bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS
Authors: Uchiyama Shinichiro , Toyoda Kazunori , Kitagawa Kazuo , Okada Yasushi , Ameriso Sebastian , Mundl Hardi , Berkowitz Scott , Yamada Takashi , Liu Yan Yun , Hart Robert G ,   on behalf of the NAVIGATE ESUS Investigators
Published: May 2019

Background Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients. Methods and results Among 3972 stroke patients in cerebral hemispheres with intracranial arterial imaging, 502 (12.6%) patients met the criteria for BAD. BAD was associated with younger age (years; OR: 0.97, 95% CI: 0.96–0.98), race (Asian; OR: 1.78, 95% CI: 1.44–2.21), region (Eastern Europe; OR: 2.49, 95% CI: 1.87–3.32), and higher National Institute of Health Stroke Scale (OR: 1.17, 95% CI: 1.12–1.22) at randomization. During follow-up, stroke or systemic embolism (2.5%/year vs. 6.2%/year, p = 0.0022), stroke (2.1%/year vs. 6.2%/year, p = 0.0008), and ischemic stroke (2.1%/year vs. 5.9%/year, p = 0.0013) occurred less frequently in BAD than non-BAD patients. There were no differences in annual rates of stroke or systemic embolism (2.5%/year vs. 2.5%/year, HR: 1.01, 95% CI: 0.33–3.14) or major bleeding (1.3%/year vs. 0.8%/year, HR: 1.51, 95% CI: 0.25–9.05) between rivaroxaban and aspirin groups among BAD patients. Conclusions BAD was relatively common, especially in Asian and from Eastern Europe among embolic stroke of undetermined source patients. Stroke severity was higher at randomization but recurrence of stroke was fewer in BAD than non-BAD patients. The efficacy and safety of rivaroxaban and aspirin did not differ among BAD patients.
A qualitative study to identify indicators of the quality of wound closure
Authors: Blencowe NS , Rooshenas L , Tolkien Z , Bera KD , Gould Brown H , Elliott D , Reeves BC , Blazeby JM 
Published: May 2019

Background: Wound healing after surgery may be complicated by surgical site infection (SSI). SSI development may be influenced by surgical techniques surrounding primary wound closure; for example, the standard to which surgical wounds are closed at the end of an operation. Aim: This study aimed to identify indicators of the quality of wound closure, and factors affecting this, to enable the future development of a tool to measure the quality of wound closure in the context of abdominal surgery. Methods: This study was undertaken within the context of an ongoing feasibility study comparing dressing strategies for patients undergoing abdominal surgery. Content analysis of published literature, non-participant observations of wound closure in the operating theatre, and semi-structured interviews with clinicians were used to identify indicators of the quality of wound closure. Results: A long list ( n = 38 domains) was categorized into visible markers indicating the quality of wound closure (e.g. suture visibility, apposition of wound edges, evidence of gaps in the wound or tethering of the skin edges), factors that might influence this (e.g. surgeon’s expertise, time taken to closure the wounds) and patient factors (e.g. obesity, skin conditions). Conclusions: This is the first study to investigate what is meant by ‘good wound closure’ and factors that might influence it. Findings will result in the development of a tool to assess quality of primary wound closure.
A network meta‐analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection
Authors: Rokkas Theodore , Gisbert Javier P , Gasbarrini Antonio , Hold Georgina L , Tilg Herbert , Malfertheiner Peter , Megraud Francis , O'Morain Colm 
Published: May 2019

BackgroundRecurrence remains a challenge in Clostridium difficile infection (CDI), and in this field fecal microbiota transplantation (FMT) has attracted significant interest. Network meta‐analysis (NWM) has been established as an evidence‐synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials. So far no NWM exists concerning therapeutic interventions for recurrent CDI (rCDI).ObjectiveIn this NWM we assessed the comparative effectiveness of various therapies for rCDI to examine the efficacy rank order and determine the optimum therapeutic approach.MethodsA Bayesian network meta‐analysis was performed to investigate the efficacy rank order of rCDI interventions.ResultsSix eligible RCTs were entered into an NWM. They included 348 rCDI patients, in whom seven therapeutic interventions were used, i.e. donor fecal microbiota transplantation (DFMT), vancomycin, fidaxomicin, vancomycin + DFMT, vancomycin + bowel lavage, autologous FMT and placebo. DFMT showed the highest efficacy in comparison with vancomycin [odds ratio (95% credible interval), 20.02 (7.05–70.03)] and fidaxomicin (22.01 (4.38–109.63)).ConclusionThis NWM showed that DFMT is the optimum therapeutic approach for rCDI, as it was the most efficacious among various therapeutic interventions, particularly in comparison with commonly used antibiotics such as vancomycin or fidaxomicin.
Relationship Between Lower Limb Tightness and Practice Time Among Adolescent Baseball Players With Symptomatic Osgood-Schlatter Disease
Authors: Omodaka Takuya , Ohsawa Takashi , Tajika Tsuyoshi , Shiozawa Hiroyuki , Hashimoto Syogo , Ohmae Hiroaki , Shitara Hitoshi , Ichinose Tsuyoshi , Sasaki Tsuyoshi , Hamano Noritaka , Takagishi Kenji , Chikuda Hirotaka 
Published: May 2019

Background: Osgood-Schlatter disease (OSD) is characterized by traction apophysitis of the tibial tuberosity. Few studies on symptomatic and asymptomatic OSD have correlated findings with clinical examination. Purpose: To investigate the relationship between lower limb tightness and practice time among adolescent baseball players with symptomatic OSD. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The study participants were 402 male baseball players (N = 804 knees) with a mean ± SD age of 10.9 ± 1.5 years (range, 7-14 years). Participant age, height, body weight, body mass index, practice time per week, range of motion of the hip and ankle joints, heel-buttock distance (HBD), and straight-legged raise angle were evaluated. Tibial tuberosity development, as assessed with ultrasonography, was classified into 4 stages: cartilaginous, apophyseal, epiphyseal, and bony. Knees that were classified as apophyseal or epiphyseal were investigated. Participants were divided into 3 groups: non-OSD, asymptomatic OSD, and symptomatic OSD. Results: Of 400 knees in the apophyseal and epiphyseal stages, 23 knees had asymptomatic OSD, and 11 had symptomatic OSD. Players with symptomatic OSD practiced for significantly longer than the non-OSD group ( P = .001) and asymptomatic OSD group ( P = .001). Players with symptomatic OSD also had a larger HBD ( P = .006) and smaller range of motion regarding internal rotation of hip ( P = .023) and dorsiflexion of the ankle ( P = .013) than the non-OSD group. Conclusion: Players with symptomatic OSD had longer practice times than the non-OSD and asymptomatic OSD players. Symptomatic OSD was also associated with tightness of the lower limbs as assessed by the HBD and range of motion in the hip and ankle joints.
Antibiotic treatment for pneumonia complicating stroke: Recommendations from the pneumonia in stroke consensus (PISCES) group
Authors: Kishore Amit K , Jeans Adam R , Garau Javier , Bustamante Alejandro , Kalra Lalit , Langhorne Peter , Chamorro Angel , Urra Xabier , Katan Mira , Napoli Mario Di , Westendorp Willeke , Nederkoorn Paul J , van de Beek Diederik , Roffe Christine , Woodhead Mark , Montaner Joan , Meisel Andreas , Smith Craig J 
Published: May 2019

Purpose The microbiological aetiology of pneumonia complicating stroke is poorly characterised. In this second Pneumonia in Stroke ConsEnsuS statement, we propose a standardised approach to empirical antibiotic therapy in pneumonia complicating stroke, based on likely microbiological aetiology, to improve antibiotic stewardship. Methods Systematic literature searches of multiple databases were undertaken. An evidence review and a round of consensus consultation were completed prior to a final multi-disciplinary consensus meeting in September 2017, held in Barcelona, Spain. Consensus was approached using a modified Delphi technique and defined a priori as 75% agreement between the consensus group members. Findings: No randomised trials to guide antibiotic treatment of pneumonia complicating stroke were identified. Consensus was reached for the following: (1) Stroke-associated pneumonia may be caused by organisms associated with either community-acquired or hospital-acquired pneumonia; (2) Treatment for early stroke-associated pneumonia (<72 h of stroke onset) should cover community-acquired pneumonia organisms; (3) Treatment for late stroke-associated pneumonia (≥72 h and within seven days of stroke onset) should cover community-acquired pneumonia organisms plus coliforms +/− Pseudomonas spp. if risk factors; (4) No additional antimicrobial cover is required for patients with dysphagia or aspiration; (5) Pneumonia occurring after seven days from stroke onset should be treated as for hospital-acquired pneumonia; (6) Treatment should continue for at least seven days for each of these scenarios. Discussion Consensus recommendations for antibiotic treatment of the spectrum of pneumonia complicating stroke are proposed. However, there was limited evidence available to formulate consensus on choice of specific antibiotic class for pneumonia complicating stroke. Conclusion Further studies are required to inform evidence-based treatment of stroke-associated pneumonia including randomised trials of antibiotics and validation of candidate biomarkers.
Multilevel Sleep Surgery Including the Palate in Nonsyndromic, Neurologically Intact Children with Obstructive Sleep Apnea
Authors: Cohn Jason E. , Relyea George E. , Daggumati Srihari , McKinnon Brian J. 
Published: May 2019

ObjectiveTo examine the effects of multilevel sleep surgery, including palate procedures, on obstructive sleep apnea parameters in the pediatric population.Study DesignA case series with chart review was conducted to identify nonsyndromic, neurologically intact pediatric patients who underwent either uvulectomy or uvulopalatopharyngoplasty as part of multilevel sleep surgery from 2011 through 2017.SettingA tertiary care, university children’s hospital.Subjects and MethodsUnpaired Student t test was used to compare average pre‐ and postsurgical apnea‐hypopnea index (AHI) and oxygen saturation nadir (OSN). Paired Student t test was used to compare the mean pre‐ and postsurgical AHI and OSN within the same patient for the effects of adenotonsillectomy (T&A) vs multilevel sleep surgery.ResultsIn patients who underwent T&A previously, multilevel sleep surgery, including palate procedures, resulted in improved OSA severity in 6 (86%) patients and worsened OSA in 1 (14%) patient. Multilevel sleep surgery, including palate procedures, significantly decreased mean AHI from 37.98 events/h preoperatively to 8.91 events/h postoperatively (P =. 005). However, it did not significantly decrease OSN.ConclusionThis study includes one of the largest populations of children in whom palate procedures as a part of multilevel sleep surgery have been performed safely with no major complications and a low rate of velopharyngeal insufficiency. Therefore, palatal surgery as a part of multilevel sleep surgery is not necessarily the pariah that we have traditional thought it is in pediatric otolaryngology.
Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation
Authors: Fine Noah , Barzilay Oriyah , Sun Chunxiang , Wellappuli Nimali , Tanwir Farzeen , Chadwick Jeffrey W. , Oveisi Morvarid , Tasevski Nikola , Prescott David , Gargan Martin , Philpott Dana J. , Dror Yigal , Glogauer Michael 
Published: May 2019

AbstractPolymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of “primed for recruitment” PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue. One hour after acute peritoneal insult, pPMNs became the dominant PMN population in bone marrow (BM) and blood, returning to baseline levels with resolution of inflammation. PMN priming was induced by the granulopoietic factors granulocyte-macrophage–colony-stimulating factor (GM-CSF) and granulocyte–colony-stimulating factor (G-CSF). High levels of pPMNs were observed in neutropenic mice and in pediatric neutropenic patients who were resistant to infection, highlighting an important role of this population in innate immune function.
A systematic review and meta-analysis of supplemental education in patients treated with oral anticoagulation
Authors: Paquette Miney , Witt Daniel M. , Holbrook Anne , Skov Jane , Ansell Jack , Schünemann Holger J. , Wiercioch Wojtek , Nieuwlaat Robby 
Published: May 2019

Abstract
Oral anticoagulants (OACs) are indicated for treatment and prevention of thromboembolic diseases. Supplemental patient education (education) has been proposed to improve outcomes, and this systematic review assesses the effect of education on mortality, thromboembolic events (TEEs) including venous thromboembolism (VTE), and bleeding in patients taking OACs. Randomized controlled trials were included, and 2 authors independently screened articles and assessed risk of bias. In 9 trials (controls, n = 720; intervention group patients, n = 646), 4 assessed critical outcomes of mortality, TEEs (VTE, stroke, and systemic embolism), and bleeding to estimate absolute risk ratios. When comparing education with usual care, in 1000 patients, there may be 12 fewer deaths (95% confidence interval [CI], 19 fewer to 154 more) and 16 fewer bleeding events (95% CI, 34 fewer to 135 more), but this evidence is uncertain; the evidence also suggests 6 fewer VTEs (95% CI, 10 fewer to 16 more) and 8 fewer TEEs (95% CI, 16 fewer to 18 more). The mean difference in time in therapeutic range may be 2.4% higher in the education group compared with usual care (95% CI, 2.79% lower to 7.58% higher). We also found very low certainty of evidence for a large increase in knowledge scores (standardized mean difference, 0.84 standard deviation units higher; 95% CI, 0.51-1.16). Overall, the certainty of evidence was low to very low because of serious risk of bias and serious imprecision. Additional sufficiently powered trials or different approaches to education are required to better assess supplemental education effects on outcomes in patients taking OACs.
Cost-effectiveness of tyrosine kinase inhibition in first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer.
Authors: Han Jiaqi , Hu Huabin , Liao Mengting , She Longjiang , Yao Linli , Ding Dong , Zeng Shan , Liang-Fang Shen , Huang Jin 
Published: May 2019

e20504 Background: Patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR) mutation have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the economic efficiency of this application is unclear, especially in limited health resource settings. To inform policy makers about the value of these medications, we developed a Markov model to compare the cost-effectiveness of these strategies. Methods: A Markov model was developed to compare the cost-effectiveness of chemotherapy, gefitinib, erlotinib, afatinib and osimertinib treatments from a public payers’ perspective in the U.S and China. Health states consisted of progression-free survival, progressive disease, and death. Model transition, adverse event probabilities, disease progression, and death were obtained from randomized clinical trials and network meta-analysis. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) over a 10-year lifetime horizon were calculated. One-way and probabilistic sensitivity analyses were performed by multiple potentially modifiable parameters. Results: The tyrosine kinase inhibitors were more cost-effective than chemotherapy treatment in both the U.S and China. In the U.S, compared with erlotinib, afatinib had an ICER of $241,420/QALY while osimertinib had an ICER of $351,315/QALY. In China, the incremental utility for osimertinib versus gefitinib was 0.68QALYs, and the ICER was $25,622/QALY. The probability sensitivity analyses also illustrated that the erlotinib was the optimal treatment at a willingness-to-pay (WTP) threshold of $150,000/QALY in the U.S and osimertinib was the most cost-effective treatment at a WTP of $26,508/QALY in China. Conclusions: Based on our current analysis, erlotinib appears to be the preferred first-line treatment for advanced EGFR mutation-positive NSCLC patients in the US at a WTP of $150,000/QALY. However, because of the price reduction and more health benefits, osimertinib was considered to be most cost-effective at a WTP of $26,508/QALY in China.
Immunotherapeutic efficacy in NSCLC and patients’ smoking status: A meta-analysis.
Authors: Wang Shanshan , Wang Guoqiang , Xu Yu , Cai Shangli , Xiong Jianping 
Published: May 2019

e20510 Background: In non-small cell lung cancer (NSCLC), tumour mutational burden (TMB) has been validated in predicting the clinical benefit of immunotherapy. Smoke, delivering the carcinogens that form covalently bound DNA adducts into respiratory system, is the critical cause of miscoding events and mutational burden in NSCLC. However, the predictive potential of tobacco consumption in immunotherapy remains controversial. Here, we did a meta-analysis to assess the heterogeneity of immune checkpoint inhibitor (ICI) efficacy in NSCLC patients with or without smoking habit. Methods: We systematically searched PubMed, the Cochrane Central library and Embase, for the randomized controlled trials (RCTs) of ICIs (inhibitors of PD-1, PD-L1, CTLA-4, or combination) in NSCLC. The studies were excluded due to the unpublished hazard ratio (HR) for both progression-free survival (PFS) and overall survival (OS) according to smoking status. Pooled estimates of survival HR and 95% confidence interval (CI) in smokers and non-smokers were performed using a random-effects model, and the heterogeneity between the two estimates was assessed using an interaction test by Review Manager. Results: In total, 13 eligible RCTs of FDA-approved ICIs (concerning ipilimumab, nivolumab, pembrolizumab, atezolizumab, and avelumab) containing 8154 patients with NSCLC (6800 [83.4%] smokers and 1354 [16.6%] non-smokers) were included for analysis. Compared to standard treatment, a prolonged PFS was observed in smokers treated with ICIs (pooled HR, 0.72, 95% CI 0.63-0.81, P < 0·001) instead of non-smokers (pooled HR, 0.98, 95% CI 0.73-1.31, P = 0·90). The pooled HR of OS between immunotherapy and standard treatment was 0.77 (95% CI 0.69-0.86, P < 0·001) in smokers and 0.78 (95%CI 0.59-1.02, P = 0·07) in non-smokers. Similar results were observed among sub-groups according to the different histology (squamous and non-squamous), class of ICIs (anti-PD-1 or PD-L1) and lines of treatment (first-line or subsequent). The difference in efficacy between smokers and non-smokers treated with ICIs was also significant (HR 0.75, 95% CI 0.62-0.92, P = 0·005). Conclusions: ICIs can improve PFS and OS for patients with advanced NSCLC, but the magnitude of benefit depends on smoking history, especially for PFS. Future clinical trials are supposed to include more non-smokers and concentrate on enhancing the efficacy of ICIs in the NSCLC patients without cigarette consumption, possibly discovering distinctive immunotherapeutic approaches in smokers and non-smokers.
The mutation profile of EGFR in resectable Chinese lung cancer patients.
Authors: Mao Wenjun , Chen Ruo , Chen Jingyu , Liu Feng , He Yijun , Ye Shugao , Lu Rongguo , Qi Martin , Zheng Mingfeng 
Published: May 2019

e20519 Background: The frequency of EGFR mutation in Asian advanced lung cancer patients is about 40% and the application of EGFR tyrosine kinase inhibitors (TKIs) has become a standard treatment therapy. Several studies showed that usage of EGFR TKIs in adjuvant or neo-adjuvant therapy was promising, while the mutation profile of EGFR mutations in resectable Chinese lung cancer patients was still scanty. Our study investigated EGFR mutation profile and its correlation with clinicopathological factors. Methods: 343 resectable patients with lung cancer were selected for eligibility criteria, and tumor tissues were collected for gene detection. EGFR genetic testing was performed by amplification refractory mutation system PCR (ARMS-PCR) with specific sensitive mutation sites. The clinicopathological factors of study population were recorded based on pre-design protocol. Chi-square or fish exact test were used to statistic analysis Results: A total of 343 patients were enrolled in study. 42.6% (146/343) patients were male, 20.4% (68/333) patients were smokers, the adenocarcinoma accounted for 93.8 % (319/340), and stage 0, I, II, III was 7.3% (25/343), 68.8% (236/343), 8.5% (29/343), 15.5% (53/343), respectively. The frequency of EGFR mutation was 54.2% (186/343) in whole population, and the proportion of EGFR L858R, 19Del, 719X, 768I, 861Q mutation was 31.2% (107/343), 21.3% (73/343), 1.2% (4/343), 1.0% (3/343), 1.0% (3/343), respectively. 1.2% (4/343) patients presented EGFR co-mutation (EGFR G719X/S768I; L858R/S768I; G719X/S768I; L858R/L861Q) .The mutation frequency of EGFR mutation was associated with sex, smoking, differentiation, pathology (P = 0.0076, < 0.0001, < 0.0001, < 0.0001, respectively). In subgroup analysis, the incidence of two main mutation types, EGFR L858R and 19del, were associated with disease stage (P = 0.044) and age (P = 0.035). Conclusions: EGFR mutation in resectable lung cancer was a common phenomenon as advanced stage and our study might provide useful informations for using EGFR-TKIs in further adjuvant or neo-adjuvant therapy.