain: a systematic review with meta-analysis.

PubMed

Lim, Edwin Choon Wyn; Poh, Ruby Li Choo; Low, Ai Ying; Wong, Wai Pong

2011-02-01

A systematic review with meta-analysis. To compare pain and disability in individuals with persistent nonspecific low back pain who were treated with Pilates exercises compared to minimal or other interventions. Searches of Medline, CINAHL, Embase, Cochrane library, PEDro, and ProQuest Dissertations and Thesis databases were conducted. Randomized controlled trials (RCTs) were selected and reviewed if they compared pain and disability in individuals with persistent nonspecific low back pain who were treated with Pilates exercises compared to other treatment approaches. Quality of the trials was evaluated. Data for pain and disability scores were extracted. Narrative synthesis plus meta-analyses were performed, with either a fixed-effects or random-effects model, standardized mean differences (SMDs), and tests for heterogeneity. Seven RCTs were identified and included in the meta-analyses. Data pooling was performed using RevMan 5. When compared to minimal intervention, Pilates-based exercise provided superior pain relief (pooled SMD, -2.72; 95% CI: -5.33, -0.11; P = .04) but the pooled disability scores were not significantly different (pooled SMD, -0.74; 95% CI: -1.81, 0.33;P = .17). No significant differences were found when comparing Pilates-based exercise to other forms of exercise for pain (pooled SMD, 0.03; 95% CI: -0.52, 0.58; P = .92) or disability scores (pooled SMD, -0.41; 95% CI: -0.96, 0.14; P = .14). Pilates-based exercises are superior to minimal intervention for pain relief. Existing evidence does not establish superiority of Pilates-based exercise to other forms of exercise to reduce pain and disability for patients with persistent nonspecific low back pain. However, the relatively low quality of existing studies and the heterogeneity of pooled studies in this systematic review combine to suggest that these results should be interpreted with caution. Therapy, level 1a.

Collaborative palliative care for advanced heart failure: outcomes and costs from the 'Better Together' pilot study.

PubMed

Pattenden, Jill F; Mason, Anne R; Lewin, R J P

2013-03-01

Patients with heart failure often receive little supportive or palliative care. 'Better Together' was a 2-year pilot study of a palliative care service for patients with advanced congestive heart failure (CHF). To determine if the intervention made it more likely that patients would be cared for and die in their place of choice, and to investigate its cost-effectiveness. This pragmatic non-randomised pilot evaluation was set in two English primary care trusts (Bradford and Poole). Prospective patient-level data on outcomes and costs were compared with data from a historical control group of clinically comparable patients. Outcomes included death in preferred place of care (available only for the intervention group) and 'hospital admissions averted'. Costs included medical procedures, inpatient care and the direct cost of providing the intervention. 99 patients were referred. Median survival from referral was 48 days in Bradford and 31 days in Poole. Most patients who died did so in their preferred place of death (Bradford 70%, Poole 77%). An estimated 14 and 18 hospital admissions for heart failure were averted in Bradford and Poole, respectively. The average cost-per-heart failure admission averted was £1529 in Bradford, but the intervention was cost saving in Poole. However, there was considerable uncertainty around these cost-effectiveness estimates. This pilot study provides tentative evidence that a collaborative home-based palliative care service for patients with advanced CHF may increase the likelihood of death in place of choice and reduce inpatient admissions. These findings require confirmation using a more robust methodological framework.

Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.

PubMed

Rudd, G D; Haverkamp, W; Mason, J W; Wenger, T; Jay, G; Hebert, D; Doty, P; Horstmann, R

2015-11-01

To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS). Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS. Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine. Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

RAS mutation prevalence among patients with metastatic colorectal cancer: a meta-analysis of real-world data.

PubMed

Kafatos, George; Niepel, Daniela; Lowe, Kimberley; Jenkins-Anderson, Sophie; Westhead, Hal; Garawin, Tamer; Traugottová, Zuzana; Bilalis, Antonios; Molnar, Edit; Timar, Jozsef; Toth, Erika; Gouvas, Nikolaos; Papaxoinis, George; Murray, Samuel; Mokhtar, Nadia; Vosmikova, Hana; Fabian, Pavel; Skalova, Alena; Wójcik, Piotr; Tysarowski, Andrzej; Barugel, Mario; van Krieken, J Han; Trojan, Jörg

2017-07-27

A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

Organ donation in trauma victims: A systematic review and meta-analysis.

PubMed

Cameron, Adam; Erdogan, Mete; Lanteigne, Sara; Hetherington, Alexandra; Green, Robert S

2018-06-01

Although trauma patients represent a large pool of potential organ donors (PODs), the donor conversion rates (DCRs) in this population are unclear. Our primary objective was to synthesize published evidence on DCRs in trauma patients. As a secondary objective, we investigated factors that affect organ donation (OD) in the trauma population. We searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) and gray literature for articles on OD in trauma patients (PROSPERO 2017: CRD42017070388). Articles were excluded if it was not possible to calculate the DCR (actual organ donors divided by PODs). We pooled DCRs and performed subgroups analysis by trauma subpopulation, patients' age, and study publication date. We identified 27 articles with a total of 123,142 participants. Cohorts ranged in size from 28 to 120,512 patients (median, 132), with most studies performed in the United States. Conversion rates among individual studies ranged from 14.0% to 75.2% (median, 49.3%). All 27 studies were included in the meta-analysis. We found a pooled DCR of 48.1% using the random effects model. There was a high level of heterogeneity between studies (I = 97.4%). Upon subgroup analysis, we found DCRs were higher in head trauma patients compared with traumatic cardiac arrest patients (45.3% vs 20.9%, p < 0.001), in pediatric patients compared with adults (61.0% vs 38.0%, p = 0.018), and in studies published after 2007 compared with those published before (50.8% vs 43.9%, p < 0.001). Few studies assessed for factors associated with OD in trauma patients. We found variation in DCRs among trauma patients (range, 14.0-75.2%) and estimated a pooled DCR of 48.1%. Our results are limited by heterogeneity across studies, which may be attributable to differences in study design and population, definitions of a POD, and in the institutional criteria and processes regarding OD. Systematic reviews and meta-analyses level III.

A meta-analysis of confocal laser endomicroscopy for the detection of neoplasia in patients with Barrett's esophagus.

PubMed

Xiong, Yi-Quan; Ma, Shu-Juan; Zhou, Jun-Hua; Zhong, Xue-Shan; Chen, Qing

2016-06-01

Barrett's esophagus (BE) is considered the most important risk factor for development of esophageal adenocarcinoma. Confocal laser endomicroscopy (CLE) is a recently developed technique used to diagnose neoplasia in BE. This meta-analysis was performed to assess the accuracy of CLE for diagnosis of neoplasia in BE. We searched EMBASE, PubMed, Cochrane Library, and Web of Science to identify relevant studies for all articles published up to June 27, 2015 in English. The quality of included studies was assessed using QUADAS-2. Per-patient and per-lesion pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (CIs) were calculated. In total, 14 studies were included in the final analysis, covering 789 patients with 4047 lesions. Seven studies were included in the per-patient analysis. Pooled sensitivity and specificity were 89% (95% CI: 0.82-0.94) and 83% (95% CI: 0.78-0.86), respectively. Ten studies were included in the per-lesion analysis. Compared with the PP analysis, the corresponding pooled sensitivity declined to 77% (95% CI: 0.73-0.81) and specificity increased to 89% (95% CI: 0.87-0.90). Subgroup analysis showed that probe-based CLE (pCLE) was superior to endoscope-based CLE (eCLE) in pooled specificity [91.4% (95% CI: 89.7-92.9) vs 86.1% (95% CI: 84.3-87.8)] and AUC for the sROC (0.885 vs 0.762). Confocal laser endomicroscopy is a valid method to accurately differentiate neoplasms from non-neoplasms in BE. It can be applied to BE surveillance and early diagnosis of esophageal adenocarcinoma. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Transnasal endoscopic evaluation of swallowing: a bedside technique to evaluate ability to swallow pureed diets in elderly patients with dysphagia.

PubMed

Sakamoto, Torao; Horiuchi, Akira; Nakayama, Yoshiko

2013-08-01

Endoscopic evaluation of swallowing (EES) is not commonly used by gastroenterologists to evaluate swallowing in patients with dysphagia. To use transnasal endoscopy to identify factors predicting successful or failed swallowing of pureed foods in elderly patients with dysphagia. EES of pureed foods was performed by a gastroenterologist using a small-calibre transnasal endoscope. Factors related to successful versus unsuccessful swallowing of pureed foods were analyzed with regard to age, comorbid diseases, swallowing activity, saliva pooling, vallecular residues, pharyngeal residues and airway penetration⁄aspiration. Unsuccessful swallowing was defined in patients who could not eat pureed foods at bedside during hospitalization. Logistic regression analysis was used to identify independent predictors of swallowing of pureed foods. During a six-year period, 458 consecutive patients (mean age 80 years [range 39 to 97 years]) were considered for the study, including 285 (62%) men. Saliva pooling, vallecular residues, pharyngeal residues and penetration⁄aspiration were found in 240 (52%), 73 (16%), 226 (49%) and 232 patients (51%), respectively. Overall, 247 patients (54%) failed to swallow pureed foods. Multivariate logistic regression analysis demonstrated that the presence of pharyngeal residues (OR 6.0) and saliva pooling (OR 4.6) occurred significantly more frequently in patients who failed to swallow pureed foods. Pharyngeal residues and saliva pooling predicted impaired swallowing of pureed foods. Transnasal EES performed by a gastroenterologist provided a unique bedside method of assessing the ability to swallow pureed foods in elderly patients with dysphagia.

Immobilization in External Rotation Versus Internal Rotation After Primary Anterior Shoulder Dislocation: A Meta-analysis of Randomized Controlled Trials.

PubMed

Whelan, Daniel B; Kletke, Stephanie N; Schemitsch, Geoffrey; Chahal, Jaskarndip

2016-02-01

The recurrence rate after primary anterior shoulder dislocation is high, especially in young, active individuals. Recent studies have suggested external rotation immobilization as a method to reduce the rate of recurrent shoulder dislocation in comparison to traditional sling immobilization. To assess and summarize evidence from randomized controlled trials on the effect of internal rotation versus external rotation immobilization on the rate of recurrence after primary anterior shoulder dislocation. Meta-analysis. PubMed, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and abstracts from recent proceedings were searched for eligible studies. Two reviewers selected studies for inclusion, assessed methodological quality, and extracted data. Six randomized controlled trials (632 patients) were included in this review. Demographic and prognostic variables measured at baseline were similar in the pooled groups. The average age was 30.1 years in the pooled external rotation group and 30.3 years in the pooled internal rotation group. Two studies found that external rotation immobilization reduced the rate of recurrence after initial anterior shoulder dislocation compared with conventional internal rotation immobilization, whereas 4 studies failed to find a significant difference between the 2 groups. This meta-analysis suggested no overall significant difference in the rate of recurrence among patients treated with internal rotation versus external rotation immobilization (risk ratio, 0.69; 95% CI, 0.42-1.14; P = .15). There was no significant difference in the rate of compliance between internal and external rotation immobilization (P = .43). The Western Ontario Shoulder Instability Index scores were pooled across 3 studies, and there was no significant difference between the 2 groups (P = .54). Immobilization in external rotation is not significantly more effective in reducing the recurrence rate after primary anterior shoulder dislocation than immobilization in internal rotation. Additionally, this review suggests that there is minimal difference in patients' perceptions of their health-related quality of life after immobilization in internal versus external rotation. © 2015 The Author(s).

The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis

PubMed Central

Miravitlles, Marc; Chapman, Kenneth R; Chuecos, Ferran; Ribera, Anna; Gil, Esther Garcia

2016-01-01

Background Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life. This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status. Methods Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7. Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate. Results Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male). In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05). Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients. Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05). Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001). In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05). The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients. Conclusion Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used. Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms. PMID:27621610

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

PubMed

Tang, Xingxing; Du, Peng; Yang, Yong

2017-10-01

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

Identifying sexual orientation health disparities in adolescents: analysis of pooled data from the Youth Risk Behavior Survey, 2005 and 2007.

PubMed

Mustanski, Brian; Van Wagenen, Aimee; Birkett, Michelle; Eyster, Sandra; Corliss, Heather L

2014-02-01

We studied sexual orientation disparities in health outcomes among US adolescents by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and 2007 for 14 jurisdictions. Here we describe the methodology for pooling and analyzing these data sets. Sexual orientation-related items assessed sexual orientation identity, gender of sexual contacts, sexual attractions, and harassment regarding sexual orientation. Wording of items varied across jurisdictions, so we created parallel variables and composite sexual minority variables. We used a variety of statistical approaches to address issues with the analysis of pooled data and to meet the aims of individual articles, which focused on a range of health outcomes and behaviors related to cancer, substance use, sexual health, mental health, violence, and injury.

Identifying Sexual Orientation Health Disparities in Adolescents: Analysis of Pooled Data From the Youth Risk Behavior Survey, 2005 and 2007

PubMed Central

Van Wagenen, Aimee; Birkett, Michelle; Eyster, Sandra; Corliss, Heather L.

2014-01-01

We studied sexual orientation disparities in health outcomes among US adolescents by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and 2007 for 14 jurisdictions. Here we describe the methodology for pooling and analyzing these data sets. Sexual orientation–related items assessed sexual orientation identity, gender of sexual contacts, sexual attractions, and harassment regarding sexual orientation. Wording of items varied across jurisdictions, so we created parallel variables and composite sexual minority variables. We used a variety of statistical approaches to address issues with the analysis of pooled data and to meet the aims of individual articles, which focused on a range of health outcomes and behaviors related to cancer, substance use, sexual health, mental health, violence, and injury. PMID:24328640

Liposomal bupivacaine versus traditional bupivacaine for pain control after total hip arthroplasty

PubMed Central

Ma, Ting-Ting; Wang, Yu-Hui; Jiang, Yun-Feng; Peng, Cong-Bin; Yan, Chao; Liu, Zi-Gui; Xu, Wei-Xing

2017-01-01

Abstract Background: In the past, the efficacy of local infiltration of liposomal bupivacaine for total hip arthroplasty (THA) patients was in debate. Therefore, this meta-analysis was conducted to determine whether local infiltration of liposomal bupivacaine provides better pain relief after THA. Methods: We searched Web of Science, PubMed, Embase, and the Cochrane Library databases to the April 2017. Any studies comparing liposomal bupivacaine and traditional bupivacaine were included in our meta-analysis. The outcomes included visual analog scale (VAS) at 24, 48, and 72 hours, total morphine consumption at 24 hours, and the length of hospital stay. We assessed the pooled data using a random-effect model. Results: Six studies were finally included in this meta-analysis. Our pooled data analysis demonstrated that liposomal bupivacaine was more effective than the traditional bupivacaine in terms of VAS at 24 hours (P  =  .018) and the length of hospital stay (P  =  .000). There was no significant difference in terms of the VAS at 48 and 72 hours and total morphine consumption at 24 hours (P >.05). Conclusion: Compared with the traditional bupivacaine, liposomal bupivacaine shows better pain control at 24 hours and reduces the length of hospital stay after THA. Its economic costs must be assessed in multimodal center randomized controlled trials when being recommended as a long-acting alternative analgesic agent for a THA patient. PMID:28640101

Chronic disease management interventions for people with chronic kidney disease in primary care: a systematic review and meta-analysis.

PubMed

Galbraith, Lauren; Jacobs, Casey; Hemmelgarn, Brenda R; Donald, Maoliosa; Manns, Braden J; Jun, Min

2018-01-01

Primary care providers manage the majority of patients with chronic kidney disease (CKD), although the most effective chronic disease management (CDM) strategies for these patients are unknown. We assessed the efficacy of CDM interventions used by primary care providers managing patients with CKD. The Medline, Embase and Cochrane Central databases were systematically searched (inception to November 2014) for randomized controlled trials (RCTs) assessing education-based and computer-assisted CDM interventions targeting primary care providers managing patients with CKD in the community. The efficacy of CDM interventions was assessed using quality indicators [use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), proteinuria measurement and achievement of blood pressure (BP) targets] and clinical outcomes (change in BP and glomerular filtration rate). Two independent reviewers evaluated studies for inclusion, quality and extracted data. Random effects models were used to estimate pooled odds ratios (ORs) and weighted mean differences for outcomes of interest. Five studies (188 clinics; 494 physicians; 42 852 patients with CKD) were included. Two studies compared computer-assisted intervention strategies with usual care, two studies compared education-based intervention strategies with computer-assisted intervention strategies and one study compared both these intervention strategies with usual care. Compared with usual care, computer-assisted CDM interventions did not increase the likelihood of ACEI/ARB use among patients with CKD {pooled OR 1.00 [95% confidence interval (CI) 0.83-1.21]; I2 = 0.0%}. Similarly, education-related CDM interventions did not increase the likelihood of ACEI/ARB use compared with computer-assisted CDM interventions [pooled OR 1.12 (95% CI 0.77-1.64); I2 = 0.0%]. Inconsistencies in reporting methods limited further pooling of data. To date, there have been very few randomized trials testing CDM interventions targeting primary care providers with the goal of improving care of people with CKD. Those conducted to date have shown minimal impact, suggesting that other strategies, or multifaceted interventions, may be required to enhance care for patients with CKD in the community. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

PubMed

Gracie, David J; Irvine, Andrew J; Sood, Ruchit; Mikocka-Walus, Antonina; Hamlin, P John; Ford, Alexander C

2017-03-01

Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I 2 =50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I 2 =0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I 2 =42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I 2 =0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I 2 =22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease)

PubMed Central

Ondo, William G.; Grieger, Frank; Moran, Kimberly; Kohnen, Ralf; Roth, Thomas

2016-01-01

Study Objectives: Determine the minimal clinically important change (MCIC), a measure determining the minimum change in scale score perceived as clinically beneficial, for the international restless legs syndrome (IRLS) and restless legs syndrome 6-item questionnaire (RLS-6) in patients with moderate to severe restless legs syndrome (RLS/Willis-Ekbom disease) treated with the rotigotine transdermal system. Methods: This post hoc analysis analyzed data from two 6-mo randomized, double-blind, placebo-controlled studies (SP790 [NCT00136045]; SP792 [NCT00135993]) individually and as a pooled analysis in rotigotine-treated patients, with baseline and end of maintenance IRLS and Clinical Global Impressions of change (CGI Item 2) scores available for analysis. An anchor-based approach and receiver operating characteristic (ROC) curves were used to determine the MCIC for the IRLS and RLS-6. We specifically compared “much improved vs minimally improved,” “much improved/very much improved vs minimally improved or worse,” and “minimally improved or better vs no change or worse” on the CGI-2 using the full analysis set (data as observed). Results: The MCIC IRLS cut-off scores for SP790 and SP792 were similar. Using the pooled SP790+SP792 analysis, the MCIC total IRLS cut-off score (sensitivity, specificity) for “much improved vs minimally improved” was −9 (0.69, 0.66), for “much improved/very much improved vs minimally improved or worse” was −11 (0.81, 0.84), and for “minimally improved or better vs no change or worse” was −9 (0.79, 0.88). MCIC ROC cut-offs were also calculated for each RLS-6 item. Conclusions: In patients with RLS, the MCIC values derived in the current analysis provide a basis for defining meaningful clinical improvement based on changes in the IRLS and RLS-6 following treatment with rotigotine. Citation: Ondo WG, Grieger F, Moran K, Kohnen R, Roth T. Post hoc analysis of data from two clinical trials evaluating the minimal clinically important change in international restless legs syndrome sum score in patients with restless legs syndrome (Willis-Ekbom Disease). J Clin Sleep Med 2016;12(1):63–70. PMID:26446245

Implantable cardioverter defibrillators for primary prevention in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

PubMed

Akel, Tamer; Lafferty, James

2017-06-01

Implantable cardioverter defibrillators (ICDs) have proved their favorable outcomes on survival in selected patients with cardiomyopathy. Although previous meta-analyses have shown benefit for their use in primary prevention, the evidence remains less robust for patients with nonischemic cardiomyopathy (NICM) in comparison to patients with coronary artery disease (CAD). To evaluate the effect of ICD therapy on reducing all-cause mortality and sudden cardiac death (SCD) in patients with NICM. PubMed (1993-2016), the Cochrane Central Register of Controlled Trials (2000-2016), reference lists of relevant articles, and previous meta-analyses. Search terms included defibrillator, heart failure, cardiomyopathy, randomized controlled trials, and clinical trials. Eligible trials were randomized controlled trials with at least an arm of ICD, an arm of medical therapy and enrolled some patients with NICM. The primary endpoint in the trials should include all-cause mortality or mortality from SCD. Hazard ratios (HRs) for all-cause mortality and mortality from SCD were either extracted or calculated along with their standard errors. Of the 1047 abstracts retained by the initial screen, eight randomized controlled trials were identified. Five of these trials reported relevant data regarding patients with NICM and were subsequently included in this meta-analysis. Pooled analysis of HRs suggested a statistically significant reduction in all-cause mortality among a total of 2573 patients randomized to ICD vs medical therapy (HR 0.80; 95% CI, 0.67-0.96; P=.02). Pooled analysis of HRs for mortality from SCD was also statistically significant (n=1677) (HR 0.51; 95% CI, 0.34-0.76; P=.001). ICD implantation is beneficial in terms of all-cause mortality and mortality from SCD in certain subgroups of patients with NICM. © 2017 John Wiley & Sons Ltd.

Clinical outcomes in middle cerebral artery trunk occlusions versus secondary division occlusions after mechanical thrombectomy: pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials.

PubMed

Shi, Zhong-Song; Loh, Yince; Walker, Gary; Duckwiler, Gary R

2010-05-01

The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

PubMed

Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta-Analysis of Randomized Trials.

PubMed

Campbell, Bruce C V; Hill, Michael D; Rubiera, Marta; Menon, Bijoy K; Demchuk, Andrew; Donnan, Geoffrey A; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M; Stouch, Bruce C; Mitchell, Peter J; Jovin, Tudor G; Saver, Jeffrey L; Goyal, Mayank

2016-03-01

Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality. The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. © 2016 The Authors.

Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer.

PubMed

Shi, Bing; Zhang, Xiu-Bing; Xu, Jian; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treating patients with non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib-based regimens with regard to response and safety for patients with NSCLC were identified using a predefined search strategy. Pooled response rates of treatment were calculated. With icotinib-based regimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible for inclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985) with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinib-based regimens. This evidence based analysis suggests that icotinib based regimens are associated with mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.

Behavior of R-Square for Pooled Data Sets.

ERIC Educational Resources Information Center

Adams, Arthur J.; Shiffler, Ronald E.

1989-01-01

New methods of analysis--equations and graphs for iso-r(sup 2) contours--were introduced and used to illustrate location effects for pooled data sets. The "r(sup 2)" is the coefficient of determination. Results are used to highlight imprecise statements in the literature about the behavior of the correlation coefficient for pooled data…

Role of D-dimer in the Development of Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis

PubMed Central

Dai, Junna; Qi, Xingshun; Li, Hongyu; Guo, Xiaozhong

2015-01-01

Background and Aims: A meta-analysis was performed to explore the role of the D-dimer in the development of portal vein thrombosis (PVT) in liver cirrhosis. Methods: All papers were searched via PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang, and VIP databases. A standardized mean difference (SMD) with 95% confidence interval (CI) was pooled. Results: Overall, 284 studies were initially identified, of which 21 were included. Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT (pooled SMD = 1.249, 95%CI = 0.740–1.758). After the portal hypertension-related surgery, cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT (pooled SMD = 0.820, 95%CI = −0.122–0.286), but a higher postoperative value of D-dimer concentration than those without PVT (pooled SMD = 2.505, 95%CI = 0.975–4.036). Notably, the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT (pooled SMD = 0.137, 95%CI = −0.827–1.101), but that at the 7th post-operative day was higher in cirrhotic patients with PVT than in those without PVT (pooled SMD = 1.224, 95%CI = 0.277–2.171). Conclusion: D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis. In addition, postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension-related surgery. PMID:26021776

Multiple effects of probiotics on different types of diabetes: a systematic review and meta-analysis of randomized, placebo-controlled trials.

PubMed

Wang, Xia; Juan, Qi-Fang; He, Yu-Wei; Zhuang, Li; Fang, Yuan-Yuan; Wang, Yong-Hong

2017-05-24

A systematic review and meta-analysis was designed to evaluate the effect of probiotics on diabetes and its associated risk factors. We systematically searched the Cochrane Library, PubMed, EMBASE and Web of Science to June 2016. We also hand-searched the citation lists of included studies and previously identified systematic reviews to identify further relevant trials. Our primary outcome variables included glucose, glycated hemoglobin (HbA1c) and insulin. The pooled standardized mean difference was used to compare the effect between the probiotics and controlled groups, and the pooled standardized mean difference effect size with a 95% confidence interval (CI) was estimated using a random-effect model. Heterogeneity was assessed with Cochran's Q and Higgins I2 tests. Two reviewers assessed trial quality and extracted data independently. The analysis and bias for each included study was performed and assessed using Review Manager 5.2. Eighteen randomized, placebo-controlled studies (n=1056 participants, 527 consuming probiotics, 529 not consuming probiotics) were included for analysis. Comparing the probiotics groups with the control groups, there were statistically significant pooled standardized mean differences on the reduction of glucose (-0.61, 95% CI -0.98, -0.24; p=0.001), insulin (-0.49, 95% CI -0.93, -0.04; p=0.03) and HbA1c (-0.39, 95% CI -0.60, -0.19%; p=0.0001). Subgroup analysis also indicated statistical significance on the reduction of low-density lipoprotein cholesterol (LDL-C) in non-type 2 diabetes (non-T2DM) mellitus patients with diabetes, for the pooled standardized mean difference was -0.29 (95% CI -0.54, -0.04; p=0.02). Probiotics may have beneficial effects on the reduction of glucose, insulin and HbA1c for diabetes, especially for T2DM mellitus patients.

A clinical study and meta-analysis of carotid stenosis with coexistent intracranial aneurysms.

PubMed

Yang, Ximeng; Lu, Jun; Wang, Junjie; Wang, Lijun; Qi, Peng; Hu, Shen; Chen, Kunpeng; Wang, Daming

2018-06-01

Carotid stenosis (CS) and intracranial aneurysms (IAs) may concur in one person. We studied the prevalence of IAs in CS patients in our retrospectively collected database and systematically reviewed this issue. Five hundred and fifty-seven CS (≥50%) patients confirmed by DSA in our hospital from 2010-06 to 2015-06 were screened for coexistent IAs. After searching the related literatures from English and Chinese journal literature databases, a meta-analysis was performed to pool the prevalence of CS with coexistent IAs. Subgroup analyses were performed to explore the causes of heterogeneity among studies. IAs were detected in 98(17.0%) out of the 577 CS patients. 12 literatures and the present study including a total of 6965 CS patients and 446 cases with coexistent IAs. The pooled prevalence of CS with coexistent IAs was 6.3% (95%CI: 4.2-8.3%) in all the CS patients. The pooled RR for female to male CS patients to have coexistent IAs was 1.67 (95%CI: 1.34-2.08, P = 0.000). 3 studies and the present study were carried out in Asian countries with a pooled prevalence of 10.8% (95%CI: 5.3-16.3%); 6 studies in European countries with 3.0% (95%CI: 2.2-3.7%); and 3 studies in USA with 6.0% (95%CI: 2.2-9.7%). There was a statistically significant difference between the three subgroups (P < 0.001). The prevalence of IAs in CS patients seems higher in our clinical study and the meta-analysis than in the general population and previously reported. The eastern and the women CS patients have a higher risk for coexistent IAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication: a systematic review and meta-analysis of randomized-controlled trials.

PubMed

Sachdeva, Aarti; Nagpal, Jitender

2009-01-01

To evaluate the effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication. Systematic review of randomized controlled trials. Electronic databases and hand search of reviews, bibliographies of books and abstracts and proceedings of international conferences. Included trials had to be randomized or quasi-randomized and controlled, using fermented milk-based probiotics in the intervention group, treating Helicobacter-infected patients and evaluating improvement or eradication of H. pylori as an outcome. The search identified 10 eligible randomized controlled trials. Data were available for 963 patients, of whom 498 were in the treatment group and 465 in the control group. The pooled odds ratio (studies n=9) for eradication by intention-to-treat analysis in the treatment versus control group was 1.91 (1.38-2.67; P<0.0001) using the fixed effects model; test for heterogeneity (Cochran's Q=5.44; P=0.488). The pooled risk difference was 0.10 (95% CI 0.05-0.15; P<0.0001) by the fixed effects model (Cochran's Q=13.41; P=0.144). The pooled odds ratio for the number of patients with any adverse effect was 0.51 (95% CI 0.10-2.57; P=0.41; random effects model; heterogeneity by Cochran's Q=68.5; P<0.0001). Fermented milk-based probiotic preparations improve H. pylori eradication rates by approximately 5-15%, whereas the effect on adverse effects is heterogeneous.

Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis.

PubMed

Cohen, Stephen M; Vogel, Jon D; Marcet, Jorge E; Candiotti, Keith A

2014-01-01

Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

Population pharmacokinetic drug–drug interaction pooled analysis of existing data for rifabutin and HIV PIs

PubMed Central

Hennig, Stefanie; Svensson, Elin M.; Niebecker, Ronald; Fourie, P. Bernard; Weiner, Marc H.; Bonora, Stefano; Peloquin, Charles A.; Gallicano, Keith; Flexner, Charles; Pym, Alex; Vis, Peter; Olliaro, Piero L.; McIlleron, Helen; Karlsson, Mats O.

2016-01-01

Objectives Extensive but fragmented data from existing studies were used to describe the drug–drug interaction between rifabutin and HIV PIs and predict doses achieving recommended therapeutic exposure for rifabutin in patients with HIV-associated TB, with concurrently administered PIs. Methods Individual-level data from 13 published studies were pooled and a population analysis approach was used to develop a pharmacokinetic model for rifabutin, its main active metabolite 25-O-desacetyl rifabutin (des-rifabutin) and drug–drug interaction with PIs in healthy volunteers and patients who had HIV and TB (TB/HIV). Results Key parameters of rifabutin affected by drug–drug interaction in TB/HIV were clearance to routes other than des-rifabutin (reduced by 76%–100%), formation of the metabolite (increased by 224% in patients), volume of distribution (increased by 606%) and distribution to the peripheral compartment (reduced by 47%). For des-rifabutin, clearance was reduced by 35%–76% and volume of distribution increased by 67%–240% in TB/HIV. These changes resulted in overall increased exposure to rifabutin in TB/HIV patients by 210% because of the effects of PIs and 280% with ritonavir-boosted PIs. Conclusions Given together with non-boosted or ritonavir-boosted PIs, rifabutin at 150 mg once daily results in similar or higher exposure compared with rifabutin at 300 mg once daily without concomitant PIs and may achieve peak concentrations within an acceptable therapeutic range. Although 300 mg of rifabutin every 3 days with boosted PI achieves an average equivalent exposure, intermittent doses of rifamycins are not supported by current guidelines. PMID:26832753

CT colonography of colorectal polyps: a metaanalysis.

PubMed

Sosna, Jacob; Morrin, Martina M; Kruskal, Jonathan B; Lavin, Philip T; Rosen, Max P; Raptopoulos, Vassilios

2003-12-01

For proper evaluation of the accuracy of CT colonography, prospective multiinstitutional trials would be ideal. Until these trials are available, data can be collectively analyzed. The purpose of this study is to use metaanalysis to assess the reported accuracy of CT colonography compared with conventional colonoscopy for detecting colorectal polyps. Articles comparing CT colonography and conventional colonoscopy were identified, and a standardized form was used to extract relevant study data. Fisher's exact test and the Mantel-Haenszel test were used for pooling of data. A 95% confidence interval (CI) was selected to determine sensitivity and specificity, and the Kruskal-Wallis exact test was used to identify trends relating to polyp size. Meta-analysis methods were used to test strength of results. Comparisons were made for the percentage of polyps detected grouped by size (> or = 10 mm, 6-9 mm, < or = 5 mm) and the percentage of patients identified who had polyps of the same size. Fourteen studies fulfilled all the study inclusion criteria and gave a total of 1,324 patients and 1,411 polyps. The pooled per-patient sensitivity for polyps 10 mm or larger was (sensitivity [95% CI]) 0.88 (0.84-0.93), for polyps 6-9 mm it was 0.84 (0.80-0.89), and for polyps 5 mm or smaller it was 0.65 (0.57-0.73). The pooled per-polyp sensitivity for polyps 10 mm or larger was 0.81 (0.76-0.85), for polyps 6-9 mm it was 0.62 (0.58-0.67), and for polyps 5 mm or smaller it was 0.43 (0.39-0.47). Sensitivity for detection of polyps increased as the polyp size increased (p < 0.00005). The pooled overall specificity for detection of polyps larger than 10 mm was 0.95 (0.94-0.97). The specificity and sensitivity of CT colonography are high for polyps larger than 10 mm.

Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials.

PubMed

Warach, Steven; Al-Rawi, Yasir; Furlan, Anthony J; Fiebach, Jochen B; Wintermark, Max; Lindstén, Annika; Smyej, Jamal; Bharucha, David B; Pedraza, Salvador; Rowley, Howard A

2012-09-01

The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.

External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

NASA Astrophysics Data System (ADS)

Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

2009-01-01

Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

Impact of Dobutamine in Patients With Septic Shock: A Meta-Regression Analysis.

PubMed

Nadeem, Rashid; Sockanathan, Shivani; Singh, Mukesh; Hussain, Tamseela; Kent, Patrick; AbuAlreesh, Sarah

2017-05-01

Septic shock frequently requires vasopressor agents. Conflicting evidence exists for use of inotropes in patients with septic shock. Data from English studies on human adult septic shock patients were collected. A total of 83 studies were reviewed, while 11 studies with 21 data sets including 239 patients were pooled for meta-regression analysis. For VO2, pooled difference in means (PDM) was 0.274. For cardiac index (CI), PDM was 0.783. For delivery of oxygen, PDM was -0.890. For heart rate, PDM was -0.714. For left ventricle stroke work index, PDM was 0.375. For mean arterial pressure, PDM was -0.204. For mean pulmonary artery pressure, PDM was 0.085. For O2 extraction, PDM was 0.647. For PaCO2, PDM was -0.053. For PaO2, PDM was 0.282. For pulmonary artery occlusive pressure, PDM was 0.270. For pulmonary capillary wedge pressure, PDM was 0.300. For PVO2, PDM was -0.492. For right atrial pressure, PDM was 0.246. For SaO2, PDM was 0.604. For stroke volume index, PDM was 0.446. For SvO2, PDM was -0.816. For systemic vascular resistance, PDM was -0.600. For systemic vascular resistance index, PDM was 0.319. Meta-regression analysis was performed for VO2, DO2, CI, and O2 extraction. Age was found to be significant confounding factor for CI, DO2, and O2 extraction. APACHE score was not found to be a significant confounding factor for any of the parameters. Dobutamine seems to have a positive effect on cardiovascular parameters in patients with septic shock. Prospective studies with larger samples are required to further validate this observation.

Albumin in Burn Shock Resuscitation: A Meta-Analysis of Controlled Clinical Studies.

PubMed

Navickis, Roberta J; Greenhalgh, David G; Wilkes, Mahlon M

2016-01-01

Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07-0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.

Prognostic Value of MicroRNAs in Coronary Artery Diseases: A Meta-Analysis.

PubMed

Kim, Ji Suk; Pak, Kyoungjune; Goh, Tae Sik; Jeong, Dae Cheon; Han, Myoung Eun; Kim, Jihyun; Oh, Sae Ock; Kim, Chi Dae; Kim, Yun Hak

2018-06-01

Coronary artery diseases (CADs) are the leading causes of death in the world. Recent studies have reported that differentially expressed microRNAs (miRNAs) are associated with prognosis or major adverse cardiac events (MACEs) in CAD patients. In a previous meta-analysis, the authors made serious mistakes that we aimed to correct through an updated systematic review and meta-analysis of the prognostic value of altered miRNAs in patients with CADs. We performed a systematic search of MEDLINE (from inception to May 2017) and EMBASE (from inception to May 2017) for English-language publications. Studies of CADs with results on miRNAs that reported survival data or MACEs were included. Data were extracted from each publication independently by two reviewers. After reviewing 515 articles, a total eight studies were included in this study. We measured pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miRNA 133a with a fixed-effect model (pooled HR, 2.35; 95% CI, 1.56-3.55). High expression of miRNA 133a, 208b, 126, 197, 223, and 122-5p were associated with high mortality. Additionally, high levels of miRNA 208b, 499-5p, 134, 328, and 34a were related with MACEs. The present study confirmed that miRNA 133a, which was associated with high mortality in CAD patients, holds prognostic value in CAD. More importantly, this study corrected issues raised against a prior meta-analysis and provides accurate information. © Copyright: Yonsei University College of Medicine 2018.

Psoriasis increases risk of new-onset atrial fibrillation: a systematic review and meta-analysis of prospective observational studies.

PubMed

Upala, Sikarin; Shahnawaz, Afeefa; Sanguankeo, Anawin

2017-08-01

Psoriasis is a common chronic immune-mediated dermatological disease that increases the risk of cardiovascular disease. We conducted a systematic review and meta-analysis to evaluate the association between psoriasis and atrial fibrillation from prospective observational studies. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through November 2015. The inclusion criterion was the prospective observational study that assessed the risk of new-onset atrial fibrillation in adults with psoriasis. Outcome was the adjusted hazard ratio (HR) of atrial fibrillation comparison between patients with psoriasis and controls. Pooled HR and 95% confidence intervals (CI) were calculated using a random-effects model. The initial search yielded 176 articles. Fifteen articles underwent full-length review and data were extracted from 4 observational studies. Incidence of atrial fibrillation was ascertained by cardiologist-reviewed electrocardiograms. There was a significant increased risk of new-onset atrial fibrillation in patients with psoriasis compared to controls with a pooled HR 1.42 (95%CI 1.22-1.65). Our meta-analysis of prospective studies demonstrated that patients with psoriasis have increased risk of new-onset atrial fibrillation. Future interventional studies addressing the impact of psoriasis treatment and prevention of atrial fibrillation should be performed.

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.

PubMed

Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

2015-05-01

Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT. Copyright © 2015 Elsevier Inc. All rights reserved.

Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk; Gniadecki, Robert; Iversen, Lars

2015-05-01

Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gymore » in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.« less

Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis.

PubMed

Kamal, Faisal; Khan, Muhammad Ali; Khan, Zubair; Cholankeril, George; Hammad, Tariq A; Lee, Wade M; Ahmed, Aijaz; Waters, Bradford; Howden, Colin W; Nair, Satheesh; Satapathy, Sanjaya K

2017-10-01

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus.

PubMed

Hirshberg, Boaz; Parker, Artist; Edelberg, Helen; Donovan, Mark; Iqbal, Nayyar

2014-10-01

A post hoc pooled analysis was undertaken to evaluate the safety of saxagliptin in patients with type 2 diabetes mellitus, with attention to events of special interest for dipeptidyl peptidase-4 inhibitors. Pooled analyses were performed for 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy, and a subset of 11 saxagliptin + metformin studies. Adverse events and events of special interest (gastrointestinal adverse events, infections, hypersensitivity, pancreatitis, skin lesions, lymphopenia, thrombocytopenia, hypoglycaemia, bone fracture, severe cutaneous adverse reactions, opportunistic infection, angioedema, malignancy, worsening renal function, and specific laboratory events) were assessed; incidence rates (events/100 person-years) and incidence rates ratios (saxagliptin/control) were calculated (Mantel-Haenszel method). In both pooled datasets, the incidence rates for deaths, serious adverse events, discontinuations due to adverse events, pancreatitis, malignancy, and most other events of special interest, excepting bone fractures and hypersensitivity, were similar between treatments, with 95% confidence intervals (CIs) for incidence rates ratios including 1. In the 20-study pool, the incidence rates per 100 person-years was higher with saxagliptin versus control for bone fractures [1.1 vs 0.6; incidence rates ratio (95% CI), 1.81 (1.04-3.28)] and hypersensitivity adverse events [1.3 vs 0.8; 1.67 (1.01-2.87)]. Pooled data from 20 studies confirm that saxagliptin has a favourable safety and benefit-risk profile. Copyright © 2013 John Wiley & Sons, Ltd.

Circulating human papillomavirus DNA as a surveillance tool in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

PubMed

Jensen, Kristina Kvist; Grønhøj, Christian; Jensen, David H; von Buchwald, Christian

2018-05-15

The incidence of human papillomavirus-induced (HPV+) head and neck squamous cell carcinoma (HNSCC) i.e. especially oropharyngeal cancers (OPSCC) is increasing and a significant proportion of patients encounter disease progression. A simple and sensitive test to identify patients with progression is an unmet need. To systematically review the literature and carry out a meta-analysis of studies, investigated circulating HPV-DNA as a biomarker for disease progression in patients with HNSCC. A systematic review and meta-analysis. PubMed, Embase and the Cochrane Library were systematically searched for articles published in English from January 1980 to November 2017. Search terms used were related to HPV, cancer sites, blood-based biomarkers and terms for specific use settings. Articles reviewed and selected by authors and data on study design, demographic variables, location, HPV status, number of pre treatment blood tests, number of post treatment blood tests, blood HPV status and number of recurrences and length of follow-up was extracted. A meta-analysis of HPV-DNA as a diagnostic test for recurrence by means of a hierarchical summary receiver operating curve (HSROC) model was performed. We identified five studies (n=600 subjects) examining circulating HPV-DNA in patients with HNSCC. In these five studies (n=411) patients had both pre and post treatment blood samples. The pooled sensitivity, in detecting a recurrence was estimated to be 54% (95% CI: 32%-74%), while the pooled specificity was 98% (95% CI: 93-99.4%). The pooled false-positive rate is 2% (95% CI: 0.6%-7%). The area under the curve (AUC) of the summary HSROC was 0.93. Positive predictive value was estimated to 93% and the negative predictive value to 94%. Plasma HPV-DNA is a promising tool for surveillance in patients with HPV-related HNSCC i.e. OPSCC and has a high specificity. By recent technical advances and by increasing follow-up blood samples the sensitivity could likely be improved. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Balneotherapy for osteoarthritis. A cochrane review.

PubMed

Verhagen, Arianne; Bierma-Zeinstra, Sita; Lambeck, Johan; Cardoso, Jefferson Rosa; de Bie, Rob; Boers, Maarten; de Vet, Henrica C W

2008-06-01

Balneotherapy (or spa therapy, mineral baths) for patients with arthritis is one of the oldest forms of therapy. We assessed effectiveness of balneotherapy for patients with osteoarthritis (OA). We performed a broad search strategy to retrieve eligible studies, selecting randomized controlled trials comparing balneotherapy with any intervention or with no intervention. Two authors independently assessed quality and extracted data. Disagreements were solved by consensus. In the event of clinical heterogeneity or lack of data we refrained from statistical pooling. Seven trials (498 patients) were included in this review: one performed an intention-to-treat analysis, 2 provided data for our own analysis, and one reported a "quality of life" outcome. We found silver-level evidence of mineral baths compared to no treatment (effect sizes 0.34-1.82). Adverse events were not measured or found in included trials. We found silver-level evidence concerning the beneficial effects of mineral baths compared to no treatment. Of all other balneological treatments, no clear effects were found. However, the scientific evidence is weak because of the poor methodological quality and the absence of an adequate statistical analysis and data presentation.

Incorporating nurse absenteeism into staffing with demand uncertainty.

PubMed

Maass, Kayse Lee; Liu, Boying; Daskin, Mark S; Duck, Mary; Wang, Zhehui; Mwenesi, Rama; Schapiro, Hannah

2017-03-01

Increased nurse-to-patient ratios are associated negatively with increased costs and positively with improved patient care and reduced nurse burnout rates. Thus, it is critical from a cost, patient safety, and nurse satisfaction perspective that nurses be utilized efficiently and effectively. To address this, we propose a stochastic programming formulation for nurse staffing that accounts for variability in the patient census and nurse absenteeism, day-to-day correlations among the patient census levels, and costs associated with three different classes of nursing personnel: unit, pool, and temporary nurses. The decisions to be made include: how many unit nurses to employ, how large a pool of cross-trained nurses to maintain, how to allocate the pool nurses on a daily basis, and how many temporary nurses to utilize daily. A genetic algorithm is developed to solve the resulting model. Preliminary results using data from a large university hospital suggest that the proposed model can save a four-unit pool hundreds of thousands of dollars annually as opposed to the crude heuristics the hospital currently employs.

Effects of lorcaserin on pre-existing valvulopathy: A pooled analysis of phase 3 trials.

PubMed

Weissman, Neil J; Smith, Steven R; Fain, Randi; Hall, Nancy; Shanahan, William R

2017-01-01

To evaluate the effects of lorcaserin in patients with pre-existing Food and Drug Administration (FDA)-defined valvulopathy. This is a pooled, post hoc analysis of three Phase 3 studies. BLOOM and BLOSSOM patients were 18 to 65 years of age without diabetes and with a body mass index (BMI) of 27 to 29.9 kg/m 2 and ≥1 weight-related comorbidity or a BMI of 30 to 45 kg/m 2 . BLOOM-DM patients had a BMI of 27 to 45 kg/m 2 and type 2 diabetes. Patients were treated with placebo, lorcaserin 10 mg once daily, or lorcaserin 10 mg twice daily. Serial echocardiographs were obtained at baseline and every 6 months. Included patients (N = 169) had FDA-defined valvulopathy at baseline and a week 52 echocardiogram. At week 52, 35.5% and 52.7% of patients experienced changes from baseline in aortic and mitral regurgitation, respectively. Numerically greater proportions of patients taking lorcaserin versus placebo had decreases in aortic (33.0% vs. 28.3%) or mitral (41.3% vs. 36.7%) regurgitation. Fewer patients taking lorcaserin versus placebo had increases in aortic (2.8% vs. 6.7%) or mitral (8.3% vs. 21.7%) regurgitation. No adverse event-related discontinuation was due to a valve problem. These data suggest that lorcaserin does not adversely affect valvular disease in patients with pre-existing FDA-defined valvulopathy. © 2016 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Amrubicin for relapsed small-cell lung cancer: a systematic review and meta-analysis of 803 patients

PubMed Central

Horita, Nobuyuki; Yamamoto, Masaki; Sato, Takashi; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Shibata, Yuji; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Kobayashi, Nobuaki; Shinkai, Masaharu; Kudo, Makoto; Kaneko, Takeshi

2016-01-01

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57–69%, I2 = 53%), 28% (95% CI 21–35%, I2 = 71%), and 10% (95% CI 6–14%, I2 = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61–78%, I2 = 83%), 36% (95% CI 28–44%, I2 = 80%), and 15% (95% CI 8–21%, I2 = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%. PMID:26750506

Does high-flow nasal cannula oxygen improve outcome in acute hypoxemic respiratory failure? A systematic review and meta-analysis.

PubMed

Lin, Si-Ming; Liu, Kai-Xiong; Lin, Zhi-Hong; Lin, Pei-Hong

2017-10-01

To evaluate the efficacy of high-flow nasal cannula (HFNC) in the rate of intubation and mortality for patients with acute hypoxemic respiratory failure. We searched Pubmed, EMBASE, and the Cochrane Library for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the rate of intubation; secondary outcome was mortality in the hospital. Study-level data were pooled using a random-effects model when I2 was >50% or a fixed-effects model when I2 was <50%. Eight randomized controlled studies with a total of 1,818patients were considered. Pooled analysis showed that no statistically significant difference was found between groups regarding the rate of intubation (odds ratio [OR] = 0.79; 95% confidence interval [CI]: 0.60-1.04; P = 0.09; I2 = 36%) and no statistically significant difference was found between groups regarding hospital mortality (OR = 0.89; 95% CI: 0.62-127; P = 0.51; I2 = 47%). The use of HFNC showed a trend toward reduction in the intubation rate, which did not meet statistical significance, in patients with acute respiratory failure compared with conventional oxygen therapy (COT) and noninvasive ventilation (NIV). Moreover no difference in mortality. So, Large, well-designed, randomized, multi-center trials are needed to confirm the effects of HFNC in acute hypoxemic respiratory failure patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of digital tomosynthesis and chest radiography for the detection of pulmonary nodules: systematic review and meta-analysis

PubMed Central

Kim, Jun H; Lee, Kyung H; Kim, Kyoung-Tae; Ahn, Hyeong S; Kim, Yeo J; Lee, Ha Y; Jeon, Yong S

2016-01-01

Objective: To compare the diagnostic accuracy of digital tomosynthesis (DTS) with that of chest radiography for the detection of pulmonary nodules by meta-analysis. Methods: A systematic literature search was performed to identify relevant original studies from 1 January 1 1976 to 31 August 31 2016. The quality of included studies was assessed by quality assessment of diagnostic accuracy studies-2. Per-patient data were used to calculate the sensitivity and specificity and per-lesion data were used to calculate the detection rate. Summary receiver-operating characteristic curves were drawn for pulmonary nodule detection. Results: 16 studies met the inclusion criteria. 1017 patients on a per-patient basis and 2159 lesions on a per-lesion basis from 16 eligible studies were evaluated. The pooled patient-based sensitivity of DTS was 0.85 [95% confidence interval (CI) 0.83–0.88] and the specificity was 0.95 (0.93–0.96). The pooled sensitivity and specificity of chest radiography were 0.47 (0.44–0.51) and 0.37 (0.34–0.40), respectively. The per-lesion detection rate was 2.90 (95% CI 2.63–3.19). Conclusion: DTS has higher diagnostic accuracy than chest radiography for detection of pulmonary nodules. Chest radiography has low sensitivity but similar specificity, comparable with that of DTS. Advances in knowledge: DTS has higher diagnostic accuracy than chest radiography for the detection of pulmonary nodules. PMID:27759428

Bayesian Analysis of Silica Exposure and Lung Cancer Using Human and Animal Studies.

PubMed

Bartell, Scott M; Hamra, Ghassan Badri; Steenland, Kyle

2017-03-01

Bayesian methods can be used to incorporate external information into epidemiologic exposure-response analyses of silica and lung cancer. We used data from a pooled mortality analysis of silica and lung cancer (n = 65,980), using untransformed and log-transformed cumulative exposure. Animal data came from chronic silica inhalation studies using rats. We conducted Bayesian analyses with informative priors based on the animal data and different cross-species extrapolation factors. We also conducted analyses with exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure. The pooled animal data exposure-response coefficient was markedly higher (log exposure) or lower (untransformed exposure) than the coefficient for the pooled human data. With 10-fold uncertainty, the animal prior had little effect on results for pooled analyses and only modest effects in some individual studies. One-fold uncertainty produced markedly different results for both pooled and individual studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and marked changes in some individual studies. The animal prior had more impact for smaller human studies and for one-fold versus three- or 10-fold uncertainty. Adjustment for Berkson error using Bayesian methods had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. See video abstract at, http://links.lww.com/EDE/B160.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients

PubMed Central

Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-01-01

Abstract Background: Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. Methods: A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I2) assessment was performed. Results: Six randomized controlled trials comparing 253 pediatric patients (age range, 2–18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were −7.15 (95% CI: −10.77 to −3.54; I2 = 96%; P = 0.0001) and −17.32 (95% CI: −29.31 to −5.32; I2 = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was −6.00 (95% CI: −11.46 to −0.53; I2 = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27–1.71; I2 = 59%; P = 0.41). Conclusion: We suggest that sugammadex is fast and effective in reversing rocuronium-induced NMB in pediatric patients. Although there was no evidence of a higher incidence of adverse events with sugammadex compared to that with neostigmine or placebo, much more data regarding the safety of sugammadex in pediatric patients may be still required. PMID:27559972

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

PubMed Central

Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

2013-01-01

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox.

PubMed

Hong, Soonchang; Lee, Ji Hyun; Kim, Kyung Min; Lee, Jun Won; Youn, Young Jin; Ahn, Min Soo; Ahn, Sung Gyun; Lee, Seung Hwan; Yoon, Junghan; Choe, Kyung Hoon; Yoo, Byung Su

2018-01-01

Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355-0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450-1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696-1.319) in women. In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men. © Copyright: Yonsei University College of Medicine 2018

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

PubMed

Goyal, Mayank; Menon, Bijoy K; van Zwam, Wim H; Dippel, Diederik W J; Mitchell, Peter J; Demchuk, Andrew M; Dávalos, Antoni; Majoie, Charles B L M; van der Lugt, Aad; de Miquel, Maria A; Donnan, Geoffrey A; Roos, Yvo B W E M; Bonafe, Alain; Jahan, Reza; Diener, Hans-Christoph; van den Berg, Lucie A; Levy, Elad I; Berkhemer, Olvert A; Pereira, Vitor M; Rempel, Jeremy; Millán, Mònica; Davis, Stephen M; Roy, Daniel; Thornton, John; Román, Luis San; Ribó, Marc; Beumer, Debbie; Stouch, Bruce; Brown, Scott; Campbell, Bruce C V; van Oostenbrugge, Robert J; Saver, Jeffrey L; Hill, Michael D; Jovin, Tudor G

2016-04-23

In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. Medtronic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing

PubMed Central

García-Chequer, A.J.; Méndez-Tenorio, A.; Olguín-Ruiz, G.; Sánchez-Vallejo, C.; Isa, P.; Arias, C.F.; Torres, J.; Hernández-Angeles, A.; Ramírez-Ortiz, M.A.; Lara, C.; Cabrera-Muñoz, M.L.; Sadowinski-Pine, S.; Bravo-Ortiz, J.C.; Ramón-García, G.; Diegopérez-Ramírez, J.; Ramírez-Reyes, G.; Casarrubias-Islas, R.; Ramírez, J.; Orjuela, M.A.; Ponce-Castañeda, M.V.

2016-01-01

Genes are frequently lost or gained in malignant tumors and the analysis of these changes can be informative about the underlying tumor biology. Retinoblastoma is a pediatric intraocular malignancy, and since deletions in chromosome 13 have been described in this tumor, we performed genome wide sequencing with the Illumina platform to test whether recurrent losses could be detected in low coverage data from DNA pools of Rb cases. An in silico reference profile for each pool was created from the human genome sequence GRCh37p5; a chromosome integrity score and a graphics 40 Kb window analysis approach, allowed us to identify with high resolution previously reported non random recurrent losses in all chromosomes of these tumors. We also found a pattern of gains and losses associated to clear and dark cytogenetic bands respectively. We further analyze a pool of medulloblastoma and found a more stable genomic profile and previously reported losses in this tumor. This approach facilitates identification of recurrent deletions from many patients that may be biological relevant for tumor development. PMID:26883451

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact.

PubMed

Borren, Nienke Z; Ghadermarzi, Shadi; Hutfless, Susan; Ananthakrishnan, Ashwin N

2017-01-01

Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. We systematically searched PubMed/Medline and Embase for publications from Asia between 2000-16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.

Transnasal endoscopic evaluation of swallowing: A bedside technique to evaluate ability to swallow pureed diets in elderly patients with dysphagia

PubMed Central

Sakamoto, Torao; Horiuchi, Akira; Nakayama, Yoshiko

2013-01-01

BACKGROUND: Endoscopic evaluation of swallowing (EES) is not commonly used by gastroenterologists to evaluate swallowing in patients with dysphagia. OBJECTIVE: To use transnasal endoscopy to identify factors predicting successful or failed swallowing of pureed foods in elderly patients with dysphagia. METHODS: EES of pureed foods was performed by a gastroenterologist using a small-calibre transnasal endoscope. Factors related to successful versus unsuccessful swallowing of pureed foods were analyzed with regard to age, comorbid diseases, swallowing activity, saliva pooling, vallecular residues, pharyngeal residues and airway penetration/aspiration. Unsuccessful swallowing was defined in patients who could not eat pureed foods at bedside during hospitalization. Logistic regression analysis was used to identify independent predictors of swallowing of pureed foods. RESULTS: During a six-year period, 458 consecutive patients (mean age 80 years [range 39 to 97 years]) were considered for the study, including 285 (62%) men. Saliva pooling, vallecular residues, pharyngeal residues and penetration/aspiration were found in 240 (52%), 73 (16%), 226 (49%) and 232 patients (51%), respectively. Overall, 247 patients (54%) failed to swallow pureed foods. Multivariate logistic regression analysis demonstrated that the presence of pharyngeal residues (OR 6.0) and saliva pooling (OR 4.6) occurred significantly more frequently in patients who failed to swallow pureed foods. CONCLUSIONS: Pharyngeal residues and saliva pooling predicted impaired swallowing of pureed foods. Transnasal EES performed by a gastroenterologist provided a unique bedside method of assessing the ability to swallow pureed foods in elderly patients with dysphagia. PMID:23936875

Endovascular Therapy is Effective and Safe for Patients with Severe Ischemic Stroke: Pooled Analysis of IMS III and MR CLEAN Data

PubMed Central

Broderick, Joseph P.; Berkhemer, Olvert A.; Palesch, Yuko Y.; Dippel, Diederik W.J.; Foster, Lydia D.; Roos, Yvo B.W.E.M.; van der Lugt, Aad; Tomsick, Thomas A.; Majoie, Charles B.L.M.; van Zwam, Wim H.; Demchuk, Andrew M.; van Oostenbrugge, Robert J.; Khatri, Pooja; Lingsma, Hester F.; Hill, Michael D.; Roozenbeek, Bob; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig S.; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Kit

2015-01-01

Background and Purpose We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (NIHSS ≥20) following a pre-specified analysis plan. Methods The pooled analysis of the IMS III and MR CLEAN trial included participants with an NIHSS ≥20 prior to intravenous (IV) t-PA treatment (IMS III) or randomization (MR CLEAN) who were treated with IV t-PA ≤ 3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy following IV t-PA would have improved 90-day outcome (distribution of modified Rankin scale [mRS] scores), as compared to those who received IV t-PA alone. Results Among 342 participants in the pooled analysis (194 from IMS III, 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared to the IV t-PA group (adjusted odds ratio [aOR] 1.78; 95% confidence interval [CI] 1.20-2.66). In the logistic regression model of the dichotomous outcome (mRS 0-2, or ‘functional independence’), the endovascular group had superior outcomes (aOR 1.97; 95% CI 1.09-3.56). Functional independence (mRS ≤2) at 90 days was 25% in the endovascular group as compared to 14% in the IV t-PA group. Conclusions Endovascular therapy following IV t-PA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. PMID:26486865

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

PubMed Central

Siristatidis, Charalampos; Sergentanis, Theodoros N.; Vogiatzi, Paraskevi; Kanavidis, Prodromos; Chrelias, Charalampos; Papantoniou, Nikolaos; Psaltopoulou, Theodora

2015-01-01

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS. PMID:26241855

Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies.

PubMed

Lally, John; Ajnakina, Olesya; Stubbs, Brendon; Cullinane, Michael; Murphy, Kieran C; Gaughran, Fiona; Murray, Robin M

2017-12-01

Background Remission and recovery rates for people with first-episode psychosis (FEP) remain uncertain. Aims To assess pooled prevalence rates of remission and recovery in FEP and to investigate potential moderators. Method We conducted a systematic review and meta-analysis to assess pooled prevalence rates of remission and recovery in FEP in longitudinal studies with more than 1 year of follow-up data, and conducted meta-regression analyses to investigate potential moderators. Results Seventy-nine studies were included representing 19072 patients with FEP. The pooled rate of remission among 12301 individuals with FEP was 58% (60 studies, mean follow-up 5.5 years). Higher remission rates were moderated by studies from more recent years. The pooled prevalence of recovery among 9642 individuals with FEP was 38% (35 studies, mean follow-up 7.2 years). Recovery rates were higher in North America than in other regions. Conclusions Remission and recovery rates in FEP may be more favourable than previously thought. We observed stability of recovery rates after the first 2 years, suggesting that a progressive deteriorating course of illness is not typical. Although remission rates have improved over time recovery rates have not, raising questions about the effectiveness of services in achieving improved recovery. © The Royal College of Psychiatrists 2017.

Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: A meta-analysis.

PubMed

Chen, Yan; Shi, Xiu-E; Tian, Jin-Hui; Yang, Xu-Juan; Wang, Yong-Feng; Yang, Ke-Hu

2018-05-01

Neoadjuvant chemotherapy (NAC) increases breast conservation rates in patients with resectable breast cancer at the associated cost of higher locoregional recurrence rates; however, the magnitude of the survival benefits of NAC for these patients remains undefined. Therefore, we aimed to clarify the survival benefit of NAC versus postoperative chemotherapy by conducting an updated meta-analysis of randomized clinical trials (RCTs). The authors searched the Cochrane Library, PubMed, Embase, Web of Science, Chinese biomedical literature database, and Chinese Scientific Journals full-text database from their inception to December 2016. The authors identified relevant RCTs that compared NAC with postoperative chemotherapy in the treatment of operable breast cancer. The main endpoints were overall survival (OS) and recurrence-free survival (RFS). A total of 21 citations representing 16 unique studies were eligible. There were 787 deaths among 2794 patients assigned to NAC groups and 816 deaths among 2799 patients assigned to adjuvant chemotherapy groups. A meta-analysis of data indicated that there was no significant benefit in terms of OS ([hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.94-1.13, P = .51) and RFS (HR = 1.01, 95% CI: 0.93-1.10, P = .80) between the NAC and postoperative chemotherapy groups. The pooled HR estimate for OS was not influenced by NAC cycles, the total number of chemotherapy cycles, administration of tamoxifen, administration of adjuvant chemotherapy, or type of NAC regimen. Subgroup analysis showed that the pooled HR estimate for RFS was influenced by anthracycline-containing regimens. Patients with a pathological complete response had superior survival outcomes compared with patients who had residual disease. The survival benefits for patients with operable breast cancer who received either NAC or adjuvant chemotherapy based on anthracycline regimens were comparable.

The role of SISCOM in preoperative evaluation for patients with epilepsy surgery: A meta-analysis.

PubMed

Chen, Tong; Guo, Liang

2016-10-01

To assess the specific value of subtraction ictal and inter-ictal SPECT co-registered to MRI (SISCOM) in identifying the epileptogenic zone (EZ) and predicting postoperative outcomes in epileptic surgical patients. A meta-analysis of studies published from January 1995 to June 2015 was conducted through a comprehensive literature search, and 11 studies were included. R software was first used to calculate a pooled positive rate, concordant rate and positive predictive value (PPV) for good outcomes. Stata software was then used to explore the relationship between SISCOM localization and surgical outcomes, including a subgroup analysis for extra-temporal lobe epilepsy. The unweighted positive and concordant rates of SISCOM were 85.9% and 65.3%, respectively. In 142 MRI-negative patients, the SISCOM positive rate was 83.8%. The pooled PPV of 178 surgical patients with concordant SISCOM was 56%. In the meta-analysis of 275 surgical patients, the seizure-free odds ratio was 3.28-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.90, 5.67)]. For extra-temporal lobe epilepsy, the seizure-free odds ratio was 2.44-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.34, 4.43)]. Our data indicate that SISCOM has moderate sensitivity in localizing the epileptogenic zone and can provide complementary information when MRI is negative. Furthermore, SISCOM localization concordant with the gold standard demonstrates slightly higher predictive value for good surgical outcomes. Further research is required to explore the influence of SISCOM localization results in temporal lobe versus extra-temporal lobe epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies.

PubMed

Dréno, Brigitte; Bettoli, Vincenzo; Ochsendorf, Falk; Layton, Alison M; Perez, Montserrat; Dakovic, Rada; Gollnick, Harald

2014-01-01

The efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% (Clin-RA) were evaluated in three 12-week randomised studies. To perform a pooled analysis of data from these studies to evaluate Clin-RA's efficacy and safety in a larger overall population, in subgroups of adolescents and according to acne severity. 4550 patients were randomised to Clin-RA, clindamycin, tretinoin and vehicle. Evaluations included percentage change in lesions, treatment success rate, proportions of patients with ≥50% or ≥80% continuous reduction in lesions, adverse events and cutaneous tolerability. In the overall population, the percentage reduction in inflammatory, non-inflammatory and total lesions and the treatment success rate were significantly greater with Clin-RA compared with clindamycin, tretinoin and vehicle alone (all p<0.01). The percentage reduction in all types of lesions was also significantly greater with Clin-RA in the adolescent subgroup (2915 patients, p<0.002) and in patients with mild/moderate acne (3662 patients, p<0.02) versus comparators. In patients with severe acne (n = 880), the percentage reduction in all lesion types was significantly greater with Clin-RA versus vehicle (p<0.0001). A greater proportion of Clin-RA treated patients had a ≥50% or ≥80% continuous reduction in all types of lesions at week 12 compared with clindamycin, tretinoin and vehicle. Adverse event frequencies in the active and vehicle groups were similar. Baseline-adjusted mean tolerability scores over time were <1 (mild) and similar in all groups. Clin-RA is safe, has superior efficacy to its component monotherapies and should be considered as one of the first-line therapies for mild-to-moderate facial acne.

Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data.

PubMed

D'Urzo, Anthony D; Kerwin, Edward M; Chapman, Kenneth R; Decramer, Marc; DiGiovanni, Robert; D'Andrea, Peter; Hu, Huilin; Goyal, Pankaj; Altman, Pablo

2015-01-01

Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 μg, placebo (both delivered via the Breezhaler device), or tiotropium 18 μg (delivered via the HandiHaler device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated. The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data. The overall safety profile of glycopyrronium was similar to its comparators indicating no increase in the overall risk for any of the investigated safety end points.

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data.

PubMed

Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

2015-01-01

Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61-2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61-2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61-9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

State of the science in ovarian cancer quality of life research: a systematic review.

PubMed

Hess, Lisa M; Stehman, Frederick B

2012-09-01

Health-related quality of life (HRQOL) has become an increasingly important focus of outcomes in cancer care with the movement toward more patient-oriented research. Quality-of-life outcomes are important in ovarian cancer, which has not yet benefitted from improved survival outcomes as have other diseases. This study was designed to systematically assess and summarize HRQOL in ovarian cancer. A systematic search strategy was initiated to identify published literature measuring HRQOL of women with a diagnosis of ovarian cancer (OC). Data were synthesized to evaluate HRQOL and patient-reported outcome data at various time points: before, during, and after chemotherapy. Data were pooled and summary statistics compared across published studies. Comparisons of means were conducted using analysis of variance. There were 170 publications meeting all eligibility criteria, representing 139 unique studies of patients with ovarian cancer, where QOL data were collected. Within this literature, more than 90 different patient-reported outcome (PRO) instruments were administered. The most common HRQOL instruments included the European Organisation for Research and Treatment of Cancer QLQ-C30 and the Functional Assessment of Cancer Therapy. Few studies alone demonstrated significant differences in QOL between the experimental and comparison arm or throughout the treatment period. Pooled data, however, show that baseline QOL may significantly improve, particularly after completion of chemotherapy treatment. Despite the increase in assessment and reporting of QOL in ovarian cancer research studies during the past 15 years, there remains little consistency in the types and format of data collected. There is a need to enhance the standardized collection and reporting of HRQOL data from research involving women with ovarian cancer so that research can build on the cumulative knowledge base to improve outcomes in this patient population.

A general framework for the regression analysis of pooled biomarker assessments.

PubMed

Liu, Yan; McMahan, Christopher; Gallagher, Colin

2017-07-10

As a cost-efficient data collection mechanism, the process of assaying pooled biospecimens is becoming increasingly common in epidemiological research; for example, pooling has been proposed for the purpose of evaluating the diagnostic efficacy of biological markers (biomarkers). To this end, several authors have proposed techniques that allow for the analysis of continuous pooled biomarker assessments. Regretfully, most of these techniques proceed under restrictive assumptions, are unable to account for the effects of measurement error, and fail to control for confounding variables. These limitations are understandably attributable to the complex structure that is inherent to measurements taken on pooled specimens. Consequently, in order to provide practitioners with the tools necessary to accurately and efficiently analyze pooled biomarker assessments, herein, a general Monte Carlo maximum likelihood-based procedure is presented. The proposed approach allows for the regression analysis of pooled data under practically all parametric models and can be used to directly account for the effects of measurement error. Through simulation, it is shown that the proposed approach can accurately and efficiently estimate all unknown parameters and is more computational efficient than existing techniques. This new methodology is further illustrated using monocyte chemotactic protein-1 data collected by the Collaborative Perinatal Project in an effort to assess the relationship between this chemokine and the risk of miscarriage. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Association between switching antiepileptic drug products and healthcare utilization: A systematic review.

PubMed

Kwan, Patrick; Palmini, André

2017-08-01

There is ongoing concern whether switching between different antiepileptic drug (AED) products may compromise patient care. We systematically reviewed changes in healthcare utilization following AED switch. We searched MEDLINE and EMBASE databases (1980-October 2016) for studies that assessed the effect of AED switching in patients with epilepsy on outpatient visits, emergency room visits, hospitalization and hospital stay duration. A total of 14 articles met the inclusion criteria. All were retrospective studies. Four provided findings for specific AEDs only (lamotrigine, topiramate, phenytoin and divalproex), 9 presented pooled findings from multiple AEDs, and 1 study provided both specific (lamotrigine, topiramate, oxcarbazepine, and levetiracetam) and pooled findings. Three studies found an association between a switch of topiramate and an increase in healthcare utilization. Another three studies found that a brand-to-generic lamotrigine switch was not associated with an increased risk of emergently treated events (ambulance use, ER visits or hospitalization). The outcomes of the pooled AED switch studies were inconsistent; 5 studies reported an increased healthcare utilization while 5 studies did not. Studies that have examined the association between an AED switch and a change in healthcare utilization report conflicting findings. Factors that may explain these inconsistent outcomes include inter-study differences in the type of analysis undertaken (pooled vs individual AED data), the covariates used for data adjustment, and the type of switch examined. Future medical claim database studies employing a prospective design are encouraged to address these and other factors in order to enhance inter-study comparability and extrapolation of findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children

PubMed Central

Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Zhou, Zongguang

2017-01-01

Importance Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. Objective To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. Data Sources The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Study Selection Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data Extraction and Synthesis Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. Main Outcomes and Measures The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. Results A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P = .91; I2 = 0%). Conclusions and Relevance This meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith. PMID:28346589

A web-oriented software for the optimization of pooled experiments in NGS for detection of rare mutations.

PubMed

Evangelista, Daniela; Zuccaro, Antonio; Lančinskas, Algirdas; Žilinskas, Julius; Guarracino, Mario R

2016-02-17

The cost per patient of next generation sequencing for detection of rare mutations may be significantly reduced using pooled experiments. Recently, some techniques have been proposed for the planning of pooled experiments and for the optimal allocation of patients into pools. However, the lack of a user friendly resource for planning the design of pooled experiments forces the scientists to do frequent, complex and long computations. OPENDoRM is a powerful collection of novel mathematical algorithms usable via an intuitive graphical user interface. It enables researchers to speed up the planning of their routine experiments, as well as, to support scientists without specific bioinformatics expertises. Users can automatically carry out analysis in terms of costs associated with the optimal allocation of patients in pools. They are also able to choose between three distinct pooling mathematical methods, each of which also suggests the optimal configuration for the submitted experiment. Importantly, in order to keep track of the performed experiments, users can save and export the results of their experiments in standard tabular and charts contents. OPENDoRM is a freely available web-oriented application for the planning of pooled NGS experiments, available at: http://www-labgtp.na.icar.cnr.it/OPENDoRM. Its easy and intuitive graphical user interface enables researchers to plan theirs experiments using novel algorithms, and to interactively visualize the results.

The efficacy of problem-solving treatments after deliberate self-harm: meta-analysis of randomized controlled trials with respect to depression, hopelessness and improvement in problems.

PubMed

Townsend, E; Hawton, K; Altman, D G; Arensman, E; Gunnell, D; Hazell, P; House, A; Van Heeringen, K

2001-08-01

Brief problem-solving therapy is regarded as a pragmatic treatment for deliberate self-harm (DSH) patients. A recent meta-analysis of randomized controlled trials (RCTs) evaluating this approach indicated a trend towards reduced repetition of DSH but the pooled odds ratio was not statistically significant. We have now examined other important outcomes using this procedure, namely depression, hopelessness and improvement in problems. Six trials in which problem-solving therapy was compared with control treatment were identified from an extensive literature review of RCTs of treatments for DSH patients. Data concerning depression, hopelessness and improvement in problems were extracted. Where relevant statistical data (e.g. standard deviations) were missing these were imputed using various statistical methods. Results were pooled using meta-analytical procedures. At follow-up, patients who were offered problem-solving therapy had significantly greater improvement in scores for depression (standardized mean difference = -0.36; 95% CI -0.61 to -0.11) and hopelessness (weighted mean difference =-3.2; 95% CI -4.0 to -2.41), and significantly more reported improvement in their problems (odds ratio = 2.31; 95% CI 1.29 to 4.13), than patients who were in the control treatment groups. Problem-solving therapy for DSH patients appears to produce better results than control treatment with regard to improvement in depression, hopelessness and problems. It is desirable that this finding is confirmed in a large trial, which will also allow adequate testing of the impact of this treatment on repetition of DSH.

Side differences in cerebrovascular accidents after cardiac surgery: a statistical analysis of neurologic symptoms and possible implications for anatomic mechanisms of aortic particle embolization.

PubMed

Boivie, Patrik; Edström, Cecilia; Engström, Karl Gunnar

2005-03-01

Aortic manipulation and particle embolization have been identified to cause cerebrovascular accidents in cardiac surgery. Recent data suggest that left-hemispheric cerebrovascular accident (right-sided symptoms) is more common, and this has been interpreted as being caused by aortic cannula stream jets. Our aim was to evaluate symptoms of cerebrovascular accident and side differences from a retrospective statistical analysis. During a 2-year period, 2641 consecutive cardiac surgery cases were analyzed. Patients positive for cerebrovascular accident were extracted from a database designed to monitor clinical symptoms. A protocol was used to confirm symptom data with the correct diagnosis in patient records. Patients were subdivided into 3 groups: control, immediate cerebrovascular accident, and delayed cerebrovascular accident. Among pooled patients, immediate and delayed cerebrovascular accidents were 3.0% and 0.9%, respectively. The expected predisposing factors behind immediate cerebrovascular accidents were significant, although the type of operation affected this search. Aortic quality was a strong predictor ( P < .001). The rate of delayed cerebrovascular accident was unaffected by surgery group. Left-sided symptoms of immediate cerebrovascular accident were approximately twice as frequent ( P = .016) as on the contralateral side. This phenomenon was observed for pooled patients and for isolated coronary bypass procedures (n = 1882; P = .025). Immediate cerebrovascular accident and aortic calcifications are linked. The predominance of left-sided symptoms may suggest that aortic manipulation and anatomic mechanisms in the aortic arch are more likely to cause cerebrovascular accidents than effects from cannula stream jets.

The Risk of Coronary Heart Disease in Patients with Kidney Stones: A Systematic Review and Meta-analysis.

PubMed

Cheungpasitporn, Wisit; Thongprayoon, Charat; Mao, Michael A; O'Corragain, Oisin A; Edmonds, Peter J; Erickson, Stephen B

2014-11-01

The reported risk of coronary heart disease (CHD) in patients with a history of kidney stones is conflicting. The objective of this meta-analysis was to assess the association between a history of kidney stones and CHD risk. A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 04, 2014. Studies that reported odds ratios or hazard ratios comparing the risk of CHD in patients with a history of kidney stones versus those without a history of kidney stones were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Seven study populations from four cohort studies and one cross-sectional study were identified and included in the data analysis. The pooled risk ratio (RR) of CHD in patients with kidney stones was 1.24 (95% CI, 1.10-1.40). This result remained significant (RR, 1.23 [95% CI, 1.08-1.41]) when the sensitivity analysis was restricted to only cohort studies. A history of kidney stones was associated with increased CHD risk in females (RR, 1.43 [95% CI, 1.12-1.82]), whereas the association was not significant in males (RR, 1.14 [95% CI, 0.94-1.38]). Our study demonstrates a statistically significant increased risk of CHD in female patients with prior kidney stones. This finding suggests that a history of kidney stones is a risk factor for CHD in females and may impact clinical management.

Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis.

PubMed

Tham, Tristan; Bardash, Yonatan; Herman, Saori Wendy; Costantino, Peter David

2018-05-14

The purposes of this systematic review and meta-analysis were to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and prognosis in head and neck cancer. A systematic review and meta-analysis were done to investigate the role of NLR in overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and progression-free survival (PFS). For qualitative analysis, 33 cohorts with over 10 072 patients were included. For quantitative analysis, 15 studies were included with 5562 patients. The pooled data demonstrated that an elevated NLR significantly predicted poorer OS and DSS. An elevated pretreatment NLR is a prognostic marker for head and neck cancer. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients who might benefit from adjuvant therapy. © 2018 Wiley Periodicals, Inc.

Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl; Stiphout, Ruud G.P.M. van; Nout, Remi A.

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variablesmore » which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.« less

A secure distributed logistic regression protocol for the detection of rare adverse drug events

PubMed Central

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-01-01

Background There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. Objective To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. Methods We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. Results The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. Conclusion The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models. PMID:22871397

A secure distributed logistic regression protocol for the detection of rare adverse drug events.

PubMed

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-05-01

There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models.

Mass spectrometric identification of diagnostic markers for chronic prostatitis in seminal plasma by analysis of seminal plasma protein clinical samples.

PubMed

Rokka, A; Mehik, A; Tonttila, P; Vaarala, M

2017-08-15

There are few specific diagnostic markers for chronic prostatitis. Therefore, we used mass spectrometry to evaluate differences in seminal plasma protein expression among patients with prostatitis and young and middle-aged healthy controls. We analysed pooled seminal plasma protein samples from four prostatitis patients (two pools), three young controls (one pool), and three middle-aged controls (one pool). The samples were analysed by liquid chromatography-tandem mass spectrometry. Of the 349 proteins identified, 16 were differentially expressed between the two control pools. Five proteins were up- or down-regulated in both of the prostatitis pools compared to middle-aged controls but not between young and middle-aged pools. Progestagen-associated endometrial protein (PAEP) was over-expressed in prostatitis samples compared to young and middle-aged controls. Our findings and those of previous studies indicate that PAEP is a potential seminal plasma marker for chronic prostatitis. In conclusion, we found age-related changes in seminal plasma protein expression. PAEP expression in seminal plasma should be investigated further to evaluate its potential as a diagnostic marker for chronic prostatitis.

Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies.

PubMed

Draelos, Zoe Diana; Stein Gold, Linda F; Murrell, Dedee F; Hughes, Matilda H; Zane, Lee T

2016-02-01

Two post hoc analyses assessed the antipruritic activity of crisaborole topical ointment, 2% (crisaborole; Anacor Pharmaceuticals, Inc., Palo Alto, CA), a first-in-class boron-based phosphodiesterase-4 inhibitor in development for treatment of mild to moderate atopic dermatitis (AD). Two pooled analyses included data from 4 studies evaluating crisaborole in AD (study 1, phase 1b, systemic exposure, safety, and pharmacokinetics [PK] under maximal-use conditions in children and adolescents; study 2, phase 2a, safety and PK in adolescents; study 3, phase 2a, efficacy and safety in adults; study 4, phase 2, efficacy and safety in adolescents). Pooled data from studies 1 and 2 included whole body assessments; studies 3 and 4 included target lesion assessments. Pruritus severity was evaluated using a 4-point rating scale (0=none to 3=severe). Efficacy assessments included percent change from baseline in pruritus severity scores at days 8 (first pooled assessment), 15, 22, and 29 (whole body assessments) or days 15 (first pooled assessment), 22, and 29 (target lesions). Paired t-tests comparing change from baseline against zero were used to calculate P values. Categorical shifts in pruritus severity were also assessed (no to mild pruritus, 0-1.5; moderate to severe pruritus, 2-3). In the pooled analysis of studies 1 and 2 (N=57), the percent change from baseline in pruritus severity scores were 63.0% and 64.9% at days 8 and 29, respectively (P<0.001 for each). Similar results were observed in the pooled analysis of studies 3 and 4 (N=67). In both analyses, most patients had mild to no pruritus from the first time point assessed through the remainder of treatment. Treatment with crisaborole topical ointment, 2% resulted in statistically significant reductions in pruritus severity at the first time point evaluated in both analyses. These findings provide preliminary evidence of the antipruritic activity of crisaborole topical ointment, 2%.

Clinical Decision Rules for Pulmonary Embolism in Hospitalized Patients: A Systematic Literature Review and Meta-analysis.

PubMed

Bass, Anne R; Fields, Kara G; Goto, Rie; Turissini, Gregory; Dey, Shirin; Russell, Linda A

2017-11-01

Background  Clinical decision rules (CDRs) for pulmonary embolism (PE) have been validated in outpatients, but their performance in hospitalized patients is not well characterized. Objectives  The goal of this systematic literature review was to assess the performance of CDRs for PE in hospitalized patients. Methods  We performed a structured literature search using Medline, EMBASE and the Cochrane library for articles published on or before January 18, 2017. Two authors reviewed all titles, abstracts and full texts. We selected prospective studies of symptomatic hospitalized patients in which a CDR was used to estimate the likelihood of PE. The diagnosis of PE had to be confirmed using an accepted reference standard. Data on hospitalized patients were solicited from authors of studies in mixed populations of outpatients and hospitalized patients. Study characteristics, PE prevalence and CDR performance were extracted. The methodological quality of the studies was assessed using the QUADAS instrument. Results  Twelve studies encompassing 3,942 hospitalized patients were included. Studies varied in methodology (randomized controlled trials and observational studies) and reference standards used. The pooled sensitivity of the modified Wells rule (cut-off ≤ 4) in hospitalized patients was 72.1% (95% confidence interval [CI], 63.7-79.2) and the pooled specificity was 62.2% (95% CI, 52.6-70.9). The modified Wells rule (cut-off ≤ 4) plus D-dimer testing had a pooled sensitivity 99.7% (95% CI, 96.7-100) and pooled specificity 10.8% (95% CI, 6.7-16.9). The efficiency (proportion of patients stratified into the 'PE unlikely' group) was 8.4% (95% CI, 4.1-16.5), and the failure rate (proportion of low likelihood patients who were diagnosed with PE during follow-up) was 0.1% (95% CI, 0-5.3). Conclusion  In symptomatic hospitalized patients, use of the Wells rule plus D-dimer to rule out PE is safe, but allows very few patients to forgo imaging. Schattauer GmbH Stuttgart.

Pooled individual patient data from five countries were used to derive a clinical prediction rule for coronary artery disease in primary care.

PubMed

Aerts, Marc; Minalu, Girma; Bösner, Stefan; Buntinx, Frank; Burnand, Bernard; Haasenritter, Jörg; Herzig, Lilli; Knottnerus, J André; Nilsson, Staffan; Renier, Walter; Sox, Carol; Sox, Harold; Donner-Banzhoff, Norbert

2017-01-01

To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care. Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies. The most parsimonious rule included six equally weighted predictors: age ≥55 (males) or ≥65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is <2. The area under the ROC curve was 0.84. We applied this rule to a study setting with a CAD prevalence of 13.2% using a prediction score cutoff of <2 (i.e., -1, 0, or +1). When the score was <2, the probability of CAD was 2.1% (95% CI: 1.1-3.9%); when the score was ≥ 2, it was 43.0% (95% CI: 35.8-50.4%). Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between patient data and pooled clinical management decisions.

PubMed

Ludbrook, G I; O'Loughlin, E J; Corcoran, T B; Grant, C

2013-01-01

A strong relationship between patient data and preoperative clinical decisions could potentially be used to support clinical decisions in preoperative management. The aim of this exploratory study was to determine the relationship between key patient data and pooled clinical opinions on management. In a previous study, panels of anaesthetists compared the quality of computer-assisted patient health assessments with outpatient consultations and made decisions on the need for preoperative tests, no preoperative outpatient assessment, possible postoperative intensive care unit/high dependency unit requirements and aspiration prophylaxis. In the current study, the relationship between patient data and these decisions was examined using binomial logistic regression analysis. Backward stepwise regression was used to identify independent predictors of each decision (at P >0.15), which were then incorporated into a predictive model. The number of factors related to each decision varied: blood picture (four factors), biochemistry (six factors), coagulation studies (three factors), electrocardiography (eight factors), chest X-ray (seven factors), preoperative outpatient assessment (17 factors), intensive care unit requirement (eight factors) and aspiration prophylaxis (one factor). The factor types also varied, but included surgical complexity, age, gender, number of medications or comorbidities, body mass index, hypertension, central nervous system condition, heart disease, sleep apnoea, smoking, persistent pain and stroke. Models based on these relationships usually demonstrated good sensitivity and specificity, with receiver operating characteristics in the following areas under curve: blood picture (0.75), biochemistry (0.86), coagulation studies (0.71), electrocardiography (0.90), chest X-ray (0.85), outpatient assessment (0.85), postoperative intensive care unit requirement (0.88) and aspiration prophylaxis (0.85). These initial results suggest modelling of patient data may have utility supporting clinicians' preoperative decisions.

Geographic and temporal validity of prediction models: Different approaches were useful to examine model performance

PubMed Central

Austin, Peter C.; van Klaveren, David; Vergouwe, Yvonne; Nieboer, Daan; Lee, Douglas S.; Steyerberg, Ewout W.

2017-01-01

Objective Validation of clinical prediction models traditionally refers to the assessment of model performance in new patients. We studied different approaches to geographic and temporal validation in the setting of multicenter data from two time periods. Study Design and Setting We illustrated different analytic methods for validation using a sample of 14,857 patients hospitalized with heart failure at 90 hospitals in two distinct time periods. Bootstrap resampling was used to assess internal validity. Meta-analytic methods were used to assess geographic transportability. Each hospital was used once as a validation sample, with the remaining hospitals used for model derivation. Hospital-specific estimates of discrimination (c-statistic) and calibration (calibration intercepts and slopes) were pooled using random effects meta-analysis methods. I2 statistics and prediction interval width quantified geographic transportability. Temporal transportability was assessed using patients from the earlier period for model derivation and patients from the later period for model validation. Results Estimates of reproducibility, pooled hospital-specific performance, and temporal transportability were on average very similar, with c-statistics of 0.75. Between-hospital variation was moderate according to I2 statistics and prediction intervals for c-statistics. Conclusion This study illustrates how performance of prediction models can be assessed in settings with multicenter data at different time periods. PMID:27262237

Comprehensive analysis of correlation coefficients estimated from pooling heterogeneous microarray data

PubMed Central

2013-01-01

Background The synthesis of information across microarray studies has been performed by combining statistical results of individual studies (as in a mosaic), or by combining data from multiple studies into a large pool to be analyzed as a single data set (as in a melting pot of data). Specific issues relating to data heterogeneity across microarray studies, such as differences within and between labs or differences among experimental conditions, could lead to equivocal results in a melting pot approach. Results We applied statistical theory to determine the specific effect of different means and heteroskedasticity across 19 groups of microarray data on the sign and magnitude of gene-to-gene Pearson correlation coefficients obtained from the pool of 19 groups. We quantified the biases of the pooled coefficients and compared them to the biases of correlations estimated by an effect-size model. Mean differences across the 19 groups were the main factor determining the magnitude and sign of the pooled coefficients, which showed largest values of bias as they approached ±1. Only heteroskedasticity across the pool of 19 groups resulted in less efficient estimations of correlations than did a classical meta-analysis approach of combining correlation coefficients. These results were corroborated by simulation studies involving either mean differences or heteroskedasticity across a pool of N > 2 groups. Conclusions The combination of statistical results is best suited for synthesizing the correlation between expression profiles of a gene pair across several microarray studies. PMID:23822712

Do corticosteroids reduce the risk of fat embolism syndrome in patients with long-bone fractures? A meta-analysis.

PubMed

Bederman, S Samuel; Bhandari, Mohit; McKee, Michael D; Schemitsch, Emil H

2009-10-01

Fat embolism syndrome (FES) is a potentially lethal condition most commonly seen in polytrauma patients with multiple long-bone fractures. Treatment has centred around supportive care and early fracture fixation. Several small clinical trials have suggested corticosteroids benefit patients with FES, but this treatment remains controversial. Our objective was to determine the effect of corticosteroids in preventing FES in patients with long-bone fractures. We conducted a meta-analysis of published studies of patients with long-bone fractures who were randomly assigned to groups receiving corticosteroids or standard treatment for the prevention of FES (1966-2006). Data were extracted on quality, population, intervention and outcomes. Our primary outcome was the development of FES. We used random-effects models to pool results across studies, assessing for study heterogeneity. Of the 104 studies identified, 7 met our eligibility criteria. Overall, the quality of the trials was poor. Our pooled analysis of 389 patients found that corticosteroids reduced the risk of FES by 78% (95% confidence interval [CI] 43%-92%) and that only 8 patients needed to be treated (95% CI 5-13 patients) to prevent 1 case of FES. Similarly, corticosteroids significantly reduced the risk of hypoxia. We found no differences in the rates of mortality or infection. Rates of avascular necrosis were not reported in any of these studies. Evidence suggests that corticosteroids may be beneficial in preventing FES and hypoxia but not mortality in patients with long-bone fractures. The risk of infection is not increased with the use of corticosteroids. However, methodological limitations of these trials necessitate a large confirmatory randomized trial.

Do corticosteroids reduce the risk of fat embolism syndrome in patients with long-bone fractures? A meta-analysis

PubMed Central

Bederman, S. Samuel; Bhandari, Mohit; McKee, Michael D.; Schemitsch, Emil H.

2009-01-01

Background Fat embolism syndrome (FES) is a potentially lethal condition most commonly seen in polytrauma patients with multiple long-bone fractures. Treatment has centred around supportive care and early fracture fixation. Several small clinical trials have suggested corticosteroids benefit patients with FES, but this treatment remains controversial. Our objective was to determine the effect of corticosteroids in preventing FES in patients with long-bone fractures. Methods We conducted a meta-analysis of published studies of patients with long-bone fractures who were randomly assigned to groups receiving corticosteroids or standard treatment for the prevention of FES (1966–2006). Data were extracted on quality, population, intervention and outcomes. Our primary outcome was the development of FES. We used random-effects models to pool results across studies, assessing for study heterogeneity. Results Of the 104 studies identified, 7 met our eligibility criteria. Overall, the quality of the trials was poor. Our pooled analysis of 389 patients found that corticosteroids reduced the risk of FES by 78% (95% confidence interval [CI] 43%–92%) and that only 8 patients needed to be treated (95% CI 5–13 patients) to prevent 1 case of FES. Similarly, corticosteroids significantly reduced the risk of hypoxia. We found no differences in the rates of mortality or infection. Rates of avascular necrosis were not reported in any of these studies. Conclusion Evidence suggests that corticosteroids may be beneficial in preventing FES and hypoxia but not mortality in patients with long-bone fractures. The risk of infection is not increased with the use of cortisosteroids. However, methodological limitations of these trials necessitate a large confirmatory randomized trial. PMID:19865573

Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

2016-01-01

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson's disease.

PubMed

Schapira, A H V; Stocchi, F; Borgohain, R; Onofrj, M; Bhatt, M; Lorenzana, P; Lucini, V; Giuliani, R; Anand, R

2013-02-01

Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to 'intervention', defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Sialendoscopy for the management of juvenile recurrent parotitis: a systematic review and meta-analysis.

PubMed

Ramakrishna, Jayant; Strychowsky, Julie; Gupta, Michael; Sommer, Doron D

2015-06-01

To determine the effectiveness and safety of sialendoscopy for the treatment of juvenile recurrent parotitis (JRP). The study was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search strategy in MEDLINE, EMBASE, the Cochrane library, and Google Scholar was completed and limited to studies published in English. Relevant reference lists were reviewed. Two independent reviewers selected prospective or retrospective studies of pediatric patients treated with interventional sialendoscopy for the management of JRP. Outcome measures included rates of successful treatment (no further episodes of parotid swelling or need for further sialendoscopy) and complications, Two reviewers appraised the level of evidence using the Oxford Clinical Evidence-based Medicine (OCEBM) guidelines, extracted data, and resolved discrepancies by consensus. Weighted pooled proportion, 95% confidence interval (CI), and test results for heterogeneity and publication bias are reported. Seven studies were included. Levels of evidence varied from OCEBM level 3 to 4. The weighted pooled proportion of success rates for no further episodes by patient (n = 120) was 73% (95% CI: 64%-82%) and by gland (n = 165) 81% (95% CI: 75%-87%). The weighted pooled proportion of success rates for no further sialendoscopy by patient was 87% (95% CI: 81%-93%). Heterogeneity was low, and publication bias was not detected. There were no major complications reported. Surgical techniques and endoscopic findings are summarized. The results from this analysis suggest that sialendoscopy is effective and safe for the treatment of JRP and may be offered to appropriate patients. NA © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Self-expandable metal stents for malignant gastric outlet obstruction: A pooled analysis of prospective literature.

PubMed

van Halsema, Emo E; Rauws, Erik A J; Fockens, Paul; van Hooft, Jeanin E

2015-11-21

To provide an overview of the clinical outcomes of self-expandable metal stent (SEMS) placement for malignant gastric outlet obstruction (MGOO). A systematic literature search was performed in PubMed of the literature published between January 2009 and March 2015. Only prospective studies that reported on the clinical success of stent placement for MGOO were included. The primary endpoint was clinical success, defined according to the definition used in the original article. Data were pooled and analyzed using descriptive statistics. Subgroup analyses were performed for partially covered SEMSs (PCSEMSs) and uncovered SEMSs (UCSEMSs) using Fisher's exact test. A total of 19 studies, including 1281 patients, were included in the final analysis. Gastric (42%) and pancreatic (37%) cancer were the main causes of MGOO. UCSEMSs were used in 76% of patients and PCSEMSs in 24%. The overall pooled technical success rate was 97.3% and the clinical success rate was 85.7%. Stent dysfunction occurred in 19.6% of patients, mainly caused by re-obstruction (12.6%) and stent migration (4.3%), and was comparable between PCSEMSs and UCSEMSs (21.2% vs 19.1%, respectively, P = 0.412). Re-obstruction was more common with UCSEMSs (14.9% vs 5.1%, P < 0.001) and stent migration was more frequent after PCSEMS placement (10.9% vs 2.2%, P < 0.001). The overall perforation rate was 1.2%. Bleeding was reported in 4.1% of patients, including major bleeding in 0.8%. The median stent patency ranged from 68 to 307 d in five studies. The median overall survival ranged from 49 to 183 d in 13 studies. The clinical outcomes in this large population showed that enteral stent placement was feasible, effective and safe. Therefore, stent placement is a valid treatment option for the palliation of MGOO.

Effect of Transcranial Direct Current Stimulation in Patients With Tinnitus: A Meta-Analysis and Systematic Review.

PubMed

Wang, Tang-Chuan; Tyler, Richard S; Chang, Ta-Yuan; Chen, Jui-Cheng; Lin, Chia-Der; Chung, Hsiung-Kwang; Tsou, Yung-An

2018-02-01

Subjective tinnitus is a phantom sensation experienced without any external source of sound that profoundly impacts the quality of life. Some investigations have claimed that transcranial direct current stimulation (tDCS) reduces tinnitus, but studies on tDCS have demonstrated variable results. This meta-analysis aimed to examine the effect of tDCS on patients with tinnitus. We searched for articles published through January 5, 2016, in Medline, Cochrane, EMBASE, and Google Scholar using the following keywords: tinnitus, transcranial direct current stimulation, and tDCS. The study outcomes were change in magnitude estimates of loudness (loudness), tinnitus-related distress (distress), and Tinnitus Handicap Inventory (THI). Pooled results demonstrated that tDCS did not have a beneficial effect on loudness (pooled standardized difference in means = 0.674, 95% CI, -0.089 to 1.437, P = .083). Further, the pooled results demonstrated a greater reduction in distress for the tDCS group (pooled standardized difference in means = 0.634, 95% CI, 0.021-1.247, P = .043). We conclude that the pooled results demonstrated a greater reduction in distress for groups treated with tDCS as compared with those administered a sham treatment.

p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial.

PubMed

Sonnenblick, Amir; Salgado, Roberto; Brohée, Sylvain; Zahavi, Tamar; Peretz, Tamar; Van den Eynden, Gert; Rouas, Ghizlane; Salmon, Asher; Francis, Prudence A; Di Leo, Angelo; Crown, John P A; Viale, Giuseppe; Daly, Laura; Javdan, Bahar; Fujisawa, Sho; De Azambuja, Evandro; Lieveke, Ameye; Piccart, Martine J; Bromberg, Jacqueline F; Sotiriou, Christos

2018-02-01

In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression signature identified patients with a good prognosis irrespective of the luminal subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer.

Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis.

PubMed

Jaafar, Mohamed Hasif; Safi, Sher Zaman; Tan, Maw-Pin; Rampal, Sanjay; Mahadeva, Sanjiv

2018-05-01

The role of gastritis in dyspepsia remains controversial. We aimed to examine the efficacy of rebamipide, a gastric mucosal protective agent, in both organic and functional dyspepsia. A systematic review and meta-analysis was performed. The following databases were searched using the keywords ("rebamipide" OR "gastroprotective agent*" OR "mucosta") AND ("dyspepsia" OR "indigestion" OR "gastrointestinal symptoms"): PubMed, Wed of Science, Embase, CINAHL, Cochrane Clinical Trials Register. The primary outcome was dyspepsia or upper GI symptom score improvement. Pooled analysis of the main outcome data were presented as risk ratio (RR) for dichotomous data and standardized mean difference (SMD) for continuous data. From an initial 248 records, 17 randomised controlled trial (RCT) publications involving 2170 subjects (1224 rebamipide, 946 placebo/control) were included in the final analysis. Twelve RCTs were conducted in subjects with organic dyspepsia (peptic ulcer disease, reflux esophagitis or NSAID-induced gastropathy) and five RCTs were conducted in patients with functional dyspepsia (FD). Overall, dyspepsia symptom improvement was significantly better with rebamipide compared to placebo/control drug (RR 0.77, 95% CI = 0.64-0.93; SMD -0.46, 95% CI = -0.83 to -0.09). Significant symptom improvement was observed both in pooled RR and SMD in subjects with organic dyspepsia (RR 0.72, 95% CI = 0.61-0.86; SMD -0.23, 95% CI = -0.4 to -0.07), while symptom improvement in FD was observed in pooled SMD but not RR (SMD -0.62, 95% CI = -1.16 to -0.08; RR 1.01, 95% CI = 0.71-1.45). Rebamipide is effective in organic dyspepsia and may improve symptoms in functional dyspepsia.

Very-short-term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients.

PubMed

Muñoz, Manuel; Gómez-Ramírez, Susana; Cuenca, Jorge; García-Erce, José Antonio; Iglesias-Aparicio, Daniel; Haman-Alcober, Sami; Ariza, Daniel; Naveira, Enrique

2014-02-01

Postoperative nosocomial infection (PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions (ABTs), anemia, and iron deficiency are manageable with perioperative intravenous (IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI. Pooled data on ABT, PNI, 30-day mortality, and length of hospital stay (LHS) from 2547 patients undergoing elective lower-limb arthroplasty (n = 1186) or hip fracture repair (n = 1361) were compared between patients who received either very-short-term perioperative IV iron (200-600 mg; n = 1538), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU), or standard treatment (n = 1009). Compared to standard therapy, perioperative IV iron reduced rates of ABT (32.4% vs. 48.8%; p = 0.001), PNI (10.7% vs. 26.9%; p = 0.001), and 30-day mortality (4.8% vs. 9.4%; p = 0.003) and the LHS (11.9 days vs. 13.4 days; p = 0.001) in hip fracture patients. These benefits were observed in both transfused and nontransfused patients. Also in elective arthroplasty, IV iron reduced ABT rates (8.9% vs. 30.1%; p = 0.001) and LHS (8.4 days vs.10.7 days; p = 0.001), without differences in PNI rates (2.8% vs. 3.7%; p = 0.417), and there was no 30-day mortality. Despite known limitations of pooled observational analyses, these results suggest that very-short-term perioperative administration of IV iron, with or without rHuEPO, in major lower limb orthopedic procedures is associated with reduced ABT rates and LHS, without increasing postoperative morbidity or mortality. © 2013 American Association of Blood Banks.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis.

PubMed

Ruanpeng, Darin; Ungprasert, Patompong; Sangtian, Jutarat; Harindhanavudhi, Tasma

2017-09-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture. The current meta-analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, Mantel-Haenszel analysis. A total of 20 studies with 8286 patients treated with SGLT2 inhibitors were included. The pooled risk ratio of bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95% confidence interval, 0.42-1.07). The pooled risk ratio for canagliflozin, dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37-1.19), 0.84 (95% confidence interval, 0.22-3.18), and 0.57 (95% confidence interval, 0.20-1.59), respectively. Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta-analysis. However, the results were limited by short duration of treatment/follow-up and low incidence of the event of interest. Copyright © 2017 John Wiley & Sons, Ltd.

Patient-reported benefit of ReSTOR® multi-focal intraocular lenses after cataract surgery: Results of Principal Component Analysis on clinical trial data

PubMed Central

Berdeaux, Gilles; Viala, Muriel; Roborel de Climens, Aude; Arnould, Benoit

2008-01-01

Background Restoration of functional distance and near vision independently of additional correction remains a goal for cataract surgery. ReSTOR®, a new multi-focal intraocular lens (IOL) addresses this issue with an improvement in both distance and near vision, often without need for glasses. This analysis attempted to discuss the patient-reported benefit of ReSTOR® using a full but organised representation of data. Methods Two non-randomised, open-label clinical trials conducted in Europe and the United-States were conducted to compare the efficacy of ReSTOR® to AcrySof® mono-focal IOLs. A total of 710 patients in need of bilateral cataract extraction were included in the pooled study. The TyPE, a patient questionnaire, was fully completed by 672 of them before and after each eye surgery. The TyPE, composed of 67 items measuring overall visual functioning in both conditions (with and without wearing glasses), evaluates limitations, troubles and satisfaction in distance and near vision. A principal component analysis (PCA) of the TyPE questionnaire was performed on pooled data from baseline and post-surgery observations in order to fully represent the change in the TyPE data over time. ReSTOR® and mono-focal groups were used as illustrative variables. The coordinates of the first 2 factors were compared between visits and between IOLs (ReSTOR® vs. mono-focal), using paired t-tests and t-tests, respectively. Results The first factor of the PCA explained 55% of the variance and represented 'visual functioning and patient satisfaction'. The second factor explained 6% of the variance and was interpreted as 'independence from glasses'. An overall difference in factorial coordinates in both factors was seen between baseline and the first eye surgery, and between the first and the second eye surgery. No difference between ReSTOR® and mono-focal IOL groups was observed at baseline. After surgery, ReSTOR® treated-patients had higher coordinates on both "visual functioning and satisfaction" and "independence from glasses" factors. Findings observed on the factorial plan were supported by statistical comparisons of factorial coordinates. Conclusion Both mono-focal and ReSTOR®-implanted patients improved their visual functioning after bilateral cataract surgery. Moreover, ReSTOR® patients reported an additional benefit in independence from glasses as well as in visual functioning and patient satisfaction. PMID:18218068

Patient-reported benefit of ReSTOR multi-focal intraocular lenses after cataract surgery: results of principal component analysis on clinical trial data.

PubMed

Berdeaux, Gilles; Viala, Muriel; Roborel de Climens, Aude; Arnould, Benoit

2008-01-24

Restoration of functional distance and near vision independently of additional correction remains a goal for cataract surgery. ReSTOR, a new multi-focal intraocular lens (IOL) addresses this issue with an improvement in both distance and near vision, often without need for glasses. This analysis attempted to discuss the patient-reported benefit of ReSTOR using a full but organised representation of data. Two non-randomised, open-label clinical trials conducted in Europe and the United-States were conducted to compare the efficacy of ReSTOR to AcrySof mono-focal IOLs. A total of 710 patients in need of bilateral cataract extraction were included in the pooled study. The TyPE, a patient questionnaire, was fully completed by 672 of them before and after each eye surgery. The TyPE, composed of 67 items measuring overall visual functioning in both conditions (with and without wearing glasses), evaluates limitations, troubles and satisfaction in distance and near vision. A principal component analysis (PCA) of the TyPE questionnaire was performed on pooled data from baseline and post-surgery observations in order to fully represent the change in the TyPE data over time. ReSTOR and mono-focal groups were used as illustrative variables. The coordinates of the first 2 factors were compared between visits and between IOLs (ReSTOR vs. mono-focal), using paired t-tests and t-tests, respectively. The first factor of the PCA explained 55% of the variance and represented 'visual functioning and patient satisfaction'. The second factor explained 6% of the variance and was interpreted as 'independence from glasses'. An overall difference in factorial coordinates in both factors was seen between baseline and the first eye surgery, and between the first and the second eye surgery. No difference between ReSTOR and mono-focal IOL groups was observed at baseline. After surgery, ReSTOR treated-patients had higher coordinates on both "visual functioning and satisfaction" and "independence from glasses" factors. Findings observed on the factorial plan were supported by statistical comparisons of factorial coordinates. Both mono-focal and ReSTOR-implanted patients improved their visual functioning after bilateral cataract surgery. Moreover, ReSTOR patients reported an additional benefit in independence from glasses as well as in visual functioning and patient satisfaction.

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis.

PubMed

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2014-07-01

No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea. To compare the effcacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be infuenced by interindividual variability. Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. Dr Schwartzberg is a consultant to and Dr Cox an employee at Esai. Mr Ballinari is a member of staff at and Dr Thorn consults for Helsinn Healthcare SA. Funding to support this study and the preparation of this manuscript was provided by Eisai Inc. 2014 FrontlineMedical Communications.

Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: a meta-analysis.

PubMed

Zhang, Yan; Li, Lixiang; Guo, Chuanguo; Mu, Dan; Feng, Bingcheng; Zuo, Xiuli; Li, Yanqing

2016-06-13

Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases, affecting 11.2 % of people worldwide. Previous studies have shown that probiotic treatment may benefit IBS patients. However, the effect of probiotics and the appropriate type, dose, and treatment duration for IBS are still unclear. The aim of the current study was to assess the efficacy of different probiotic types, doses and treatment durations in IBS patients diagnosed by Rome III criteria via a meta-analysis of randomized controlled trials (RCTs). Medline, EMBASE, and the Cochrane Central Register of Controlled Trials up to October 2015 were searched. RCTs including comparisons between the effects of probiotics and placebo on IBS patients diagnosed by Rome III criteria were eligible. Dichotomous data were pooled to obtain the relative risk (RR) with a 95 % confidence interval (CI), whereas continuous data were pooled using a standardized mean difference (SMD) with a 95 % CI. Twenty-one RCTs were included in this meta-analysis. Probiotic therapy was associated with more improvement than placebo administration in overall symptom response (RR: 1.82, 95 % CI 1.27 to 2.60) and quality of life (QoL) (SMD: 0.29, 95 % CI 0.08 to 0.50), but not in individual IBS symptoms. Single probiotics, a low dose, and a short treatment duration were more effective with respect to overall symptom response and QoL. No differences were detected in individual IBS symptoms in the subgroup analyses. Probiotics are an effective pharmacological therapy in IBS patients. Single probiotics at a low dose and with a short treatment duration appear to be more effective in improving overall symptom response and QoL, but more evidence for these effects is still needed.

Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma.

PubMed

Fu, Yucheng; Lan, Tao; Cai, Hongliu; Lu, Anwei; Yu, Wei

2018-05-01

A large number of studies have reported the relationships between serum lactate dehydrogenase (LDH) and prognosis of osteosarcoma. However, the result is still controversial and no consensus has been reached. Therefore, we performed a meta-analysis to evaluate the prognostic role of serum LDH in osteosarcoma patients. We performed the systematic computerized search for eligible articles from PubMed, Embase, and Cochrane databases until December 21, 2017. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) of overall survival (OS) and event-free survival (EFS) were obtained to assess the prognostic value of serum LDH. A total of 18 studies with 2543 osteosarcoma patients were included. Overall, 15 studies assessed the elevated serum LDH level on OS and the pooled HR was 1.87 (95% CI = 1.58-2.20). Meanwhile, the pooled HR to evaluate the relationship between serum LDH and EFS in 9 studies was 1.78 (95% CI = 1.51-2.10). The same results were acquired when these studies were stratified by Enneking stage, geographic region, and sample size. No heterogeneity existed between these subgroups (P > .05). Begg's funnel plot and Egger's test (OS: P = .04; EFS: P = .34) showed that possible publication bias might exist in OS studies. Sensitivity analysis suggested the pooled HR was robust. This meta-analysis demonstrates that elevated serum LDH level is apparently associated with lower EFS rate and serum LDH could be a prognostic biomarker for osteosarcoma patients.

Preoperative intra-aortic balloon pump in patients undergoing coronary bypass surgery: a systematic review and meta-analysis.

PubMed

Dyub, Adel M; Whitlock, Richard P; Abouzahr, Labib L; Cinà, Claudio S

2008-01-01

To assess the effectiveness of preoperative intra-aortic balloon pump (IABP) placement in high-risk patients undergoing coronary bypass surgery (CABG). The primary outcome was hospital mortality and secondary outcomes were IABP-related complications (bleeding, leg ischemia, aortic dissection). MEDLINE, EMBASE, Cochrane registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs), and cohort studies that fulfilled our a priori inclusion criteria. Eligibility decisions, relevance, study validity, and data extraction were performed in duplicate using pre-specified criteria. Meta-analysis was conducted using a random effects model. Ten publications fulfilled our eligibility criteria, of which four were RCTs and six were cohort studies with controls. There were statistical as well as clinical heterogeneity among included studies. A total of 1034 patients received preoperative IABP and 1329 did not receive preoperative IABP. The pooled odds ratio (OR) for hospital mortality in patients treated with preoperative IABP was 0.41 (95% CI, 0.21-0.82, p = 0.01). The number needed to treat was 17. The pooled OR for hospital mortality from randomized trials was 0.18 (95% CI, 0.06-0.57, p = 0.003) and from cohort studies was 0.54 (95% CI, 0.24-1.2, p = 0.13). Overall, 3.7% (13 of 349) of patients who received preoperative IABP developed either limb ischemia or haematoma at the IABP insertion site, and most of these complications improved after discontinuation of IABP. Evidence from this meta-analysis support the use of preoperative IABP in high-risk patients to reduce hospital mortality.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis.

PubMed

van Dijken, Bart R J; van Laar, Peter Jan; Holtman, Gea A; van der Hoorn, Anouk

2017-10-01

Treatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas. Databases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included. Anatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51-81) and 77% (45-93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60-80) and specificity of 87% (77-93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82-91) with a specificity of 86% (77-91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73-98) and specificity was 85% (76-92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79-97) and specificity was 95% (65-99). Advanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas. • Treatment response assessment in high-grade gliomas with anatomical MRI is unreliable • Novel advanced MRI techniques have been studied, but diagnostic accuracy is unknown • Meta-analysis demonstrates that advanced MRI showed higher diagnostic accuracy than anatomical MRI • Highest diagnostic accuracy for spectroscopy and perfusion MRI • Supports the incorporation of advanced MRI in high-grade glioma treatment response assessment.

Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis.

PubMed

Park, Sungjin; Moon, SeongRyeol; Lee, Kiyoung; Park, Ie Byung; Lee, Dae Ho; Nam, Seungyoon

2018-01-01

Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN. PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed. Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value < 0.0001) downregulated in blood from patients with diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy. Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies. © 2018 The Author(s). Published by S. Karger AG, Basel.

Efficacy of cognitive-behavioral therapy in patients with bipolar disorder: A meta-analysis of randomized controlled trials.

PubMed

Chiang, Kai-Jo; Tsai, Jui-Chen; Liu, Doresses; Lin, Chueh-Ho; Chiu, Huei-Ling; Chou, Kuei-Ru

2017-01-01

Although cognitive behavioral therapy (CBT) is considered a promising adjuvant to pharmacotherapy for treating bipolar disorder (BD), its efficacy is unproven. The present review and meta-analysis evaluated the treatment outcomes of patients with BD treated with CBT plus medication and compared these data with the outcomes of those who received standard care alone. Electronic searches from inception to July 31, 2016, were performed using PubMed, Medline OVID, Cochrane Library, EMBASE, CINAHL plus, and PsycINFO. In the extensive electronic literature search, keywords such as "bipolar disorder," "manic-depressive psychosis," "bipolar affective disorder," "bipolar depression," "cognitive therapy," "cognitive-behavioral therapy," and "psychotherapy" were transformed into MeSH terms, and only randomized controlled trials (RCTs) were included. The pooled odds ratios (ORs) of relapse rates and Hedges's g, along with 95% confidence intervals (CIs), for the mean differences in the levels of depression, mania, and psychosocial functioning were calculated. Further subgroup analyses were conducted according to the characteristics of the CBT approaches, patients, and therapists, if the data were available. A total of 19 RCTs comprising 1384 patients with type I or II BD were enrolled in our systematic review and meta-analysis. The main analysis revealed that CBT could lower the relapse rate (pooled OR = 0.506; 95% CI = 0.278 -0.921) and improve depressive symptoms (g = -0.494; 95% CI = -0.963 to -0.026), mania severity (g = -0.581; 95% CI = -1.127 to -0.035), and psychosocial functioning (g = 0.457; 95% CI = 0.106-0.809). CBT is effective in decreasing the relapse rate and improving depressive symptoms, mania severity, and psychosocial functioning, with a mild-to-moderate effect size. Subgroup analyses indicated that improvements in depression or mania are more potent with a CBT treatment duration of ≥90 min per session, and the relapse rate is much lower among patients with type I BD.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

PubMed

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Residual disease at the bronchial stump is positively associated with the risk of bronchoplerual fistula in patients undergoing lung cancer surgery: a meta-analysis

PubMed Central

Li, Shuangjiang; Fan, Jun; Zhou, Jian; Ren, Yutao; Shen, Cheng; Che, Guowei

2016-01-01

OBJECTIVES Residual disease at the bronchial stump (RDBS) is regarded as an important factor possibly resulting in bronchopleural fistula (BPF) after lung cancer surgery, but this has not been confirmed. We conducted this meta-analysis to evaluate the effects of RDBS on BPF formation in patients undergoing lung cancer surgery. METHODS PubMed and EMBASE databases were searched for full-text articles that met our eligibility criteria. Odds ratios (ORs) with 95% confidence interval (95% CI) served as the summarized outcomes. Q-test and I2 statistic were used to evaluate the level of heterogeneity, determining the fixed-effect model or random-effect model for quantitative synthesis. Sensitivity analysis was conducted to identify the possible origins of heterogeneity. The publication bias was assessed by Begg's test. RESULTS A total of eight retrospective observational studies were included in our meta-analysis. In overall analysis, the pooled outcomes indicated that RDBS was significantly associated with BPF formation after lung cancer surgery (OR: 3.12; 95% CI: 1.72–5.64; P < 0.001). In subgroup analysis, the pooled outcomes revealed a significantly increased risk of post-pneumonectomy BPF in patients with RDBS (OR: 2.78; 95% CI: 1.06–7.28; P = 0.037). The subgroup analysis assessing the effects of RDBS on post-lobectomy BPF was given up due to the scarcity of available data. No heterogeneity was revealed within this meta-analysis. No evidence for publication bias was detected by Begg's test. CONCLUSIONS Our meta-analysis indicates that RDBS is positively associated with the increased risk of BPF in patients undergoing lung cancer surgery. The further analysis also reveals an increased risk of post-pneumonectomy BPF in patients with RDBS. More accurate and comprehensive evidence should be collected and summarized in updated meta-analyses. PMID:26614527

Prognostic Significance of Hyponatremia in Acute Intracerebral Hemorrhage: Pooled Analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies.

PubMed

Carcel, Cheryl; Sato, Shoichiro; Zheng, Danni; Heeley, Emma; Arima, Hisatomi; Yang, Jie; Wu, Guojun; Chen, Guofang; Zhang, Shihong; Delcourt, Candice; Lavados, Pablo; Robinson, Thompson; Lindley, Richard I; Wang, Xia; Chalmers, John; Anderson, Craig S

2016-07-01

To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). Clinical hospital sites in 21 countries. Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.

The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

PubMed

Van Den Berg, Patricia; Body, Richard

2018-03-01

The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

Demonstration of a software design and statistical analysis methodology with application to patient outcomes data sets

PubMed Central

Mayo, Charles; Conners, Steve; Warren, Christopher; Miller, Robert; Court, Laurence; Popple, Richard

2013-01-01

Purpose: With emergence of clinical outcomes databases as tools utilized routinely within institutions, comes need for software tools to support automated statistical analysis of these large data sets and intrainstitutional exchange from independent federated databases to support data pooling. In this paper, the authors present a design approach and analysis methodology that addresses both issues. Methods: A software application was constructed to automate analysis of patient outcomes data using a wide range of statistical metrics, by combining use of C#.Net and R code. The accuracy and speed of the code was evaluated using benchmark data sets. Results: The approach provides data needed to evaluate combinations of statistical measurements for ability to identify patterns of interest in the data. Through application of the tools to a benchmark data set for dose-response threshold and to SBRT lung data sets, an algorithm was developed that uses receiver operator characteristic curves to identify a threshold value and combines use of contingency tables, Fisher exact tests, Welch t-tests, and Kolmogorov-Smirnov tests to filter the large data set to identify values demonstrating dose-response. Kullback-Leibler divergences were used to provide additional confirmation. Conclusions: The work demonstrates the viability of the design approach and the software tool for analysis of large data sets. PMID:24320426

Demonstration of a software design and statistical analysis methodology with application to patient outcomes data sets.

PubMed

Mayo, Charles; Conners, Steve; Warren, Christopher; Miller, Robert; Court, Laurence; Popple, Richard

2013-11-01

With emergence of clinical outcomes databases as tools utilized routinely within institutions, comes need for software tools to support automated statistical analysis of these large data sets and intrainstitutional exchange from independent federated databases to support data pooling. In this paper, the authors present a design approach and analysis methodology that addresses both issues. A software application was constructed to automate analysis of patient outcomes data using a wide range of statistical metrics, by combining use of C#.Net and R code. The accuracy and speed of the code was evaluated using benchmark data sets. The approach provides data needed to evaluate combinations of statistical measurements for ability to identify patterns of interest in the data. Through application of the tools to a benchmark data set for dose-response threshold and to SBRT lung data sets, an algorithm was developed that uses receiver operator characteristic curves to identify a threshold value and combines use of contingency tables, Fisher exact tests, Welch t-tests, and Kolmogorov-Smirnov tests to filter the large data set to identify values demonstrating dose-response. Kullback-Leibler divergences were used to provide additional confirmation. The work demonstrates the viability of the design approach and the software tool for analysis of large data sets.

Diagnostic Accuracy of Coronary Computed Tomography Before Aortic Valve Replacement: Systematic Review and Meta-Analysis.

PubMed

Chaikriangkrai, Kongkiat; Jhun, Hye Yeon; Shantha, Ghanshyam Palamaner Subash; Abdulhak, Aref Bin; Tandon, Rudhir; Alqasrawi, Musab; Klappa, Anthony; Pancholy, Samir; Deshmukh, Abhishek; Bhama, Jay; Sigurdsson, Gardar

2018-07-01

In aortic stenosis patients referred for surgical and transcatheter aortic valve replacement (AVR), the evidence of diagnostic accuracy of coronary computed tomography angiography (CCTA) has been limited. The objective of this study was to investigate the diagnostic accuracy of CCTA for significant coronary artery disease (CAD) in patients referred for AVR using invasive coronary angiography (ICA) as the gold standard. We searched databases for all diagnostic studies of CCTA in patients referred for AVR, which reported diagnostic testing characteristics on patient-based analysis required to pool summary sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio. Significant CAD in both CCTA and ICA was defined by >50% stenosis in any coronary artery, coronary stent, or bypass graft. Thirteen studies evaluated 1498 patients (mean age, 74 y; 47% men; 76% transcatheter AVR). The pooled prevalence of significant stenosis determined by ICA was 43%. Hierarchical summary receiver-operating characteristic analysis demonstrated a summary area under curve of 0.96. The pooled sensitivity, specificity, and positive-likelihood and negative-likelihood ratios of CCTA in identifying significant stenosis determined by ICA were 95%, 79%, 4.48, and 0.06, respectively. In subgroup analysis, the diagnostic profiles of CCTA were comparable between surgical and transcatheter AVR. Despite the higher prevalence of significant CAD in patients with aortic stenosis than with other valvular heart diseases, our meta-analysis has shown that CCTA has a suitable diagnostic accuracy profile as a gatekeeper test for ICA. Our study illustrates a need for further study of the potential role of CCTA in preoperative planning for AVR.

Management and postoperative outcome in primary lung cancer and heart disease co-morbidity: a systematic review and meta-analysis

PubMed Central

Analitis, Antonis; Michaelides, Stylianos A.; Charalabopoulos, Konstantinos A.; Tzonou, Anastasia

2016-01-01

Background Co-morbidity of primary lung cancer (LC) and heart disease (HD), both requiring surgical therapy, characterizes a high risk group of patients necessitating prompt diagnosis and treatment. The aim of this study is the review of available evidence guiding the management of these patients. Methods Postoperative outcome of patients operated for primary LC (first meta-analysis) and for both primary LC and HD co-morbidity (second meta-analysis), were studied. Parameters examined in both meta-analyses were thirty-day postoperative mortality, postoperative complications, three- and five-year survival probabilities. The last 36 years were reviewed by using the PubMed data base. Thirty-seven studies were qualified for both meta-analyses. Results The pooled 30-day mortality percentages (%) were 4.16% [95% confidence interval (CI): 2.68–5.95] (first meta-analysis) and 5.26% (95% CI: 3.47–7.62) (second meta-analysis). Higher percentages of squamous histology and lobectomy, were significantly associated with increased (P=0.001) and decreased (P<0.001) thirty-day postoperative mortality, respectively (first meta-analysis). The pooled percentages for postoperative complications were 34.32% (95% CI: 24.59–44.75) (first meta-analysis) and 45.59% (95% CI: 35.62–55.74) (second meta-analysis). Higher percentages of squamous histology (P=0.001), lobectomy (P=0.002) and p-T1 or p-T2 (P=0.034) were associated with higher proportions of postoperative complications (second meta-analysis). The pooled three- and five- year survival probabilities were 68.25% (95% CI: 45.93–86.86) and 52.03% (95% CI: 34.71–69.11), respectively. Higher mean age (P=0.046) and percentage lobectomy (P=0.009) significantly reduced the five-year survival probability. Conclusions Lobectomy and age were both accompanied by reduced five-year survival rate. Also, combined aorto-coronary bypass grafting (CABG) with lobectomy for squamous pT1 or pT2 LC displayed a higher risk of postoperative complications. Moreover, medical decision between combined or staged surgery is suggested to be individualized based on adequacy of coronary arterial perfusion, age, patient’s preoperative performance status (taking into account possible co-morbidities per patient), tumor’s staging and extent of lung resection. PMID:27386487

A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens.

PubMed

Providência, Rui; Grove, Erik Lerkevang; Husted, Steen; Barra, Sérgio; Boveda, Serge; Morais, João

2014-12-01

Previous studies evaluating the ability of novel oral anticoagulants (NOAC) to prevent thromboembolism in patients with non-valvular atrial fibrillation (AF) have identified differences between the efficacy and safety of the drugs tested. Whether these differences reflect differences in direct thrombin or Xa inhibition, different dosing regimens or specific aspects of each agent or trial has not yet been explored. A search was performed on MEDLINE, EMBASE and COCHRANE, and ongoing studies were tracked on clinicaltrials.gov. Phase III randomized controlled trials of direct thrombin inhibitors (DTI) and factor Xa inhibitors (FXaI) vs. warfarin in patients with AF were eligible. Data were pooled using random-effects, according to the Mantel-Haenszel model. Sensitivity analyses were performed on DTI, FXaI, once-daily and twice-daily regimens. Seven studies were pooled, including a total of 80,290 patients. Both DTI and FXaI outperformed warfarin regarding stroke or systemic embolism, intracranial bleeding, total and cardiovascular mortality. No significant differences were found between DTI and FXaI or between once-daily and twice-daily regimens. Some drugs performed worse than warfarin regarding some secondary endpoints, including: edoxaban 30 mg bid on ischaemic stroke, dabigatran on acute myocardial infarction, dabigatran 150 mg bid and rivaroxaban 20mgod on gastrointestinal bleeding. Our pooled data do not support the hypothesis of a significant class-effect of DTI or FXaI, nor the benefit of once-daily vs. twice-daily dosing in the setting of AF, reinforcing that the choice of NOAC should be adapted to the specific patient and focused on the agent itself, rather than the pharmacological class or dosing regimen.

Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, Christian, E-mail: christian.weiss@kgu.d; Arnold, Dirk; Dellas, Kathrin

2010-10-01

Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recordedmore » for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.« less

The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis.

PubMed

Qin, J C; Fan, L; Qin, A P

2017-01-01

To evaluate the effect of dehydroepiandrosterone (DHEA) therapy on the ovarian response and pregnancy outcome in patients with diminished ovarian reserve (DOR). Eligible studies, published before August 31, 2015, were identified from PubMed, EMBASE, the Cochrane library. Outcome measures were the number of retrieved oocytes, cancellation rate of IVF cycles, clinical pregnancy rate and miscarriage rate. We adopted Revman 5.0 software to pool the data from the eligible studies. A total of 9 studies, four were RCTs, four retrospective studies, one prospective studies, including 540 cases and 668 controls, were available for analysis. The pooled analysis showed that the clinical pregnancy rates were increased significantly in DOR patients who were pre-treated with DHEA (OR=1.47, 95% CI: 1.09-1.99), whereas no differences were found in the number of oocytes retrieved, the cancellation rate of IVF cycles and the miscarriage rate between the cases and controls (WMD= -0.69, 95% CI: -2.18-0.81; OR=0.74, 95% CI: 0.51-1.08; OR=0.34, 95% CI: 0.10-1.24). However, it is worth noting that when data were restricted to RCTs, there was a non-significant difference in the clinical pregnancy rate (OR=1.08, 95% CI: 0.67-1.73). We concluded that DHEA supplementation in DOR patients might improve the pregnancy outcomes. To further confirm this effect, more randomized controlled trials with large sample sizes are needed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Prognostic Role of Angiotensin II Type 1 Receptor Autoantibody in Non-Gravid Hypertension and Pre-eclampsia

PubMed Central

Lei, Jinghui; Li, Yafeng; Zhang, Suli; Wu, Ye; Wang, Pengli; Liu, Huirong

2016-01-01

Abstract Angiotensin II type 1 receptor autoantibody (AT1-AA) is found in patients with non-gravid hypertension or pre-eclampsia, but the relationship is uncertain. The aim of the present study was to assess the association between AT1-AA and high blood pressure using meta-analysis, and to evaluate the prognosis value of AT1-AA for hypertensive diseases. Literature search from PubMed, Embase, and Cochrane databases were conducted using keywords “hypertension” or “pre-eclampsia,” “angiotensin II receptor type 1 autoantibody,” and its aliases from April 1999 to December 2015. Studies evaluating the association between AT1-AA and non-gravid hypertension or pre-eclampsia were included in this analysis. The quality of the eligible studies was assessed based on the Newcastle–Ottawa Scale with some modifications. Two researchers then independently reviewed all included studies and extracted all relevant data. Association between AT1-AA and hypertension was tested with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Finally, we evaluated whether AT1-AA predicted the prognosis of hypertension by using a summary receiver-operating characteristic (ROC) curve and sensitivity analysis. Ten studies were finally included in this meta-analysis. AT1-AA showed more significant association with pre-eclampsia than that with non-gravid hypertension (pooled OR 32.84, 95% CI 17.19–62.74; and pooled OR 4.18, 95% CI 2.20–7.98, respectively). Heterogeneity among studies was also detected probably due to different hypertensive subtypes and AT1-AA measuring methods. Area under summary ROC curve (AUC) of pre-eclampsia was 0.92 (sensitivity 0.76; specificity 0.86). Area under the ROC curve of overall hypertensive diseases or non-gravid hypertension was lower than that of pre-eclampsia (0.86 and 0.72, respectively) with lower sensitivities (0.46 and 0.26, respectively). The major limitation of this analysis was the publication bias due to lack of unpublished data and the language limitation during literature search. Prospective study with large simple size and specific measuring data collection are needed to enhance our findings in the future. Our analysis confirms that elevated AT1-AA in serum is significantly associated with hypertensive disorder, especially pre-eclampsia. AT1-AA may be a valuable indicator for poorer prognosis of patients with pre-eclampsia, and could be used in patients with hypertensive disease for risk evaluation and making individual treatment decision. PMID:27124051

Pooling Data from Multiple Longitudinal Studies: The Role of Item Response Theory in Integrative Data Analysis

PubMed Central

Curran, Patrick J.; Hussong, Andrea M.; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J.; Zucker, Robert A.

2010-01-01

There are a number of significant challenges encountered when studying development over an extended period of time including subject attrition, changing measurement structures across group and developmental period, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that overcomes many of the challenges of single sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this paper we focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. We present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. We describe and demonstrate each step in the analysis and we conclude with a discussion of potential limitations and directions for future research. PMID:18331129

Consistent and significant improvement of nighttime voiding frequency (nocturia) with silodosin in men with LUTS suggestive of BPH: pooled analysis of three randomized, placebo-controlled, double-blind phase III studies.

PubMed

Eisenhardt, Andreas; Schneider, Tim; Cruz, Francisco; Oelke, Matthias

2014-10-01

Nocturia is prevalent and bothersome in men with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). α-Adrenoceptor antagonists without subtype selectivity have inconsistently shown significant effects on nocturia in these patients. We explored the effects of the α1A-adrenoceptor subtype-selective antagonist silodosin on nocturia by analyzing three placebo-controlled registration studies. Responses to question 7 of the IPSS questionnaire were analyzed for the entire study population and patients with ≥ 2 voids/night at baseline. Improvement/worsening rates for nocturia were calculated for once-daily silodosin 8 mg and placebo. Silodosin effects on the mean number of nocturnal voids were compared with placebo, and the number of patients in whom nocturia was reduced to <2 times was calculated. In total, 1,479 men were treated with silodosin or placebo; 1,266 men (85 %) had ≥ 2 voids/night at baseline. Compared to placebo, more men treated with silodosin reported about nocturia improvement (53.4 vs. 42.8 %, p < 0.0001) and fewer patients about worsening (9.0 vs. 14.3 %, p < 0.0001). Silodosin significantly reduced nocturia within each study and pooled cohort compared to placebo (p < 0.001). In men with ≥ 2 nocturnal voids at baseline, 61 and 49 % of patients with silodosin and placebo had reductions of ≥ 1 voids/night, respectively (p = 0.0003), and significantly more patients with silodosin had <2 nocturia episodes at study end compared to placebo (29.3 vs. 19.0 %; p = 0.0002). Although a weak impact on nocturia is already known from α-adrenoceptor antagonists without subtype selectivity, the individual placebo-controlled studies and the pooled data analysis showed that the α1A-adrenoceptor subtype-selective antagonist silodosin consistently and significantly improves nocturia in men with LUTS/BPH.

Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children: A Meta-analysis.

PubMed

Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Li, Yuan; Zhou, Zongguang

2017-05-01

Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P = .91; I2 = 0%). This meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith.

Generating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques.

PubMed

Teutonico, D; Musuamba, F; Maas, H J; Facius, A; Yang, S; Danhof, M; Della Pasqua, O

2015-10-01

Clinical Trial Simulations (CTS) are a valuable tool for decision-making during drug development. However, to obtain realistic simulation scenarios, the patients included in the CTS must be representative of the target population. This is particularly important when covariate effects exist that may affect the outcome of a trial. The objective of our investigation was to evaluate and compare CTS results using re-sampling from a population pool and multivariate distributions to simulate patient covariates. COPD was selected as paradigm disease for the purposes of our analysis, FEV1 was used as response measure and the effects of a hypothetical intervention were evaluated in different populations in order to assess the predictive performance of the two methods. Our results show that the multivariate distribution method produces realistic covariate correlations, comparable to the real population. Moreover, it allows simulation of patient characteristics beyond the limits of inclusion and exclusion criteria in historical protocols. Both methods, discrete resampling and multivariate distribution generate realistic pools of virtual patients. However the use of a multivariate distribution enable more flexible simulation scenarios since it is not necessarily bound to the existing covariate combinations in the available clinical data sets.

[The gene pool of Belgorod oblast population: study of biochemical gene markers in populations of Ukraine and Belarus and the position of the Belgorod population in the Eastern Slavic gene pool system].

PubMed

Lependina, I N; Churnosov, M I; Artamentova, L A; Ishchuk, M A; Tegako, O V; Balanovskaia, E V

2008-04-01

The characteristics of the gene pools of indigenous populations of Ukraine and Belarus have been studied using 28 alleles of 10 loci of biochemical gene markers (HP, GC, TF, PI, C'3, ACP1, GLO1, PGM1, ESD, and 6-PGD). The gene pools of the Russian and Ukrainian indigenous populations of Belgorod oblast (Russia) and the indigenous populations of Ukraine and Belarus have been compared. Cluster analysis, multidimensional scaling, and factor analysis of the obtained data have been used to determine the position of the Belgorod population gene pool in the Eastern Slavic gene pool system.

Probiotic supplementation for management of cardiovascular risk factors in adults with type II diabetes: A systematic review and meta-analysis.

PubMed

Hendijani, Fatemeh; Akbari, Vajihe

2018-04-01

The effectiveness of probiotics in control of hypertension and dyslipidemia in diabetic patients remains unclear. Therefore, we systematically reviewed relevant data to elucidate the effects of probiotics on blood pressure and lipid profile of type 2 diabetic patients. We searched PubMed, ISI Web of Knowledge, Scopus, The Cochrane Library, ClinicalTrials.gov, ProQuest Dissertations and Theses databases until May 2016. The primary outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Other biochemical response and adverse effects were considered as secondary outcomes. Data was extracted from included studies and pooled in meta-analysis whenever possible (both standardized mean difference (SMD) analysis and weighted mean difference (WMD) analysis were performed). Eleven eligible randomized controlled trial (n = 641) were identified. Pooling data from these trials demonstrated probiotic consumption significantly decreased SBP (WMD, -3.28 mmHg; 95% confidence interval [CI], -5.38 to -1.18), DBP (WMD, -2.13 mmHg; 95% CI, -4.5 to 0.24), LDL-C (WMD, 8.32 mg/dl; 95% CI, -15.24 to -1.4), TC (WMD, -12.19 mg/dl; 955 CI -17.62 to -6.75) and TG (WMD, -24.48 mg/dl; 95% CI, -33.77 to -11.18) in type 2 diabetic patients compared with placebo. The methodological quality varied across trials included in this study. This systematic review suggests probiotics supplementation may be helpful for control of dyslipidemia and hypertension in type 2 diabetic patients. Conducting more trails with large sample size and long follow-up time still is necessary to develop clinical practice guidelines for management of cardiovascular risk factors in patient with type 2 diabetes. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

PubMed

McInnes, G; Evans, M; Del Prato, S; Stumvoll, M; Schweizer, A; Lukashevich, V; Shao, Q; Kothny, W

2015-11-01

To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients. © 2015 John Wiley & Sons Ltd.

Adjuvant NY-ESO-1 vaccine immunotherapy in high-risk resected melanoma: a retrospective cohort analysis.

PubMed

Lattanzi, Michael; Han, Joseph; Moran, Una; Utter, Kierstin; Tchack, Jeremy; Sabado, Rachel Lubong; Berman, Russell; Shapiro, Richard; Huang, Hsin-Hui; Osman, Iman; Bhardwaj, Nina; Pavlick, Anna C

2018-05-18

Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls. All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables. A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01). In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.

Risk of malignancy in ankylosing spondylitis: a systematic review and meta-analysis.

PubMed

Deng, Chuiwen; Li, Wenli; Fei, Yunyun; Li, Yongzhe; Zhang, Fengchun

2016-08-18

Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis &rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03-1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

Evaluation of Current Consensus Statement Recommendations for Accelerated Partial Breast Irradiation: A Pooled Analysis of William Beaumont Hospital and American Society of Breast Surgeon MammoSite Registry Trial Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkinson, J. Ben; Beitsch, Peter D.; Shah, Chirag

Purpose: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. Methods and Materials: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS intomore » suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group. Results: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93). Conclusions: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort.« less

The performance of magnetic resonance imaging in the detection of triangular fibrocartilage complex injury: a meta-analysis.

PubMed

Wang, Z X; Chen, S L; Wang, Q Q; Liu, B; Zhu, J; Shen, J

2015-06-01

The aim of this study was to evaluate the accuracy of magnetic resonance imaging in the detection of triangular fibrocartilage complex injury through a meta-analysis. A comprehensive literature search was conducted before 1 April 2014. All studies comparing magnetic resonance imaging results with arthroscopy or open surgery findings were reviewed, and 25 studies that satisfied the eligibility criteria were included. Data were pooled to yield pooled sensitivity and specificity, which were respectively 0.83 and 0.82. In detection of central and peripheral tears, magnetic resonance imaging had respectively a pooled sensitivity of 0.90 and 0.88 and a pooled specificity of 0.97 and 0.97. Six high-quality studies using Ringler's recommended magnetic resonance imaging parameters were selected for analysis to determine whether optimal imaging protocols yielded better results. The pooled sensitivity and specificity of these six studies were 0.92 and 0.82, respectively. The overall accuracy of magnetic resonance imaging was acceptable. For peripheral tears, the pooled data showed a relatively high accuracy. Magnetic resonance imaging with appropriate parameters are an ideal method for diagnosing different types of triangular fibrocartilage complex tears. © The Author(s) 2015.

Validation of the pooled cohort risk score in an Asian population - a retrospective cohort study.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2014-11-20

The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score. This is a 10-year retrospective cohort study of randomly selected patients aged 40-79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998-2007 were recorded. A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12. The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.

Medical Therapy Versus Balloon Angioplasty for CTEPH: A Systematic Review and Meta-Analysis.

PubMed

Phan, Kevin; Jo, Helen E; Xu, Joshua; Lau, Edmund M

2018-01-01

A significant number of chronic thromboembolic pulmonary hypertension (CTEPH) patients will have an inoperable disease. Medical therapy and balloon pulmonary angioplasty (BPA) have provided alternate therapeutic options for patients with inoperable CTEPH, although there are a limited number of published studies examining the outcomes. Thus, our study aims to evaluate and compare the efficacy of medical therapy and BPA in patients with inoperable CTEPH. An electronic search of six databases was performed and the search results were screened against established criteria for inclusion into this study. Data was extracted and meta-analytical techniques were used to analyse the data. Pooled data from RCTs revealed that medical therapy, compared with a placebo, was associated with a significant improvement of at least one functional class (p=0.038). With regards to pulmonary haemodynamics, medical therapy also resulted in a significant reduction in both mean pulmonary arterial pressure (mPAP) (p=0.002) and pulmonary vascular resistance (PVR) (p<0.001). From the included observational studies, the 6-minute walk distance (6MWD) significantly increased following medical therapy by an average of 22.8% (p<0.001). The pooled improvement in 6MWD was found to be significantly higher in the BPA group when compared to medical therapy for CTEPH (p=0.001). Pooled data from available observational studies of medical therapy or BPA all demonstrated significant improvements in mPAP and PVR for pre versus post intervention comparisons. The improvement in mPAP (p=0.002) and PVR (p=0.002) were significantly greater for BPA intervention when compared to medical therapy. High-quality evidence supports the use of targeted medical therapy in improving haemodynamics in patients with inoperable CTEPH. There is only moderate-quality evidence from observational studies supporting the efficacy of BPA in improving both haemodynamics and exercise capacity. Further RCTs and prospective observational studies comparing medical therapy and BPA in patients with inoperable CTEPH are required. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Early mobilization after stroke: an example of an individual patient data meta-analysis of a complex intervention.

PubMed

Craig, Louise E; Bernhardt, Julie; Langhorne, Peter; Wu, Olivia

2010-11-01

Very early mobilization (VEM) is a distinctive characteristic of care in some stroke units; however, evidence of the effectiveness of this approach is limited. To date, only 2 phase II trials have compared VEM with standard care: A Very Early Rehabilitation Trial (AVERT) in Australia and the recently completed Very Early Rehabilitation or Intensive Telemetry after Stroke trial in the United Kingdom. The Very Early Rehabilitation or Intensive Telemetry after Stroke protocol was designed to complement that of AVERT in a number of key areas. The aim of this analysis was to investigate the impact of VEM on independence by pooling data from these 2 comparable trials. Individual data from the 2 trials were pooled. Overall, patients were between 27 and 97 years old, had first or recurring stroke, and were treated within 36 hours after stroke onset. The primary outcome was independence, defined as modified Rankin scale score of 0 to 2 at 3 months. The secondary outcomes included complications of immobility and activities of daily living. Logistic regression was used to assess the effect of VEM on outcome, adjusting for known confounders including age, baseline stroke severity, and premorbid modified Rankin scale score. Findings-All patients in AVERT and Very Early Rehabilitation or Intensive Telemetry after Stroke were included, resulting in 54 patients in the VEM group and 49 patients in the standard care group. The baseline characteristics of VEM patients were largely comparable with standard care patients. Time to first mobilization from symptom onset was significantly shorter among VEM patients (median, 21 hours; interquartile range, 15.8-27.8 hours) compared with standard care patients (median, 31 hours; interquartile range, 23.0-41.2 hours). VEM patients had significantly greater odds of independence compared with standard care patients (adjusted odds ratio, 3.11; 95% confidence interval, 1.03-9.33). Planned collaborations between stroke researchers to conduct trials with common protocols and outcome measures can help advance rehabilitation science. VEM was associated with improved independence at 3 months compared with standard care. However, both trials are limited by small sample sizes. Larger trials (such as AVERT phase III) are still needed in this field.

Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis.

PubMed

Rodríguez-Zúñiga, M J M; Cortez-Franco, F; Quijano-Gomero, E

2017-05-01

Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included. We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies. Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; P=.03). In studies using the Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies. The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-III criteria are used for diagnosis. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Jing; Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yorke, Ellen D.

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax. Methods and Materials: Published studies on lung toxicity in patients with early-stage non–small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT. Results: Eighty-eight studiesmore » (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT. Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk.« less

Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Tang, Yurong; Xiong, Wenjie; Shen, Xiaoxue; Jiang, Ling; Lin, Lin

2017-01-01

Aim We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D). Methods We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software. Results We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43–1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]). Conclusions Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events. PMID:28291778

Titanium cages versus autogenous iliac crest bone grafts in anterior cervical discectomy and fusion treatment of patients with cervical degenerative diseases: a systematic review and meta-analysis.

PubMed

Shao, Ming-Hao; Zhang, Fan; Yin, Jun; Xu, Hao-Cheng; Lyu, Fei-Zhou

2017-05-01

A systematic review and partial meta-analysis is conducted to compare the efficacy and safety of anterior cervical decompression and fusion procedures employing either rectangular titanium cages or iliac crest autografts in patients suffering from cervical degenerative disc diseases. Medline, PubMed, CENTRAL, and Google Scholar databases were searched up to June 2015, using the key words cervical discectomy; bone transplantation; titanium cages; and iliac crest autografts. Outcomes of interbody fusion rates were compared using odds ratios (ORs) with 95% confidence intervals (CIs). Values of the Japanese Orthopaedic Association score, and visual analog scale before and after operation were also compared. The rate of interbody fusion was similar between patients in the iliac crest autograft and titanium cage groups (pooled OR = 0.33, 95% CI = 0.07 to 1.66, P = .178). The overall analysis showed that patients in the two groups did not have significantly different post-surgery Japanese Orthopaedic Association score (pooled difference in means = -0.05, 95% CI = 0.73 to 0.63, P = .876). Improvement in arm and neck pain scores were assessed with a visual analog scale and differed significantly between patients in the iliac crest autograft and titanium cage groups (pooled difference in means = 0.16, 95% CI = -0.44 to 0.76, P = .610; and pooled difference in means = -0.44, 95% CI = -2.23 to 1.36, P = .634, respectively). Our results suggest that the use of titanium cages constitutes a safe and efficient alternative to iliac crest bone autografts for anterior cervical discectomy with fusion.

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact

PubMed Central

Borren, Nienke Z.; Ghadermarzi, Shadi; Hutfless, Susan

2017-01-01

Background Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. Methods We systematically searched PubMed/Medline and Embase for publications from Asia between 2000–16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Results Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. Conclusions In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity. PMID:28463987

Contrast induced nephropathy in patients undergoing intravenous (IV) contrast enhanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis.

PubMed

Moos, Shira I; van Vemde, David N H; Stoker, Jaap; Bipat, Shandra

2013-09-01

To summarize the incidence of contrast-induced nephropathy (CIN) and associations between CIN incidence and risk factors in patients undergoing intravenous contrast-enhanced computed tomography (CECT) with low- or iso-osmolar iodinated contrast medium. This review is performed in accordance with the preferred reporting items in systematic reviews and meta-analysis (PRISMA) guidelines. We searched the MEDLINE, EMBASE and Cochrane databases from 2002 till November 2012. Two reviewers included papers and extracted data. The pooled data were analysed by either fixed or random-effects approach depending on heterogeneity defined as the I(2) index. 42 articles with 18,790 patients (mean age 61.5 years (range: 38-83 years)) were included. The mean baseline eGFR was 59.8 mL/min and ranged from 4 to 256 mL/min. Of all patients 45.0% had an estimated glomerular filtration rate (eGFR)<60 mL/min, 55.2% had hypertension; 20.2% had diabetes mellitus (DM) and 6.5% had congestive heart failure (CHF). The overall pooled CIN incidence, defined as a SCr increase of ≥ 25% or ≥ 0.5mg/dL, was 4.96% (95%CI: 3.79-6.47). Data analysis showed associations between CIN and the presence of renal insufficiency, DM, malignancy, age>65 years and use of non-steroidal anti-inflammatory drugs (NSAID's) with odds ratios of 1.73 (95%CI: 1.06-2.82), 1.87 (95%CI: 1.55-2.26), 1.79 (95%CI: 1.03-3.11), 1.95 (95%CI: 1.02-3.70) and 2.32 (95%CI: 1.04-5.19), respectively while hypertension, anaemia and CFH were not associated (p=0.13, p=0.38, p=0.40). The mean incidence of CIN after intravenous iodinated CECT was low and associated with renal insufficiency, diabetes, presence of malignancy, old age and NSAID's use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

PubMed Central

Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

2017-01-01

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; n = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (p = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML. PMID:28212292

Research on Optimization of Pooling System and Its Application in Drug Supply Chain Based on Big Data Analysis

PubMed Central

2017-01-01

Reform of drug procurement is being extensively implemented and expanded in China, especially in today's big data environment. However, the pattern of supply mode innovation lags behind procurement improvement. Problems in financial strain and supply break frequently occur, which affect the stability of drug supply. Drug Pooling System is proposed and applied in a few pilot cities to resolve these problems. From the perspective of supply chain, this study analyzes the process of setting important parameters and sets out the tasks of involved parties in a pooling system according to the issues identified in the pilot run. The approach is based on big data analysis and simulation using system dynamic theory and modeling of Vensim software to optimize system performance. This study proposes a theoretical framework to resolve problems and attempts to provide a valuable reference for future application of pooling systems. PMID:28293258

Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features.

PubMed

Mallinckrodt, Craig H; Watkin, John G; Liu, Chaofeng; Wohlreich, Madelaine M; Raskin, Joel

2005-01-04

The most prominent feature of melancholic depression is a near-total loss of the capacity to derive pleasure from activities or other positive stimuli. Additional symptoms can include psychomotor disturbances, anorexia, excessive guilt, and early awakening from sleep. Melancholic patients may exhibit treatment responses and outcomes that differ from those of non-melancholic patients. Pooled data from double-blind, placebo-controlled studies were utilized to compare the efficacy of duloxetine in depressed patients with and without melancholic features. Efficacy data were pooled from 8 double-blind, placebo-controlled clinical trials of duloxetine. The presence of melancholic features (DSM-IV criteria) was determined using results from the Mini International Neuropsychiatric Interview (MINI). Patients (aged >or= 18 years) meeting DSM-IV criteria for major depressive disorder (MDD) received duloxetine (40-120 mg/d; melancholic, N = 759; non-melancholic, N = 379) or placebo (melancholic, N = 519; non-melancholic, N = 256) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 subscales (Maier, anxiety, retardation, sleep), the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and Visual Analog Scales (VAS) for pain. In data from all 8 studies, duloxetine's advantage over placebo did not differ significantly between melancholic and non-melancholic patients (treatment-by-melancholic status interactions were not statistically significant). Duloxetine demonstrated significantly greater improvement in depressive symptom severity, compared with placebo, within both melancholic and non-melancholic cohorts (p

Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

PubMed

Meng, Rongqin; Wang, Yang; He, Liang; He, Yuanqing; Du, Zedong

2018-04-01

Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.

Conducting Privacy-Preserving Multivariable Propensity Score Analysis When Patient Covariate Information Is Stored in Separate Locations.

PubMed

Bohn, Justin; Eddings, Wesley; Schneeweiss, Sebastian

2017-03-15

Distributed networks of health-care data sources are increasingly being utilized to conduct pharmacoepidemiologic database studies. Such networks may contain data that are not physically pooled but instead are distributed horizontally (separate patients within each data source) or vertically (separate measures within each data source) in order to preserve patient privacy. While multivariable methods for the analysis of horizontally distributed data are frequently employed, few practical approaches have been put forth to deal with vertically distributed health-care databases. In this paper, we propose 2 propensity score-based approaches to vertically distributed data analysis and test their performance using 5 example studies. We found that these approaches produced point estimates close to what could be achieved without partitioning. We further found a performance benefit (i.e., lower mean squared error) for sequentially passing a propensity score through each data domain (called the "sequential approach") as compared with fitting separate domain-specific propensity scores (called the "parallel approach"). These results were validated in a small simulation study. This proof-of-concept study suggests a new multivariable analysis approach to vertically distributed health-care databases that is practical, preserves patient privacy, and warrants further investigation for use in clinical research applications that rely on health-care databases. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The use of vitamin K supplementation to achieve INR stability: a systematic review and meta-analysis.

PubMed

Kramps, Melissa; Flanagan, Abigail; Smaldone, Arlene

2013-10-01

Systematically review and quantitatively synthesize evidence on use of oral vitamin K supplementation in reducing international normalized ratio (INR) variability. PubMed, The Cochrane Library, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Turning Research Into Practice (TRIP), Web of Science were searched for studies meeting predetermined inclusion/exclusion criteria. Five studies meeting criteria (three randomized trials, one quasi-experimental pre-post study, one retrospective case series) were appraised for quality and data synthesized by two reviewers. Pooled effect size of time in INR therapeutic range (TTR) was estimated using random effects meta-analysis. Pooled effect size representing data from four studies (678 subjects) was 0.31, 95% confidence interval 0.03-0.59 (Cochran Q = 7.1; p = .07; I(2) = 57.8) and favored vitamin K supplementation. Given wide variability among individual studies, there is not enough evidence to advise for or against the routine use of vitamin K supplementation to achieve INR stability. However, evidence does suggest that it may be of some benefit for some patients with INR instability. There is insufficient evidence to support routine supplementation with vitamin K in patients on chronic anticoagulation therapy but select patients, particularly those with persistent INR instability despite known adherence to regimen and no dietary or drug-drug interactions, may benefit from the intervention. Future research is warranted. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

PubMed Central

Griesdale, Donald E.G.; de Souza, Russell J.; van Dam, Rob M.; Heyland, Daren K.; Cook, Deborah J.; Malhotra, Atul; Dhaliwal, Rupinder; Henderson, William R.; Chittock, Dean R.; Finfer, Simon; Talmor, Daniel

2009-01-01

Background Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. Results We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU. PMID:19318387

Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials.

PubMed

Albers, Gregory W

2004-12-01

This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

Pooled Patient-Level Meta-analysis of Children and Adults Completing a Computer-Based Anxiety Intervention Targeting Attentional Bias

PubMed Central

Price, Rebecca B.; Wallace, Meredith; Kuckertz, Jennie M.; Amir, Nader; Graur, Simona; Cummings, Logan; Popa, Paul; Carlbring, Per; Bar-Haim, Yair

2016-01-01

Computer-based approaches, such as Attention Bias Modification (ABM), could help improve access to care for anxiety. Study-level meta-analyses of ABM have produced conflicting findings and leave critical questions unresolved regarding ABM’s mechanisms of action and clinical potential. We pooled patient-level datasets from randomized controlled trials of children and adults with high-anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was tested as an outcome and a mechanistic mediator and moderator of anxiety reduction. Diagnostic remission and Liebowitz Social Anxiety Scale (LSAS) were clinical outcomes available in enough studies to enable pooling. Per-patient data were obtained on at least one outcome from 13/16 eligible studies [86% of eligible participants; n=778]. Significant main effects of ABM on diagnostic remission (ABM—22.6%, control—10.8%; OR=2.57; p=.006) and AB (β*(95%CI)=−.63(−.83, −.42); p<.00005) were observed. There was no main effect of ABM on LSAS. However, moderator analyses suggested ABM was effective for patients who were younger (≤37y), trained in the lab, and/or assessed by clinicians. Under the same conditions where ABM was effective, mechanistic links between AB and anxiety reduction were supported. Under these specific circumstances, ABM reduces anxiety and acts through its target mechanism, supporting ABM’s theoretical basis while simultaneously suggesting clinical indications and refinements to improve its currently limited clinical potential. PMID:27693664

Comparing Clinical Characteristics and Outcomes of Young-onset and Late-onset Colorectal Cancer: An International Collaborative Study.

PubMed

Rho, Young Soo; Gilabert, Marine; Polom, Karol; Aladashvili, Archil; Kopeckova, Katerina; Megdanova, Vera; Coleman, Niamh; Greally, Megan; Marrelli, Daniele; Roviello, Franco; McDermott, Ray; Petrova, Veneta; Mihaylova, Zhasmina; Bortlicek, Zbynek; Prausova, Jana; Batist, Gerald; Azoulay, Laurent; Kavan, Petr

2017-12-01

Compared with the general population, the incidence of young-onset (YO) colorectal cancer (CRC) is increasing. However, a significant knowledge gap exists in the clinical characteristics, treatment patterns, and outcomes for these patients. Six international tertiary cancer centers conducted a retrospective study. Patients with YO CRC (aged 18-44 years) and LO CRC (aged > 44 years) diagnosed with histologically proven colorectal adenocarcinoma from June 2003 to June 2014 were enrolled. Patients were randomly chosen from each center's database, and the patient demographics and treatment information were collected. The data were then centralized, and the final analysis was performed at a single institution. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival and mortality, and YO was compared with LO. Site-specific HRs were pooled using a random-effects meta-analysis. Overall, 498 patients, including 224 with YO (129 men; mean age, 37 ± 5.5 years) and 274 with LO (167 men; mean age, 64.8 ± 9.5 years) CRC, were included. At the diagnosis, 137 patients (61.2%) and 122 patients (44.5%) with YO and LO CRC had metastatic disease, respectively. For both cohorts, the 3 most common presenting symptoms were pain, hematochezia, and weight loss. Surgery was performed in 141 YO (63.0%) and 219 LO (79.9%) patients. The longitudinal noncurative treatment patterns were similar, but more biologic therapy was used for these YO patients. The pooled progression-free survival analysis results for first-line noncurative treatment favored LO (HR, 1.96; 95% CI, 1.04-3.68). The mortality analysis showed no significant differences between the 2 groups (YO: HR, 1.53; 95% CI, 0.91-2.58). Despite similar treatment patterns and survival outcomes, YO disease might be clinically more aggressive. Copyright © 2017 Elsevier Inc. All rights reserved.

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials.

PubMed

Adsit, Sandra; Zaldivar, Enrique Rivas; Sofen, Howard; Dei-Cas, Ignacio; Maldonado-García, César; Peñaranda, Elkin O; Puig, Luís; Meng, Xiangyi; Fox, Todd; Guana, Adriana

2017-06-01

There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients. Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup. Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator's Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52. Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients. Novartis Pharmaceutical Corporation.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

PubMed

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

PubMed Central

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

Effect of adalimumab on work productivity and indirect costs in moderate to severe Crohn’s disease: A meta-analysis

PubMed Central

Binion, David G; Louis, Edouard; Oldenburg, Bas; Mulani, Parvez; Bensimon, Arielle G; Yang, Mei; Chao, Jingdong

2011-01-01

OBJECTIVE: To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn’s disease (CD) using a meta-analysis of clinical trials. METHODS: Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation. RESULTS: The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: −9% (−10% to −7%) for absenteeism; −22% (−26% to −18%) for presenteeism; and −25% (−30% to −20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively. CONCLUSION: Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer’s perspective. PMID:21912760

The Efficacy of Adenotonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review.

PubMed

Nation, Javan; Brigger, Matthew

2017-09-01

Objective Determine the efficacy of adenotonsillectomy in children with Down syndrome. Data Sources Databases included PubMed, EMBASE, CINAHL, and Google Scholar. The search was inclusive of all references available through January 5, 2017. Review Methods A systematic review of the medical literature addressing adenotonsillectomy in treating obstructive sleep apnea in children with Down syndrome was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were pooled using a random-effects model where possible. The quality of studies was graded using the Methodological Index for Nonrandomized Studies criteria. Results Of the 957 articles screened, 5 met inclusion for the qualitative analysis and 3 met criteria for the quantitative analysis. The findings of the qualitative analysis were that adenotonsillectomy has a positive effect on children with Down syndrome but in many cases is noncurative, up to 75% need postoperative breathing support, there is a high rate of immediate postoperative airway needs, and there is no change in sleep efficiency or architecture. The articles consistently reported moderate success in improving polysomnographic parameters, and limited pooling of the data demonstrated a mean decrease of the apnea-hypopnea index by 51% (95% confidence interval [CI], 46%-55%). Conclusion A 51% reduction in the preoperative apnea-hypopnea index can be expected with the intervention of adenotonsillectomy alone in children with Down syndrome. This information is useful for counseling and managing patient and family expectations. It also serves as a reminder to clinicians to obtain a postoperative sleep study, as many of these patients will need nighttime airway support or secondary sleep surgery.

The Impact of Aortic Occlusion Balloon on Mortality After Endovascular Repair of Ruptured Abdominal Aortic Aneurysms: A Meta-analysis and Meta-regression Analysis.

PubMed

Karkos, Christos D; Papadimitriou, Christina T; Chatzivasileiadis, Theodoros N; Kapsali, Nikoletta S; Kalogirou, Thomas E; Giagtzidis, Ioakeim T; Papazoglou, Konstantinos O

2015-12-01

We aimed to investigate whether the use of aortic occlusion balloon (AOB) has an impact on mortality of patients undergoing endovascular repair of ruptured abdominal aortic aneurysms (RAAAs). A meta-analysis of the English-language literature was undertaken through February 2013. Articles reporting data on outcome after endovascular repair of RAAAs were identified and information regarding the use of AOB was sought. Included in this meta-analysis were 39 eligible studies reporting 1277 patients. The pooled perioperative mortality was 21.6% (95% CI 18.1-25.1%). There was significant within-study heterogeneity (I(2) 50.2%, P < 0.001). A total of 200 patients required AOB with an estimated pooled proportion of 14.1% (8.9-19.3%). Individual random-effects meta-regression investigating the effect of AOB and other risk factors on mortality revealed a significant linear association of hemodynamic instability, bifurcated endograft approach, and primary conversion to open repair with mortality and a nonlinear (second degree polynomial) association of AOB with mortality. On multivariable meta-regression models, both hemodynamic instability and AOB were found to be statistically significant, independent predictors of mortality. In particular, there was a statistically significant negative correlation between AOB and mortality and a positive effect of hemodynamic instability on mortality. In practical terms, mortality was significantly higher in studies with a higher proportion of hemodynamically unstable patients and lower in studies with a higher rate of AOB use. This study provides meta-analytical evidence that the use of an AOB in unstable RAAA patients undergoing endovascular repair may improve the results.

Impact of remote ischaemic preconditioning on major clinical outcomes in patients undergoing cardiovascular surgery: A meta-analysis with trial sequential analysis of 32 randomised controlled trials.

PubMed

Wang, Shifei; Li, Hairui; He, Nvqin; Sun, Yili; Guo, Shengcun; Liao, Wangjun; Liao, Yulin; Chen, Yanmei; Bin, Jianping

2017-01-15

The impact of remote ischaemic preconditioning (RIPC) on major clinical outcomes in patients undergoing cardiovascular surgery remains controversial. We systematically reviewed the available evidence to evaluate the potential benefits of RIPC in such patients. PubMed, Embase, and Cochrane Library databases were searched for relevant randomised controlled trials (RCTs) conducted between January 2006 and March 2016. The pooled population of patients who underwent cardiovascular surgery was divided into the RIPC and control groups. Trial sequential analysis was applied to judge data reliability. The pooled relative risks (RRs) with 95% confidence intervals (CIs) between the groups were calculated for all-cause mortality, major adverse cardiovascular and cerebral events (MACCEs), myocardial infarction (MI), and renal failure. RIPC was not associated with improvement in all-cause mortality (RR, 1.04; 95%CI, 0.82-1.31; I 2 =26%; P>0.05) or MACCE incidence (RR, 0.90; 95%CI, 0.71-1.14; I 2 =40%; P>0.05) after cardiovascular surgery, and both results were assessed by trial sequential analysis as sufficient and conclusive. Nevertheless, RIPC was associated with a significantly lower incidence of MI (RR, 0.87; 95%CI, 0.76-1.00; I 2 =13%; P≤0.05). However, after excluding a study that had a high contribution to heterogeneity, RIPC was associated with increased rates of renal failure (RR, 1.53; 95%CI, 1.12-2.10; I 2 =5%; P≤0.05). In patients undergoing cardiovascular surgery, RIPC reduced the risk for postoperative MI, but not that for MACCEs or all-cause mortality, a discrepancy likely related to the higher rate of renal failure associated with RIPC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

PubMed Central

2014-01-01

Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

Targeted and Non-Targeted Analysis of Serum Pools to Provide Chemical Exposure Data for Exposure Modeling and Chemical Prioritization

EPA Science Inventory

Biomonitoring data can help inform the development and calibration of high-throughput exposure modeling for use in prioritization and risk evaluation. A pilot project was conducted to evaluate the feasibility of using pooled banked blood samples to generate initial data on popul...

The effectiveness of disease management programmes in reducing hospital re-admission in older patients with heart failure: a systematic review and meta-analysis of published reports.

PubMed

Gonseth, Jonás; Guallar-Castillón, Pilar; Banegas, José R; Rodríguez-Artalejo, Fernando

2004-09-01

To systematically evaluate the published evidence regarding the effectiveness of disease management programmes (DMPs) reducing hospital re-admissions among elderly patients with heart failure (HF). Computerised search of MEDLINE (1966 to 31 August 2003) and EMBASE (1966 to 31 August 2003). The Cochrane Library was also searched, and reference lists of review articles on the topic, and of all relevant studies identified, were scanned. Search and selection of studies, data-extraction using standardised forms, and assessment of study quality was performed by two reviewers. The end-point was the proportion of persons who underwent hospital re-admission, and pooled relative risks (RR) were used to summarise the effectiveness of DMPs. The meta-analysis included 54 articles, comprising 27 randomised and 27 non-randomised controlled studies. Randomised studies consistently suggested that, in comparison with usual care, DMP reduced the frequency of re-admission for HF or cardiovascular disease by 30% (pooled RR 0.70; confidence interval (CI) 95% 0.62-0.79), all-cause re-admission by 12% (pooled RR 0.88, 95% CI: 0.79-0.97), and the combined event of re-admission or death by 18% (pooled RR 0.82, 95% CI: 0.72-0.94). The results displayed no substantial variation when only DMPs with home visits, out-patient visits to a clinic, or patient follow-up longer than 6 months were included. For DMPs with out-patient clinical visits, however, the reduction in re-admission for HF or cardiovascular disease, and for all causes, did not attain statistical significance. The magnitude of DMP benefits reported by non-randomised studies was more than double that reported by randomised studies. Practically all the non-randomised studies failed to control for confounding factors, such as severity, co-morbidity and drug therapy. DMPs are effective at reducing re-admissions among elderly patients with HF. Their effectiveness is close to that observed in clinical trials evaluating drugs for HF, such as angiotensin-converting enzyme inhibitors, beta-blockers or digoxin. However, since none of the DMP studies compared different interventions directly, we do not know the relative effectiveness of types of healthcare delivery within the DMP.

Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis

PubMed Central

Giacco, Domenico; McCabe, Rose; Kallert, Thomas; Hansson, Lars; Fiorillo, Andrea; Priebe, Stefan

2012-01-01

Background Having friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships. Methods Data from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N = 1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale. Results Seven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms. Conclusions Higher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends. PMID:23185552

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

PubMed

Paramsothy, Sudarshan; Paramsothy, Ramesh; Rubin, David T; Kamm, Michael A; Kaakoush, Nadeem O; Mitchell, Hazel M; Castaño-Rodríguez, Natalia

2017-10-01

Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD. A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model. In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT. FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

The Effect of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) on Erectile Function: A Systematic Review and Meta-Analysis.

PubMed

Chen, Xiang; Zhou, ZhiRui; Qiu, XiaoChun; Wang, Bin; Dai, JiCan

2015-01-01

High prevalence of erectile dysfunction (ED) has been observed in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, whether or not CP/CPPS is a risk factor of ED remains unknown and controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between CP/CPPS and ED. PubMed, Embase, Web of Science, and The Cochrane Library were searched up to November 11, 2014 to identify studies reporting the association between CP/CPPS and ED. Case-control, cohort and cross-sectional studies were included. Quality of the included studies was assessed. The odds ratio of ED and the mean difference of five-item International Index of Erectile Function (IIEF-5) score were pooled using a random effects model. Subgroup analysis and sensitivity analyses were performed. Three cross-sectional studies, two case-control studies, and four retrospective studies with 31,956 participants were included to calculate the pooled odds ratio of ED, and two studies with 1499 participants were included to calculate the pooled mean difference of IIEF-5 scores. A strong correlation was found between CP/CPPS and ED (pooled odds ratio: 3.02, 95% CI: 2.18-4.17, P < 0.01), with heterogeneity across studies (I2 = 65%; P < 0.01). A significant decrease in the IIFE-5 score was observed in the CP/CPPS group (pooled mean difference: -4.54, 95% CI: -5.11--3.98; P < 0.01). Our study indicates that patients with CP/CPPS have an increased risk of suffering from ED. Assessment of erectile function is necessary for the therapy of patients with CP/CPPS. Further evidence is necessary to confirm the relationship between CP/CPPS and ED.

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials.

PubMed

Goss, G; Tsai, C-M; Shepherd, F A; Ahn, M-J; Bazhenova, L; Crinò, L; de Marinis, F; Felip, E; Morabito, A; Hodge, R; Cantarini, M; Johnson, M; Mitsudomi, T; Jänne, P A; Yang, J C-H

2018-03-01

Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases, and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261). Patients with T790M-positive advanced NSCLC, who had progressed following prior epidermal growth factor receptor-tyrosine kinase inhibitor treatment, received osimertinib 80 mg od (n = 411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment; prior CNS treatment was allowed. Patients with ≥1 measurable CNS lesion (per RECIST 1.1) on baseline brain scan by blinded independent central neuroradiology review (BICR) were included in the evaluable for CNS response set (cEFR). The primary outcome for this CNS analysis was CNS objective response rate (ORR) by BICR; secondary outcomes included CNS duration of response, disease control rate (DCR) and progression-free survival (PFS). Of 128 patients with CNS metastases on baseline brain scans, 50 were included in the cEFR. Confirmed CNS ORR and DCR were 54% [27/50; 95% confidence interval (CI) 39-68] and 92% (46/50; 95% CI 81-98), respectively. CNS response was observed regardless of prior radiotherapy to the brain. Median CNS duration of response (22% maturity) was not reached (range, 1-15 months); at 9 months, 75% (95% CI 53-88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable). The safety profile observed in the cEFR was consistent with the overall patient population. Osimertinib demonstrated clinically meaningful efficacy against CNS metastases, with a high DCR, encouraging ORR, and safety profile consistent with that reported previously. NCT01802632; NCT02094261.

Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis.

PubMed

Wells, Alvin F; Greenwald, Maria; Bradley, John D; Alam, Jahangir; Arora, Vipin; Kartman, Cynthia E

2018-06-01

This article evaluates the efficacy and safety of baricitinib 4 mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA). In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L were randomized to placebo or orally administered baricitinib 4 mg daily or subcutaneously administered adalimumab 40 mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6 mg/L were randomized to placebo or baricitinib 2 or 4 mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4 mg-treated, 716 placebo-treated patients). Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24. Baricitinib 4 mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups. Eli Lilly & Company and Incyte Corporation. ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.

Efficacy and safety of tofacitinib in older and younger patients with rheumatoid arthritis.

PubMed

Curtis, Jeffrey R; Schulze-Koops, Hendrik; Takiya, Liza; Mebus, Charles A; Terry, Ketti K; Biswas, Pinaki; Jones, Thomas V

2017-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the efficacy and safety of tofacitinib 5 or 10 mg twice daily (BID), in patients with moderate to severe RA, aged ≥65 and <65 years. Data were pooled from five Phase 3 trials and, separately, from two open-label long-term extension (LTE) studies (data cut-off April, 2012). Patients received tofacitinib, or placebo (Phase 3 only), with/without conventional synthetic DMARDs (mainly methotrexate). Clinical efficacy outcomes from Phase 3 studies were evaluated at Month 3. Safety evaluations using pooled Phase 3 data (Month 12) and pooled LTE data (Month 24) compared exposure-adjusted incidence rates (IRs; with 95% confidence intervals [CIs]), in older versus younger patients. In Phase 3 and LTE studies, 15.3% (475/3111) and 16.1% (661/4102) of patients, respectively, were aged ≥65 years. Consequently, exposure to tofacitinib was lower in older versus younger patients in Phase 3 (259.2 vs. 1554.9 patient years [pt-yrs]) and LTE (962.1 vs. 5071.7 pt-yrs) studies. Probability ratios for ACR responses and HAQ-DI improvement from baseline ≥0.22 (Month 3) favoured tofacitinib and were similar in older and younger patients, with overlapping CIs. IRs for SAEs and discontinuations due to AEs were generally numerically higher in older versus younger patients, irrespective of treatment. Older patients receiving tofacitinib 5 or 10 mg BID had a similar probability of ACR20 or ACR50 response and, due to comorbidities, a numerically higher risk of SAEs and discontinuations due to AEs compared with younger patients.

Peginesatide in patients with anemia undergoing hemodialysis.

PubMed

Fishbane, Steven; Schiller, Brigitte; Locatelli, Francesco; Covic, Adrian C; Provenzano, Robert; Wiecek, Andrzej; Levin, Nathan W; Kaplan, Mark; Macdougall, Iain C; Francisco, Carol; Mayo, Martha R; Polu, Krishna R; Duliege, Anne-Marie; Besarab, Anatole

2013-01-24

Peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease. We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point--death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia--with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide once monthly or continued to receive epoetin one to three times a week, with the doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher in the comparison of peginesatide with epoetin. The aim of evaluating the composite safety end point in the pooled cohort was to exclude a hazard ratio with peginesatide relative to the comparator ESA of more than 1.3. In an analysis involving 693 patients from EMERALD 1 and 725 from EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin levels (mean between-group difference, -0.15 g per deciliter; 95% confidence interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, -0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in the EMERALD studies. The proportions of patients with adverse and serious adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort. Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research.

PubMed

Schmucker, Christine M; Blümle, Anette; Schell, Lisa K; Schwarzer, Guido; Oeller, Patrick; Cabrera, Laura; von Elm, Erik; Briel, Matthias; Meerpohl, Joerg J

2017-01-01

A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data.

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research

PubMed Central

Blümle, Anette; Schell, Lisa K.; Schwarzer, Guido; Oeller, Patrick; Cabrera, Laura; von Elm, Erik; Briel, Matthias; Meerpohl, Joerg J.

2017-01-01

Background A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Methods and findings Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04–1.28 and 1.34, 95% CI 1.09–1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Conclusions Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data. PMID:28441452

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy.

PubMed

Iftikhar, Imran H; Alghothani, Lana; Sardi, Alejandro; Berkowitz, David; Musani, Ali I

2017-07-01

Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

Effects of Neck Radiation Therapy on Extra-Cranial Carotid Arteries Atherosclerosis Disease Prevalence: Systematic Review and a Meta-Analysis

PubMed Central

Bashar, Khalid; Healy, Donagh; Clarke-Moloney, Mary; Burke, Paul; Kavanagh, Eamon; Walsh, Stewart-Redmond

2014-01-01

Introduction Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli. Aim To evaluate the effect of radiation therapy on ECCA atherosclerosis progression. Methods Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT. Results Eight studies were included in the final analysis with total of 1070 patients – 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001). Conclusion The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT. PMID:25329500

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

PubMed

Poordad, Fred; Nelson, David R; Feld, Jordan J; Fried, Michael W; Wedemeyer, Heiner; Larsen, Lois; Cohen, Daniel E; Cohen, Eric; Mobashery, Niloufar; Tatsch, Fernando; Foster, Graham R

2017-10-01

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported. In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2). This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

PubMed Central

Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

2015-01-01

Background. Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61–2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61–2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma. PMID:26618165

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

PubMed

Saffian, S M; Duffull, S B; Wright, Dfb

2017-08-01

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Outcome trends and safety measures after 30 years of laparoscopic cholecystectomy: a systematic review and pooled data analysis.

PubMed

Pucher, Philip H; Brunt, L Michael; Davies, Neil; Linsk, Ali; Munshi, Amani; Rodriguez, H Alejandro; Fingerhut, Abe; Fanelli, Robert D; Asbun, Horacio; Aggarwal, Rajesh

2018-05-01

Laparoscopic cholecystectomy (LC), one of the most commonly performed surgical procedures, remains associated with significant major morbidity including bile leak and bile duct injury (BDI). The effect of changes in practice over time, and of interventions to improve patient safety, on morbidity rates is not well understood. The aim of this review was to describe current incidence rates and trends for BDI and other complications during and after LC, and to identify risk factors and preventative measures associated with morbidity and BDI. PubMed, MEDLINE, and Web of Science database searches and data extraction were conducted for studies which reported individual complications and complication rates following laparoscopic cholecystectomy in a representative population. Outcomes data were pooled. Meta-regression analysis was performed to assess factors associated with conversion, morbidity, and BDI rates. One hundred and fifty-one studies reporting outcomes for 505,292 patients were included in the final quantitative synthesis. Overall morbidity, BDI, and mortality rates were 1.6-5.3%, 0.32-0.52%, and 0.08-0.14%, respectively. Reported BDI rates reduced over time (1994-1999: 0.69(0.52-0.84)% versus 2010-2015 0.22(0.02-0.40)%, p = 0.011). Meta-regression analysis suggested higher conversion rates in developed versus developing countries (4.7 vs. 3.4%), though a greater degree of reporting bias was present in these studies, with no other significant associations identified. Overall, trends suggest a reduction in BDI over time with unchanged morbidity and mortality rates. However, data and reporting are heterogenous. Establishment of international outcomes registries should be considered.

PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease.

PubMed

Salameh, Habeeb; Raff, Evan; Erwin, Angelika; Seth, Devanshi; Nischalke, Hans Dieter; Falleti, Edmondo; Burza, Maria Antonella; Leathert, Julian; Romeo, Stefano; Molinaro, Antonio; Corradini, Stefano Ginanni; Toniutto, Pierluigi; Spengler, Ulrich; Ulrich, Spengler; Daly, Ann; Day, Christopher P; Kuo, Yong-Fang; Singal, Ashwani K

2015-06-01

The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity. Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I(2) statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses. Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients. PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.

Cortical thickness abnormalities in trichotillomania: international multi-site analysis.

PubMed

Chamberlain, Samuel R; Harries, Michael; Redden, Sarah A; Keuthen, Nancy J; Stein, Dan J; Lochner, Christine; Grant, Jon E

2018-06-01

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes.

Association of Malignancy Prevalence With Test Properties and Performance of the Gene Expression Classifier in Indeterminate Thyroid Nodules.

PubMed

Al-Qurayshi, Zaid; Deniwar, Ahmed; Thethi, Tina; Mallik, Tilak; Srivastav, Sudesh; Murad, Fadi; Bhatia, Parisha; Moroz, Krzysztof; Sholl, Andrew B; Kandil, Emad

2017-04-01

It is crucial for clinicians to know the malignancy prevalence within each indeterminate cytologic category to estimate the performance of the gene expression classifier (GEC). To examine the variability in the performance of the GEC. This retrospective cohort study of patients with Bethesda category III and IV thyroid nodules used single-institution data from January 1, 2013, through February 29, 2016. Expected negative predictive value (NPV) was calculated by adopting published sensitivity and specificity. Observed NPV was calculated based on the true-negative rate. Outcomes were compared with pooled data from 11 studies published January 1, 2010, to January 31, 2016. A total of 145 patients with 154 thyroid nodules were included in the study (mean [SD] age, 56.0 [16.2] years; 106 females [73.1%]). Malignancy prevalence was 45%. On the basis of this prevalence, the expected NPV is 85% and the observed NPV is 69%. If the prevalence is assumed to be 25%, the expected NPV would be 94%, whereas the observed NPV would be 85%. Pooled data analysis of 11 studies comprising 1303 participants revealed a malignancy prevalence of 31% (95% CI, 29%-34%) and a pooled NPV of 92% (95% CI, 87%-96%). In this study, variability in the performance of the GEC was not solely a function of malignancy prevalence and may have been attributable to intrinsic variability of the test sensitivity and specificity. The utility of the GEC in practice is elusive because of this variability. A better definition of the GEC's intrinsic properties is needed.

Implementation of a polling protocol for predicting celiac disease in videocapsule analysis.

PubMed

Ciaccio, Edward J; Tennyson, Christina A; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

2013-07-16

To investigate the presence of small intestinal villous atrophy in celiac disease patients from quantitative analysis of videocapsule image sequences. Nine celiac patient data with biopsy-proven villous atrophy and seven control patient data lacking villous atrophy were used for analysis. Celiacs had biopsy-proven disease with scores of Marsh II-IIIC except in the case of one hemophiliac patient. At four small intestinal levels (duodenal bulb, distal duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were analyzed. Twenty-four measurements were used for image characterization. These measurements were determined by quantitatively processing the videocapsule images via techniques for texture analysis, motility estimation, volumetric reconstruction using shape-from-shading principles, and image transformation. Each automated measurement method, or automaton, was polled as to whether or not villous atrophy was present in the small intestine, indicating celiac disease. Each automaton's vote was determined based upon an optimized parameter threshold level, with the threshold levels being determined from prior data. A prediction of villous atrophy was made if it received the majority of votes (≥ 13), while no prediction was made for tie votes (12-12). Thus each set of images was classified as being from either a celiac disease patient or from a control patient. Separated by intestinal level, the overall sensitivity of automata polling for predicting villous atrophy and hence celiac disease was 83.9%, while the specificity was 92.9%, and the overall accuracy of automata-based polling was 88.1%. The method of image transformation yielded the highest sensitivity at 93.8%, while the method of texture analysis using subbands had the highest specificity at 76.0%. Similar results of prediction were observed at all four small intestinal locations, but there were more tie votes at location 4 (ileum). Incorrect prediction which reduced sensitivity occurred for two celiac patients with Marsh type II pattern, which is characterized by crypt hyperplasia, but normal villous architecture. Pooled from all levels, there was a mean of 14.31 ± 3.28 automaton votes for celiac vs 9.67 ± 3.31 automaton votes for control when celiac patient data was analyzed (P < 0.001). Pooled from all levels, there was a mean of 9.71 ± 2.8128 automaton votes for celiac vs 14.32 ± 2.7931 automaton votes for control when control patient data was analyzed (P < 0.001). Automata-based polling may be useful to indicate presence of mucosal atrophy, indicative of celiac disease, across the entire small bowel, though this must be confirmed in a larger patient set. Since the method is quantitative and automated, it can potentially eliminate observer bias and enable the detection of subtle abnormality in patients lacking a clear diagnosis. Our paradigm was found to be more efficacious at proximal small intestinal locations, which may suggest a greater presence and severity of villous atrophy at proximal as compared with distal locations.

Implementation of a polling protocol for predicting celiac disease in videocapsule analysis

PubMed Central

Ciaccio, Edward J; Tennyson, Christina A; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

2013-01-01

AIM: To investigate the presence of small intestinal villous atrophy in celiac disease patients from quantitative analysis of videocapsule image sequences. METHODS: Nine celiac patient data with biopsy-proven villous atrophy and seven control patient data lacking villous atrophy were used for analysis. Celiacs had biopsy-proven disease with scores of Marsh II-IIIC except in the case of one hemophiliac patient. At four small intestinal levels (duodenal bulb, distal duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were analyzed. Twenty-four measurements were used for image characterization. These measurements were determined by quantitatively processing the videocapsule images via techniques for texture analysis, motility estimation, volumetric reconstruction using shape-from-shading principles, and image transformation. Each automated measurement method, or automaton, was polled as to whether or not villous atrophy was present in the small intestine, indicating celiac disease. Each automaton’s vote was determined based upon an optimized parameter threshold level, with the threshold levels being determined from prior data. A prediction of villous atrophy was made if it received the majority of votes (≥ 13), while no prediction was made for tie votes (12-12). Thus each set of images was classified as being from either a celiac disease patient or from a control patient. RESULTS: Separated by intestinal level, the overall sensitivity of automata polling for predicting villous atrophy and hence celiac disease was 83.9%, while the specificity was 92.9%, and the overall accuracy of automata-based polling was 88.1%. The method of image transformation yielded the highest sensitivity at 93.8%, while the method of texture analysis using subbands had the highest specificity at 76.0%. Similar results of prediction were observed at all four small intestinal locations, but there were more tie votes at location 4 (ileum). Incorrect prediction which reduced sensitivity occurred for two celiac patients with Marsh type II pattern, which is characterized by crypt hyperplasia, but normal villous architecture. Pooled from all levels, there was a mean of 14.31 ± 3.28 automaton votes for celiac vs 9.67 ± 3.31 automaton votes for control when celiac patient data was analyzed (P < 0.001). Pooled from all levels, there was a mean of 9.71 ± 2.8128 automaton votes for celiac vs 14.32 ± 2.7931 automaton votes for control when control patient data was analyzed (P < 0.001). CONCLUSION: Automata-based polling may be useful to indicate presence of mucosal atrophy, indicative of celiac disease, across the entire small bowel, though this must be confirmed in a larger patient set. Since the method is quantitative and automated, it can potentially eliminate observer bias and enable the detection of subtle abnormality in patients lacking a clear diagnosis. Our paradigm was found to be more efficacious at proximal small intestinal locations, which may suggest a greater presence and severity of villous atrophy at proximal as compared with distal locations. PMID:23858375

Mutational analysis of immunoglobulin E-binding epitopes of beta-casein and beta-lactoglobulin showed a heterogeneous pattern of critical amino acids between individual patients and pooled sera.

PubMed

Cocco, R R; Järvinen, K-M; Han, N; Beyer, K; Sampson, H A

2007-06-01

For immunotherapeutic approaches, 'critical' amino acids (AAs) within allergenic epitopes are replaced with alternate AAs to eliminate IgE antibody binding. To determine the critical AAs for IgE binding in beta-casein and beta-lactoglobulin (BLG). Peptides of 10-14 AAs in length were synthesized on a derivatized cellulose membrane with single AA substitutions (alanine or glycine) at each position. Membranes were incubated with a pool of sera from 15 cow's milk-allergic patients and individual sera from six of the 15 patients. In cases where no decrease in binding occurred with a single AA substitution, peptides with two AA substitutions were generated and labelled. Using pooled patient sera, single AA substitutions led to complete elimination of binding to six of 11 peptides for beta-casein and to all six peptides for BLG. Substituting two AAs led to an elimination of binding to four of the remaining five beta-casein epitopes. However, in three of the 11 modified beta-casein peptides and five of the six BLG peptides, no decrease in IgE binding occurred in at least one individual patient. For these patients, critical AAs other than those defined by the patient serum pool were identified, indicating a heterogeneous pattern of IgE recognition. These results indicate that AAs critical for IgE binding are more heterogeneous than initially defined by pooled milk-allergic patient sera. For future immunotherapeutic interventions with mutated peptides, critical AAs should also be identified with individual patient sera to account for heterogeneity of IgE binding between patients.

miRNAs as biomarkers for diagnosis of heart failure: A systematic review and meta-analysis.

PubMed

Yan, Hualin; Ma, Fan; Zhang, Yi; Wang, Chuan; Qiu, Dajian; Zhou, Kaiyu; Hua, Yimin; Li, Yifei

2017-06-01

With the rapid development of molecular biology, the kind of mircoRNA (miRNA) has been introduced into emerging role both in cardiac development and pathological procedure. Thus, we conduct this meta-analysis to find out the role of circulating miRNA as a biomarker in detecting heart failure. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials registry center to identify relevant studies up to August 2016. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 14.0 to estimate the publication bias and meta-regression. Besides, we took use of SPSS 17.0 to evaluate variance between several groups. Information on true positive, false positive, false negative, and true negative, as well as the quality of research was extracted. We use results from 10 articles to analyze the pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.74 (95% confidence interval [CI], 0.72 to 0.75); pooled specificity, 0.69 (95%CI, 0.67 to 0.71); and area under the summary receiver operating characteristic curves value (SROC), 0.7991. The miRNA-423-5p (miR-423-5p) detection was: pooled sensitivity, 0.81 (95%CI, 0.76 to 0.85); pooled specificity, 0.67 (95%CI, 0.61 to 0.73); and SROC, 0.8600. However, taken the same patients population, we extracted the data of BNP for detecting heart failure and performed meta-analysis with acceptable SROC as 0.9291. Among the variance analysis, the diagnostic performance of miR-423-5p claimed significant advantages of other pooled results. However, the combination of miRNAs and BNP could increase the accuracy of detecting of heart failure. Unfortunately, there was no dramatic advantage of miR-423-5p compared to BNP protocol. Despite interstudy variability, the performance test of miRNA for detecting heart failure revealed that miR-423-5p demonstrated the potential to be a biomarker. However, other miRNAs were not able to provide enough evidence on promising diagnostic value for heart failure based on the current data. Moreover, the combination of miRNAs and BNP could work as a better method to detection. Unfortunately, BNP was still the most convinced biomarker for such disease.

p-Akt as a potential poor prognostic factor for gastric cancer: a systematic review and meta-analysis.

PubMed

Cao, Fang; Zhang, Cong; Han, Wei; Gao, Xiao-Jiao; Ma, Jun; Hu, Yong-Wei; Gu, Xing; Ding, Hou-Zhong; Zhu, Li-Xia; Liu, Qin

2017-08-29

To understand the relationship between p-Akt expression and the prognosis of patients with gastric cancer, we searched six databases, Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang and CBM for relevant articles in order to conduct this metaanalysis. The pooled hazard ratios and corresponding 95%CI of overall survival were calculated to evaluate the prognostic value of p-Akt expression in patients with gastric cancer. With 2261 patients combined from 13 available studies, the pooled HR showed a poor prognosis in patients with gastric cancer in the univariate analysis (HR=1.88, 95%CI:1.45-2.43, P<0.00001), and the group "univariate analysis+estimate" (HR=1.41, 95%CI: 1.01-1.97, P=0.04), but not in multivariate analysis (HR=0.66, 95%CI: 0.29-1.52, P=0.33) and estimate (HR=1.13, 95%CI: 0.65-1.95, P=0.67). In conclusion, our results indicated that p-Akt was likely to be an indicator of poor prognosis in patients with gastric cancer.

Semi-Professional Rugby League Players have Higher Concussion Risk than Professional or Amateur Participants: A Pooled Analysis.

PubMed

King, Doug; Hume, Patria; Gissane, Conor; Clark, Trevor

2017-02-01

A combined estimate of injuries within a specific sport through pooled analysis provides more precise evidence and meaningful information about the sport, whilst controlling for between-study variation due to individual sub-cohort characteristics. The objective of this analysis was to review all published rugby league studies reporting injuries from match and training participation and report the pooled data estimates for rugby league concussion injury epidemiology. A systematic literature analysis of concussion in rugby league was performed on published studies from January 1990 to October 2015. Data were extracted and pooled from 25 studies that reported the number and incidence of concussions in rugby league match and training activities. Amateur rugby league players had the highest incidence of concussive injuries in match activities (19.1 per 1000 match hours) while semi-professional players had the highest incidence of concussive injuries in training activities (3.1 per 1000 training hours). This pooled analysis showed that, during match participation activities, amateur rugby league participants had a higher reported concussion injury rate than professional and semi-professional participants. Semi-professional participants had nearly a threefold greater concussion injury risk than amateur rugby league participants during match participation. They also had nearly a 600-fold greater concussion injury risk than professional rugby league participants during training participation.

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

PubMed Central

Lord, Richard; Burr, Nicholas E; Mohammed, Noor; Subramanian, Venkataraman

2018-01-01

AIM To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chromoendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). METHODS We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. RESULTS We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). CONCLUSION Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results. PMID:29563760

Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.

PubMed

Shen, Xiao-Ming; Zhou, Chong; Lian, Lian; Li, Li-Qun; Li, Wei; Tao, Min

2015-04-01

The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.

Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Zachary D.; Batra, Sachin; Limb, Charles J.

2011-11-15

Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data whenmore » Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test. Results: Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.« less

Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis

PubMed Central

Maher, Chris G; Ferreira, Manuela L; Ferreira, Paulo H; Hancock, Mark; Oliveira, Vinicius C; McLachlan, Andrew J; Koes, Bart

2012-01-01

Objective To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica. Design Systematic review. Data source International Pharmaceutical Abstracts, PsycINFO, Medline, Embase, Cochrane Central Register of Clinical Trials (CENTRAL), CINAHL, and LILACS. Study selection Randomised controlled trials assessing the efficacy and tolerability of drugs versus placebo or other treatment for sciatica. Data extraction Two independent reviewers extracted data and assessed methodological quality using the PEDro scale. Pain and disability outcomes were converted to a common 0 to 100 scale. Data were pooled with a random effects model, and the GRADE approach was used in summary conclusions. Results Twenty three published reports met the inclusion criteria. The evidence to judge the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and opioid analgesics ranged from moderate to low quality. Most of the pooled estimates did not favour the active treatment over placebo. The pooled results of two trials of corticosteroids (mean difference in overall and leg pain −12.2, 95% confidence interval −20.9 to −3.4) and a single trial of the anticonvulsant gabapentin for chronic sciatica (mean difference in overall pain relief −26.6, −38.3 to −14.9) showed some benefits but only in the short term. The median rate of adverse events was 17% (interquartile range 10-30%) for the active drugs and 11% (3-23%) for placebo. Trial limitations included failure to use validated outcome measures, lack of long term follow-up, and small sample size. Conclusions As the existing evidence from clinical trials is of low quality, the efficacy and tolerability of drugs commonly prescribed for the management of sciatica in primary care is unclear. PMID:22331277

Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis

PubMed Central

2012-01-01

Background To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow. PMID:23176540

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

PubMed

Wedam, Suparna B; Beaver, Julia A; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shenghui; Goldberg, Kirsten B; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Kluetz, Paul; McKee, Amy; Pazdur, Richard

2018-04-20

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

Infarct size, left ventricular function, and prognosis in women compared to men after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: results from an individual patient-level pooled analysis of 10 randomized trials.

PubMed

Kosmidou, Ioanna; Redfors, Björn; Selker, Harry P; Thiele, Holger; Patel, Manesh R; Udelson, James E; Magnus Ohman, E; Eitel, Ingo; Granger, Christopher B; Maehara, Akiko; Kirtane, Ajay; Généreux, Philippe; Jenkins, Paul L; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W

2017-06-01

Studies have reported less favourable outcomes in women compared with men after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). Whether sex-specific differences in the magnitude or prognostic impact of infarct size or post-infarction cardiac function explain this finding is unknown. We pooled patient-level data from 10 randomized primary PCI trials in which infarct size was measured within 1 month (median 4 days) by either cardiac magnetic resonance imaging or technetium-99m sestamibi single-photon emission computed tomography. We assessed the association between sex, infarct size, and left ventricular ejection fraction (LVEF) and the composite rate of death or heart failure (HF) hospitalization within 1 year. Of 2632 patients with STEMI undergoing primary PCI, 587 (22.3%) were women. Women were older than men and had a longer delay between symptom onset and reperfusion. Infarct size did not significantly differ between women and men, and women had higher LVEF. Nonetheless, women had a higher 1-year rate of death or HF hospitalization compared to men, and while infarct size was a strong independent predictor of 1-year death or HF hospitalization (P < 0.0001), no interaction was present between sex and infarct size or LVEF on the risk of death or HF hospitalization. In this large-scale, individual patient-level pooled analysis of patients with STEMI undergoing primary PCI, women had a higher 1-year rate of death or HF hospitalization compared to men, a finding not explained by sex-specific differences in the magnitude or prognostic impact of infarct size or by differences in post-infarction cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Spectrophotometry or visual inspection to most reliably detect xanthochromia in subarachnoid hemorrhage: systematic review.

PubMed

Chu, Kevin; Hann, Angus; Greenslade, Jaimi; Williams, Julian; Brown, Anthony

2014-09-01

We assess the sensitivity and specificity of xanthochromia as adjudicated by visual inspection and spectrophotometry at predicting the presence of cerebral aneurysm in patients with suspected subarachnoid hemorrhage who have a normal computed tomography (CT) head scan result. A systematic review was performed. MEDLINE and EMBASE databases were searched. Relevant studies with clinical data on the diagnostic accuracy of visual inspection or spectrophotometry were considered. Patients who had a normal CT head scan result followed by a lumbar puncture were included in this review. Sensitivities, specificities, and heterogeneity (I(2)) were calculated. Subgroup analyses were performed to explore reasons for the heterogeneity. There were major methodological limitations in the studies found. Twenty-two relevant articles were heterogeneous in regard to time to lumbar puncture, spectrophotometry methods, and follow-up of patients not undergoing cerebral angiography. Twelve of the 22 studies selected patients on the basis of a cerebral aneurysm or subarachnoid hemorrhage on imaging, or a positive lumbar puncture result. These studies were excluded from our initial analysis, which included only patients with clinically suspected subarachnoid hemorrhage. In this initial analysis, pooled estimates of sensitivity and specificity for spectrophotometry were 87% (95% confidence interval [CI] 71% to 96%; I(2)=26%) and 86% (95% CI 84% to 88%; I(2)=96%), respectively. For visual inspection, pooled sensitivity and specificity were 83% (95% CI 59% to 96%; I(2)=52%) and 96% (95% CI 93% to 97%; I(2)=76%), respectively. Sensitivity estimates are difficult to interpret without knowing time to lumbar puncture. The heterogeneity in the underlying studies, combined with significant overlap in pooled confidence limits, makes it impossible to provide a definite conclusion about the diagnostic accuracy of spectrophotometry versus visual inspection. Copyright © 2014 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis.

PubMed

Markar, Sheraz R; Arya, Shobhit; Karthikesalingam, Alan; Hanna, George B

2013-12-01

Due to the significant contribution of anastomotic leak, with its disastrous consequences to patient morbidity and mortality, multiple parameters have been proposed and individually meta-analyzed for the formation of the ideal esophagogastric anastomosis following cancer resection. The purpose of this pooled analysis was to examine the main technical parameters that impact on anastomotic integrity. Medline, Embase, trial registries, and conference proceedings were searched. Technical factors evaluated included hand-sewn versus stapled esophagogastric anastomosis (EGA), cervical versus thoracic EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. The outcome of interest was the incidence of anastomotic leak, for which pooled odds ratios were calculated for each technical factor. No significant difference in the incidence of anastomotic leak was demonstrated for the following technical factors: hand-sewn versus stapled EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. Four randomized, controlled trials comprising 298 patients were included that compared cervical and thoracic EGA. Anastomotic leak was seen more commonly in the cervical group (13.64 %) than in the thoracic group (2.96 %). Pooled analysis demonstrated a significantly increased incidence of anastomotic leak in the cervical group (pooled odds ratio = 4.73; 95 % CI 1.61-13.9; P = 0.005). A tailored surgical approach to the patient's physiology and esophageal cancer stage is the most important factor that influences anastomotic integrity after esophagectomy.

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments.

PubMed

Canver, Matthew C; Haeussler, Maximilian; Bauer, Daniel E; Orkin, Stuart H; Sanjana, Neville E; Shalem, Ophir; Yuan, Guo-Cheng; Zhang, Feng; Concordet, Jean-Paul; Pinello, Luca

2018-05-01

CRISPR (clustered regularly interspaced short palindromic repeats) genome-editing experiments offer enormous potential for the evaluation of genomic loci using arrayed single guide RNAs (sgRNAs) or pooled sgRNA libraries. Numerous computational tools are available to help design sgRNAs with optimal on-target efficiency and minimal off-target potential. In addition, computational tools have been developed to analyze deep-sequencing data resulting from genome-editing experiments. However, these tools are typically developed in isolation and oftentimes are not readily translatable into laboratory-based experiments. Here, we present a protocol that describes in detail both the computational and benchtop implementation of an arrayed and/or pooled CRISPR genome-editing experiment. This protocol provides instructions for sgRNA design with CRISPOR (computational tool for the design, evaluation, and cloning of sgRNA sequences), experimental implementation, and analysis of the resulting high-throughput sequencing data with CRISPResso (computational tool for analysis of genome-editing outcomes from deep-sequencing data). This protocol allows for design and execution of arrayed and pooled CRISPR experiments in 4-5 weeks by non-experts, as well as computational data analysis that can be performed in 1-2 d by both computational and noncomputational biologists alike using web-based and/or command-line versions.

Meta-analysis for aggregated survival data with competing risks: a parametric approach using cumulative incidence functions.

PubMed

Bonofiglio, Federico; Beyersmann, Jan; Schumacher, Martin; Koller, Michael; Schwarzer, Guido

2016-09-01

Meta-analysis of a survival endpoint is typically based on the pooling of hazard ratios (HRs). If competing risks occur, the HRs may lose translation into changes of survival probability. The cumulative incidence functions (CIFs), the expected proportion of cause-specific events over time, re-connect the cause-specific hazards (CSHs) to the probability of each event type. We use CIF ratios to measure treatment effect on each event type. To retrieve information on aggregated, typically poorly reported, competing risks data, we assume constant CSHs. Next, we develop methods to pool CIF ratios across studies. The procedure computes pooled HRs alongside and checks the influence of follow-up time on the analysis. We apply the method to a medical example, showing that follow-up duration is relevant both for pooled cause-specific HRs and CIF ratios. Moreover, if all-cause hazard and follow-up time are large enough, CIF ratios may reveal additional information about the effect of treatment on the cumulative probability of each event type. Finally, to improve the usefulness of such analysis, better reporting of competing risks data is needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A novel strategy using MASCOT Distiller for analysis of cleavable isotope-coded affinity tag data to quantify protein changes in plasma.

PubMed

Leung, Kit-Yi; Lescuyer, Pierre; Campbell, James; Byers, Helen L; Allard, Laure; Sanchez, Jean-Charles; Ward, Malcolm A

2005-08-01

A novel strategy consisting of cleavable Isotope-Coded Affinity Tag (cICAT) combined with MASCOT Distiller was evaluated as a tool for the quantification of proteins in "abnormal" patient plasma, prepared by pooling samples from patients with acute stroke. Quantification of all light and heavy cICAT-labelled peptide ion pairs was obtained using MASCOT Distiller combined with a proprietary software. Peptides displaying differences were selected for identification by MS. These preliminary results show the promise of our approach to identify potential biomarkers.

Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

PubMed

Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

2016-03-15

Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis.

PubMed

Park, Chan Hyuk; Kim, Eun Hye; Roh, Yun Ho; Kim, Ha Yan; Lee, Sang Kil

2014-01-01

Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis. We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics. Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%). PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.

Predictors of In-Hospital Mortality after Decompressive Hemicraniectomy for Malignant Ischemic Stroke.

PubMed

Kamran, Saadat; Salam, Abdul; Akhtar, Naveed; Alboudi, Aymen; Ahmad, Arsalan; Khan, Rabia; Nazir, Rashed; Nadeem, Muhammad; Inshasi, Jihad; ElSotouhy, Ahmed; Al Sulaiti, Ghanim; Shuaib, Ashfaq

2017-09-01

The purpose of this retrospective multicenter, pooled-data analysis was to determine the factors associated with in-hospital mortality in decompressive hemicraniectomy (DHC) for malignant middle cerebral artery (MMCA) stroke. The authors reviewed pooled DHC database from 3 countries for patients with MMCA with hospital mortality in spite of DHC to identify factors that predicted in-hospital mortality after DHC. The identified factors were applied to the group of patients who were selected for DHC but either refused surgery and died or stabilized and did not undergo DHC. There were 137 patients who underwent DHC. Multiple logistic regression analysis showed middle cerebral artery (MCA) with additional infarcts (odds ratio [OR], 7.9: 95% confidence interval [CI], 2.4-26; P = .001), preoperative midline shift of septum pellucidum of 1 cm or more (OR, 3.83: 95% CI, 1.13-12.96; P = .031), and patients who remained unconscious on day 7 postoperatively (8.82: 95% CI; OR, 1.08-71.9; P = .042) were significant independent predictors for in-hospital mortality. The identified factors were applied to the group of MMCA patients not operated (n = 19 refused, n = 47 stabilized) single (P < .001), and two predictive factors (P < .001) were significantly more common in patients who died. Whereas two predicative factors were identified in only 9%-18.2% of survivors, the presence of all three predictive factors was seen only in patients who expired (P < .001). The Hosmer-Lemeshow goodness-of-fit statistics (chi-square = 4.65; P value = .589) indicate that the model adequately describes the data. Direct physical factors, such as MCA with additional territory infarct, extent of midline shift, and postoperative consciousness level, bore a significant relationship to in-hospital mortality in MMCA patients undergoing DHC. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical inertia in the pharmacological management of hypertension: A systematic review and meta-analysis.

PubMed

Milman, Tal; Joundi, Raed A; Alotaibi, Naif M; Saposnik, Gustavo

2018-06-01

Clinical Inertia is defined as "failure of health care providers to initiate or intensify therapy according to current guidelines". This phenomenon is gaining increasing attention as a major cause of clinicians' failure to adequately manage hypertension, thus leading to an increased incidence of cardiovascular events. We performed a systematic review and meta-analysis of randomized controlled trials to determine whether interventions aimed at reducing clinical inertia in the pharmacological treatment of hypertension improve blood pressure (BP) control. MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched from the start of their database until October 3, 2017 for the MESH terms "Hypertension" or "Blood Pressure", their subheadings, and the keywords "Therapeutic Inertia" or "Clinical Inertia". Studies were included if they addressed pharmacologic hypertension management, clinical inertia, were randomized controlled trials, reported an outcome describing prescriber behavior, and were available in English. Data for the included studies was extracted by two independent observers. Quality of studies was analyzed using the Cochrane Risk of Bias Assessment. Data was pooled for statistical analysis using both fixed- and random-effects models. The primary study outcome was the percentage of patients achieving blood pressure control as defined by the Joint National Committee guidelines or study authors. Of 474 citations identified, ten met inclusion criteria comprising a total of 26,871 patients, and eight were selected for meta-analysis. Interventions included Physician Education, Physician Reminders, Patient Education, Patient Reminders, Ambulatory BP Monitoring, Digital Medication Offerings, Physician Peer Visits, and Pharmacist-led Counselling. Pooled event rates revealed more patients with controlled BP in the intervention group versus control (55%, 95% CI 46-63% versus 45%, 95% CI 37-53%) and interventions significantly improved the odds of BP control (OR = 1.19, 95% CI = 1.12-1.27, P < .001). Heterogeneity in the quantitative analysis was moderate. Addressing clinical inertia through physician reminders, ambulatory BP monitoring, and educational interventions for primary care providers was associated with an improvement in blood pressure control. Our findings encourage further research to investigate strategies at reducing clinical inertia in the management of hypertension.

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies.

PubMed

Rule, Simon; Dreyling, Martin; Goy, Andre; Hess, Georg; Auer, Rebecca; Kahl, Brad; Cavazos, Nora; Liu, Black; Yang, Shiyi; Clow, Fong; Goldberg, Jenna D; Beaupre, Darrin; Vermeulen, Jessica; Wildgust, Mark; Wang, Michael

2017-11-01

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease. © 2017 John Wiley & Sons Ltd.

Effects of endovascular cooling on infarct size in ST-segment elevation myocardial infarction: A patient-level pooled analysis from randomized trials.

PubMed

Dae, Michael; O'Neill, William; Grines, Cindy; Dixon, Simon; Erlinge, David; Noc, Marko; Holzer, Michael; Dee, Anne

2018-06-01

This study sought to examine the relationship between temperature at reperfusion and infarct size. Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent. We performed a patient-level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single-photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR). In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4-25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1-19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re-infarction due to stent thrombosis between hypothermia and control patients. The present study, drawn from a patient-level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion. © 2017 The Authors. Journal of Interventional Cardiology Published by Wiley Periodicals, Inc.

Bone mineral density is decreased in fibromyalgia syndrome: a systematic review and meta-analysis.

PubMed

Upala, Sikarin; Yong, Wai Chung; Sanguankeo, Anawin

2017-04-01

Previous studies have shown that fibromyalgia syndrome (FMS) is associated with low level of physical activity and exercise, which may lead to an increased risk of osteoporosis. However, studies of bone mineral density (BMD) in fibromyalgia have shown conflicting results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between FMS and BMD. A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through May 2016. The inclusion criterion was the observational studies' assessment of the association between fibromyalgia and bone mineral density in adult subjects. Fibromyalgia was diagnosed in accordance with the American College of Rheumatology criteria for the diagnosis of fibromyalgia syndrome. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Pooled mean difference (MD) of BMD at each site and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The between-study heterogeneity of effect size was quantified using the Q statistic and I 2 . Data were extracted from four observational studies involving 680 subjects. At lumbar spine (L2-L4), BMD is significantly decreased in patients with FMS compared with controls with pooled MD of -0.02 (95% CI -0.03 to -0.01, P value = 0.003, I 2  = 0%) (Fig. 1). At femoral neck, BMD is not significantly decreased in patients with FMS compared with controls with pooled MD of 0.01 (95% CI -0.02 to 0.01, P value = 0.23, I 2  = 0%) (Fig. 2). In this meta-analysis, we observe that BMD at lumbar spine is decreased in FMS compared with normal individuals. Patients with FMS should be assessed for risk of osteoporosis. Fig. 1 Forest plot of bone mineral density at the lumbar spine, for patients with and without fibromyalgia syndrome. CI-confidence interval Fig. 2 Forest plot of bone mineral density at the femoral neck, for patients with and without fibromyalgia syndrome. CI-confidence interval.

Statistical model specification and power: recommendations on the use of test-qualified pooling in analysis of experimental data

PubMed Central

Colegrave, Nick

2017-01-01

A common approach to the analysis of experimental data across much of the biological sciences is test-qualified pooling. Here non-significant terms are dropped from a statistical model, effectively pooling the variation associated with each removed term with the error term used to test hypotheses (or estimate effect sizes). This pooling is only carried out if statistical testing on the basis of applying that data to a previous more complicated model provides motivation for this model simplification; hence the pooling is test-qualified. In pooling, the researcher increases the degrees of freedom of the error term with the aim of increasing statistical power to test their hypotheses of interest. Despite this approach being widely adopted and explicitly recommended by some of the most widely cited statistical textbooks aimed at biologists, here we argue that (except in highly specialized circumstances that we can identify) the hoped-for improvement in statistical power will be small or non-existent, and there is likely to be much reduced reliability of the statistical procedures through deviation of type I error rates from nominal levels. We thus call for greatly reduced use of test-qualified pooling across experimental biology, more careful justification of any use that continues, and a different philosophy for initial selection of statistical models in the light of this change in procedure. PMID:28330912

Genetic variation in the TNF/TRAF2/ASK1/p38 kinase signaling pathway as markers for postoperative pulmonary complications in lung cancer patients.

PubMed

Hildebrandt, Michelle A T; Roth, Jack A; Vaporciyan, Ara A; Pu, Xia; Ye, Yuanqing; Correa, Arlene M; Kim, Jae Y; Swisher, Stephen G; Wu, Xifeng

2015-07-13

Post-operative pulmonary complications are the most common morbidity associated with lung resection in non-small cell lung cancer (NSCLC) patients. The TNF/TRAF2/ASK1/p38 kinase pathway is activated by stress stimuli and inflammatory signals. We hypothesized that genetic polymorphisms within this pathway may contribute to risk of complications. In this case-only study, we genotyped 173 germline genetic variants in a discovery population of 264 NSCLC patients who underwent a lobectomy followed by genotyping of the top variants in a replication population of 264 patients. Complications data was obtained from a prospective database at MD Anderson. MAP2K4:rs12452497 was significantly associated with a decreased risk in both phases, resulting in a 40% reduction in the pooled population (95% CI:0.43-0.83, P = 0.0018). In total, seven variants were significant for risk in the pooled analysis. Gene-based analysis supported the involvement of TRAF2, MAP2K4, and MAP3K5 as mediating complications risk and a highly significant trend was identified between the number of risk genotypes and complications risk (P = 1.63 × 10(-8)). An inverse relationship was observed between association with clinical outcomes and complications for two variants. These results implicate the TNF/TRAF2/ASK1/p38 kinase pathway in modulating risk of pulmonary complications following lobectomy and may be useful biomarkers to identify patients at high risk.

Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

PubMed

Al-Adra, D P; Gill, R S; Axford, S J; Shi, X; Kneteman, N; Liau, S-S

2015-01-01

Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

PubMed Central

Tian, Yun; Wang, Jirong; Ye, Ying; Sun, Liqun; Fan, Yingrui; Wang, Li; Li, Juan; Wang, Zhaoxia; Wang, Keming

2014-01-01

To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN. PMID:25029444

Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease: A Meta-Analysis.

PubMed

Wagle Shukla, Aparna; Shuster, Jonathan J; Chung, Jae Woo; Vaillancourt, David E; Patten, Carolynn; Ostrem, Jill; Okun, Michael S

2016-04-01

Several studies have reported repetitive transcranial magnetic stimulation (rTMS) therapy as an effective treatment for the control of motor symptoms in Parkinson disease. The objective of the study is to quantify the overall efficacy of this treatment. Systematic review and meta-analysis. We reviewed the literature on clinical rTMS trials in Parkinson disease since the technique was introduced in 1980. We used the following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. Patients with Parkinson disease who were participating in prospective clinical trials that included an active arm and a control arm and change in motor scores on Unified Parkinson's Disease Rating Scale as the primary outcome. We pooled data from 21 studies that met these criteria. We then analyzed separately the effects of low- and high-frequency rTMS on clinical motor improvements. The overall pooled mean difference between treatment and control groups in the Unified Parkinson's Disease Rating Scale motor score was significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS therapy was effective when low-frequency stimulation (≤ 1 Hz) was used with a pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P = .005). There was a trend for significance when high-frequency stimulation (≥ 5 Hz) studies were evaluated with a pooled mean difference of 3.9 points (95% confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at short-term follow-up (immediately after a treatment protocol) with a pooled mean difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1 points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient data to statistically analyze the effects of rTMS when we specifically examined bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods. rTMS therapy in patients with Parkinson disease results in mild-to-moderate motor improvements and has the potential to be used as an adjunct therapy for the treatment of Parkinson disease. Future large, sample studies should be designed to isolate the specific clinical features of Parkinson disease that respond well to rTMS therapy. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

PubMed

Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

2014-09-01

Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Prophylactic cranial irradiation in resected small cell lung cancer: A systematic review with meta-analysis

PubMed Central

Yang, Yang; Zhang, Danhong; Zhou, Xia; Bao, Wuan; Ji, Yonglin; Sheng, Liming; Cheng, Lei; Chen, Ying; Du, Xianghui; Qiu, Guoqin

2018-01-01

Background: The use of PCI in early operable patients with small cell lung cancer (SCLC) is still controversial. Therefore, we conducted a systematic review with meta-analysis to investigate the effects of PCI in resected SCLC patients. Methods: Relevant studies were identified from PubMed and EMBASE databases, the pooled hazard risks were obtained by the random-effects model. We also analyzed the brain metastasis (BM) risk in p-stage I patients without PCI. Results: Five retrospective studies were identified and a total of 1691 patients were included in our analysis, 315 of them received PCI. For all the resected patients, PCI was associated with improved overall survival (HR: 0.52, 95% CI: 0.33-0.82), and reduced brain metastasis risk (RR: 0.50, 95%CI: 0.32-0.78). However, with regard to p-stage I patients, no survival benefit was brought by PCI (HR: 0.87, 95% CI: 0.34-2.24). Moreover, the pooled analysis of 7 studies found that the 5-year brain metastasis risk was relatively low (12%, 95% CI: 8%-17%) for p-stage I patients without PCI. Conclusions: PCI might be associated with a favorable survival advantage and reduced BM risk in complete resected SCLC patients, except for p-stage I patients. PMID:29344290

Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy.

PubMed

Selmer, Randi; Haglund, Bengt; Furu, Kari; Andersen, Morten; Nørgaard, Mette; Zoëga, Helga; Kieler, Helle

2016-10-01

Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Diagnostic accuracy of CT in assessing extra-regional lymphadenopathy in pancreatic and peri-ampullary cancer: a systematic review and meta-analysis.

PubMed

Tseng, Dorine S J; van Santvoort, Hjalmar C; Fegrachi, Samira; Besselink, Marc G; Zuithoff, Nicolaas P A; Borel Rinkes, Inne H; van Leeuwen, Maarten S; Molenaar, I Quintus

2014-12-01

Computed tomography (CT) is the most widely used method to assess resectability of pancreatic and peri-ampullary cancer. One of the contra-indications for curative resection is the presence of extra-regional lymph node metastases. This meta-analysis investigates the accuracy of CT in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. We systematically reviewed the literature according to the PRISMA guidelines. Studies reporting on CT assessment of extra-regional lymph nodes in patients undergoing pancreatoduodenectomy were included. Data on baseline characteristics, CT-investigations and histopathological outcomes were extracted. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were calculated for individual studies and pooled data. After screening, 4 cohort studies reporting on CT-findings and histopathological outcome in 157 patients with pancreatic or peri-ampullary cancer were included. Overall, diagnostic accuracy, specificity and NPV varied from 63 to 81, 80-100% and 67-90% respectively. However, PPV and sensitivity ranged from 0 to 100% and 0-38%. Pooled sensitivity, specificity, PPV and NPV were 25%, 86%, 28% and 84% respectively. CT has a low diagnostic accuracy in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Therefore, suspicion of extra-regional lymph node metastases on CT alone should not be considered a contra-indication for exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis.

PubMed

van der Waaij, Laurens A; van Dullemen, Hendrik M; Porte, Robert J

2005-09-01

Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the value of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. A search in PubMed was performed with the search terms cyst, pancrea, and fluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scatter grams. Cutoff levels were determined. Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% of MCAC (n = 111). Most pancreatic cystic tumors should be resected without the need for cyst fluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine the optimal therapeutic strategy.

Advantages of Integrative Data Analysis for Developmental Research

ERIC Educational Resources Information Center

Bainter, Sierra A.; Curran, Patrick J.

2015-01-01

Amid recent progress in cognitive development research, high-quality data resources are accumulating, and data sharing and secondary data analysis are becoming increasingly valuable tools. Integrative data analysis (IDA) is an exciting analytical framework that can enhance secondary data analysis in powerful ways. IDA pools item-level data across…

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure.

PubMed

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-05-01

Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): -2.65 to -0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = -0.25 mg/dL; 95% CI: -0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64-1.56; p = 0.993). Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

PubMed Central

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-01-01

Introduction Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed. PMID:25626761

Multiple incentives in encouraging car pool formation on a university campus

PubMed Central

Jacobs, Harvey E.; Fairbanks, David; Poche, Cheryl E.; Bailey, Jon S.

1982-01-01

The effects of a combined token economy and reserved parking program were evaluated as a means of increasing car pooling among students on a university campus. Following a baseline period, students in two experimental parking lots were notified of the availability of reserved parking and coupons redeemable for 25 cents in merchandise for each occupant of automobiles containing two or more people. Two control lots also were monitored for a comparison of treatment effects. Results indicated variable increases in car pooling in the two experimental lots and no increase in the control lots. Removal of the 25-cent coupons from one treatment lot (reserved parking only) did not adversely affect rates of car pooling. An analysis of individual automobile occupancy rates among car poolers indicated distinct patterns of car pooling and underscored the importance of individual subject data analysis in the present situation. A cost-benefit analysis indicated that even moderately effective car pool programs can be cost-effective on both a public and personal level. PMID:16795653

Capturing the true burden of dystonia on patients: the Cervical Dystonia Impact Profile (CDIP-58).

PubMed

Cano, S J; Warner, T T; Linacre, J M; Bhatia, K P; Thompson, A J; Fitzpatrick, R; Hobart, J C

2004-11-09

To develop a new rating scale for measuring the health impact of cervical dystonia (CD) that includes patients' perceptions and complements existing observer dependent clinician rating scales. Scale development was in three stages. In Stage 1, a large pool of items was generated from patient interviews (n = 25), expert opinion, and literature review. In Stage 2, these items were administered by postal survey to people with CD. The resulting data were analyzed using Rasch item analysis to construct, from the item pool, a rating scale that satisfied criteria for rigorous measurement. In Stage 3, the measurement properties of this rating scale were examined in an independent sample of people with CD. In Stage 1, 150 items concerning the health impact of CD were generated. In Stage 2, 556 people completed questionnaires (87% response rate) and a 58-item rating scale measuring the health impact of CD in eight areas was constructed (CD Impact Profile, CDIP-58). In Stage 3, CDIP-58 data from 391 people (87% response rate) were received. Analyses supported the measurement of eight unidimensional constructs (infit mean square range 0.62 to 1.50), item calibration (33.37 to 67.56), and patient separation statistics (2.59 to 3.38). Items demonstrated stable calibrations in subgroups of people with CD supporting the stability of the CDIP-58. The CDIP-58 is a reliable and valid patient-based rating scale measuring the health impact of CD in eight health dimensions.

Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis.

PubMed

Schweizer, Marin; Perencevich, Eli; McDanel, Jennifer; Carson, Jennifer; Formanek, Michelle; Hafner, Joanne; Braun, Barbara; Herwaldt, Loreen

2013-06-13

To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures. Systematic review and meta-analysis. PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and clinicaltrials.gov were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed. Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care. Patients undergoing cardiac operations or total joint replacement procedures. DATA EXTRACTION AND STUDY APPRAISAL: Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I(2) statistics. 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with Staphylococcus aureus (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only S aureus carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant S aureus (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible S aureus infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56). Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by S aureus or other Gram positive bacteria.

The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PubMed

Asherson, P; Stes, S; Nilsson Markhed, M; Berggren, L; Svanborg, P; Kutzelnigg, A; Deberdt, W

2015-06-01

To investigate the effects of atomoxetine on emotional control in adults with ADHD. We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life. Copyright © 2015. Published by Elsevier Masson SAS.

Usefulness of the admission electrocardiogram to predict long-term outcomes after non-ST-elevation acute coronary syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials).

PubMed

Damman, Peter; Holmvang, Lene; Tijssen, Jan G P; Lagerqvist, Bo; Clayton, Tim C; Pocock, Stuart J; Windhausen, Fons; Hirsch, Alexander; Fox, Keith A A; Wallentin, Lars; de Winter, Robbert J

2012-01-01

The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data. Copyright © 2012 Elsevier Inc. All rights reserved.

Persistent right ventricular dysfunction, functional capacity limitation, exercise intolerance, and quality of life impairment following pulmonary embolism: Systematic review with meta-analysis.

PubMed

Sista, Akhilesh K; Miller, Larry E; Kahn, Susan R; Kline, Jeffrey A

2017-02-01

Long-term right ventricular (RV) function, functional capacity, exercise capacity, and quality of life following pulmonary embolism (PE), and the impact of thrombolysis, are unclear. A systematic review of studies that evaluated these outcomes with ⩾ 3-month mean follow-up after PE diagnosis was performed. For each outcome, random effects meta-analyses were performed. Twenty-six studies (3671 patients) with 18-month median follow-up were included. The pooled prevalence of RV dysfunction was 18.1%. Patients treated with thrombolysis had a lower, but not statistically significant, risk of RV dysfunction versus those treated with anticoagulation (odds ratio: 0.51, 95% CI: 0.24 to 1.13, p=0.10). Pooled prevalence of at least mild functional impairment (NYHA II-IV) was 33.2%, and at least moderate functional impairment (NYHA III-IV) was 11.3%. Patients treated with thrombolysis had a lower, but not statistically significant, risk of at least moderate functional impairment versus those treated with anticoagulation (odds ratio: 0.48, 95% CI: 0.15 to 1.49, p=0.20). Pooled 6-minute walk distance was 415 m (95% CI: 372 to 458 m), SF-36 Physical Component Score was 44.8 (95% CI: 43 to 46), and Pulmonary Embolism Quality of Life (QoL) Questionnaire total score was 9.1. Main limitations included heterogeneity among studies for many outcomes, variation in the completeness of data reported, and inclusion of data from non-randomized, non-controlled, and retrospective studies. Persistent RV dysfunction, impaired functional status, diminished exercise capacity, and reduced QoL are common in PE survivors. The effect of thrombolysis on RV function and functional status remains unclear.

Does access to clinical study reports from the European Medicines Agency reduce reporting biases? A systematic review and meta-analysis of randomized controlled trials on the effect of erythropoiesis-stimulating agents in cancer patients

PubMed Central

Grabik, Michael; Tonia, Thomy; Jüni, Peter; Pétavy, Frank; Pignatti, Francesco

2017-01-01

Since 2010, the European Medicines Agency (EMA) has provided access to clinical study reports (CSRs). We requested CSRs for randomized controlled trials (RCTs) of erythropoiesis-stimulating agents (ESAs) in cancer patients from EMA and identified RCT publications with literature searches. We assessed CSR availability and completeness, the impact of unreported and unpublished data obtained from CSRs on the effects of ESAs on quality of life (QoL) of cancer patients, and discrepancies between data reported in the public domain and in CSRs. We used random-effects meta-analyses to evaluate the effect of ESAs on QoL measured with Functional Assessment of Cancer Therapy-Anemia (FACT-An), FACT-Fatigue (FACT-F) and FACT-Anemia Total (FACT-An Total) stratified by data source and the impact of discrepancies on QoL, mortality, adverse events, and clinical effectiveness outcomes. We identified 94 eligible RCTs; CSRs or other study documentation were available for 17 (18%) RCTs at EMA. Median report length was 1,825 pages (range 72–14,569). Of 180 outcomes of interest reported in the EMA documentation, 127 (71%) were publicly available. For 80 of those (63%) we noted discrepancies, but these had little impact on the pooled effect estimates. Of 27 QoL outcomes reported in the CSRs, 17 (63%) were unpublished. Including six unpublished comparisons (pooled mean difference [MD] 0.20; 95% confidence interval [CI] -1.93, 2.33) reduced the pooled effect of ESAs for FACT-An from MD 5.51 (95% CI 4.20, 6.82) in published data to MD 3.21 (95% CI 1.38, 5.03), which is below a clinically important difference (defined as MD ≥4). Effects were similar for FACT-F and FACT-An Total. Access to CSRs from EMA reduced reporting biases for QoL outcomes. However, EMA received documentation for a fraction of all RCTs on effects of ESAs in cancer patients. Additional efforts by other agencies and institutions are needed to make CSRs universally available for all RCTs. PMID:29228059

Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials.

PubMed

Koenighofer, Martin; Lion, Thomas; Bodenteich, Angelika; Prieschl-Grassauer, Eva; Grassauer, Andreas; Unger, Hermann; Mueller, Christian A; Fazekas, Tamás

2014-01-01

Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3-5 (visit 2). Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. Pooled data from ISRCTN52519535 and ISRCTN80148028.

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies

PubMed Central

2012-01-01

Background For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields. PMID:22862891

Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis.

PubMed

Liu, Xuefang; Ming, Xinliang; Jing, Wei; Luo, Ping; Li, Nandi; Zhu, Man; Yu, Mingxia; Liang, Chunzi; Tu, Jiancheng

2018-05-11

Aims: Increasing studies are indicating that long non-coding RNA X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focused our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. Methods: We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to January 3, 2018). Fifteen studies which matched to our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Results: Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR=1.81, 95% CI: 1.45-2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR=2.24, 95% CI: 1.73-2.92) than in non-digestive system tumors (pooled HR=1.22, 95% CI: 0.60-2.45). Additionally, elevated expression levels of XIST were connection with distant metastasis and tumor stage. Conclusion: XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors. ©2018 The Author(s).

Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis.

PubMed

Zheng, Qiaomei; Mao, Hongluan; Xu, Ying; Zhao, Jing; Wei, Xuan; Liu, Peishu

2016-07-01

To investigate whether postoperative GnRH agonist (GnRH-a) treatment can prevent endometriosis recurrence. This meta-analysis searched PubMed, Embase and Cochrane Library for relevant studies published online before June 2015. Seven randomized controlled trials including 328 patients with postoperative GnRH-a treatment and 394 patients in control group were included in the meta-analysis. In the meta-analysis, the recurrence rate of GnRH-a group compared with control group was evaluated with odds ratio (OR) and its 95 % confidence interval (CI). Heterogeneity, small study effect and publication bias were, respectively, assessed using Higgins I (2), sensitivity analysis and funnel plot. Postoperative GnRH-a treatment for endometriosis (pooled OR = 0.71; 95 % CI 0.52-0.96) was superior to expectant or placebo treatment in prevention of the recurrence. The recurrence rate decreased significantly in patients who received 6 months GnRH-a treatment (pooled OR = 0.59, 95 % CI 0.38-0.90), whereas no significant difference of recurrence rate existed between patients with 3 months post-surgical GnRH-a therapy and the control group (pooled OR = 0.87, 95 % CI 0.56-1.34). No significant heterogeneity and small study effect were found in the meta-analysis. However, publication bias did existed in the present meta-analysis. Longer-term (6 months) postoperative administration of GnRH-a can decrease the recurrence risk of endometriosis, whereas 3 months duration of GnRH-a therapy makes no significant difference in preventing the recurrence of endometriosis. Therefore, instead of a 3 month therapy, the duration of the postoperative administration should be longer enough (6 months) to prevent the recurrence of endometriosis.

Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer.

PubMed

Morcos, Peter N; Nueesch, Eveline; Jaminion, Felix; Guerini, Elena; Hsu, Joy C; Bordogna, Walter; Balas, Bogdana; Mercier, Francois

2018-05-10

Alectinib is a selective and potent anaplastic lymphoma kinase (ALK) inhibitor that is active in the central nervous system (CNS). Alectinib demonstrated robust efficacy in a pooled analysis of two single-arm, open-label phase II studies (NP28673, NCT01801111; NP28761, NCT01871805) in crizotinib-resistant ALK-positive non-small-cell lung cancer (NSCLC): median overall survival (OS) 29.1 months (95% confidence interval [CI]: 21.3-39.0) for alectinib 600 mg twice daily (BID). We investigated exposure-response relationships from final pooled phase II OS and safety data to assess alectinib dose selection. A semi-parametric Cox proportional hazards model analyzed relationships between individual median observed steady-state trough concentrations (C trough,ss ) for combined exposure of alectinib and its major metabolite (M4), baseline covariates (demographics and disease characteristics) and OS. Univariate logistic regression analysis analyzed relationships between C trough,ss and incidence of adverse events (AEs: serious and Grade ≥ 3). Overall, 92% of patients (n = 207/225) had C trough,ss data and were included in the analysis. No statistically significant relationship was found between C trough,ss and OS following alectinib treatment. The only baseline covariates that statistically influenced OS were baseline tumor size and prior crizotinib treatment duration. Larger baseline tumor size and shorter prior crizotinib treatment were both associated with shorter OS. Logistic regression confirmed no significant relationship between C trough,ss and AEs. Alectinib 600 mg BID provides systemic exposures at plateau of response for OS while maintaining a well-tolerated safety profile. This analysis confirms alectinib 600 mg BID as the recommended global dose for patients with crizotinib-resistant ALK-positive NSCLC.

Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.

PubMed

Vegter, S; Tolley, K; Wilson Waterworth, T; Jones, H; Jones, S; Jewell, D

2013-08-01

The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC. © 2013 John Wiley & Sons Ltd.

Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.

PubMed

Mitsui, Jun; Fukuda, Yoko; Azuma, Kyo; Tozaki, Hirokazu; Ishiura, Hiroyuki; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

2010-07-01

We have recently found that multiple rare variants of the glucocerebrosidase gene (GBA) confer a robust risk for Parkinson disease, supporting the 'common disease-multiple rare variants' hypothesis. To develop an efficient method of identifying rare variants in a large number of samples, we applied multiplexed resequencing using a next-generation sequencer to identification of rare variants of GBA. Sixteen sets of pooled DNAs from six pooled DNA samples were prepared. Each set of pooled DNAs was subjected to polymerase chain reaction to amplify the target gene (GBA) covering 6.5 kb, pooled into one tube with barcode indexing, and then subjected to extensive sequence analysis using the SOLiD System. Individual samples were also subjected to direct nucleotide sequence analysis. With the optimization of data processing, we were able to extract all the variants from 96 samples with acceptable rates of false-positive single-nucleotide variants.

Intervention strategies for improving patient adherence to follow-up in the era of mobile information technology: a systematic review and meta-analysis.

PubMed

Lin, Haotian; Wu, Xiaohang

2014-01-01

Patient adherence to follow-up plays a key role in the medical surveillance of chronic diseases and affects the implementation of clinical research by influencing cost and validity. We previously reported a randomized controlled trial (RCT) on short message service (SMS) reminders, which significantly improved follow-up adherence in pediatric cataract treatment. RCTs published in English that reported the impact of SMS or telephone reminders on increasing or decreasing the follow-up rate (FUR) were selected from Medline, EMBASE, PubMed, and the Cochrane Library through February 2014. The impacts of SMS and telephone reminders on the FUR of patients were systematically evaluated by meta-analysis and bias was assessed. We identified 13 RCTs reporting on 3276 patients with and 3402 patients without SMS reminders and 8 RCTs reporting on 2666 patients with and 3439 patients without telephone reminders. For the SMS reminders, the majority of the studies (>50%) were at low risk of bias, considering adequate sequence generation, allocation concealment, blinding, evaluation of incomplete outcome data, and lack of selective reporting. For the studies on the telephone reminders, only the evaluation of incomplete outcome data accounted for more than 50% of studies being at low risk of bias. The pooled odds ratio (OR) for the improvement of follow-up adherence in the SMS group compared with the control group was 1.76 (95% CI [1.37, 2.26]; P<0.01), and the pooled OR for the improvement of follow-up adherence in the telephone group compared with the control group was 2.09 (95% CI [1.85, 2.36]; P<0.01); both sets showed no evidence of publication bias. SMS and telephone reminders could both significantly improve the FUR. Telephone reminders were more effective but had a higher risk of bias than SMS reminders.

Acarbose reduces body weight irrespective of glycemic control in patients with diabetes: results of a worldwide, non-interventional, observational study data pool.

PubMed

Schnell, Oliver; Weng, Jianping; Sheu, Wayne H-H; Watada, Hirotaka; Kalra, Sanjay; Soegondo, Sidartawan; Yamamoto, Noriyuki; Rathod, Rahul; Zhang, Cheryl; Grzeszczak, Wladyslaw

2016-01-01

The objective of this study is to examine the effect of acarbose, an alpha-glucosidase inhibitor, on body weight in a real-life setting by pooling data from post-marketing surveillance. Data from 10 studies were pooled (n=67,682) and the effect of acarbose on body weight was analysed taking into account baseline body weight, glycemic parameters and other baseline characteristics. The mean relative reduction in body weight was 1.45 ± 3.24% at the 3-month visit (n=43,510; mean baseline 73.4 kg) and 1.40 ± 3.28% at the last visit (n=54,760; mean baseline 73.6 kg) (both p<0.0001). These reductions were dependent on baseline body weight (overweight: -1.33 ± 2.98% [n=13,498; mean baseline 71.6 kg]; obese: -1.98 ± 3.40% [n=20,216; mean baseline 81.3 kg]). When analysed by baseline glycemic parameter quartiles, the reduction was independent of fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c) and postprandial glucose excursion (PPGE). A bivariate analysis of covariance identified female sex, South East Asian and East Asian ethnicity, younger age, higher body mass index, short duration of diabetes, and no previous treatment as factors likely to impact positively on body weight reduction with acarbose. This post-hoc analysis showed that acarbose treatment reduces body weight independent of glycemic control status but dependent on baseline body weight. Copyright © 2016. Published by Elsevier Inc.

Prognostic Value of MicroRNA-196a in Asian Cancer Patients: a Meta-Analysis.

PubMed

Cai, Xiaodong; Liu, Xiaodi; Lu, Nian; Xiao, Min; Li, Zhong

2016-11-01

Growing evidence from studies has shown that microRNA-196a (miR-196a) is correlated with treatment response and prognosis in Asian cancer patients. However, the studies reveal that the role of miR-196a is not totally consistent, making it rational to perform a meta-analysis to assess the prognostic value of miR-196a in cancers. This meta-analysis was conducted by searching PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI), and Web of Science. Baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and p-value were extracted from studies investigating the association between clinical outcomes in Asian patients with cancers and the expression of miR-196a. The pooled HRs and CIs were calculated. 13 studies were included to assess the prognostic role of miR-196a in cancer patients. The pooled HR of higher miR-196a expression for overall survival (OS) was 3.08 (95% CI: 2.32 - 4.10, p < 0.001). For disease free survival (DFS) and recurrence free survival (RFS), the pooled HR is 3.83 (95% CI: 2.39 - 6.12, p < 0.001). No obvious between-study heterogeneity was shown among included studies. Hence, a fixed model was utilized. In our subgroup analysis, the results remain consistent. It shows that higher expression of miR-196a was both associated with poor OS and RFS/DFS in different kinds of cancers. The present meta-analysis suggested that higher expression of miR-196a might predict poor prognosis in Asian cancer patients.

Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis.

PubMed

Nathan, Steven D; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Glaspole, Ian; Glassberg, Marilyn K; Kardatzke, David R; Daigl, Monica; Kirchgaessler, Klaus-Uwe; Lancaster, Lisa H; Lederer, David J; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; Noble, Paul W

2017-01-01

In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120. We also did meta-analyses of these data and data from two Japanese trials of pirfenidone versus placebo-Shionogi Phase 2 (SP2) and Shionogi Phase 3 (SP3; trial durations 36-52 weeks). At week 52, the relative risk of death for all four mortality outcomes was significantly lower in the pirfenidone group than in the placebo group in the pooled population (all-cause mortality hazard ratio [HR] 0·52 [95% CI 0·31-0·87; p=0·0107]; treatment-emergent all-cause mortality 0·45 [0·24-0·83; 0·0094]; idiopathic-pulmonary-fibrosis-related mortality 0·35 [0·17-0·72; 0·0029]; treatment-emergent idiopathic-pulmonary-fibrosis-related mortality 0·32 [0·14-0·76; 0·0061]). Consistent with the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed a clinically relevant and significant risk reduction in the pirfenidone group compared with the placebo group. Over 120 weeks, we noted significant differences in the pooled analysis favouring pirfenidone therapy compared with placebo for treatment-emergent all-cause mortality (p=0·0420), idiopathic-pulmonary-fibrosis-related mortality (0·0237), and treatment-emergent idiopathic-pulmonary-fibrosis-related (0·0132) mortality; similar results were shown by meta-analyses. Several analytic approaches demonstrated that pirfenidone therapy is associated with a reduction in the relative risk of mortality compared with placebo over 120 weeks. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of Celiac Disease in Patients with Iron Deficiency Anemia - a Systematic Review with Meta-analysis.

PubMed

Mahadev, Srihari; Laszkowska, Monika; Sundström, Johan; Björkholm, Magnus; Lebwohl, Benjamin; Green, Peter Hr; Ludvigsson, Jonas F

2018-04-21

Anemia is common in patients with celiac disease and a frequent presentation. Guidelines recommend screening iron-deficient patients with anemia for celiac disease. However, the reported prevalence of celiac disease among patients with iron-deficiency anemia (IDA) varies. We performed a systematic review to determine the prevalence of biopsy-verified celiac disease in patients with IDA. We performed a systematic review of manuscripts published in PubMed Medline or EMBASE through July 2017 for the term celiac disease combined with anemia or iron-deficiency. We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of celiac disease. Meta-regression was used to assess subgroup heterogeneity. We identified 18 studies comprising 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of celiac disease was 4.8% (n=143). Using a weighted pooled analysis, we demonstrated a prevalence of biopsy-confirmed celiac disease 3.2% (95% CI, 2.6%-3.9%) in patients with IDA. However, heterogeneity was high (I 2 = 67.7%). The prevalence of celiac disease was not significantly higher in studies with a mean participant age older or younger than years, nor in studies with a mixed-sex vs female-predominant (≥60%) population. On meta-regression, year of publication, the proportion of females, age at celiac disease testing, and the prevalence of in the general population were not associated with the prevalence of celiac disease in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of celiac disease was 5.5% (95% CI, 4.1%-6.9%). In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of celiac disease. This prevalence value justifies the practice of testing patients with IDA for celiac disease. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Esophagectomy for End-Stage Achalasia: Systematic Review and Meta-analysis.

PubMed

Aiolfi, Alberto; Asti, Emanuele; Bonitta, Gianluca; Bonavina, Luigi

2018-05-01

Indications for surgery and clinical outcomes of esophagectomy in the management of end-stage achalasia are not clearly defined. The aim of this systematic review and meta-analysis was to provide evidence-based information to help in the decision-making and in the choice of surgical technique. An extensive literature search was conducted to identify all reports on esophagectomy for end-stage achalasia patients over the past three decades. MEDLINE, Embase and Cochrane databases were thoroughly consulted matching the terms "achalasia," "end-stage achalasia," "esophagectomy" and "esophageal resection" with "AND" and "OR." Short- and long-term outcome data were extracted. Pooled prevalence of pneumonia, anastomotic leakage and mortality were calculated using Freeman-Tukey double arcsine transformation and DerSimonian-Laird estimator in random effect meta-analysis. Heterogeneity among studies was evaluated using I 2 -index and Cochrane Q test. Meta-regression was used to address the effect of potential confounders. Eight papers published between 1989 and 2014 matched the inclusion criteria. In total, 1307 patients were included. Esophagectomy was performed through a transthoracic (78.7%) or a transhiatal (21.3%) approach. The stomach was used as an esophageal substitute in 95% of patients. Pooled prevalence of pneumonia, anastomotic leakage and mortality were 10% (95% CI 4-18%), 7% (95% CI 4-10%) and 2% (95% CI 1-3%), respectively. Esophagectomy for end-stage achalasia is safe and effective. Based on the results of this study, esophagectomy should be performed without hesitation in patients who are fit for major surgery and present with disabling symptoms, poor quality of life and dolichomegaesophagus recalcitrant to multiple endoscopic dilatations and/or surgical myotomies.

The Necessity for Routine Pre-operative Ultrasound Mapping Before Arteriovenous Fistula Creation: A Meta-analysis.

PubMed

Georgiadis, G S; Charalampidis, D G; Argyriou, C; Georgakarakos, E I; Lazarides, M K

2015-05-01

Existing guidelines suggest routine use of pre-operative color Doppler ultrasound (DUS) vessel mapping before the creation of arteriovenous fistulae (AVF); however, there is controversy about its benefit over traditional clinical examination or selective ultrasound use. This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing routine DUS mapping before the creation of AVF with patients for whom the decision for AVF placement was based on clinical examination and selective ultrasound use. A search of MEDLINE/PubMed, SCOPUS, and the Cochrane Library was carried out in June 2014. The analyzed outcome measures were the immediate failure rate and the early/midterm adequacy of the fistula for hemodialysis. Additionally, assessment of the methodological quality of the included studies was carried out. Five studies (574 patients) were analyzed. A random effects model was used to pool the data. The pooled odds ratio (OR) for the immediate failure rate was 0.32 (95% confidence interval [CI] 0.17-0.60; p < .01), which was significantly in favor of the DUS mapping group. The pooled OR for the early/midterm adequacy for hemodialysis was 0.66 (95% CI 0.42-1.03; p = .06), with a trend in favor of the DUS mapping group; however, subgroup analysis revealed that routine DUS mapping was more beneficial than selective DUS (p < .05). The available evidence, based mainly on moderate quality RCTs, suggests that the pre-operative clinical examination should always be supplemented with routine DUS mapping before AVF creation. This policy avoids negative surgical explorations and significantly reduces the immediate AVF failure rate. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Reduced Risk of Barrett's Esophagus in Statin Users: Case-Control Study and Meta-Analysis.

PubMed

Beales, Ian L P; Dearman, Leanne; Vardi, Inna; Loke, Yoon

2016-01-01

Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett's esophagus. The purpose of this study was to examine the association between statin use and the presence of Barrett's esophagus in patients having their first gastroscopy. We have performed a case-control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett's esophagus. Male Barrett's cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case-control studies. Regular statin use was associated with a significantly lower incidence of Barrett's esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37-0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21-0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett's was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett's, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett's esophagus [pooled adjusted OR 0.63 (95 % CI 0.51-0.77)]. Statin use is associated with a reduced incidence of a new diagnosis of Barrett's esophagus.

The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial Stewardship Implications.

PubMed

Parente, Diane M; Cunha, Cheston B; Mylonakis, Eleftherios; Timbrook, Tristan T

2018-01-11

Recent literature has highlighted MRSA nasal screening as a possible antimicrobial stewardship program (ASP) tool for avoiding unnecessary empiric MRSA therapy for pneumonia, yet current guidelines recommend MRSA therapy based on risk factors. The objective of this meta-analysis was to evaluate the diagnostic value of MRSA nasal screening in MRSA pneumonia. Pubmed and EMBASE were searched from inception to November 2016 for English studies evaluating MRSA nasal screening and development of MRSA pneumonia. Data analysis was performed using a bivariate random-effects model to estimate pooled sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Twenty-two studies, comprising of 5,163 patients met our inclusion criteria. Pooled sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types was 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA pneumonia, the calculated PPV was 44.8% while the NPV was 96.5%. The pooled sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) were at 85% and 92.1%, respectively. For CAP and HCAP both the PPV and NPV increased to 56.8% and 98.1%, respectively. In comparison, for MRSA ventilated-associated pneumonia (VAP), the sensitivity, specificity, PPV, NPV was 40.3%, 93.7%, 35.7%, and 94.8%, respectively. Nares screening for MRSA had a high specificity and NPV for ruling out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, utilization of MRSA nares screening is a valuable tool for AMS to streamline empiric antibiotic therapy, especially among patients with pneu. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PROPOSALS FOR THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR RADIOGRAPHY FOR ADULT PATIENTS BASED ON REGIONAL DOSE SURVEYS IN RUSSIAN FEDERATION.

PubMed

Vodovatov, A V; Balonov, M I; Golikov, V Yu; Shatsky, I G; Chipiga, L A; Bernhardsson, C

2017-04-01

In 2009-2014, dose surveys aimed to collect adult patient data and parameters of most common radiographic examinations were performed in six Russian regions. Typical patient doses were estimated for the selected examinations both in entrance surface dose and in effective dose. 75%-percentiles of typical patient effective dose distributions were proposed as preliminary regional diagnostic reference levels (DRLs) for radiography. Differences between the 75%-percentiles of regional typical patient dose distributions did not exceed 30-50% for the examinations with standardized clinical protocols (skull, chest and thoracic spine) and a factor of 1.5 for other examinations. Two different approaches for establishing national DRLs were evaluated: as a 75%-percentile of a pooled regional sample of patient typical doses (pooled method) and as a median of 75%-percentiles of regional typical patient dose distributions (median method). Differences between pooled and median methods for effective dose did not exceed 20%. It was proposed to establish Russian national DRLs in effective dose using a pooled method. In addition, the local authorities were granted an opportunity to establish regional DRLs if the local radiological practice and typical patient dose distributions are significantly different. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis.

PubMed

Cheungpasitporn, W; Thongprayoon, C; O'Corragain, O A; Edmonds, P J; Ungprasert, P; Kittanamongkolchai, W; Erickson, S B

2015-03-01

The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer. A literature search was performed from inception until June 2014. Studies that reported odds ratios or hazard ratios comparing the risk of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the upper urinary tract in patients with the history of kidney stones versus those without the history of kidney stones were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Seven studies were included in our analysis to assess the association between a history of kidney stones and RCC. The pooled RR of RCC in patients with kidney stones was 1.76 (95% CI, 1.24-2.49). The subgroup analysis found that the history of kidney stones was associated with increased RCC risk only in males (RR, 1.41 [95% CI, 1.11-1.80]), but not in females (RR, 1.13 [95% CI, 0.86-1.49]). Five studies were selected to assess the association between a history of kidney stones and TCC. The pooled RR of TCC in patients with kidney stones was 2.14 (95% CI, 1.35-3.40). Our study demonstrates a significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Primary Immunodeficiencies: “New” Disease in an Old Country

PubMed Central

Lee, Pamela P W; Lau, Yu-Lung

2009-01-01

Primary immunodeficiency disorders (PIDs) are rare inborn errors of the immune system. Patients with PIDs are unique models that exemplify the functional and phenotypic consequences of various immune defects underlying infections, autoimmunity, lymphoproliferation, allergy and cancer. Over 150 PID syndromes were characterized in the past 60 years, with an ever growing list of new entities being discovered. Because of their rarity, multi-center collaboration for pooled data analysis and molecular studies is important to gain meaningful insights into the phenotypic and genetic diversities of PIDs. In this article, we summarize our research findings on PIDs in Chinese population in the past 20 years. Close collaboration among various immunology centers, cross-referrals and systematic data analysis constitute the foundation for research on PIDs. Future directions include establishment of a national PID registry, raising awareness of PIDs and securing sufficient resources for patient care and scientific research. PMID:20003815

Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis.

PubMed

van de Kerkhof, Peter C M; Griffiths, Christopher E M; Reich, Kristian; Leonardi, Craig L; Blauvelt, Andrew; Tsai, Tsen-Fang; Gong, Yankun; Huang, Jiaqing; Papavassilis, Charis; Fox, Todd

2016-07-01

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. We reviewed safety data from the secukinumab psoriasis phase II/III program. Data were pooled from 10 phase II/III secukinumab psoriasis studies. Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). There was a limited number of patients in comparator groups and the exposure to placebo was short. Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis.

PubMed

Abushouk, Abdelrahman Ibrahim; Ahmed, Hussien; Ismail, Ammar; Elmaraezy, Ahmed; Badr, Ahmed Said; Gadelkarim, Mohamed; Elnenny, Mohammed

2017-07-01

We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.

Survival after in-hospital cardiac arrest among cerebrovascular disease patients.

PubMed

Fehnel, Corey R; Trepman, Alissa; Steele, Dale; Khan, Muhib A; Silver, Brian; Mitchell, Susan L

2018-05-19

Stroke is a leading cause of death and disability, and while preferences for cardiopulmonary resuscitation (CPR) are frequently discussed, there is limited evidence detailing outcomes after CPR among acute cerebrovascular neurology (inclusive of stroke, subarachnoid hemorrhage (SAH)) patients. Systematic review and meta-analysis of PubMed and Cochrane libraries from January 1990 to December 2016 was conducted among stroke patients undergoing in-hospital CPR. Primary data from studies meeting inclusion criteria at two levels were extracted: 1) studies reporting survival to hospital discharge after CPR with cerebrovascular primary admitting diagnosis, and 2) studies reporting survival to hospital discharge after CPR with cerebrovascular comorbidity. Meta-analysis generated weighted, pooled survival estimates for each population. Of 818 articles screened, there were 176 articles (22%) that underwent full review. Three articles met primary inclusion criteria, with an estimated 8% (95% Confidence Interval (CI) 0.01, 0.14) rate of survival to hospital discharge from a pooled sample of 561 cerebrovascular patients after in-hospital CPR. Twenty articles met secondary inclusion criteria, listing a cerebrovascular comorbidity, with an estimated rate of survival to hospital discharge of 16% (95% CI 0.14, 0.19). All studies demonstrated wide variability in adherence to Utstein guidelines, and neurological outcomes were detailed in only 6 (26%) studies. Among the few studies reporting survival to hospital discharge after CPR among acute cerebrovascular patients, survival is lower than general inpatient populations. These findings synthesize the limited empirical basis for discussions about resuscitation among stroke patients, and highlight the need for more disease stratified reporting of outcomes after inpatient CPR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diabetes mellitus as a risk factor for incident chronic kidney disease and end-stage renal disease in women compared with men: a systematic review and meta-analysis.

PubMed

Shen, Yanjue; Cai, Rongrong; Sun, Jie; Dong, Xue; Huang, Rong; Tian, Sai; Wang, Shaohua

2017-01-01

Diabetes mellitus is a strong risk factor for chronic kidney disease and end-stage renal disease. Whether sex differences in chronic kidney disease and end-stage renal disease incidence exist among diabetic patients remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative effect of diabetes on chronic kidney disease and end-stage renal disease risk in women compared with men. We systematically searched Embase, PubMed, and the Cochrane Library for both cohort and case-control studies until October 2015. Studies were selected if they reported a sex-specific relationship between diabetes mellitus and chronic kidney disease or end-stage renal disease. We generated pooled estimates across studies using random-effects meta-analysis after log transformation with inverse variance weighting. Ten studies with data from more than 5 million participants were included. The pooled adjusted risk ratio of chronic kidney disease associated with diabetes mellitus was 3.34 (95 % CI 2.27, 4.93) in women and 2.84 (95 % CI 1.73, 4.68) in men. The data showed no difference in diabetes-related chronic kidney disease risk between the sexes (pooled adjusted women-to-men relative risk ratio was 1.14 [95 % CI 0.97, 1.34]) except for end-stage renal disease-the pooled adjusted women-to men relative risk ratio was 1.38 (95 % CI 1.22, 1.55; p = 0.114, I² = 38.1 %). The study found no evidence of a sex difference in the association between diabetes mellitus and chronic kidney disease. However, the excess risk for end-stage renal disease was higher in women with diabetes than in men with the same condition, from which we assume that the female gender could accelerate the disease progression. Further studies are needed to support this notion and elucidate the underlying mechanisms.

Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

NASA Astrophysics Data System (ADS)

Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

2017-05-01

The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association ( Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

miRNAs as biomarkers for diagnosis of heart failure

PubMed Central

Yan, Hualin; Ma, Fan; Zhang, Yi; Wang, Chuan; Qiu, Dajian; Zhou, Kaiyu; Hua, Yimin; Li, Yifei

2017-01-01

Abstract Background: With the rapid development of molecular biology, the kind of mircoRNA (miRNA) has been introduced into emerging role both in cardiac development and pathological procedure. Thus, we conduct this meta-analysis to find out the role of circulating miRNA as a biomarker in detecting heart failure. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials registry center to identify relevant studies up to August 2016. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 14.0 to estimate the publication bias and meta-regression. Besides, we took use of SPSS 17.0 to evaluate variance between several groups. Information on true positive, false positive, false negative, and true negative, as well as the quality of research was extracted. Results: We use results from 10 articles to analyze the pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.74 (95% confidence interval [CI], 0.72 to 0.75); pooled specificity, 0.69 (95%CI, 0.67 to 0.71); and area under the summary receiver operating characteristic curves value (SROC), 0.7991. The miRNA-423-5p (miR-423-5p) detection was: pooled sensitivity, 0.81 (95%CI, 0.76 to 0.85); pooled specificity, 0.67 (95%CI, 0.61 to 0.73); and SROC, 0.8600. However, taken the same patients population, we extracted the data of BNP for detecting heart failure and performed meta-analysis with acceptable SROC as 0.9291. Among the variance analysis, the diagnostic performance of miR-423-5p claimed significant advantages of other pooled results. However, the combination of miRNAs and BNP could increase the accuracy of detecting of heart failure. Unfortunately, there was no dramatic advantage of miR-423-5p compared to BNP protocol. Conclusion: Despite interstudy variability, the performance test of miRNA for detecting heart failure revealed that miR-423-5p demonstrated the potential to be a biomarker. However, other miRNAs were not able to provide enough evidence on promising diagnostic value for heart failure based on the current data. Moreover, the combination of miRNAs and BNP could work as a better method to detection. Unfortunately, BNP was still the most convinced biomarker for such disease. PMID:28562533

Role of non-contrast balanced steady-state free precession megnetic resonance angiography compared to contrast-enhanced megnetic resonance angiography in diagnosing renal artery stenosis: a meta-analysis.

PubMed

Tao, Weijing; Shen, Yang; Guo, Lili; Bo, Genji

2014-01-01

Balanced steady-state free precession MR angiography (b-SSFP MRA) has shown great promise in diagnosing renal artery stenosis (RAS) as a non-contrast MR angiography (NC-MRA) method. However, results from related studies are inconsistent. The purpose of this meta-analysis was to assess the accuracy of b-SSFP MRA compared to contrast-enhanced MR angiography (CE-MRA) in diagnosing RAS. English and Chinese studies that were published prior to September 4, 2013 and that assessed b-SSFP MRA diagnostic performance in RAS patients were reviewed. Quality of the literature was assessed independently by two observers. The statistical analysis was adopted by the software of Meta-Disc version 1.4. Using the heterogeneity test, a statistical effect model was chosen to calculate different pooled weighted values. The receiver operator characteristic (ROC) space and Spearman correlation coefficient were to explore threshold effect. Sensitivity analysis and the publication bias were performed to demonstrate if the pooled estimates were stable and reliable. We produced forest plots to calculate the pooled values and corresponding 95% confidence interval (CI) of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and constructed a summary receiver operating characteristic curve (SROC) to calculate the area under the curve (AUC). A total of 10 high quality articles were used in this meta-analysis. The studies showed a high degree of heterogeneity. The "shoulder-arm" shape in the ROC plot and the Spearman correlation coefficient between the log(SEN) and log(1-SPE) suggested that there was a threshold effect. Sensitivity analysis demonstrated that the actual combined effect size was equal to the theoretical combined effect size. The publication bias was low after quality evaluation of the literature and the construction of a funnel plot. The pooled sensitivity was 0.88 (95% CI, 0.83-0.91) and pooled specificity was 0.94 (95% CI, 0.93-0.95); pooled PLR was 14.57 (95% CI, 9.78-21.71]) and pooled NLR was 0.15 (95% CI, 0.11-0.20). The AUC was 0.964 3. In contrast to CE-MRA, the b-SSFP MRA is more accurate in diagnosing RAS, and may be able to replace other diagnostic methods in patients with renal insufficiency.

Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis.

PubMed

Sun, S; Cui, Z; Zhou, M; Li, R; Li, H; Zhang, S; Ba, Y; Cheng, G

2017-02-01

Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD. A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I 2 statistic, respectively. Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I 2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I 2 =25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I 2 =0%) were found. PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully. © 2016 John Wiley & Sons Ltd.

The Mortality Risk of Conventional Antipsychotics in Elderly Patients: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

PubMed

Hulshof, Tessa A; Zuidema, Sytse U; Ostelo, Raymond W J G; Luijendijk, Hendrika J

2015-10-01

Numerous observational studies have reported an increased risk of mortality for conventional antipsychotics in elderly patients, and for haloperidol in particular. Subsequently, health authorities have warned against use of conventional antipsychotics in dementia. Experimental evidence is lacking. To assess the mortality risk of conventional antipsychotics in elderly patients with a meta-analysis of trials. Original studies were identified in electronic databases, online trial registers, and hand-searched references of published reviews. Two investigators found 28 potentially eligible studies, and they selected 17 randomized placebo-controlled trials in elderly patients with dementia, delirium, or a high risk of delirium. Two investigators independently abstracted trial characteristics and deaths, and 3 investigators assessed the risk of bias. Deaths were pooled with RevMan to obtain risk differences and risk ratios. Data of 17 trials with a total of 2387 participants were available. Thirty-two deaths occurred. The pooled risk difference of 0.1% was not statistically significant (95% confidence interval (CI) -1.0%-1.2%). The risk ratio was 1.07 (95% CI 0.54-2.13). Eleven of 17 trials tested haloperidol (n = 1799). The risk difference was 0.4% (95% CI -0.9%-1.6%), the risk ratio was 1.25 (95% CI 0.59-2.65). This meta-analysis of placebo-controlled randomized trials does not show that conventional antipsychotics in general or haloperidol in particular increase the risk of mortality in elderly patients. It questions the observational findings and the warning based on these findings. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Prognostic role of heart-type fatty acid binding protein in pulmonary embolism: a meta-analysis.

PubMed

Liu, Mingjie; Yuan, Xia; Qiu, Xianming; Shan, Xiaoxi; Lin, Dianjie; Zhu, Ling

2015-01-01

Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Our aim was to evaluate the available evidence on the accuracy of H-FABP for predicting the prognosis of adverse clinical outcomes (defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, endotracheal intubation, use of vasopressors, thrombolysis, surgical embolectomy, or admission to the intensive care unit) or mortality in patients with acute PE. Unrestricted searches of PubMed, the Cochrane Library, Web of Science and Science Direct were performed using the terms of "H-FABP" or "heart-type fatty acid binding protein" and ("pulmonary embolism" or "pulmonary thromboembolism"). A random-effect model was used to pool study results; χ(2) and I(2) testing was used to test for heterogeneity. Data of six studies were included in this analysis. 34 of 119(28.57%; 95%CI, 20.42%-36.72%) patients with elevated H-FABP levels had adverse events during follow-up compared with 24 of 475 (5.05%; 95%CI, 3.08%-7.02%) patients with normal levels. High H-FABP levels were associated with a high risk of occurrence of adverse clinical outcome (pooled OR, 10.81; 95%CI, 3.92-29.83). The results of this meta-analysis indicate that H-FABP is a good predictor for adverse outcomes in patients with acute PE. Copyright © 2014 Elsevier Ltd. All rights reserved.

GPFrontend and GPGraphics: graphical analysis tools for genetic association studies.

PubMed

Uebe, Steffen; Pasutto, Francesca; Krumbiegel, Mandy; Schanze, Denny; Ekici, Arif B; Reis, André

2010-09-21

Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.

Cellular phone use and brain tumor: a meta-analysis.

PubMed

Kan, Peter; Simonsen, Sara E; Lyon, Joseph L; Kestle, John R W

2008-01-01

The dramatic increase in the use of cellular phones has generated concerns about potential adverse effects, especially the development of brain tumors. We conducted a meta-analysis to examine the effect of cellular phone use on the risk of brain tumor development. We searched the literature using MEDLINE to locate case-control studies on cellular phone use and brain tumors. Odds ratios (ORs) for overall effect and stratified ORs associated with specific brain tumors, long-term use, and analog/digital phones were calculated for each study using its original data. A pooled estimator of each OR was then calculated using a random-effects model. Nine case-control studies containing 5,259 cases of primary brain tumors and 12,074 controls were included. All studies reported ORs according to brain tumor subtypes, and five provided ORs on patients with > or =10 years of follow up. Pooled analysis showed an overall OR of 0.90 (95% confidence interval [CI] 0.81-0.99) for cellular phone use and brain tumor development. The pooled OR for long-term users of > or =10 years (5 studies) was 1.25 (95% CI 1.01-1.54). No increased risk was observed in analog or digital cellular phone users. We found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies.

Tissue or blood: which is more suitable for detection of EGFR mutations in non-small cell lung cancer?

PubMed

Biaoxue, Rong; Shuanying, Yang

2018-01-01

Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference. We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. Investigations that provided data on EGFR mutation status in blood were searched in the databases of Medline, Embase, Ovid Technologies and Web of Science. The detect efficiency of EGFR mutations in paired blood and tissues was compared using a random-effects model of meta-analysis. Pooled sensitivity and specificity and diagnostic accuracy were calculated by receiver operating characteristic curve. A total of 19 studies with 2,922 individuals were involved in this meta-analysis. The pooled results showed the positive detection rate of EGFR mutations in lung cancer tissues was remarkably higher than that of paired blood samples (odds ratio [OR] = 1.47, p<0.001). The pooled sensitivity and specificity of blood were 0.65 and 0.91, respectively, and the area under the receiver operating characteristic curve was 0.89. Although blood had a better specificity for detecting EGFR mutations, the absence of blood positivity should not necessarily be construed as confirmed negativity. Patients with negative results for blood should decidedly undergo further biopsies to ascertain EGFR mutations.

Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

PubMed Central

Burr, Nick E; Hull, Mark A; Subramanian, Venkataraman

2016-01-01

AIM: To determine whether aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) prevent colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NA-NSAID use. Pooled odds ratios (OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger’s test. Heterogeneity was assessed using Cochran’s Q and the I2 statistic. RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80 (95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66 (95%CI: 0.06-1.39). There was significant heterogeneity (I2 > 50%) between the studies. There was no change in the effect estimates on subgroup analyses of the population studied or whether adjustment or matching was performed. CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD. PMID:27053860

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

PubMed

Rubin, David T; Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Sale, Mark E; Rolleri, Robert L; Golden, Pamela L; Barrett, Andrew C; Bortey, Enoch; Forbes, William P

2015-11-01

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.

PubMed

Lees, Kennedy R; Bluhmki, Erich; von Kummer, Rüdiger; Brott, Thomas G; Toni, Danilo; Grotta, James C; Albers, Gregory W; Kaste, Markku; Marler, John R; Hamilton, Scott A; Tilley, Barbara C; Davis, Stephen M; Donnan, Geoffrey A; Hacke, Werner; Allen, Kathryn; Mau, Jochen; Meier, Dieter; del Zoppo, Gregory; De Silva, D A; Butcher, K S; Parsons, M W; Barber, P A; Levi, C; Bladin, C; Byrnes, G

2010-05-15

Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. None. Copyright 2010 Elsevier Ltd. All rights reserved.

Ventricular Recovery and Pump Explantation in Patients Supported by Left Ventricular Assist Devices: A Systematic Review.

PubMed

Phan, Kevin; Huo, Ya Ruth; Zhao, Dong Fang; Yan, Tristan D; Tchantchaleishvili, Vakhtang

2016-01-01

Several studies have reported that a portion of patients who exhibit cardiac recovery during left ventricular assist device (LVAD) support can have their device explanted with reasonable long-term survival. The aim of this systematic review is to assess the survival and cardiac function in patients with explanted LVADs from the current literature. Electronic search was performed to identify all studies in English literature assessing LVAD explantation. All identified articles were systematically assessed using the inclusion and exclusion criteria. Selected studies were subjected to quantitative assessment. From 5 electronic databases, 11 studies (213 patients) were included. Pooled mean perioperative mortality rate of those explanted was 9.2% (95% CI, 5.0-14.5%; I = 0). Pooled mean late mortality rate was 15% (95% CI, 9.0-22.1%; I = 31%). The pooled 1, 5, and 10 year survival postexplant was 91, 76, and 65.7%, respectively. Pooled postweaning freedom from heart failure (HF) recurrence reached 81.3%. Subset analysis demonstrated that patients explanted from a continuous-flow LVAD versus pulsatile LVAD had a lower rate of HF recurrence (6.6 vs. 28.3%, p = 0.03) and LVAD reimplantation (7.5 vs. 37%, p = 0.001). Before LVAD explantation, overall mean left ventricular ejection fraction (LVEF) was 49%. Weighted pooled early and late postexplantation mean LVEF was 47.3 and 41.2%, respectively. Late postexplantation LVEF was significantly higher in the continuous-flow versus pulsatile LVAD subgroup (41.5 vs. 24%, p = 0.001). This review shows encouraging safety and 10 year survival outcomes after explantation of LVADs in carefully selected patients, with rates better than expected after a heart transplant. Recovery of the native heart is the most desirable clinical outcome in patients supported with LVADs and should be actively sought.

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis

PubMed Central

Shao, Yingjie; Xu, Bin; Chen, Lujun; Zhou, Qi; Hu, Wenwei; Zhang, Dachuan; Wu, Changping; Tao, Min; Zhu, Yibei; Jiang, Jingting

2017-01-01

Background In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. Materials and methods We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity. Results A total of 31 observational studies including 4,185 patients were enrolled. For TILs subsets, the amount of CD8+, FOXP3+, CD3+, CD57+, CD20+, CD45RO+, Granzyme B+ and T-bet+ lymphocytes was significantly associated with improved survival (P < 0.05); moreover, the amount of CD3+ TILs in intra-tumoral compartment (IT) was the most significant prognostic marker (pooled HR = 0.52; 95% CI = 0.43–0.63; P < 0.001). However, CD4+ TILs was not statistically associated with patients’ survival. FOXP3+ TILs showed bidirectional prognostic roles which had positive effect in IT (pooled HR = 1.57; 95% CI = 1.04–2.37; P = 0.033) and negative effect in extra-tumoral compartment (ET) (pooled HR = 0.76; 95% CI = 0.60–0.96; P = 0.022). Conclusions This meta-analysis suggests that some TIL subsets could serve as prognostic biomarkers in gastric cancer. High-quality randomized controlled trials are needed to decide if these TILs could serve as targets for immunotherapy in gastric cancer. PMID:28915679

The predictive value of 18F-FDG PET for pathological response of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy: a meta-analysis.

PubMed

Cong, Lihong; Wang, Shikun; Gao, Teng; Hu, Likuan

2016-12-01

We want to review the value of 18-fluoro-deoxy-glucose positron emission tomography for response prediction of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy. Studies were searched in Pubmed, Embase and Cochrane Library with specific search strategy. The published articles were included according to the criteria established in advance. The included studies were divided into two groups according to the time of the repeat positron emission tomography: during (Group A) or after neoadjuvant chemoradiotherapy (Group B). The studies that performed the repeat positron emission tomography after neoadjuvant chemoradiotherapy were graded Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity, specificity and diagnostic odds ratio were obtained for both groups on the basis of no-existing of threshold effect. Fifteen studies were included in the present study. The threshold effect did not exist in both groups. The pooled sensitivity, specificity and diagnostic odds ratio were 85%, 59%, 6.82 with 95% confidence interval 76-91%, 48-69%, 2.25-20.72 in Group A. The equivalent values were 67%, 69%, 6.34 with 95% confidence interval 60-73%, 63-74%, 2.08-19.34 in Group B. The pooled sensitivity was 90% in four studies that enrolled patients with esophageal squamous cell carcinoma merely in Group B. According to the present data, positron emission tomography should not be used routinely to guide treatment strategy in esophageal cancer patients. We speculated that positron emission tomography could be used as a tool to predict treatment response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.

PubMed

Morgan, Eileen; Halliday, Sophia R; Campbell, Gemma R; Cardwell, Chris R; Patterson, Chris C

2016-02-01

The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible. A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis. In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs. This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Safety and Efficacy of Solitaire Stent Thrombectomy

PubMed Central

Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

2016-01-01

Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Conclusions— Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. PMID:26888532

Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta-analysis.

PubMed

Dai, Cong; Jiang, Min; Sun, Ming-Jun; Cao, Qin

2018-05-01

Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta-analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients. We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Six studies comprising 625 UC patients were included in the meta-analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72-0.81) and 0.81 (95% CI, 0.76-0.85), respectively. The FIT level had a high rule-in value (positive likelihood ratio, 3.79; 95% CI, 2.85-5.03) and a moderate rule-out value (negative likelihood ratio, 0.26; 95% CI, 0.16-0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57-34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration. Our meta-analysis has found that FIT is a simple, reliable non-invasive marker for predicting MH in UC patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis.

PubMed

Nepogodiev, Dmitri

2018-06-13

Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major post-operative complications in an international cohort and to present a meta-analysis of all available prospective data. This prospective, multi-centre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma, or formation of stoma. The primary endpoint was 30-day major complications (Clavien-Dindo grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis (IPMA) was used to analyse pooled results. This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese versus normal weight patients (13.0% versus 16.2%, respectively), but this did not reach statistical significance (p=0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. IPMA demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (odds ratio 2.10, 95% confidence interval 1.49-2.96, p<0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, p<0.001), compared to normal weight patients. In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Refining the Results of a Classical SELEX Experiment by Expanding the Sequence Data Set of an Aptamer Pool Selected for Protein A

PubMed Central

2018-01-01

New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed by cloning and Sanger sequencing. PA#2/8 was identified as the only Protein A-binding aptamer from the Sanger sequence pool, and was shown to be able to bind intact cells of Staphylococcus aureus. In this study, we show the extension of the SELEX results by re-sequencing of the same aptamer pool using a medium throughput NGS approach and data analysis. Both data pools were compared. They confirm the selection of a highly complex and heterogeneous oligonucleotide pool and show consistently a high content of orphans as well as a similar relative frequency of certain sequence groups. But in contrast to the Sanger data pool, the NGS pool was clearly dominated by one sequence group containing the known Protein A-binding aptamer PA#2/8 as the most frequent sequence in this group. In addition, we found two new sequence groups in the NGS pool represented by PA-C10 and PA-C8, respectively, which also have high specificity for Protein A. Comparative affinity studies reveal differences between the aptamers and confirm that PA#2/8 remains the most potent sequence within the selected aptamer pool reaching affinities in the low nanomolar range of KD = 20 ± 1 nM. PMID:29495282

Refining the Results of a Classical SELEX Experiment by Expanding the Sequence Data Set of an Aptamer Pool Selected for Protein A.

PubMed

Stoltenburg, Regina; Strehlitz, Beate

2018-02-24

New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed by cloning and Sanger sequencing. PA#2/8 was identified as the only Protein A-binding aptamer from the Sanger sequence pool, and was shown to be able to bind intact cells of Staphylococcus aureus . In this study, we show the extension of the SELEX results by re-sequencing of the same aptamer pool using a medium throughput NGS approach and data analysis. Both data pools were compared. They confirm the selection of a highly complex and heterogeneous oligonucleotide pool and show consistently a high content of orphans as well as a similar relative frequency of certain sequence groups. But in contrast to the Sanger data pool, the NGS pool was clearly dominated by one sequence group containing the known Protein A-binding aptamer PA#2/8 as the most frequent sequence in this group. In addition, we found two new sequence groups in the NGS pool represented by PA-C10 and PA-C8, respectively, which also have high specificity for Protein A. Comparative affinity studies reveal differences between the aptamers and confirm that PA#2/8 remains the most potent sequence within the selected aptamer pool reaching affinities in the low nanomolar range of K D = 20 ± 1 nM.

Incidence, determinants and clinical impact of definite stent thrombosis on mortality in women: From the WIN-DES collaborative patient-level pooled analysis.

PubMed

Kerkmeijer, Laura S; Claessen, Bimmer E; Baber, Usman; Sartori, Samantha; Chandrasekhar, Jaya; Stefanini, Giulio G; Stone, Gregg W; Steg, P Gabriel; Chieffo, Alaide; Weisz, Giora; Windecker, Stephan; Mikhail, Ghada W; Kastrati, Adnan; Morice, Marie-Claude; Dangas, George D; de Winter, Robbert J; Mehran, Roxana

2018-07-15

Predictors and clinical outcomes of stent thrombosis (ST) in women have not been well investigated. Present study aimed to identify predictors of definite ST and its impact on mortality in women undergoing percutaneous coronary intervention (PCI). Patient-level data of women enrolled in 26 randomized trials of DES was pooled. The study population was stratified based on the presence or absence of definite ST. Cox proportional hazards models were used to determine the predictors of definite ST. To analyze the temporal impact of definite ST on mortality Cox regression with ST entered as time-updated covariate was used. Of 11,557 patients undergoing PCI with stent implantation, definite ST occurred in 105 patients (0.9%) over median follow-up of 3years. Independent predictors of ST were age (HR 1.03 per year decrease, 95% CI 1.00-1.05; p=0.041), diabetes mellitus (HR 2.25, 95% CI 1.27-3.99; p=0.005), non-ST-segment elevation myocardial infarction (NSTEMI) at presentation (HR 1.97, 95% CI 1.04-3.75; p=0.037) and stent diameter (HR 3.76 per mm decrease, 95% CI 1.66-8.53; p=0.002). Compared to women without ST, the adjusted hazard ratios for mortality in the first 7days, 8-30days, and beyond 30days from ST were 115.81 (95% CI 68.96-194.47); 37.44 (95% CI 17.31-80.98); 3.54 (95% CI 2.20-5.69), respectively. In this large-scale pooled analysis of women, definite ST was uncommon yet associated with substantial mortality risk, which peaked early and rapidly attenuated over time. Younger age, diabetes, NSTEMI and stent diameter were found to be predictors of ST. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-expandable metal stents for malignant gastric outlet obstruction: A pooled analysis of prospective literature

PubMed Central

van Halsema, Emo E; Rauws, Erik AJ; Fockens, Paul; van Hooft, Jeanin E

2015-01-01

AIM: To provide an overview of the clinical outcomes of self-expandable metal stent (SEMS) placement for malignant gastric outlet obstruction (MGOO). METHODS: A systematic literature search was performed in PubMed of the literature published between January 2009 and March 2015. Only prospective studies that reported on the clinical success of stent placement for MGOO were included. The primary endpoint was clinical success, defined according to the definition used in the original article. Data were pooled and analyzed using descriptive statistics. Subgroup analyses were performed for partially covered SEMSs (PCSEMSs) and uncovered SEMSs (UCSEMSs) using Fisher’s exact test. RESULTS: A total of 19 studies, including 1281 patients, were included in the final analysis. Gastric (42%) and pancreatic (37%) cancer were the main causes of MGOO. UCSEMSs were used in 76% of patients and PCSEMSs in 24%. The overall pooled technical success rate was 97.3% and the clinical success rate was 85.7%. Stent dysfunction occurred in 19.6% of patients, mainly caused by re-obstruction (12.6%) and stent migration (4.3%), and was comparable between PCSEMSs and UCSEMSs (21.2% vs 19.1%, respectively, P = 0.412). Re-obstruction was more common with UCSEMSs (14.9% vs 5.1%, P < 0.001) and stent migration was more frequent after PCSEMS placement (10.9% vs 2.2%, P < 0.001). The overall perforation rate was 1.2%. Bleeding was reported in 4.1% of patients, including major bleeding in 0.8%. The median stent patency ranged from 68 to 307 d in five studies. The median overall survival ranged from 49 to 183 d in 13 studies. CONCLUSION: The clinical outcomes in this large population showed that enteral stent placement was feasible, effective and safe. Therefore, stent placement is a valid treatment option for the palliation of MGOO. PMID:26604654

Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis

PubMed Central

Pathak, Neha; Dodds, Julie; Khan, Khalid

2014-01-01

Objective To determine the accuracy of testing for human papillomavirus (HPV) DNA in urine in detecting cervical HPV in sexually active women. Design Systematic review and meta-analysis. Data sources Searches of electronic databases from inception until December 2013, checks of reference lists, manual searches of recent issues of relevant journals, and contact with experts. Eligibility criteria Test accuracy studies in sexually active women that compared detection of urine HPV DNA with detection of cervical HPV DNA. Data extraction and synthesis Data relating to patient characteristics, study context, risk of bias, and test accuracy. 2×2 tables were constructed and synthesised by bivariate mixed effects meta-analysis. Results 16 articles reporting on 14 studies (1443 women) were eligible for meta-analysis. Most used commercial polymerase chain reaction methods on first void urine samples. Urine detection of any HPV had a pooled sensitivity of 87% (95% confidence interval 78% to 92%) and specificity of 94% (95% confidence interval 82% to 98%). Urine detection of high risk HPV had a pooled sensitivity of 77% (68% to 84%) and specificity of 88% (58% to 97%). Urine detection of HPV 16 and 18 had a pooled sensitivity of 73% (56% to 86%) and specificity of 98% (91% to 100%). Metaregression revealed an increase in sensitivity when urine samples were collected as first void compared with random or midstream (P=0.004). Limitations The major limitations of this review are the lack of a strictly uniform method for the detection of HPV in urine and the variation in accuracy between individual studies. Conclusions Testing urine for HPV seems to have good accuracy for the detection of cervical HPV, and testing first void urine samples is more accurate than random or midstream sampling. When cervical HPV detection is considered difficult in particular subgroups, urine testing should be regarded as an acceptable alternative. PMID:25232064

The effect of early in-hospital medication review on health outcomes: a systematic review.

PubMed

Hohl, Corinne M; Wickham, Maeve E; Sobolev, Boris; Perry, Jeff J; Sivilotti, Marco L A; Garrison, Scott; Lang, Eddy; Brasher, Penny; Doyle-Waters, Mary M; Brar, Baljeet; Rowe, Brian H; Lexchin, Joel; Holland, Richard

2015-07-01

Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in-hospital pharmacist-led medication review on patient-oriented outcomes based on observed data. We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi-random methods to allocate subjects to pharmacist-led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta-analysis. We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] -0.04 days, 95% confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design. Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient-oriented outcomes. This systematic review failed to identify an effect of pharmacist-led medication review on health outcomes. © 2015 The British Pharmacological Society.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

PubMed

Pichler, Gernot; Haller, Maria C; Kainz, Alexander; Wolf, Myles; Redon, Josep; Oberbauer, Rainer

2017-09-01

Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Improving Estimates and Forecasts of Lake Carbon Pools and Fluxes Using Data Assimilation

NASA Astrophysics Data System (ADS)

Zwart, J. A.; Hararuk, O.; Prairie, Y.; Solomon, C.; Jones, S.

2017-12-01

Lakes are biogeochemical hotspots on the landscape, contributing significantly to the global carbon cycle despite their small areal coverage. Observations and models of lake carbon pools and fluxes are rarely explicitly combined through data assimilation despite significant use of this technique in other fields with great success. Data assimilation adds value to both observations and models by constraining models with observations of the system and by leveraging knowledge of the system formalized by the model to objectively fill information gaps. In this analysis, we highlight the utility of data assimilation in lake carbon cycling research by using the Ensemble Kalman Filter to combine simple lake carbon models with observations of lake carbon pools. We demonstrate the use of data assimilation to improve a model's representation of lake carbon dynamics, to reduce uncertainty in estimates of lake carbon pools and fluxes, and to improve the accuracy of carbon pool size estimates relative to estimates derived from observations alone. Data assimilation techniques should be embraced as valuable tools for lake biogeochemists interested in learning about ecosystem dynamics and forecasting ecosystem states and processes.

Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review.

PubMed

Luo, Zhuang; Wu, Rong-Rong; Lv, Liang; Li, Peng; Zhang, Li-Yan; Hao, Qing-Lin; Li, Wei

2014-01-01

CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker.

Safety and efficacy of lorcaserin: a combined analysis of the BLOOM and BLOSSOM trials.

PubMed

Aronne, Louis; Shanahan, William; Fain, Randi; Glicklich, Alan; Soliman, William; Li, Yuhan; Smith, Steven

2014-10-01

Lorcaserin, a novel selective 5-HT2C receptor agonist, is approved by the US Food and Drug Administration (FDA) for weight management in combination with lifestyle modification for adults with obesity and adults with overweight and ≥ 1 weight-related comorbid condition. The safety and effectiveness of lorcaserin in adult patients without type 2 diabetes mellitus was established based on 2 phase III clinical trials of similar design: Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) and Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM). This report presents a prespecified analysis of pooled data from these trials. Co-primary end points in this analysis include the proportion of patients with a reduction in baseline body weight of ≥ 5% and ≥ 10%, and a change in weight from baseline. Key secondary end points include changes from baseline values in lipid parameters, quality-of-life measures, glycemic indicators, and vital signs. At week 52, more than twice as many lorcaserin-treated patients achieved a weight loss of ≥ 5% compared with placebo (lorcaserin, 47.1%; placebo, 22.6%), and lorcaserin-treated patients lost significantly more body weight (lorcaserin, -5.8%; placebo, -2.5%). A significantly greater proportion of lorcaserin-treated patients achieved a weight loss of ≥ 10% (lorcaserin, 22.4%; placebo, 8.7%). There were statistically significant improvements in lipid parameters, glycemic indicators, quality-of-life measures, and vital signs in the lorcaserin group compared with placebo. The most common adverse events associated with lorcaserin treatment were headache, upper respiratory tract infection, and nasopharyngitis. Lorcaserin-treated patients had a rate of FDA-defined valvulopathy similar to placebo. This pooled analysis of the phase III BLOOM and BLOSSOM trials shows that lorcaserin 10 mg twice daily, in combination with diet and exercise, is safe and tolerable, and is associated with statistically significant weight loss and clinically relevant improvements in cardiometabolic parameters.

Clinicopathologic features of patients with non-small cell lung cancer harboring the EML4-ALK fusion gene: a meta-analysis.

PubMed

Wang, Ying; Wang, Shumin; Xu, Shiguang; Qu, Jiaqi; Liu, Bo

2014-01-01

The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30-0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66-3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41-0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03-0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.

Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

PubMed Central

Wang, Shumin; Xu, Shiguang; Qu, Jiaqi

2014-01-01

Background The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. Methods The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Results Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. Conclusion This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR. PMID:25360721

Technical success, technique efficacy and complications of minimally-invasive imaging-guided percutaneous ablation procedures of breast cancer: A systematic review and meta-analysis.

PubMed

Mauri, Giovanni; Sconfienza, Luca Maria; Pescatori, Lorenzo Carlo; Fedeli, Maria Paola; Alì, Marco; Di Leo, Giovanni; Sardanelli, Francesco

2017-08-01

To systematically review studies concerning imaging-guided minimally-invasive breast cancer treatments. An online database search was performed for English-language articles evaluating percutaneous breast cancer ablation. Pooled data and 95% confidence intervals (CIs) were calculated. Technical success, technique efficacy, minor and major complications were analysed, including ablation technique subgroup analysis and effect of tumour size on outcome. Forty-five studies were analysed, including 1,156 patients and 1,168 lesions. Radiofrequency (n=577; 50%), microwaves (n=78; 7%), laser (n=227; 19%), cryoablation (n=156; 13%) and high-intensity focused ultrasound (HIFU, n=129; 11%) were used. Pooled technical success was 96% (95%CI 94-97%) [laser=98% (95-99%); HIFU=96% (90-98%); radiofrequency=96% (93-97%); cryoablation=95% (90-98%); microwave=93% (81-98%)]. Pooled technique efficacy was 75% (67-81%) [radiofrequency=82% (74-88); cryoablation=75% (51-90); laser=59% (35-79); HIFU=49% (26-74)]. Major complications pooled rate was 6% (4-8). Minor complications pooled rate was 8% (5-13%). Differences between techniques were not significant for technical success (p=0.449), major complications (p=0.181) or minor complications (p=0.762), but significant for technique efficacy (p=0.009). Tumour size did not impact on variables (p>0.142). Imaging-guided percutaneous ablation techniques of breast cancer have a high rate of technical success, while technique efficacy remains suboptimal. Complication rates are relatively low. • Imaging-guided ablation techniques for breast cancer are 96% technically successful. • Overall technique efficacy rate is 75% but largely inhomogeneous among studies. • Overall major and minor complication rates are low (6-8%).

The pseudomonas hot-foot syndrome.

PubMed

Fiorillo, L; Zucker, M; Sawyer, D; Lin, A N

2001-08-02

Between March and May 1998, there was an outbreak of a clinically distinct skin eruption on the soles of the feet of children who used a community wading pool. We reviewed the medical records of 40 children in whom this syndrome developed between March and May 1998. We treated 17 children and advised the attending physicians on the care of the other 23. Follow-up data were obtained for up to one year. Exquisitely painful erythematous plantar nodules developed in 40 children (age, 2 to 15 years) within 40 hours after they had used a wading pool whose floor was coated with abrasive grit. Culture of the plantar pustules from one child yielded Pseudomonas aeruginosa with a pattern on pulsed-field gel electrophoresis that was identical to that of a strain of P. aeruginosa cultured from the pool water. A skin-biopsy specimen from this patient showed a perivascular and perieccrine neutrophilic infiltrate, and a specimen from another patient showed a dermal microabscess. Thirty-seven patients were treated symptomatically; three others were treated with cephalexin. All patients recovered within 14 days, but three children had recurrences of the painful plantar nodules within 24 hours after using the pool again. Folliculitis developed in one patient. The "pseudomonas hot-foot syndrome" is characterized by the acute onset in children of exquisitely tender plantar nodules and a benign, self-limited course. This community outbreak developed after exposure to pool water containing high concentrations of P. aeruginosa.

Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure.

PubMed

Lin, Cheng-Jui; Wu, Vincent; Wu, Pei-Chen; Wu, Chih-Jen

2015-01-01

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are protein-bound uremic toxins that increase in the sera of patients with chronic kidney disease (CKD), and are not effectively removed by dialysis. The purpose of this meta-analysis was to investigate the relationships of PCS and IS with cardiovascular events and all-cause mortality in patients with CKD stage 3 and above. Medline, Cochrane, and EMBASE databases were searched until January 1, 2014 with combinations of the following keywords: chronic renal failure, end-stage kidney disease, uremic toxin, uremic retention, indoxyl sulfate, p-cresyl sulfate. Inclusion criteria were: 1) Patients with stage 1 to 5 CKD; 2) Prospective study; 3) Randomized controlled trial; 4) English language publication. The associations between serum levels of PCS and IS and the risks of all-cause mortality and cardiovascular events were the primary outcome measures. Of 155 articles initially identified, 10 prospective and one cross-sectional study with a total 1,572 patients were included. Free PCS was significantly associated with all-cause mortality among patients with chronic renal failure (pooled OR = 1.16, 95% CI = 1.03 to 1.30, P = 0.013). An elevated free IS level was also significantly associated with increased risk of all-cause mortality (pooled OR = 1.10, 95% CI = 1.03 to 1.17, P = 0.003). An elevated free PCS level was significantly associated with an increased risk of cardiovascular events among patients with chronic renal failure (pooled OR = 1.28, 95% CI = 1.10 to 1.50, P = 0.002), while free IS was not significantly associated with risk of cardiovascular events (pooled OR = 1.05, 95% CI = 0.98 to 1.13, P = 0.196). Elevated levels of PCS and IS are associated with increased mortality in patients with CKD, while PCS, but not IS, is associated with an increased risk of cardiovascular events.

A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score.

PubMed

Bonora, E; Bryzinski, B; Hirshberg, B; Cook, W

2016-05-01

To assess the efficacy and safety of saxagliptin 2.5 and 5 mg/d in patients with type 2 diabetes mellitus (T2DM) and high risk of coronary heart disease (CHD) or stroke as estimated by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Post hoc analysis of data pooled from 5 previously reported phase 3, randomized, placebo-controlled, 24-week studies was conducted. Patients were stratified into subgroups by UKPDS 10-year CHD and/or stroke risk ≥20% and CHD and stroke risk <20%. End points were adjusted mean change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 120-min postprandial glucose (PPG), and body weight and the proportion of patients achieving HbA1c <7% and ≤8% at week 24. Pooled safety data were analyzed for adverse events (AEs) and hypoglycemia. Both doses of saxagliptin reduced HbA1c, FPG, and PPG to a greater extent than placebo regardless of UKPDS risk score. The proportions of patients achieving HbA1c <7% and ≤8% were greater with saxagliptin than placebo and consistent across risk score groups. AE profile and hypoglycemia incidence were similar for saxagliptin and placebo across UKPDS risk score groups. Saxagliptin was well tolerated and improved glycemic control in patients with T2DM regardless of their CHD and stroke UKPDS risk score. Clinical trial registration numbers: Clinicaltrials.gov NCT00121641, NCT00316082, NCT00121667, NCT00313313, and NCT00295633. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Predictors of Outcome in Conservative and Minimally Invasive Surgical Management of Pain Originating From the Sacroiliac Joint

PubMed Central

Dengler, Julius; Duhon, Bradley; Whang, Peter; Frank, Clay; Glaser, John; Sturesson, Bengt; Garfin, Steven; Cher, Daniel; Rendahl, Aaron; Polly, David

2017-01-01

Study Design. A pooled patient-level analysis of two multicenter randomized controlled trials and one multicenter single-arm prospective trial. Objective. The aim of this study was to identify predictors of outcome of conservative and minimally invasive surgical management of pain originating from the sacroiliac joint (SIJ). Summary of Background Data. Three recently published prospective trials have shown that minimally invasive SIJ fusion (SIJF) using triangular titanium implants produces better outcomes than conservative management for patients with pain originating from the SIJ. Due to limitations in individual trial sample size, analyses of predictors of treatment outcome were not conducted. Methods. We pooled individual patient data from the three trials and used random effects models with multivariate regression analysis to identify predictors for treatment outcome separately for conservative and minimally invasive surgical treatment. Outcome was measured using visual analogue scale (VAS), Oswestry Disability Index (ODI), and EuroQOL-5D (EQ-5D). Results. We included 423 patients assigned to either nonsurgical management (NSM, n = 97) or SIJF (n = 326) between 2013 and 2015. The reduction in SIJ pain was 37.9 points larger [95% confidence interval (95% CI) 32.5–43.4, P < 0.0001] in the SIJF group than in the NSM group. Similarly, the improvement in ODI was 18.3 points larger (95% CI 14.3–22.4), P < 0.0001). In NSM, we found no predictors of outcome. In SIJF, a reduced improvement in outcome was predicted by smoking (P = 0.030), opioid use (P = 0.017), lower patient age (P = 0.008), and lower duration of SIJ pain (P = 0.028). Conclusions. Our results support the view that SIJF leads to better treatment outcome than conservative management of SIJ pain and that a higher margin of improvement can be predicted in nonsmokers, nonopioid users, and patients of increased age and with longer pain duration. Level of Evidence: 1 PMID:28350586

Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta-analysis of data from randomized placebo-controlled trials.

PubMed

Salsali, A; Kim, G; Woerle, H J; Broedl, U C; Hantel, S

2016-10-01

To assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta-analysis of data from eight placebo-controlled trials. Data were analysed from eight randomized placebo-controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non-fatal myocardial infarction (MI), non-fatal stroke and hospitalization for unstable angina [4-point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non-fatal MI and non-fatal stroke (3-point MACE). Risk estimates were calculated using Cox regression analysis. A total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four-point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three-point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)]. In a meta-analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4-point MACE and 3-point MACE compared with placebo. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Preoperative diffusion tensor imaging-fiber tracking for facial nerve identification in vestibular schwannoma: a systematic review on its evolution and current status with a pooled data analysis of surgical concordance rates.

PubMed

Savardekar, Amey R; Patra, Devi P; Thakur, Jai D; Narayan, Vinayak; Mohammed, Nasser; Bollam, Papireddy; Nanda, Anil

2018-03-01

OBJECTIVE Total tumor excision with the preservation of neurological function and quality of life is the goal of modern-day vestibular schwannoma (VS) surgery. Postoperative facial nerve (FN) paralysis is a devastating complication of VS surgery. Determining the course of the FN in relation to a VS preoperatively is invaluable to the neurosurgeon and is likely to enhance surgical safety with respect to FN function. Diffusion tensor imaging-fiber tracking (DTI-FT) technology is slowly gaining traction as a viable tool for preoperative FN visualization in patients with VS. METHODS A systematic review of the literature in the PubMed, Cochrane Library, and Web of Science databases was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and those studies that preoperatively localized the FN in relation to a VS using the DTI-FT technique and verified those preoperative FN tracking results by using microscopic observation and electrophysiological monitoring during microsurgery were included. A pooled analysis of studies was performed to calculate the surgical concordance rate (accuracy) of DTI-FT technology for FN localization. RESULTS Fourteen studies included 234 VS patients (male/female ratio 1:1.4, age range 17-75 years) who had undergone preoperative DTI-FT for FN identification. The mean tumor size among the studies ranged from 29 to 41.3 mm. Preoperative DTI-FT could not visualize the FN tract in 8 patients (3.4%) and its findings could not be verified in 3 patients (1.2%), were verified but discordant in 18 patients (7.6%), and were verified and concordant in 205 patients (87.1%). CONCLUSIONS Preoperative DTI-FT for FN identification is a useful adjunct in the surgical planning for large VSs (> 2.5 cm). A pooled analysis showed that DTI-FT successfully identifies the complete FN course in 96.6% of VSs (226 of 234 cases) and that FN identification by DTI-FT is accurate in 90.6% of cases (205 of 226 cases). Larger studies with DTI-FT-integrated neuronavigation are required to look at the direct benefit offered by this specific technique in preserving postoperative FN function.

Classification of Alzheimer's Disease Based on Eight-Layer Convolutional Neural Network with Leaky Rectified Linear Unit and Max Pooling.

PubMed

Wang, Shui-Hua; Phillips, Preetha; Sui, Yuxiu; Liu, Bin; Yang, Ming; Cheng, Hong

2018-03-26

Alzheimer's disease (AD) is a progressive brain disease. The goal of this study is to provide a new computer-vision based technique to detect it in an efficient way. The brain-imaging data of 98 AD patients and 98 healthy controls was collected using data augmentation method. Then, convolutional neural network (CNN) was used, CNN is the most successful tool in deep learning. An 8-layer CNN was created with optimal structure obtained by experiences. Three activation functions (AFs): sigmoid, rectified linear unit (ReLU), and leaky ReLU. The three pooling-functions were also tested: average pooling, max pooling, and stochastic pooling. The numerical experiments demonstrated that leaky ReLU and max pooling gave the greatest result in terms of performance. It achieved a sensitivity of 97.96%, a specificity of 97.35%, and an accuracy of 97.65%, respectively. In addition, the proposed approach was compared with eight state-of-the-art approaches. The method increased the classification accuracy by approximately 5% compared to state-of-the-art methods.

Prospective Analysis of Surgical Bone Margins After Partial Foot Amputation in Diabetic Patients Admitted With Moderate to Severe Foot Infections.

PubMed

Schmidt, Brian M; McHugh, Jonathan B; Patel, Rajiv M; Wrobel, James S

2018-04-01

Osteomyelitis is common in diabetic foot infections and medical management can lead to poor outcomes. Surgical management involves sending histopathologic and microbiologic specimens which guides future intervention. We examined the effect of obtainment of surgical margins in patients undergoing forefoot amputations to identify patient characteristics associated with outcomes. Secondary aims included evaluating interobserver reliability of histopathologic data at both the distal-to and proximal-to surgical bone margin. Data were prospectively collected on 72 individuals and was pooled for analysis. Standardized method to retrieve intraoperative bone margins was established. A univariate analysis was performed. Negative outcomes, including major lower extremity amputation, wound dehiscence, reulceration, reamputation, or death were recorded. Viable proximal margins were obtained in 63 out of 72 cases (87.5%). Strong interobserver reliability of histopathology was recorded. Univariate analysis demonstrated preoperative platelets, albumin, probe-to-bone testing, absolute toe pressures, smaller wound surface area were associated with obtaining viable margins. Residual osteomyelitis resulted in readmission 2.6 times more often and more postoperative complications. Certain patients were significantly different in the viable margin group versus dirty margin group. High interobserver reliability was demonstrated. Obtainment of viable margins resulted in reduced rates of readmission and negative outcomes. Prognostic, Level I: Prospective.

Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

PubMed

Veiga, Lene H S; Holmberg, Erik; Anderson, Harald; Pottern, Linda; Sadetzki, Siegal; Adams, M Jacob; Sakata, Ritsu; Schneider, Arthur B; Inskip, Peter; Bhatti, Parveen; Johansson, Robert; Neta, Gila; Shore, Roy; de Vathaire, Florent; Damber, Lena; Kleinerman, Ruth; Hawkins, Michael M; Tucker, Margaret; Lundell, Marie; Lubin, Jay H

2016-05-01

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

PubMed

Anderson, Evan J; Carbonell-Estrany, Xavier; Blanken, Maarten; Lanari, Marcello; Sheridan-Pereira, Margaret; Rodgers-Gray, Barry; Fullarton, John; Rouffiac, Elisabeth; Vo, Pamela; Notario, Gerard; Campbell, Fiona; Paes, Bosco

2017-02-01

Moderate-late preterm infants, 33-35 weeks' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants. A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants' 33-35 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. The burden of RSVH in moderate-late, 33-35 weeks' wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy.

Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis.

PubMed

Sepriano, Alexandre; Rubio, Roxana; Ramiro, Sofia; Landewé, Robert; van der Heijde, Désirée

2017-05-01

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard'). A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models. Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%). Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Diagnostic Accuracy of F-18 FDG PET/CT for Preoperative Lymph Node Staging in Newly Diagnosed Bladder Cancer Patients: A Systematic Review and Meta-Analysis.

PubMed

Ha, Hong Ku; Koo, Phillip J; Kim, Seong-Jang

2018-05-30

We aimed to assess the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for preoperative lymph node (LN) staging in newly diagnosed bladder cancer (BC) patients through a systematic review and meta-analysis. MEDLINE, Embase, and the Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for preoperative LN staging in newly diagnosed BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across 14 studies (785 patients), the pooled sensitivity was 0.57 (95% CI: 0.49-0.64) and the pooled specificity was 0.92 (95% CI: 0.87-0.95). The LR syntheses gave an overall LR+ of 7.4 (95% CI: 4.4-12.3) and an LR- of 0.47 (95% CI: 0.39-0.56). The pooled diagnostic odds ratio was 16 (95% CI: 9-28). F-18 FDG PET/CT shows a low sensitivity and high specificity for the detection of metastatic LNs in patients with newly diagnosed BC. © 2018 S. Karger AG, Basel.

HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis

NASA Astrophysics Data System (ADS)

Jaruthamsophon, Kanoot; Tipmanee, Varomyalin; Sangiemchoey, Antida; Sukasem, Chonlaphat; Limprasert, Pornprot

2017-03-01

HLA-B*15:02 screening before carbamazepine (CBZ) prescription in Asian populations is the recommended practice to prevent CBZ-induced Stevens-Johnson syndrome (CBZ-SJS). However, a number of patients have developed CBZ-SJS even having no HLA-B*15:02. Herein, we present the case of a Thai patient who had a negative HLA-B*15:02 screening result but later developed CBZ-SJS. Further HLA typing revealed HLA-B*15:21/B*13:01. HLA-B*15:21 is a member of the HLA-B75 serotype and is commonly found in Southeast Asian populations. Based on this case, we hypothesised that if all HLA-B*15:02 carriers were prevented from CBZ prescription, another common HLA-B75 serotype marker would show its association with CBZ-SJS. To test this hypothesis, we pooled data from previous association studies in Asian populations, excluded all cases with HLA-B*15:02, and analysed the association significance of HLA-B75 serotype markers. A significant association was found between CBZ-SJS and HLA-B*15:21 and HLA-B*15:11. We also applied an in silico analysis and found that all HLA-B75 serotype molecules shared similar capability in binding the CBZ molecule. In summary, this report provides the first evidence of a positive association between HLA-B*15:21 and CBZ-SJS and the first in silico analysis of CBZ binding sites and details of the molecular behaviour of HLA-B75 molecule to explain its molecular action.

Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

PubMed

Le Cleach, Laurence; Trinquart, Ludovic; Do, Giao; Maruani, Annabel; Lebrun-Vignes, Benedicte; Ravaud, Philippe; Chosidow, Olivier

2014-08-03

Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions. To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies. We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment. Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs. A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo.We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63).We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

Hybrid DNA virus in Chinese patients with seronegative hepatitis discovered by deep sequencing.

PubMed

Xu, Baoyan; Zhi, Ning; Hu, Gangqing; Wan, Zhihong; Zheng, Xiaobin; Liu, Xiaohong; Wong, Susan; Kajigaya, Sachiko; Zhao, Keji; Mao, Qing; Young, Neal S

2013-06-18

Seronegative hepatitis--non-A, non-B, non-C, non-D, non-E hepatitis--is poorly characterized but strongly associated with serious complications. We collected 92 sera specimens from patients with non-A-E hepatitis in Chongqing, China between 1999 and 2007. Ten sera pools were screened by Solexa deep sequencing. We discovered a 3,780-bp contig present in all 10 pools that yielded BLASTx E scores of 7e-05-0.008 against parvoviruses. The complete sequence of the in silico-assembled 3,780-bp contig was confirmed by gene amplification of overlapping regions over almost the entire genome, and the virus was provisionally designated NIH-CQV. Further analysis revealed that the contig was composed of two major ORFs. By protein BLAST, ORF1 and ORF2 were most homologous to the replication-associated protein of bat circovirus and the capsid protein of porcine parvovirus, respectively. Phylogenetic analysis indicated that NIH-CQV is located at the interface of Parvoviridae and Circoviridae. Prevalence of NIH-CQV in patients was determined by quantitative PCR. Sixty-three of 90 patient samples (70%) were positive, but all those from 45 healthy controls were negative. Average virus titer in the patient specimens was 1.05 e4 copies/µL. Specific antibodies against NIH-CQV were sought by immunoblotting. Eighty-four percent of patients were positive for IgG, and 31% were positive for IgM; in contrast, 78% of healthy controls were positive for IgG, but all were negative for IgM. Although more work is needed to determine the etiologic role of NIH-CQV in human disease, our data indicate that a parvovirus-like virus is highly prevalent in a cohort of patients with non-A-E hepatitis.

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors.

PubMed

Bauer, Todd M; Patel, Manish R; Forero-Torres, Andres; George, Thomas J; Assad, Albert; Du, Yining; Hurwitz, Herbert

2018-01-01

Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B). The objective of the dose-finding phase was to identify the maximum tolerated doses (MTDs) of ruxolitinib plus gemcitabine with or without nab-paclitaxel. Among 42 patients enrolled, the median age was 62.5 years, 81.0% had pancreatic cancer, and almost 62% had received prior systemic therapy. Regimen A was tolerated with standard doses of gemcitabine; regimen B was tolerated with reduced doses of gemcitabine/nab-paclitaxel or concomitant granulocyte colony-stimulating factor. The sponsor decided to terminate the study early due to the interim analysis results of the Phase III JANUS 1 study. Discontinuations were mainly due to radiologic or clinical disease progression (81.0% of patients). Median treatment durations were 55.5 days (cohort A0) and 150.5 days (pooled B cohorts). Four patients (pooled B cohorts) had dose-limiting toxicities: grade 3 pneumonia (n=1), grade 4 neutropenia (n=1), and grade 4 thrombocytopenia (n=2). The most common grade 3/4 hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. Serious AEs occurring in ≥2 patients in cohort A0 or pooled B cohorts were abdominal pain, sepsis (cohort A0), dehydration, anemia, and asthenia (pooled B cohorts). Overall response rates (ORRs) were 12.5% in cohort A0 and 38.5% in pooled B cohorts. Among patients with pancreatic cancer, ORR was 23.5% (14.0% cohort A0 30.0% pooled B cohorts). The study was terminated early prior to reaching MTDs per sponsor decision; although ruxolitinib plus gemcitabine with or without nab-paclitaxel was generally safe and well tolerated in patients with advanced solid tumors, this combination will not be pursued further.

Population subdivision and molecular sequence variation: theory and analysis of Drosophila ananassae data.

PubMed

Vogl, Claus; Das, Aparup; Beaumont, Mark; Mohanty, Sujata; Stephan, Wolfgang

2003-11-01

Population subdivision complicates analysis of molecular variation. Even if neutrality is assumed, three evolutionary forces need to be considered: migration, mutation, and drift. Simplification can be achieved by assuming that the process of migration among and drift within subpopulations is occurring fast compared to mutation and drift in the entire population. This allows a two-step approach in the analysis: (i) analysis of population subdivision and (ii) analysis of molecular variation in the migrant pool. We model population subdivision using an infinite island model, where we allow the migration/drift parameter Theta to vary among populations. Thus, central and peripheral populations can be differentiated. For inference of Theta, we use a coalescence approach, implemented via a Markov chain Monte Carlo (MCMC) integration method that allows estimation of allele frequencies in the migrant pool. The second step of this approach (analysis of molecular variation in the migrant pool) uses the estimated allele frequencies in the migrant pool for the study of molecular variation. We apply this method to a Drosophila ananassae sequence data set. We find little indication of isolation by distance, but large differences in the migration parameter among populations. The population as a whole seems to be expanding. A population from Bogor (Java, Indonesia) shows the highest variation and seems closest to the species center.

Prognostic significance of metabolic enzyme pyruvate kinase M2 in breast cancer: A meta-analysis.

PubMed

Yang, Yiming; Wu, Ke; Liu, Yulin; Shi, Liang; Tao, Kaixiong; Wang, Guobin

2017-11-01

Numerous studies have reported that aberrant pyruvate kinase M2 isoform (PKM2) expressed in cancer, indicating that PKM2 plays a critical role in tumor initiation and progression. Nevertheless, its prognostic value in breast cancer tumor is yet contentious. Therefore, we performed this meta-analysis to evaluate the prognostic significance of PKM2 in breast cancer. Eligible relevant literatures were retrieved by searching PubMed, the Cochrane Library, Embase through December 2016. Articles that comparing different PKM2 expression levels in human breast cancer tissues and prognostic significance were included. Software RevMan 5.3 and STATA (Review Manager (RevMan): [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. StataCorp. 2011. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP) were applied to analyze the outcomes. Pooled results were presented in hazardous ratios (HRs) of 5-year overall survival (OS), progression-free survival (PFS), and odds ratios (ORs) of clinicopathological features with 95% confidence intervals. Data from 6 involved studies with 895 patients were summarized. Breast cancer patients with high PKM2 had a worse OS (pooled HR = 1.65, 95% CI = 1.31-2.08, P < .001) and PFS (pooled HR = 2.49, 95% CI = 1.84-3.36, P < .00001). High PKM2 expression is related to lymph node metastasis (N1+N2+N3 vs N0, OR = 1.97, 95%CI = 1.39-2.80, P = .0001). The outcome stability was verified via sensitivity analysis. But elevated PKM2 expression was not correlated to tumor stage (T2+T3 vs T1, pooled OR = 0.80, 95% CI = 0.36-1.77, P = .58) and differential grade (G2+G3 vs G1, OR = 2.74, 95%CI = 0.76-9.84, P = .12). No publication bias was found in the included studies for OS (Begg test, P = .260; Egger test, P = .747). High PKM2 expression denotes worse OS and PFS in breast cancer patients, and correlate with the lymph node metastasis. However, there is no evidence for the impact of PKM2 expression on T stage and tumor differentiation.

Safety and efficacy of low molecular weight heparins in children: a systematic review of the literature and meta-analysis of single-arm studies.

PubMed

Bidlingmaier, Christoph; Kenet, Gili; Kurnik, Karin; Mathew, Prasad; Manner, Daniela; Mitchell, Lesley; Krümpel, Anne; Nowak-Göttl, Ulrike

2011-10-01

Within the last two decades low molecular weight heparins (LMWH) have gained increasing widespread use as anticoagulants in children. The use of LMWH has been implemented into clinical care even though there is a lack of firm evidence on the efficacy and safety of LMWH in this population due to the absence of sufficiently powered randomized controlled trials. In the absence of clinical trials, we performed a meta-analysis of available single-arm studies using LMWH in children. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1980 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients, ethnicity, venous thromboembolic events type, and frequency of recurrence and major bleedings were abstracted. Pooled incidence rates (IR) including 95% confidence intervals (95% CIs) on efficacy and safety data of LMWH administration on primary prophylaxis, as well as on secondary prophylaxis in children following symptomatic thromboembolism (TE) were shown. We included 2251 pediatric patients derived from 35 single-arm studies from 12 study countries who were eligible for analysis in the present systematic review. Pooled incidence rates (95% CI) to develop first TE on primary prophylaxis, further TE event on LMWH secondary prophylaxis, or a major bleeding event on LMWH were 0.047 (0.023 to 0.091), 0.052 (0.037 to 0.073) for efficacy, and 0.054 (0.039 to 0.074) for safety (treatment data only), respectively. Efficacy and safety data are comparable with adult data. The present systematic review suggests that use of LMWH in children as primary prophylaxis and in treatment of symptomatic thrombosis is effective and safe. However, properly designed randomized controlled trials are needed. © Thieme Medical Publishers.

Alcohol intake and gastric cancer: Meta-analyses of published data versus individual participant data pooled analyses (StoP Project).

PubMed

Ferro, Ana; Morais, Samantha; Rota, Matteo; Pelucchi, Claudio; Bertuccio, Paola; Bonzi, Rossella; Galeone, Carlotta; Zhang, Zuo-Feng; Matsuo, Keitaro; Ito, Hidemi; Hu, Jinfu; Johnson, Kenneth C; Yu, Guo-Pei; Palli, Domenico; Ferraroni, Monica; Muscat, Joshua; Malekzadeh, Reza; Ye, Weimin; Song, Huan; Zaridze, David; Maximovitch, Dmitry; Fernández de Larrea, Nerea; Kogevinas, Manolis; Vioque, Jesus; Navarrete-Muñoz, Eva M; Pakseresht, Mohammadreza; Pourfarzi, Farhad; Wolk, Alicja; Orsini, Nicola; Bellavia, Andrea; Håkansson, Niclas; Mu, Lina; Pastorino, Roberta; Kurtz, Robert C; Derakhshan, Mohammad H; Lagiou, Areti; Lagiou, Pagona; Boffetta, Paolo; Boccia, Stefania; Negri, Eva; La Vecchia, Carlo; Peleteiro, Bárbara; Lunet, Nuno

2018-05-01

Individual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer. We compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies. A total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07-1.36) vs. 1.10 (0.99-1.23)] and more heterogeneous (I 2 : 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias. Meta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Local anaesthetics and regional anaesthesia for preventing chronic pain after surgery

PubMed Central

Andreae, Michael H; Andreae, Doerthe A

2014-01-01

Background Regional anaesthesia may reduce the rate of persistent (chronic) pain after surgery, a frequent and debilitating condition. Objectives To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of persistent pain six or 12 months after surgery. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), PubMed (1966 to April 2012), EMBASE (1966 to May 2012) and CINAHL (1966 to May 2012) without any language restriction. We used a combination of free text search and controlled vocabulary search. The results were limited to randomized controlled clinical trials (RCTs). We conducted a handsearch in reference lists of included trials, review articles and conference abstracts. Selection criteria We included RCTs comparing local anaesthetics or regional anaesthesia versus conventional analgesia with a pain outcome at six or 12 months after surgery. Data collection and analysis Two authors independently assessed trial quality and extracted data, including information on adverse events. We contacted study authors for additional information. Results are presented as pooled odds ratios (OR) with 95% confidence intervals (CI), based on random-effects models (inverse variance method). We grouped studies according to surgical interventions. We employed the Chi2 test and calculated the I2 statistic to investigate study heterogeneity. Main results We identified 23 RCTs studying local anaesthetics or regional anaesthesia for the prevention of persistent (chronic) pain after surgery. Data from a total of 1090 patients with outcomes at six months and of 441 patients with outcomes at 12 months were presented. No study included children. We pooled data from 250 participants after thoracotomy, with outcomes at six months. Data favoured regional anaesthesia for the prevention of chronic pain at six months after thoracotomy with an OR of 0.33 (95% CI 0.20 to 0.56). We pooled two studies on paravertebral block for breast cancer surgery; the pooled data of 89 participants with outcomes at five to six months favoured paravertebral block with an OR of 0.37 (95% CI 0.14 to 0.94).The methodological quality of the included studies was intermediate. Adverse effects were not studied systematically and were reported sparsely. Clinical heterogeneity, attrition and sparse outcome data hampered the assessment of effects, especially at 12 months. Authors’ conclusions Epidural anaesthesia may reduce the risk of developing chronic pain after thoracotomy in about one patient out of every four patients treated. Paravertebral block may reduce the risk of chronic pain after breast cancer surgery in about one out of every five women treated. Our conclusions are significantly weakened by performance bias, shortcomings in allocation concealment, considerable attrition and incomplete outcome data. We caution that our evidence synthesis is based on only a few, small studies. More studies with high methodological quality, addressing various types of surgery and different age groups, including children, are needed. PMID:23076930