bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do we need to adjust for interim analyses in a Bayesian adaptive trial design?
Authors: Ryan Elizabeth G. , Brock Kristian , Gates Simon , Slade Daniel 
Published: June 2020

AbstractBackgroundBayesian adaptive methods are increasingly being used to design clinical trials and offer several advantages over traditional approaches. Decisions at analysis points are usually based on the posterior distribution of the treatment effect. However, there is some confusion as to whether control of type I error is required for Bayesian designs as this is a frequentist concept.MethodsWe discuss the arguments for and against adjusting for multiplicities in Bayesian trials with interim analyses. With two case studies we illustrate the effect of including interim analyses on type I/II error rates in Bayesian clinical trials where no adjustments for multiplicities are made. We propose several approaches to control type I error, and also alternative methods for decision-making in Bayesian clinical trials.ResultsIn both case studies we demonstrated that the type I error was inflated in the Bayesian adaptive designs through incorporation of interim analyses that allowed early stopping for efficacy and without adjustments to account for multiplicity. Incorporation of early stopping for efficacy also increased the power in some instances. An increase in the number of interim analyses that only allowed early stopping for futility decreased the type I error, but also decreased power. An increase in the number of interim analyses that allowed for either early stopping for efficacy or futility generally increased type I error and decreased power.ConclusionsCurrently, regulators require demonstration of control of type I error for both frequentist and Bayesian adaptive designs, particularly for late-phase trials. To demonstrate control of type I error in Bayesian adaptive designs, adjustments to the stopping boundaries are usually required for designs that allow for early stopping for efficacy as the number of analyses increase. If the designs only allow for early stopping for futility then adjustments to the stopping boundaries are not needed to control type I error. If one instead uses a strict Bayesian approach, which is currently more accepted in the design and analysis of exploratory trials, then type I errors could be ignored and the designs could instead focus on the posterior probabilities of treatment effects of clinically-relevant values.
GP awareness, practice, knowledge and confidence: evaluation of the first nation-wide dementia-focused continuing medical education program in Australia
Authors: Casey Anne-Nicole , Islam M. Mofizul , Schütze Heike , Parkinson Anne , Yen Laurann , Shell Allan , Winbolt Margaret , Brodaty Henry 
Published: June 2020

Abstract
Background
Dementia is under-diagnosed in primary care. Timely diagnosis and care management improve outcomes for patients and caregivers. This research evaluated the effectiveness of a nationwide Continuing Medical Education (CME) program to enhance dementia-related awareness, practice, knowledge and confidence of general practitioners (GPs) in Australia.

Methods
Data were collected from self-report surveys by GPs who participated in an accredited CME program face-to-face or online; program evaluations from GPs; and process evaluations from workshop facilitators. CME participants completed surveys at one or more time-points (pre-, post-program, six to 9 months follow-up) between 2015 and 2017. Paired samples t-test was used to determine difference in mean outcome scores (self-reported change in awareness, knowledge, confidence, practice) between time-points. Multivariable regression analyses were used to investigate associations between respondent characteristics and key variables. Qualitative feedback was analysed thematically.

Results
Of 1352 GPs who completed a survey at one or more time-points (pre: 1303; post: 1017; follow-up: 138), mean scores increased between pre-CME and post-program for awareness (Mpost-pre = 0.9, p <  0.0005), practice-related items (Mpost-pre = 1.3, p <  0.0005), knowledge (Mpost-pre = 2.2, p <  0.0005), confidence (Mpost-pre = 2.1, p <  0.0005). Significant increases were seen in all four outcomes for GPs who completed these surveys at both pre- and follow-up time-points. Male participants and those who had practised for five or more years showed greater change in knowledge and confidence. Age, years in practice, and education delivery method significantly predicted post-program knowledge and confidence. Most respondents who completed additional program evaluations (> 90%) rated the training as relevant to their practice. These participants, and facilitators who completed process evaluations, suggested adding more content addressing patient capacity and legal issues, locality-specific specialist and support services, case studies and videos to illustrate concepts.

Conclusions
The sustainability of change in key elements relating to health professionals’ dementia awareness, knowledge and confidence indicated that dementia CME programs may contribute to improving capacity to provide timely dementia diagnosis and management in general practice. Low follow-up response rates warrant cautious interpretation of results. Dementia CME should be adopted in other contexts and updated as more research becomes available.
A combination of single-balloon enteroscopy-assisted laparoscopy and endoscopic mucosal resection for treating gastrointestinal venous malformations in blue rubber bleb nevus syndrome: a case report
Authors: Xu Yuemei , Wu Yingjie , Dai Zhenzhen , Xia Feizhen , Xu Feng 
Published: June 2020

Abstract
Background
Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital disease characterized by multifocal venous malformations. It remains a considerable challenge in treating the gastrointestinal (GI) venous malformations due to multiple lesions throughout the GI tract, and the likelihood of recurrence. We report a case study of BRBNS in the GI tract, in which GI venous malformations and related GI bleeding were successfully treated with a combination of multiple endoscopic procedures.

Case presentation
A 17-year-old man was admitted to our hospital for dizziness and hypodynamia. The symptoms persisted for nearly 1 year. The laboratory tests revealed iron-deficiency anemia with abnormally low hemoglobin (Hb), and a strong positive fecal occult blood test. A total of four hemangiomas were detected: one in the stomach, one in the descending colon, and two in the small intestines with a high risk of hemorrhage. Under gastroendoscopy, enteroscopy, and video capsule endoscopy (VCE) throughout the GI tract, the patient underwent surgical treatment. Endoscopic mucosal resection was initially performed in the stomach and colon, and the lesions in the small intestine were resected with laparoscopy auxiliaried by single-balloon enteroscopy (SBE), during which SBE assisted in identifying the lesions. The patient well-tolerated the procedures, and had a favorable prognosis.

Conclusion
The combination of single-balloon enteroscopy-assisted laparoscopy and endoscopic mucosal resection was effective for the present case, which could be considered for patients with similar clinical conditions.
Bilateral anophthalmia and intrahepatic biliary atresia, two unusual components of Fraser syndrome: a case report
Authors: Brimo Alsaman Muhamad Zakaria , Agha Sarab , Sallah Hala , Badawi Rayan , Kitaz Mohammad Nour , Assani Abdullah , Nawfal Hamdi 
Published: June 2020

Abstract
Background
Fraser syndrome or “cryptophthalmos syndrome” is a rare autosomal recessive disease. It is characterized by a group of congenital malformations such as: crytophthalmos, syndactyly, abnormal genitalia, and malformations of the nose, ears, and larynx. Although cryptophthalmos is considered as a main feature of Fraser syndrome, its absence does not exclude the diagnosis. Clinical diagnosis can be made by Thomas Criteria. Here we present the first documented case of Fraser Syndrome in Aleppo, Syria that is characterized by bilateral anophthalmia and intrahepatic biliary atresia.

Case presentation
During pregnancy, several ultrasound scans revealed hyperechoic lungs, ascites, and unremarkable right kidney at the 19th-week visit; bilateral syndactyly on both hands and feet at the 32nd-week visit. On the 39th week of gestation, the stillborn was delivered by cesarean section due to cephalopelvic disproportion. Gross examination showed bilateral anophthalmia, bilateral syndactyly on hands and feet, low set ears, and ambiguous genitalia. Microscopic examination of the lung, spleen, liver, ovary, and kidneys revealed abnormalities in these organs.

Conclusion
The diagnosis of Fraser syndrome can be made prenatally and postnatally; prenatally by ultrasound at 18 weeks of gestation and postnatally by clinical examination using Thomas criteria. Moreover, intrahepatic biliary atresia was not described previously with Fraser syndrome; this recommends a more detailed pathologic study for Fraser syndrome cases.
A real-time electronic symptom monitoring system for patients after discharge following surgery: a pilot study in cancer-related surgery
Authors: Richards H. S. , Blazeby J. M. , Portal A. , Harding R. , Reed T. , Lander T. , Chalmers K. A. , Carter R. , Singhal R. , Absolom K. , Velikova G. , Avery K. N. L. 
Published: June 2020

Abstract
Background
Advances in peri-operative care of surgical oncology patients result in shorter hospital stays. Earlier discharge may bring benefits, but complications can occur while patients are recovering at home. Electronic patient-reported outcome (ePRO) systems may enhance remote, real-time symptom monitoring and detection of complications after hospital discharge, thereby improving patient safety and outcomes. Evidence of the effectiveness of ePRO systems in surgical oncology is lacking. This pilot study evaluated the feasibility of a real-time electronic symptom monitoring system for patients after discharge following cancer-related upper gastrointestinal surgery.

Methods
A pilot study in two UK hospitals included patients who had undergone cancer-related upper gastrointestinal surgery. Participants completed the ePRO symptom-report at discharge, twice in the first week and weekly post-discharge. Symptom-report completeness, system actions, barriers to using the ePRO system and technical performance were examined. The ePRO surgery system is an online symptom-report that allows clinicians to view patient symptom-reports within hospital electronic health records and was developed as part of the eRAPID project. Clinically derived algorithms provide patients with tailored self-management advice, prompts to contact a clinician or automated clinician alerts depending on symptom severity. Interviews with participants and clinicians determined the acceptability of the ePRO system to support patients and their clinical management during recovery.

Results
Ninety-one patients were approached, of which 40 consented to participate (27 male, mean age 64 years). Symptom-report response rates were high (range 63–100%). Of 197 ePRO completions analysed, 76 (39%) triggered self-management advice, 72 (36%) trigged advice to contact a clinician, 9 (5%) triggered a clinician alert and 40 (20%) did not require advice. Participants found the ePRO system reassuring, providing timely information and advice relevant to supporting their recovery. Clinicians regarded the system as a useful adjunct to usual care, by signposting patients to seek appropriate help and enhancing their understanding of patients’ experiences during recovery.

Conclusion
Use of the ePRO system for the real-time, remote monitoring of symptoms in patients recovering from cancer-related upper gastrointestinal surgery is feasible and acceptable. A definitive randomised controlled trial is needed to evaluate the impact of the system on patients’ wellbeing after hospital discharge.
Psychosocial, behavioral and clinical correlates of children with overweight and obesity
Authors: Thaker Vidhu V. , Osganian Stavroula K. , deFerranti Sarah D. , Sonneville Kendrin R. , Cheng Jennifer K. , Feldman Henry A. , Richmond Tracy K. 
Published: June 2020

Abstract
Background
Psychological and behavioral correlates are considered important in the development and persistence of obesity in both adults and youth. This study aimed to identify such features in youth with severe obesity (BMI ≥ 120% of 95thpercentile of sex-specific BMI-for-age) compared to those with overweight or non-severe obesity.

Methods
Youth with BMI ≥ 85th percentile were invited to participate in a prospective research registry where data was collected on attributes such as family characteristics, eating behaviors, dietary intake, physical activity, perception of health and mental well-being, and cardiometabolic parameters.

Results
In a racially/ethnically diverse cohort of 105 youth (65% female, median age 16.1 years, range 4.62–25.5), 51% had severe obesity. The body fat percent increased with the higher levels of obesity. There were no differences in the self-reported frequency of intake of sugar sweetened beverages or fresh produce across the weight categories. However, the participants with severe obesity reported higher levels of emotional eating and eating when bored (p = 0.022), levels of stress (p = 0.013), engaged in fewer sports or organized activities (p = 0.044), and had suboptimal perception of health (p = 0.053). Asthma, depression and obstructive sleep apnea were more frequently reported in youth with severe obesity. The presence of abnormal HDL-C, HOMA-IR, hs-CRP and multiple cardiometabolic risk factors were more common among youth with severe obesity.

Conclusions
Youth with severe obesity have identifiable differences in psychosocial and behavioral attributes that can be used to develop targeted intervention strategies to improve their health.
A new insight into acute lymphoblastic leukemia in children: influences of changed intestinal microfloras
Authors: Gao Xiaolin , Miao Ruixue , Zhu Yiping , Lin Chao , Yang Xue , Jia Ruizhen , Linghan Kuang , Wan Chaomin , Deng Jianjun 
Published: June 2020

Abstract
Background
Previous studies have shown that changes in intestinal microfloras are associated with both gastrointestinal (GI) and non-GI tumors. It is not clear whether there is an association between GI microflora changes and hematological malignancies.

Methods
In the current study, we used 16S rDNA gene sequencing techniques to profile the GI microbiome in children with lymphoblastic leukemia (ALL, n = 18) and matched healthy control (n = 18). Using multiple specialized software [Heatmap, Principal coordinates analysis (PCoA), Claster and Metastates], we analyzed the sequencing data for microfloral species classification, abundance and diversity.

Results
A total of 27 genera between the ALL and control groups (FDR ≤ 0.05 and/or P ≤ 0.05) showed significantly different abundance between ALL patients and healthy controls: 12 of them were predominant in healthy group and other 15 species were significantly higher in ALL group. In addition, we compared the abundance and diversity of microfloral species in ALL patients prior to and during remission stage after chemotherapy, and no significant difference was detected.

Conclusions
Compared to healthy controls, ALL patient showed significant changes of GI microfloras. Further explorations of the intestinal micro-ecology in ALL patients may provide important information to understand relationship between microfloras and ALL.
Development of a novel social incubator for health promoting initiatives in a disadvantaged region
Authors: Spitzer-Shohat Sivan , Essa-Hadad Jumanah , Rudolf Mary CJ 
Published: June 2020

AbstractBackgroundBottom-up approaches to disparity reduction present a departure from traditional service models where health services are traditionally delivered top-down. Raphael, a novel bottom-up social incubator, was developed in a disadvantaged region with the aim of ‘hatching’ innovative health improvement interventions through academia-community partnership.MethodsCommunity organizations were invited to submit proposals for incubation. Selection was made using the criteria of innovation, population neediness and potential for health impact and sustainability. Raphael partnered with organizations to pilot and evaluate their intervention with $5000 seed-funding. The evaluation was guided by the conceptual framework of technological incubators. Outcomes and sustainability were ascertained through qualitative and quantitative analysis of records and interviews at 12 months and 3–5 years, and the Community Impact of Research Oriented Partnerships (CIROP) questionnaire was administered to community partners.ResultsNinety proposals were submitted between 2013 and 2015 principally from non-governmental organizations (NGOs). Thirteen interventions were selected for ‘incubation’. Twelve successfully ‘hatched’: three demonstrated sustainability with extension locally or nationally through acquiring external competitive funding; six continued to have influence within their organizations; three failed to continue beyond the pilot. Benefits to the organisations included acquisition of skills including advocacy, teaching and health promotion, evaluation skills and ability to utilize acquired knowledge for implementation. CIROP demonstrated that individuals’ research skills were reported to improve (mean ± sd) 4.80 ± 2.49 along with confidence in being able to use knowledge acquired in everyday practice (5.50 ± 1.38) and new connections were facilitated (5.33 ± 2.25).ConclusionsRaphael, devised as a ‘social incubator’, succeeded in nurturing novel ideas engendered by community organizations that aimed to impact on health disparities. Judging by success rates of technological incubators its goals were realized to a considerable degree.
Video-assisted thoracoscopic surgery is a safe and effective method to treat intrathoracic unicentric Castleman’s disease
Authors: Wang Yan-qing , Li Shan-qing , Guo Feng 
Published: June 2020

Abstract
Background
Castleman’s disease (CD) is a rare non-clonal lymphadenopathy. Application of video-assisted thoracoscopic surgery (VATs) in intrathoracic unicentric Castleman’s disease (UCD) is rarely reported. This study is aimed to clarify the role of VATs for diagnosis and treatment in intrathoracic UCD.

Methods
The authors reviewed and identified patients who had received a histologic diagnosis of CD through VATs at our hospital from January2010 to June 2018. Clinical and radiologic variables, histopathology, type of approach, complications, and long-term effect were analyzed to evaluate the safety and efficacy of VATs.

Results
A total of 10 patients were included in this study, with 8 hyaline vascular type and 2 plasma cell type. The mean maximum diameter of the lesions was 4.66 cm. Nine cases underwent complete surgical excision by VATs, and 1 case was converted to thoracotomy. All patients had no postoperative complications. With a median follow-up of 5 years (range: 1–9 years), no tumor recurrence was found in 9 patients receiving complete tumor resection, and 1 patient with incomplete tumor resection remained symptom free without clinical or radiographic progression.

Conclusions
VATs is an alternative, minimally invasive technique for the diagnosis and treatment in patients with intrathoracic UCD.
Suppressed nuclear factor-kappa B alleviates lipopolysaccharide-induced acute lung injury through downregulation of CXCR4 mediated by microRNA-194
Authors: Chen Ruidong , Xie Fei , Zhao Jie , Yue Bin 
Published: June 2020

AbstractAcute lung injury (ALI) is a highly lethal pulmonary disease that causes edema, hypoxemia and respiratory failure. Recent evidence indicates that nuclear factor-kappa B (NF-κB) plays a crucial role in ALI development. However, the regulatory mechanism of NF-κB on ALI remains enigmatic. In this study, we investigated potential molecular mechanism of NF-κB on ALI induced by lipopolysaccharide (LPS). BALB/c mice were subjected to intratracheal spraying of LPS to generate an ALI mode, with the activity of NF-κB in mice tissues being detected by enzyme linked immunosorbent assay (ELISA), and the number of inflammatory cells in bronchoalveolar lavage fluid being counted. Then, the macrophage cell line RAW264.7 exposed to LPS were treated with ammonium pyrrolidinedithiocarbamate (PDTC) (inhibitor of NF-κB), miR-194 mimic, or oe-chemokine receptor type 4 (CXCR4) separately or in combination. After that, ELISA and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression level of IL-1β, IL-6, TNF-α, miR-194 and CXCR4, respectively. In addition, the targeting relationship between miR-194 and CXCR4 was verified by dual-luciferase reporter gene assay. The dry/wet ratio of lung and the MPO activity were also measured to assess the inflammatory response in mice. Activation of NF-κB down-regulated the miR-194 expression in LPS-induced ALI. Overexpression of miR-194 alleviated LPS-induced ALI and reduced the expression of inflammatory factors IL-1β, IL-6 and TNF-α via targeting CXCR4. In LPS-induced ALI, NF-κB mediates the CXCR4 expression by inhibiting the expression of miR-194, thus promoting the inflammatory injury of lung.
Better cardiovascular outcomes of type 2 diabetic patients treated with GLP-1 receptor agonists versus DPP-4 inhibitors in clinical practice
Authors: Longato Enrico , Di Camillo Barbara , Sparacino Giovanni , Tramontan Lara , Avogaro Angelo , Fadini Gian Paolo 
Published: June 2020

Abstract
Background
Cardiovascular outcome trials in high-risk patients showed that some GLP-1 receptor agonists (GLP-1RA), but not dipeptidyl-peptidase-4 inhibitors (DPP-4i), can prevent cardiovascular events in type 2 diabetes (T2D). Since no trial has directly compared these two classes of drugs, we performed a comparative outcome analysis using real-world data.

Methods
From a database of ~ 5 million people from North-East Italy, we retrospectively identified initiators of GLP-1RA or DPP-4i from 2011 to 2018. We obtained two balanced cohorts by 1:1 propensity score matching. The primary outcome was the 3-point major adverse cardiovascular events (3P-MACE; a composite of death, myocardial infarction, or stroke). 3P-MACE components and hospitalization for heart failure were secondary outcomes.

Results
From 330,193 individuals with T2D, we extracted two matched cohorts of 2807 GLP-1RA and 2807 DPP-4i initiators, followed for a median of 18 months. On average, patients were 63 years old, 60% male; 15% had pre-existing cardiovascular disease. The rate of 3P-MACE was lower in patients treated with GLP-1RA compared to DPP4i (23.5 vs. 34.9 events per 1000 person-years; HR: 0.67; 95% C.I. 0.53–0.86; p = 0.002). Rates of myocardial infarction (HR 0.67; 95% C.I. 0.50–0.91; p = 0.011) and all-cause death (HR 0.58; 95% C.I. 0.35–0.96; p = 0.034) were lower among GLP-1RA initiators. The as-treated and intention-to-treat approaches yielded similar results.

Conclusions
Patients initiating a GLP-1RA in clinical practice had better cardiovascular outcomes than similar patients who initiated a DPP-4i. These data strongly confirm findings from cardiovascular outcome trials in a lower risk population.