bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial
Authors: Gullo Giuseppe , Eustace Alex J. , Canonici Alexandra , Collins Denis M. , Kennedy Michael J. , Grogan Liam , Breathhnach Oscar , McCaffrey John , Keane Maccon , Martin Michael J. , Gupta Rajnish , Leonard Gregory , O’Connor Miriam , Calvert Paula M. , Donnellan Paul , Walshe Janice , McDermott Enda , Scott Kathleen , Hernando Andres , Parker Imelda , Murray David W. , O’Farrell Alice C. , Maratha Ashwini , Dicker Patrick , Rafferty Mairin , Murphy Verena , O’Donovan Norma , Gallagher William M. , Ky Bonnie , Tryfonopoulos Dimitrios , Moulton Brian , Byrne Annette T. , Crown John 
Published: July 2019

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients. Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF). Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity. Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further. Trial Registration ClinicalTrials.gov Identifier: NCT00911716.
Learnings From SAAHAS—A Queer Affirmative CBT-Based Group Therapy Intervention for LGBTQIA+ Individuals in Mumbai, India
Authors: Wandrekar Jagruti , Nigudkar Advaita 
Published: July 2019

Background: There are few published research studies documenting intervention modalities used with LGBTQIA+ individuals in India. This is a pilot study documenting possibly the first of its kind therapy group named SAAHAS based in Mumbai. Methodology: SAAHAS was a free, open group for therapy meant for queer individuals. The therapeutic approach used was queer affirmative cognitive behavior therapy. Facilitators were queer psychologists. A survey was conducted to assess the needs of potential participants. Recruitment protocol, group, and session formats and structures are described here. Evaluation was primarily through anonymous participant feedback. Results: A total of 71 participants completed the intake survey, 28 participants attended at least one group session, and 78% of these were cis-gay men, with low representation of lesbian, bisexual women and transgender and gender nonconforming individuals. Over one year, 12 monthly sessions were conducted. Feedback suggested that the participants liked the group, found it to be a safe space, and reported an improvement in mental health, reduction of distress, reduction of feelings of isolation, and acquisition of knowledge and skills to tackle problems faced by queer people. Peer support, safe space, expert-cum-peer facilitator stance, and queer affirmative cognitive behavior therapy-based therapeutic approach may have contributed to group efficacy. Conclusion: The SAAHAS therapy group experience provides a useful low-cost therapeutic framework for queer individuals in India.
Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial
Authors: Muss Hyman B. , Polley Mei-Yin C. , Berry Donald A. , Liu Heshan , Cirrincione Constance T. , Theodoulou Maria , Mauer Ann M. , Kornblith Alice B. , Partridge Ann H. , Dressler Lynn G. , Cohen Harvey J. , Kartcheske Patricia A. , Perez Edith A. , Wolff Antonio C. , Gralow Julie R. , Burstein Harold J. , Mahmood Ahmad A. , Sutton Linda M. , Magrinat Gustav , Parker Barbara A. , Hart Ronald D. , Grenier Debjani , Hurria Arti , Jatoi Aminah , Norton Larry , Hudis Clifford A. , Winer Eric P. , Carey Lisa 
Published: July 2019

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.
Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study
Authors: Highland Krista B. , Soumoff Alyssa A. , Spinks Elizabeth A. , Kemezis Patricia A. , Buckenmaier Chester C. 
Published: July 2019

BACKGROUND:
Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs.

METHODS:
Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models.

RESULTS:
In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48–3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, −0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models.

CONCLUSIONS:
No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.
Major Neurologic Complications Associated With Postdural Puncture Headache in Obstetrics: A Retrospective Cohort Study
Authors: Guglielminotti Jean , Landau Ruth , Li Guohua 
Published: July 2019

BACKGROUND:
Increased risks of cerebral venous thrombosis or subdural hematoma, bacterial meningitis, persistent headache, and persistent low back pain are suggested in obstetric patients with postdural puncture headache (PDPH). Acute postpartum pain such as PDPH may also lead to postpartum depression. This study tested the hypothesis that PDPH in obstetric patients is associated with significantly increased postpartum risks of major neurologic and other maternal complications.

METHODS:
This retrospective cohort study consisted of 1,003,803 women who received neuraxial anesthesia for childbirth in New York State hospitals between January 2005 and September 2014. The primary outcome was the composite of cerebral venous thrombosis and subdural hematoma. The 4 secondary outcomes were bacterial meningitis, depression, headache, and low back pain. PDPH and complications were identified during the delivery hospitalization and up to 1 year postdelivery. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using the inverse probability of treatment weighting approach.

RESULTS:
Of the women studied, 4808 (0.48%; 95% CI, 0.47–0.49) developed PDPH, including 264 cases (5.2%) identified during a readmission with a median time to readmission of 4 days. The incidence of cerebral venous thrombosis and subdural hematoma was significantly higher in women with PDPH than in women without PDPH (3.12 per 1000 neuraxial or 1:320 vs 0.16 per 1000 or 1:6250, respectively; P < .001). The incidence of the 4 secondary outcomes was also significantly higher in women with PDPH than in women without PDPH. The aORs associated with PDPH were 19.0 (95% CI, 11.2–32.1) for the composite of cerebral venous thrombosis and subdural hematoma, 39.7 (95% CI, 13.6–115.5) for bacterial meningitis, 1.9 (95% CI, 1.4–2.6) for depression, 7.7 (95% CI, 6.5–9.0) for headache, and 4.6 (95% CI, 3.3–6.3) for low back pain. Seventy percent of cerebral venous thrombosis and subdural hematoma were identified during a readmission with a median time to readmission of 5 days.

CONCLUSIONS:
PDPH is associated with substantially increased postpartum risks of major neurologic and other maternal complications, underscoring the importance of early recognition and treatment of anesthesia-related complications in obstetrics.
Beall-ing O
Authors: Joaquin Jeremiah Joven 
Published: July 2019

In “A neglected reply to Prior’s dilemma” Beall [2012] presents a Weak Kleene framework where Prior’s dilemma for Hume’s no-ought-fromis thesis fails. It fails in the framework because addition, the inference rule that one of its horns relies on, is invalid. In this paper, we show that a more general result is necessary for the viability of Beall’s proposal – a result, which implies that Hume’s thesis holds in the proposed framework. We prove this result and thus show that Beall’s proposal is indeed viable.
Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19
Authors: Xie Xiaoyan , Liu Miao , Meng Qiang 
Published: July 2019

ObjectivesOsteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.MethodsMSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone.ResultsThe results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation.ConclusionThese data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2.
P003 Young Investigator The role of probiotics in primary and secondary prevention of pouchitis: A systematic review and meta-analysis
Authors: Shadi Hamdeh , Osama Altayar , Jihan Fathallah , Leonard Baidoo , Stephen Hanauer 
Published: July 2019

BACKGROUND:
Pouchitis is the most common long-term complication after ileal pouch anal anastomosis (IPAA) surgery. Its cumulative incidence is approximately 50% after a 10-year follow up. Several trials have looked at the use of probiotics in prevention of pouchitis, and showed a significant decrease in the development of pouchitis, but other showed no difference. Our data is very limited and the most recent Cochrane review in 2015 showed a possible benefit of probiotics in maintaining the remission, but it's not widely used in practice, especially in primary prevention. In this systematic review and meta-analysis, we aimed to discern whether probiotics are actually beneficial in primary and secondary prevention of pouchitis.

METHODS:
A comprehensive search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted from each database's inception to May 20, 2017 to search for comparative studies of probiotics use in the prevention of primary (first episode) and secondary (recurrent episodes) pouchitis. The outcome of interest was the development of pouchitis.

RESULTS:
Nine studies with a total of 376 patients were included. The use of probiotics in the primary prevention was associated with a decreased incidence of pouchitis (RR, 0.18; 95% CI, 0.08–0.39; P < 0.01; heterogeneity I2: 0%) with a NNT of 3.2, and their use in the secondary prevention was associated with a decreased incidence of recurrent pouchitis compared to placebo (RR, 0.20; 95% CI, 0.11–0.36; P < 0.01; heterogeneity I2: 0%). Overall risk of developing pouchitis was decreased with the use of probiotics use (RR, 0.19; 95% CI, 0.12–0.30; P < 0.01; heterogeneity I2: 0%) with a NNT of 2. Sub-group analysis included only studies that used VSL#3 showed a significant decrease in pouchitis in both primary prevention (RR, 0.23; 95% CI, 0.10–0.50; P < 0.01; heterogeneity I2: 0%), secondary prevention (RR, 0.17; 95% CI, 0.09–0.31; P < 0.01; heterogeneity I2: 0%), and overall risk (RR, 0.19; 95% CI, 0.12–0.36; P < 0.01; heterogeneity I2: 0%).

CONCLUSION(S):
The current systematic review and meta-analysis showed that probiotics are superior to placebo in the primary and secondary prevention of pouchitis with a very significant NNT. These findings suggest the use of probiotics in patients after ileal pouch anal anastomosis (IPAA) surgery for primary prevention, or in patients with recurrent pouchitis.
P005 Trends of hospitalization in ulcerative colitis in patients in the United States from 2000 to 2014
Authors: Prashanth Rawla , Tagore Sunkara 
Published: July 2019

BACKGROUND:
The prevalence of ulcerative colitis (UC) has increased over time and is one of the most important gastrointestinal causes of frequent admissions to hospital in the United States. The cost burden of UC has been steadily increasing. The primary objective of our study was to analyze patient demographics, cost burden, mortality and length of stay associated with UC hospital admissions.

METHODS:
Nationwide inpatient sample (NIS) database was used to identify UC discharges in all patients from 2000 to 2014 using ICD-9-CM Codes (ICD9), Principal Diagnosis: 556.0 Ulcerative Enterocolitis, 556.1 Ulcerative Ileocolitis, 556.2 Ulcerative Proctitis, 556.3 Ulcerative Proctosigmoidtis, 556.4 Pseudopolyposis Colon, 556.5 Left sided Ulcerative Colitis, 556.6 Universal Ulcerative Colitis, 556.8 Other Ulcerative Colitis, 556.9 Ulcerative Colitis Unspecified as the principal discharge diagnosis. NIS is the largest all-payer inpatient care database in the United States, containing data on more than 7 million hospital stays. It has a large sample size which is ideal for developing national and regional estimates.

RESULTS:
A total of 517,191,644 discharges with a diagnosis of UC were analyzed from 2000 to 2014 from the NIS database. The number of hospitalizations increased from 27,452 in 2000 to 37,565 in 2014, a 36.8% increase. In-hospital mortality decreased from 0.94% in 2000 to 0.39% in 2014, a decrease of 58.5%. Mean length of hospital stay has decreased from 6.9 days to 5.8 days (15.9% decrease) during the same period, but the mean hospital charges increased from $18,552 in 2000 to $45,465 in 2014 (145% increase). The proportion of males to females with UC is slowly trending up from 2000 to 2014. Aggregate charges increased from 0.51 billion dollars to 1.70 billion dollars.

CONCLUSION(S):
Overall in-hospital mortality associated with UC has decreased but the number of hospitalizations and mean cost has increased over the years. This represents a significant cost burden on the healthcare system and patients. The decrease in mortality can be attributed to early diagnosis and early institution of newer and aggressive treatments. The number of hospitalizations due to UC has been steadily increasing, and further research needs to be done on finding out the reasons for increased causes of hospitalization and ways to decrease the cost burden on patients and hospitals.
P006  Probiotics treatment in Crohn's disease: A systematic review and meta-analysis of randomized clinical trial
Authors: Muhammed Elfaituri , Alkomos Mina Fransawy , Ammar Kalo , Nguyen Thi Linh Hue , Abdulmoate Alshareef , Mai Nhu Y. , Nada Gaballa , Tran Loc , Bisher Sawaf , Saed Enabi , Sherihan E. Galal , Tarek Ahmed , Thai Le Ba Nghia , Nguyen Tien Huy 
Published: July 2019

BACKGROUND:
Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD) is chronic idiopathic, relapsing nonspecific inflammatory characterized by transmural inflammation can involve any element of the gastrointestinal tract, although its etiology is unclear yet, the recent studies have shown the associations between the alteration of gut microbiota and CD, furthermore, several studies suggest using probiotic, prebiotic, and synbiotic agents to manipulate the gut microbiota in the management of Crohn's disease. This study aims to bring together the evidence available on the clinical effect of probiotics in Crohn's disease patients.

METHODS:
To identify all relevant studies, PubMed, MEDLINE, Scopus, Web of Science, and other databases were searched. Randomized clinical trials (RCTs) compared probiotic treatment with placebo were included in this meta-analysis. Primary outcomes were clinical remission and maintenance of remission. Secondary outcomes were adverse events, relapse rate, and endoscopic recurrence rate.

RESULTS:
Eight randomized clinical trials (RCTs) studies were included for meta-analysis. In the probiotic group, there was no significant difference in term of clinical remission compared to placebo, with an odds ratio of 0.89 (95% CI, 0.33–2.35; P > 0.05). Also, there was no significant difference in terms of adverse events rate between the 2 groups with 62 out of 162 (38.2%) in the probiotic group compared with 59 out of 162 (36.4%) in placebo groups; odds ratio 1.08 (95% CI, 0.08–1.78; P > 0.05). On the other hand, there was no significant difference in terms of relapse rate between 2 groups with 52 out of 124 (41.9%) in the probiotic group compared with 52 out of 121 (42.9%) in placebo groups; odds ratio 0.99 (95% CI, 0.58–1.69; P > 0.5). Regarding endoscopic recurrence rate, there was no significant difference in 2 groups of patients who underwent postoperative follow-up with 76 out of 137 (55.4%) in the probiotic group compared with 88 out 147 (59.8%) in placebo groups; odds ratio 0.86 (95% CI, 0.52–1.42; P > 0.05).

CONCLUSION(S):
Probiotic is potentially useful in Crohn's disease management. However, it appears to be effective for induction of remission, but with no significant major short-term benefits compared to the placebo group. Finally, there remain many unanswered questions that require further studies before probiotic can be considered for use in the treatment of Crohn's disease.