bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness analysis of systematic fast-track transition from oncological treatment to specialised palliative care at home for patients and their caregivers: the DOMUS trial
Authors: Halling Christine Marie Bækø , Wolf Rasmus Trap , Sjøgren Per , Von Der Maase Hans , Timm Helle , Johansen Christoffer , Kjellberg Jakob 
Published: September 2020

Abstract
Background
While hospitals remain the most common place of death in many western countries, specialised palliative care (SPC) at home is an alternative to improve the quality of life for patients with incurable cancer. We evaluated the cost-effectiveness of a systematic fast-track transition process from oncological treatment to SPC enriched with a psychological intervention at home for patients with incurable cancer and their caregivers.

Methods
A full economic evaluation with a time horizon of six months was performed from a societal perspective within a randomised controlled trial, the DOMUS trial (Clinicaltrials.gov: NCT01885637). The primary outcome of the health economic analysis was a incremental cost-effectiveness ratio (ICER), which is obtained by comparing costs required per gain in Quality-Adjusted Life Years (QALY). The costs included primary and secondary healthcare costs, cost of intervention and informal care from caregivers. Public transfers were analysed in seperate analysis. QALYs were measured using EORTC QLQ-C30 for patients and SF-36 for caregivers. Bootstrap simulations were performed to obtain the ICER estimate.

Results
In total, 321 patients (162 in intervention group, 159 in control group) and 235 caregivers (126 in intervention group, 109 in control group) completed the study. The intervention resulted in significantly higher QALYs for patients when compared to usual care (p-value = 0.026), while being more expensive as well. In the 6 months observation period, the average incremental cost of intervention compared to usual care was €2015 per patient (p value < 0.000). The mean incremental gain was 0.01678 QALY (p-value = 0.026). Thereby, the ICER was €118,292/QALY when adjusting for baseline costs and quality of life. For the caregivers, we found no significant differences in QALYs between the intervention and control group (p-value = 0.630). At a willingness to pay of €80,000 per QALY, the probability that the intervention is cost-effective lies at 15% in the base case scenario.

Conclusion
This model of fast-track SPC enriched with a psychological intervention yields better QALYs than usual care with a large increase in costs.

Trial registration
The trial was prospectively registered 25.6.2013. Clinicaltrials.gov Identifier: NCT01885637.
From twisting to settling down as a nurse in China: a qualitative study of the commitment to nursing as a career
Authors: Ye Jiao , Mao Aimei , Wang Jialin , Okoli Chizimuzo T. C. , Zhang Yuan , Shuai Huiqiong , Lin Min , Chen Bo , Zhuang Linli 
Published: September 2020

Abstract
Background
The nurse workforce shortage, partially caused by high work turnover, is an important factor influencing the quality of patient care. Because previous studies concerning Chinese nurse work turnover were predominantly quantitative, they lacked insight into the challenges faced by nurses as they transition from university to their career. A successful transition can result in new nurses’ commitment to the career. As such, this study sought to understand how new nurses commit to the career, and focused on identifying facilitators and barriers to such commitment.

Methods
This was a qualitative study using a grounded theory design. Through purposive sampling, clinical nurses were recruited from hospitals in Western China to participate in semi-structured interviews. The data was analyzed through coding to develop categories and themes.

Results
Theoretical saturation was achieved after interviewing 25 participants. The data revealed the ‘zigzag journey’ of committing to the nursing career. The emerging core theme was “getting settled”, indicating that new nurses needed to acclimate to the work reality in the nursing career. By analyzing the data provided by the participants, the researchers concluded that the journey to getting settled in nursing compassed four stages:1) “sailing out with mixed feelings”, 2) “contemplating to leave”, 3) “struggling to stay”, and 4) “accepting the role”. For most participants, nursing was described as a way to earn a living for their family, not as a career about which they felt passionate.

Conclusions
Committing to the nursing career is a complicated long-term process. There seems to be a lack of passion for nursing among the Chinese clinical nurses participating in this study. Thus, the nurses may need continued support at different career stages to enhance their ability to remain a nurse for more than economic reasons.
Reflecting on “Marketing communications in health and medicine: perspectives from Willis-Knighton Health System”: understanding the big picture
Authors: Elrod James K. , Fortenberry John L. 
Published: September 2020

Abstract
Background
Willis-Knighton Health System’s special supplement in BMC Health Services Research, “Marketing communications in health and medicine: perspectives from Willis-Knighton Health System,” focuses on advertising, public relations, sales promotion, and related communicative avenues, associated theory, and more. Across the supplement’s articles, insights from the institution’s experiences are presented, addressing the components of the marketing communications mix, foundational elements of communication, the patronage process, and the necessity for integrating marketing communications.

Discussion
As an understanding of the big picture is crucial in marketing communications, especially given that many of its components must be effected simultaneously, this particular article takes the insights provided in the supplement and presents them in an operational framework, demonstrating the marketing communications process. This framework concisely summarizes the facets profiled in the associated articles, permitting readers to see how these pieces work in concert with one another in health and medical settings, providing a basic communications structure which healthcare establishments can use to advance their patient engagement initiatives.

Conclusions
Health and medical providers must ensure that they possess a detailed understanding of core marketing communications facets, but as they acquire associated knowledge, they also must direct attention toward understanding the interrelationships between and among these facets, permitting a global perspective of communicative operations. This particular article summarizes insights from Willis-Knighton Health System’s special supplement in BMC Health Services Research, providing a pathway toward realizing big picture marketing communications perspectives.
Impact of the Programa Mais médicos (more doctors Programme) on primary care doctor supply and amenable mortality: quasi-experimental study of 5565 Brazilian municipalities
Authors: Hone Thomas , Powell-Jackson Timothy , Santos Leonor Maria Pacheco , de Sousa Soares Ricardo , de Oliveira Felipe Proenço , Sanchez Mauro Niskier , Harris Matthew , de Oliveira de Souza Santos Felipe , Millett Christopher 
Published: September 2020

Abstract
Background
Investing in human resources for health (HRH) is vital for achieving universal health care and the Sustainable Development Goals. The Programa Mais Médicos (PMM) (More Doctors Programme) provided 17,000 doctors, predominantly from Cuba, to work in Brazilian primary care. This study assesses whether PMM doctor allocation to municipalities was consistent with programme criteria and associated impacts on amenable mortality.

Methods
Difference-in-differences regression analysis, exploiting variation in PMM introduction across 5565 municipalities over the period 2008–2017, was employed to examine programme impacts on doctor density and mortality amenable to healthcare. Heterogeneity in effects was explored with respect to doctor allocation criteria and municipal doctor density prior to PMM introduction.

Results
After starting in 2013, PMM was associated with an increase in PMM-contracted primary care doctors of 15.1 per 100,000 population. However, largescale substitution of existing primary care doctors resulting in a net increase of only 5.7 per 100,000. Increases in both PMM and total primary care doctors were lower in priority municipalities due to lower allocation of PMM doctors and greater substitution effects. The PMM led to amenable mortality reductions of − 1.06 per 100,000 (95%CI: − 1.78 to − 0.34) annually – with greater benefits in municipalities prioritised for doctor allocation and where doctor density was low before programme implementation.

Conclusions
PMM potential health benefits were undermined due to widespread allocation of doctors to non-priority areas and local substitution effects. Policies seeking to strengthen HRH should develop and implement needs-based criteria for resource allocation.
AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination
Authors: Peyrégne Stéphane , Peter Benjamin M. 
Published: September 2020

AbstractContamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses. We present AuthentiCT, a command-line tool to estimate the proportion of present-day DNA contamination in ancient DNA datasets generated from single-stranded DNA libraries. The prediction is based solely on the patterns of post-mortem damage observed on ancient DNA sequences. The method has the power to quantify contamination from as few as 10,000 mapped sequences, making it particularly useful for analysing specimens that are poorly preserved or for which little data is available.
Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni
Authors: Eissa Maha M. , El-Azzouni Mervat Z. , El-Khordagui Labiba K. , Abdel Bary Amany , El-Moslemany Riham M. , Abdel Salam Sara A. 
Published: September 2020

Abstract
Background
The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy.

Methods
Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons.

Results
Lipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures.

Conclusions
The therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.
Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation
Authors: Chidambaram Hariharakrishnan , Das Rashmi , Chinnathambi Subashchandrabose 
Published: September 2020

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-β peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous species. Tau is a microtubule-binding protein that stabilizes tubulin to form microtubules under physiological condition. In AD/ pathological condition, Tau detaches from microtubules and aggregates to form oligomers of different sizes and filamentous species such as paired helical filaments. Microglia are the resident brain macrophages that are involved in the phagocytosis of microbes, cellular debris, misfolded and aggregated proteins. Chemokine receptor, CX3CR1 is mostly expressed on microglia and is involved in maintaining the microglia in a quiescent state by binding to its ligand, fractalkine (CX3CL1), which is expressed in neurons as both soluble or membrane-bound state. Hence, under physiological conditions, the CX3CR1/CX3CL1 axis plays a significant role in maintaining the central nervous system (CNS) homeostasis. Further, CX3CR1/CX3CL1 signalling is involved in the synthesis of anti-inflammatory cytokines and also has a significant role in cytoskeletal rearrangement, migration, apoptosis and proliferation. In AD brain, the expression level of fractalkine is reduced, and hence Tau competes to interact with its receptor, CX3CR1. In microglia, phagocytosis and internalization of extracellular Tau species occurs in the presence of a chemokine receptor, CX3CR1 which binds directly to Tau and promotes its internalization. In this review, the pathophysiological roles of CX3CR1/fractalkine signalling in microglia and neurons at different stages of Alzheimer’s disease and the possible role of CX3CR1/Tau signalling has been widely discussed.
Pharmacokinetic parameters and radiomics model based on dynamic contrast enhanced MRI for the preoperative prediction of sentinel lymph node metastasis in breast cancer
Authors: Liu Meijie , Mao Ning , Ma Heng , Dong Jianjun , Zhang Kun , Che Kaili , Duan Shaofeng , Zhang Xuexi , Shi Yinghong , Xie Haizhu 
Published: September 2020

Abstract
Background
To establish pharmacokinetic parameters and a radiomics model based on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for predicting sentinel lymph node (SLN) metastasis in patients with breast cancer.

Methods
A total of 164 breast cancer patients confirmed by pathology were prospectively enrolled from December 2017 to May 2018, and underwent DCE-MRI before surgery. Pharmacokinetic parameters and radiomics features were derived from DCE-MRI data. Least absolute shrinkage and selection operator (LASSO) regression method was used to select features, which were then utilized to construct three classification models, namely, the pharmacokinetic parameters model, the radiomics model, and the combined model. These models were built through the logistic regression method by using 10-fold cross validation strategy and were evaluated on the basis of the receiver operating characteristics (ROC) curve. An independent validation dataset was used to confirm the discriminatory power of the models.

Results
Seven radiomics features were selected by LASSO logistic regression. The radiomics model, the pharmacokinetic parameters model, and the combined model yielded area under the curve (AUC) values of 0.81 (95% confidence interval [CI]: 0.72 to 0.89), 0.77 (95% CI: 0.68 to 0.86), and 0.80 (95% CI: 0.72 to 0.89), respectively, for the training cohort and 0.74 (95% CI: 0.59 to 0.89), 0.74 (95% CI: 0.59 to 0.90), and 0.76 (95% CI: 0.61 to 0.91), respectively, for the validation cohort. The combined model showed the best performance for the preoperative evaluation of SLN metastasis in breast cancer.

Conclusions
The model incorporating radiomics features and pharmacokinetic parameters can be conveniently used for the individualized preoperative prediction of SLN metastasis in patients with breast cancer.
Development of risk prediction models to predict urine culture growth for adults with suspected urinary tract infection in the emergency department: protocol for an electronic health record study from a single UK university hospital
Authors: Rockenschaub Patrick , Gill Martin J. , McNulty David , Carroll Orlagh , Freemantle Nick , Shallcross Laura 
Published: September 2020

Abstract
Background
Urinary tract infection (UTI) is a leading cause of hospital admissions and is diagnosed based on urinary symptoms and microbiological cultures. Due to lags in the availability of culture results of up to 72 h, and the limitations of routine diagnostics, many patients with suspected UTI are started on antibiotic treatment unnecessarily. Predictive models based on routinely collected clinical information may help clinicians to rule out a diagnosis of bacterial UTI in low-risk patients shortly after hospital admission, providing additional evidence to guide antibiotic treatment decisions.

Methods
Using electronic hospital records from Queen Elizabeth Hospital Birmingham (QEHB) collected between 2011 and 2017, we aim to develop a series of models that estimate the probability of bacterial UTI at presentation in the emergency department (ED) among individuals with suspected UTI syndromes. Predictions will be made during ED attendance and at different time points after hospital admission to assess whether predictive performance may be improved over time as more information becomes available about patient status. All models will be externally validated for expected future performance using QEHB data from 2018/2019.

Discussion
Risk prediction models using electronic health records offer a new approach to improve antibiotic prescribing decisions, integrating clinical and demographic data with test results to stratify patients according to their probability of bacterial infection. Used in conjunction with expert opinion, they may help clinicians to identify patients that benefit the most from early antibiotic cessation.
Pembrolizumab on pre-existing inclusion body myositis: a case report
Authors: Uchio Naohiro , Unuma Atsushi , Kakumoto Toshiyuki , Osaki Masao , Zenke Yoshitaka , Sakuta Kenichi , Kubota Akatsuki , Uesaka Yoshikazu , Toda Tatsushi , Shimizu Jun 
Published: September 2020

Abstract
Background
Cases of exacerbation of pre-existing neuromuscular diseases induced by immune checkpoint inhibitors (ICIs) have rarely been reported because patients with autoimmune diseases have generally been excluded from ICI therapy due to the increased risk of exacerbation. We describe the first case of an elderly patient who experienced exacerbation of a previously undiagnosed sporadic inclusion body myositis (sIBM), the most common myopathy in the geriatric population, which was triggered by anti-programmed cell death-1 therapy.

Case presentation
A 75-year-old man who was receiving pembrolizumab presented with limb weakness. Three years prior, he had noticed slowly progressive limb weakness, but he received no diagnosis. After the first infusion of pembrolizumab, his creatine kinase (CK) levels had increased. The neurological examination and muscle biopsy findings confirmed the diagnosis of sIBM and suggested exacerbation of sIBM induced by pembrolizumab. After the patient’s CK levels decreased, pembrolizumab was restarted. The tumor progressed after its treatment with pembrolizumab. The patient died after 15 months of follow-up.

Conclusions
In patients with slowly progressive limb weakness, sIBM should be explored before ICI therapy. In addition, if patients show high CK levels after ICI introduction, it is necessary to confirm whether they have sIBM in order to avoid unnecessary immunosuppressive therapies and assess whether they can tolerate ICI reintroduction.
Intranasal dexmedetomidine versus intranasal midazolam as pre-anesthetic medication in pediatric age group undergoing adenotonsillectomy
Authors: Saad Bassem B. , Tharwat Ayman I. , Ghobrial Haidi N. , Elfawal Sanaa M. 
Published: September 2020

AbstractBackgroundThe pre-operative period is a very stressful event for most of the individuals undergoing surgery especially the pediatric patients. So, relieving their pre-operative anxiety becomes an important concern for an anesthesiologist. Many anesthetic pre-medications are used to relieve this stress response. Of these pre-medications, midazolam and dexmedetomidine are effectively used as sedatives. The present study was planned to compare intranasal dexmedetomidine with intranasal midazolam as a pre-anesthetic medication in children. Forty-eight children aged 3–7 years, of either sex, weighing 13–22 kg, with American Society of Anesthesiologists (ASA) physical status 1 and undergoing elective adenotonsillectomy surgery were enrolled in this comparative prospective, double blinded, randomized clinical study. The children were divided into 2 groups: group D and group M, of 24 each. Forty-five minutes before induction of anesthesia, group D (n= 24) received intranasal dexmedetomidine at a dose of 1 μg/kg and group M (n= 24) received intranasal midazolam of 0.2 mg/kg.ResultsChildren who were pre-medicated with dexmedetomidine had lower sedation scores, lower anxiety levels, easier child-parent separation, better mask acceptance, and lower pain scores than those who received midazolam. The incidence of emergence agitation was decreased in both groups with no significant difference.ConclusionIntranasal dexmedetomidine seems to offer some advantages compared with midazolam. Thus, it can be used effectively and safely as a pre-anesthetic medication in children undergoing any surgical procedures under general anesthesia.
Tamoxifen-inducible cardiac-specific Cre transgenic mouse using VIPR2 intron
Authors: Chin Hyun Jung , Lee So-young , Lee Daekee 
Published: September 2020

AbstractGenetically engineered mouse models through gene deletion are useful tools for analyzing gene function. To delete a gene in a certain tissue temporally, tissue-specific and tamoxifen-inducible Cre transgenic mice are generally used. Here, we generated transgenic mouse with cardiac-specific expression of Cre recombinase fused to a mutant estrogen ligand-binding domain (ERT2) on both N-terminal and C-terminal under the regulatory region of human vasoactive intestinal peptide receptor 2 (VIPR2) intron and Hsp68 promoter (VIPR2-ERT2CreERT2). In VIPR2-ERT2CreERT2 transgenic mice, mRNA for Cre gene was highly expressed in the heart. To further reveal heart-specific Cre expression, VIPR2-ERT2CreERT2 mice mated with ROSA26-lacZ reporter mice were examined by X-gal staining. Results of X-gal staining revealed that Cre-dependent recombination occurred only in the heart after treatment with tamoxifen. Taken together, these results demonstrate that VIPR2-ERT2CreERT2 transgenic mouse is a useful model to unveil a specific gene function in the heart.