bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers
Authors: Przybytkowski Ewa , Davis Thomas , Hosny Abdelrahman , Eismann Julia , Matulonis Ursula A. , Wulf Gerburg M. , Nabavi Sheida 
Published: December 2019

Abstract
Background: BRCA1/2 germline mutation related cancers are candidates for new immune therapeutic interventions. This study was a hypothesis generating exploration of genomic data collected at diagnosis for 19 patients. The prominent tumor mutation burden (TMB) in hereditary breast and ovarian cancers in this cohort was not correlated with high global immune activity in their microenvironments. More information is needed about the relationship between genomic instability, phenotypes and immune microenvironments of these hereditary tumors in order to find appropriate markers of immune activity and the most effective anticancer immune strategies. Methods: Mining and statistical analyses of the original DNA and RNA sequencing data and The Cancer Genome Atlas data were performed. To interpret the data, we have used published literature and web available resources such as Gene Ontology, The Cancer immunome Atlas and the Cancer Research Institute iAtlas. Results: We found that BRCA1/2 germline related breast and ovarian cancers do not represent a unique phenotypic identity, but theyexpress a range of phenotypes similar to sporadic cancers. All breast and ovarian BRCA1/2 related tumors are characterized by high homologous recombination deficiency (HRD) and low aneuploidy. Interestingly, all sporadic high grade serous ovarian cancers (HGSOC) and most of the subtypes of triple negative breast cancers (TNBC) also express a high degree of HRD. Conclusions: TMB is not associated with the magnitude of the immune response in hereditary BRCA1/2 related breast and ovarian cancers or in sporadic TNBC and sporadic HGSOC. Hereditary tumors express phenotypes as heterogenous as sporadic tumors with various degree of “BRCAness” and various characteristics of the immune microenvironments. The subtyping criteria developed for sporadic tumors can be applied for the classification of hereditary tumors and possibly also characterization of their immune microenvironment. A high HRD score may be a good candidate biomarker for response to platinum, and potentially PARP-inhibition. Trial registration: Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent TNBC or HGSOC(NCT01623349). The design and the outcome of the clinical trial is not in the scope of this hypothesis generating study.
Explaining the successes and failures of tuberculosis treatment programs; a tale of two regions in rural Eastern Uganda
Authors: Izudi Jonathan , Tamwesigire Imelda K , Bajunirwe Francis 
Published: December 2019

Abstract
Background. Optimally performing tuberculosis (TB) programs are characterized by treatment success rate (TSR) of at least 90%. In rural eastern Uganda, and elsewhere in sub Saharan Africa, TSR varies considerably across district TB programs and the reasons for the differences are unclear. This study explored factors associated with the low and high TSR across four districts in rural eastern Uganda. Methods. We interviewed District TB and Leprosy Supervisors, Laboratory focal persons, and health facility TB focal persons from four districts in Eastern Uganda as key informants. Interviews were audio recorded, transcribed verbatim, and imported into ATLAs.ti where thematic content analysis was performed and results were summarized into themes. Results . The emerging themes were categorized as either facilitators of or barriers to treatment success. The emerging facilitators prevailing in the districts with high rates of treatment success were using data to make decisions and design interventions, continuous quality improvement, capacity building, and prioritization of better management of people with TB. The barriers common in districts with low rates of treatment success included lack of motivated and dedicated TB focal persons, scarce or no funding for implementing TB activities , and a poor implementation of community-based directly observed therapy short course. Conclusion. This study shows that several factors are associated with the differing rates of treatment success in rural eastern Uganda. These factors should be the focus for TB control programs in Uganda and similar settings in order to improve rates of treatment success.
Age is a predictor for the recurrence of syncope in vasovagal syncope patients with a positive head-up tilt test
Authors: Guo Yongjuan , Chen Xiaomin , Zeng Tianze , Wang Lin , Cen Lvwei 
Published: December 2019

Abstract
BACKROUND Valid predictors of the recurrence of syncope in vasovagal syncope(VVS) patients with a positive head-up tilt test (HUTT) are currently lacking. The goal of this study was to identify the predictive performance of age for the recurrence of syncope in VVS patients with a positive HUTT.METHODS in total, 175 VVS patients with a positive HUTT were followed for 6 to 32 months, and ≥1 syncope episodes during follow-up was considered the recurrence of syncope. The study population was divided into 2 groups, namely, a recurrence of syncope group (44 patients) and a no recurrence of syncope group (131 patients). The baseline clinical data, hemodynamic parameters and classification of the vasovagal syncope on the HUTT were analyzed. Logistics regression was used to analyze the effect size and confidence interval of age. A receiver operating characteristic(ROC) analysis was used to assess the predictive performance and investigate the predictive value of age by the area under the curve (AUC).RESULTS The age of recurrence of syncope group 60.0 (47.8, 66.0) years was older than that of no recurrence of syncope group 53.0 (43.0, 62.0) years, and there was a significant difference between the two groups (P < 0.05). The trend of syncope recurrence changed with age and the logistics regression model adjusted by sex showed that the elder was an increased risk of syncope recurrence in VVS with positive HUTT [OR value: 1.03, 95% confidence interval(CI) 1.008 to 1.061 p < 0.05].Age was a valid predictor for the recurrence of syncope in VVS patients with a positive HUTT (AUC: 0.688; 95%CI 0.598 to 0.777 p < 0.05). The cut-off value was 53.5 years, and the sensitivity and specificity were 72.7% and 52.7%, respectively. CONCLUSIONS Age may be a valid predictor for recurrence of syncope in VVS patients with positive HUTT. The rate of recurrence of syncope increased with increasing age, especially in old female.
CD45dimCD34+CD38-CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia .
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Ju Lan Jeong , Sung Jun Young , Jeong Yoo Kyung , Cheon Jaekyung , Koh SuJin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol 
Published: December 2019

Abstract
Background: Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation. Methods: We examined the levels of CD45 dim CD34 + CD38 - CD133 + cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cytometry. Results: Interestingly, the CD45 dim CD34 + CD38 - CD133 + cells were highly expressed in the bone marrow of patients with AML compared to that in healthy controls (HC). Moreover, the proportions of CD45 dim CD34 + CD38 - CD133 + cells were also examined in diverse hematological malignancies, including AML, CML, DLBCL, MM, MDS, HL, ALL, and CLL. LSCs were prominently detected in the BMCs isolated from patients with AML and CML, but rarely in BMCs isolated from patients with DLBCL, MM, MDS, ALL, CLL, and HL. Additionally, the high CD45 dim CD34 + CD38 - CD133 + cell counts in AML patients served as a significantly poor risk factor for overall and event free survival. Conclusions: Therefore, our results suggest that CD45 dim CD34 + CD38 - CD133 + cells in AML might potentially serve as LSCs. In addition, this cell population might represent a novel therapeutic target in AML.
Brain Natriuretic Peptide to Predict Successful Liberation from Mechanical Ventilation in Critically Ill Patients: a Systematic Review and Meta-Analysis.
Authors: Deschamps Jean , Andersen Sarah K. , Webber Jordan , Featherstone Robin , Sebastianski Meghan , Vandermeer Ben , Senaratne Janek , Bagshaw Sean M. 
Published: December 2019

Abstract
Background Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT).Methods We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of re-intubation or non-invasive ventilation at 48h). Statistical analyses include bi-variate and Moses-Littenberg models, and DerSimonian-Laird pooling of areas under ROC curve (AUROC).Results A total of 731 articles were screened. After pre-specified inclusion criteria, 18 adult and 2 pediatric studies were included. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831-0.929] and 0.828 [0.730-0.896] respectively, with a pooled AUROC of 0.92 [0.88-0.97] for successful liberation from MV. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP and post-SBT BNP were 0.89 [0.83-0.95], 0.77 [0.63-0.91], and 0.85 [0.80-0.90], respectively.Conclusion The ΔBNP during a SBT is an accurate incremental tool after SBT success by clinical indices to predict successful liberation from MV in adults. There is insufficient data to support its use as an alternate test to clinical indices of SBT or the use of ΔBNP, BNP-pre and BNP-post as an alternate or incremental test, or in pediatric patients.
Thrombocytopenia in critically ill patients with sepsis or septic shock: a systematic review and meta-analysis
Authors: Li Yuting , Li Hongxiang , Guo Jianxing , Zhang Dong 
Published: December 2019

Abstract
Background Thrombocytopenia is a common feature of sepsis or septic shock, but few meta-analyses have specifically evaluated prognostic importance of thrombocytopenia in patients with sepsis or septic shock. The objective of this meta-analysis was to evaluate the prognosis of thrombocytopenia in critically ill patients with sepsis or septic shock.Methods We searched the PubMed, Cochrane, and Embase databases for studies from inception to the 30th of November 2019. Prospective or retrospective cohort studies comparing thrombocytopenia to no thrombocytopenia in critically ill patients with sepsis or septic shock were included. All authors reported our primary outcome of short-term mortality(defined as ICU or 48-hour mortality) with clinically relevant secondary outcomes(ICU length of stay, rate of AKI, rate of mechanical ventilation). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).Results Seven studies including 4243 patients were included. The results of this meta-analysis showed that the short-term mortality of thrombocytopenia group was higher than that of the no thrombocytopenia group (odds ratio [OR]=2.01;95% CI, 1.73-2.33; P<0.00001; I2=78%).In addition, compared with no thrombocytopenia group, thrombocytopenia group showed higher rate of AKI(odds ratio [OR]=1.31;95% CI, 1.03-1.66; P=0.03 I2=65%) and longer ICU length of stay(Mean difference=1.31;95% CI, 0.66-1.96; P<0.0001; I2=50%). There was no statistically significant difference in the rate of mechanical ventilation between 2 groups (odds ratio [OR]=1.24;95% CI, 0.82-1.88; P=0.30; I2=0%).Conclusions Thrombocytopenia was associated with increased short-term mortality, ICU length of stay and rate of AKI in critically ill patients with sepsis or septic shock. The analysis of secondary outcomes showed no significant difference in the rate of mechanical ventilation between the two groups. Further randomized controlled studies of thrombocytopenia are still required.
Addressing low-value pharmacological prescribing in primary prevention of CVD through a structured evidence-based and theory-informed process for the design and testing of de-implementation strategies: the DE-imFAR study
Authors: Sanchez Alvaro , Pijoan Jose Ignacio , Pablo Susana , Mediavilla Marta Maialen , Sainz Rita , Lekue Itxasne , Gonzalez-Larragan Susana , Lantaron Gaspar , Argote Jon Imanol , García-Álvarez Arturo , Latorre Pedro Maria , Helfrich Christian D. , Grandes Gonzalo 
Published: December 2019

Abstract
Background: De-implementation or abandonment of ineffective or low-value healthcare is becoming a priority research field globally due to the growing empirical evidence of the high prevalence of such care and its impact in terms of patient safety and social inefficiency. Little is known, however, about the factors, barriers and facilitators involved or about interventions that are effective in promoting and accelerating the de-implementation of low-value healthcare. The De-imFAR study seeks to carry out a structured, evidence-based and theory-informed process involving the main stakeholders (clinicians, managers, patients and researchers) for the design, deployment and assessment of de-implementation strategies for reducing low-value pharmacological prescribing.Methods: A Phase I formative study using a systematic and comprehensive framework based on theory and evidence for the design of implementation strategies – specifically, the Behavior Change Wheel (BCW) - will be conducted to design and model de-implementation strategies to favour reductions in low-value pharmacological prescribing of statins in primary prevention of cardiovascular disease (CVD) by main stakeholders (clinicians, managers, patients and researchers) in a collegiate way. Subsequently, a Phase II comparative hybrid trial will be conducted to assess the feasibility and potential effectiveness of at least one active de-implementation strategy to reduce low-value pharmacological prescribing of statins in primary prevention of CVD compared to the usual procedures for dissemination of clinical practice guidelines ("what-not-to-do" recommendations). A mixed methods evaluation will be used: quantitative for the results of the implementation at the professional level (e.g., adoption, reach and implementation or execution of the recommended clinical practice); and qualitative to determine the feasibility and perceived impact of the de-implementation strategies from the clinicians’ perspective, and patients’ experiences related to the clinical care received.Discussion: The DE-imFAR study aims to generate valid scientific knowledge about the design and development of de-implementation strategies using theory- and evidence-based methodologies suggested by implementation science. It will explore the effectiveness of these strategies and their acceptability among clinicians, policy makers and patients. Its ultimate goal is to maximize the quality and efficiency of our health system by abandoning low-value pharmacological prescribing.
Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice
Authors: Santillo Marta , Wanat Marta , Davoudianfar Mina , Bongard Emily , Savic Sinisa , Savic Luoise , Porter Catherine , Fielding Joanne , Butler Chris , Pavitt Sue , Sandoe Jonathan , Tonkin-Crine Sarah 
Published: December 2019

Abstract
Background: To develop a behavioural intervention package to support clinicians and patients to identify and amend incorrect penicillin allergy records in English general practice. The intervention aimed to: 1) support general practice clinicians to refer patients for penicillin allergy testing (PAT), 2) support patients to attend for PAT and 3) support clinicians and patients to prescribe or consume penicillin, when indicated, following a negative PAT result.Methods: Theory-based, evidence-based and person-based approaches were utilised in the intervention development. We used evidence from a rapid review, two qualitative studies, one with patients and one with general practice clinicians, and expert consultation with the clinical research team in order to identify the intervention guiding principles and develop an intervention plan. Barriers and facilitators to the target behaviours were mapped to behaviour change theory in order to describe the proposed mechanisms of change. In the final stage, think-aloud interviews and consultations with the clinical research team were conducted to optimise intervention materials.Results: The collated evidence showed that the key barriers to referral of patients by clinicians were limited experience of referral and limited knowledge of referral criteria and PAT. Barriers for patients attending PAT were lack of knowledge of the benefits of testing and lack of motivation to get tested. Intervention materials were designed and developed to address these barriers. Conclusions: We present a novel behavioural intervention package designed to address the multiple barriers to uptake of PAT in general practice by clinicians and patients. The intervention development details how behaviour change techniques have been incorporated to hypothesise how the intervention is likely to work to help amend incorrect penicillin allergy records. The intervention will go on to be tested in a feasibility trial and randomised controlled trial in England.
Scaling-up an evidence-based intervention for osteoarthritis in real world settings: A pragmatic evaluation using the RE-AIM framework
Authors: Walker Andrew , Boaz Annette , Gibney Amber , Zambelli Zoe , Hurley Michael V 
Published: December 2019

Abstract
Background: Scaling-up and sustaining effective healthcare interventions is essential for improving healthcare; however, relatively little is known about these processes. In addition to quantitative experimental designs we need approaches that use embedded, observational studies on practice-led, naturally-occurring scale-up processes. There are also tensions between having adequately rigorous systems to monitor and evaluate scale-up well that are proportionate and pragmatic in practice. The study investigated the scale-up of an evidence-based complex intervention for knee and hip osteoarthritis (ESCAPE-pain) within ‘real-world’ settings by England’s 15 Academic Health Science Networks (AHSNs).Methods: A pragmatic evaluation of the scale-up of ESCAPE-pain using the RE-AIM framework to measure reach, effectiveness, adoption, implementation and maintenance. The evaluation used routine monitoring data collected from April 2014 to December 2019 as part of a national scale-up programme.Results: Between 2014-2018 ESCAPE-pain was adopted by over 110 clinical and non-clinical sites reaching over 9,000 people with osteoarthritis. The programme showed sustained clinical effectiveness (pain, function and quality of life) and high levels of adherence (78.5% completing 75% of the programme) within a range of real world settings. 770 people (physiotherapists and exercise professionals) have been trained to deliver ESCAPE-pain and 84.1% of sites have continued to deliver the programme post-implementation.Conclusions: ESCAPE-pain successfully moved from being an efficacious “research intervention” into an effective intervention within ‘real world’ clinical and non-clinical community settings. However, scale-up has been a gradual process requiring on-going, dedicated resources over 5 years by a national network of Academic Health Science Networks (AHSNs). Whilst the collection of monitoring and evaluation data is critical in understanding implementation and scale-up, there remain significant challenges in developing systems sufficiently rigorous, proportionate and locally acceptable.
Influence of China’s 2009 healthcare reform on the utilisation of continuum of care for maternal health services: Evidence from two cross-sectional household surveys in Shaanxi Province
Authors: Fan Xiaojing , Kumar Meghan Bruce , Zhou Zhongliang , Lee Ching-Hung , Wang Duolao , Liu Haixia , Dang Shaonong , Gao Jianmin 
Published: December 2019

Abstract
Background: Continuum of care for maternal health services (CMHS) is a proven approach to improve health and safety for mothers and newborns. This study aims to explore the influence of China’s 2009 healthcare reform on improving the CMHS utilisation. Methods: This population-based cross-sectional quantitative study included 2332 women drawn from the fourth and fifth National Health Service Surveys of Shaanxi Province, conducted in 2008 and 2013 respectively, before and after China’s 2009 healthcare reform. A generalised linear mixed model (GLMM) was applied to analyse the influence of this healthcare reform on utilisation of CMHS. Concentration curves, concentration indexes and its decomposition method were used to analyse the equity of changes in utilisation. Results: According to China’s policy defining CMHS, post-reform CMHS utilisation was higher in both rural and urban women. The rate of CMHS utilisation increased from 24.66% to 41.55% for urban women and from 18.31% to 50.49% for rural women (urban: χ2=20.64, P<0.001; rural: χ2=131.38, P<0.001). This finding is consistent when the WHO’s level of CMHS is applied for rural women after reform (12.13% vs 19.26%; χ2=10.99, P=0.001); for urban women, CMHS utilisation increased from 15.70% to 20.56% (χ2=2.57, P=0.109). The GLMM showed the rate of CMHS utilisation for urban women post-reform was five times higher than pre-reform rates (OR=5.02, 95%CL: 1.90, 13.31); it was close to 15 times higher for rural women (OR=14.70, 95%CL: 5.43, 39.76). The concentration index decreased from 0.130 pre-reform (95%CI: -0.026, 0.411) to -0.041 post-reform (95%CI: -0.096, 0.007) for urban women; it decreased from 0.104 (95%CI: -0.012, 0.222) to 0.019 (95%CI: -0.014, 0.060) for rural women. The horizontal inequity index for both groups of women also decreased (0.136 to -0.047 urban and 0.111 to 0.019 for rural). Conclusions: China’s 2009 healthcare reform has positively influenced utilisation rates and equity of utilisation of the CMHS among both urban and rural women in Shaanxi Province. We expect that similar impacts might be observed in other settings in China and, if so, may provide lessons in policy design to other countries looking to reduce maternal and newborn mortality.