bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socio-demographic and -economic factors associated with 30-day readmission for conditions targeted by the hospital readmissions reduction program: a population-based study
Authors: Murray Frances , Allen Meghan , Clark Collin M. , Daly Christopher J. , Jacobs David M. 
Published: October 2021

Abstract
Background
Early hospital readmissions remain common in patients with conditions targeted by the CMS Hospital Readmission Reduction Program (HRRP). There is still no consensus on whether readmission measures should be adjusted based on social factors, and there are few population studies within the U.S. examining how social characteristics influence readmissions for HRRP-targeted conditions. The objective of this study was to determine if specific socio-demographic and -economic factors are associated with 30-day readmissions in HRRP-targeted conditions: acute exacerbation of chronic obstructive pulmonary disease, pneumonia, acute myocardial infarction, and heart failure.

Methods
The Nationwide Readmissions Database was used to identify patients admitted with HRRP-targeted conditions between January 1, 2010 and September 30, 2015. Stroke was included as a control condition because it is not included in the HRRP. Multivariate models were used to assess the relationship between three social and economic characteristics (gender, urban/rural hospital designation, and estimated median household income within the patient’s zip code) and 30-day readmission rates using a hierarchical two-level logistic model. Age-adjusted models were used to assess relationship differences between Medicare vs. non-Medicare populations.

Results
There were 19,253,997 weighted index hospital admissions for all diagnoses and 3,613,488 30-day readmissions between 2010 and 2015. Patients in the lowest income quartile (≤$37,999) had an increased odds of 30-day readmission across all conditions (P < 0.0001). Female gender and rural hospital designation were associated with a decreased odds of 30-day readmission for most targeted conditions (P < 0.05). Similar findings were also seen in patients ≥65 years old.

Conclusions
Socio-demographic and -economic factors are associated with 30-day readmission rates and should be incorporated into tools or interventions to improve discharge planning and mitigate against readmission.
High-cost high-need patients in Medicaid: segmenting the population eligible for a national complex case management program
Authors: Quinton Jacob K. , Duru O. Kenrik , Jackson Nicholas , Vasilyev Arseniy , Ross-Degnan Dennis , O’Shea Donna L. , Mangione Carol M. 
Published: October 2021

AbstractBackgroundHigh-cost high-need patients are typically defined by risk or cost thresholds which aggregate clinically diverse subgroups into a single ‘high-need high-cost’ designation. Programs have had limited success in reducing utilization or improving quality of care for high-cost high-need Medicaid patients, which may be due to the underlying clinical heterogeneity of patients meeting high-cost high-need designations.MethodsOur objective was to segment a population of high-cost high-need Medicaid patients (N = 676,161) eligible for a national complex case management program between January 2012 and May 2015 to disaggregate clinically diverse subgroups. Patients were eligible if they were in the top 5 % of annual spending among UnitedHealthcare Medicaid beneficiaries. We usedk-means cluster analysis, identified clusters using an information-theoretic approach, and named clusters using the patients’ pattern of acute and chronic conditions. We assessed one-year overall and preventable hospitalizations, overall and preventable emergency department (ED) visits, and cluster stability.ResultsSix clusters were identified which varied by utilization and stability. The characteristic condition patterns were: 1) pregnancy complications, 2) behavioral health, 3) relatively few conditions, 4) cardio-metabolic disease, and complex illness with relatively 5) low or 6) high resource use. The patients varied by cluster by average ED visits (2.3–11.3), hospitalizations (0.3–2.0), and cluster stability (32–91%).ConclusionsWe concluded that disaggregating subgroups of high-cost high-need patients in a large multi-state Medicaid sample identified clinically distinct clusters of patients who may have unique clinical needs. Segmenting previously identified high-cost high-need populations thus may be a necessary strategy to improve the effectiveness of complex case management programs in Medicaid.
Confronting complexity and supporting transformation through health systems mapping: a case study
Authors: Hussey Anna J. , Sibbald Shannon L. , Ferrone Madonna , Hergott Alyson , McKelvie Robert , Faulds Cathy , Roberts Zofe , Scarffe Andrew D. , Meyer Matthew J. , Vollbrecht Susan , Licskai Christopher 
Published: October 2021

Abstract
Introduction
Health systems are a complex web of interacting and interconnected parts; introducing an intervention, or the allocation of resources, in one sector can have effects across other sectors and impact the entire system. A prerequisite for effective health system reorganisation or transformation is a broad and common understanding of the current system amongst stakeholders and innovators. Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are common chronic diseases with high health care costs that require an integrated health system to effectively treat.

Study description
This case study documents the first phase of system transformation at a regional level in Ontario, Canada. In this first phase, visual representations of the health system in its current state were developed using a collaborative co-creation approach, and a focus on COPD and HF. Multiple methods were used including focus groups, open-ended questionnaires, and document review, to develop a series of graphical and visual representations; a health care ecosystem map.

Results
The ecosystem map identified key sectoral components, inter-component interactions, and care requirements for patients with COPD and HF and inventoried current programs and services available to deliver this care. Main findings identified that independent system-wide navigation for this vulnerable patient group is limited, primary care is central to the accessibility of nearly half of the identified care elements, and resources are not equitably distributed. The health care ecosystem mapping helped to identify care gaps and illustrates the need to resource the primary care provider and the patient with system navigation resources and interdisciplinary team care.

Conclusion
The co-created health care ecosystem map brought a collective understanding of the health care system as it applies to COPD and HF. The map provides a blueprint that can be adapted to other disease states and health systems. Future transformation will build on this foundational work, continuing the robust interdisciplinary co-creation strategies, exploring predictive health system modelling and identifying areas for integration.
Differences in outcomes of hospitalizations for heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic cardiovascular disease
Authors: Shao Shih-Chieh , Chang Kai-Cheng , Lin Swu-Jane , Chang Shang-Hung , Hung Ming-Jui , Chan Yuk-Ying , Lai Edward Chia-Cheng 
Published: October 2021

Abstract
Background
The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD.

Methods
We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD.

Results
We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74–1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49–0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87–1.45), and the p-value for examining interaction was 0.0097.

Conclusion
In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.
Sequential drug delivery by injectable macroporous hydrogels for combined photodynamic-chemotherapy
Authors: Zhong Yuanyuan , Zhang Li , Sun Shian , Zhou Zhenghao , Ma Yunsu , Hong Hao , Yang Dongzhi 
Published: October 2021

AbstractWith hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 24.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (ϕΔ(Gel) = 0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.
Decreased exosome-delivered miR-486-5p is responsible for the peritoneal metastasis of gastric cancer cells by promoting EMT progress
Authors: Lin Xian-Ming , Wang Zhi-Jiang , Lin Yu-Xiao , Chen Hao 
Published: October 2021

Abstract
Background
The present study aims to investigate the preliminary mechanism underlying the peritoneal metastasis of gastric cancer cells.

Methods
Exosomes from GC9811 cells (Con-Exo) and from GC9811-P cells (PM-Exo) were extracted by ultracentrifugation, which were identified with transmission electron microscopy (TEM) and nanoparticle trafficking analysis, as well as the expression of CD9, CD63, and CD81 detected by Western blot assay. α-SMA expression was determined by immunofluorescence assay and Western blot assay. The levels of Snail1, E-cadherin, and Actin-related protein 3 (ACTR3) were evaluated by Western blot assay. MiRNA array was performed on exosomes to screen the differentially expressed miRNAs. The expressions of miRNAs, SMAD2, CDK4, and ACTR3 were determined by QRT-PCR. The delivery of miR-486-5p was confirmed by laser confocal detection.

Results
Firstly, TEM, nanoparticle trafficking analysis, and Western blot assays were used to confirm the successful extraction of Con-Exo and PM-Exo. The incubation of Con-Exo and PM-Exo could decrease E-cadherin expression and increase of α-SMA respectively in HMrSV5 cells, with the increased proportion of fusiform cells. More significant changes were observed in PM-Exo-treated HMrSV5 cells. Secondary, compared to Con-Exo, miR-486-5p and miR-132-3p were found downregulated, and miR-132-5p was found upregulated in PM-Exo. The transfection of miR-486-5p and miR-132-3p was observed to suppress EMT, and the transfection of miR-132-3p was observed to induce EMT. Laser confocal detection confirmed the delivery of miR-486-5p from gastric cancer cells to HMrSV5 cells through exosomes. Lastly, the expression of Mothers against decapentaplegic homolog 2 (SMAD2), cyclin-dependent kinase 4 (CDK4), and ACTR3 was found to be downregulated via miR-486-5p.

Conclusion
Decreased delivery of miR-486-5p via exosomes might be responsible for the peritoneal metastasis of gastric cancer cells by promoting epithelial-mesenchymal transition progress.
Scale-up of the Physical Activity 4 Everyone (PA4E1) intervention in secondary schools: 24-month implementation and cost outcomes from a cluster randomised controlled trial
Authors: Sutherland Rachel , Campbell Elizabeth , McLaughlin Matthew , Nathan Nicole , Wolfenden Luke , Lubans David R. , Morgan Philip J. , Gillham Karen , Oldmeadow Chris , Searles Andrew , Reeves Penny , Williams Mandy , Evans Nicole , Bailey Andrew , Boyer James , Lecathelinais Christophe , Davies Lynda , McKenzie Tom , Robertson Katie , Wiggers John 
Published: October 2021

Abstract
Background
Physical Activity 4 Everyone (PA4E1) is an evidence-based program effective at increasing adolescent physical activity (PA) and improving weight status. This study aimed to determine a) the effectiveness of an adapted implementation intervention to scale-up PA4E1 at 24-month follow-up, b) fidelity and reach, and c) the cost and cost-effectiveness of the implementation support intervention.

Methods
A cluster randomised controlled trial using a type III hybrid implementation-effectiveness design in 49 lower socio-economic secondary schools, randomised to a program (n = 24) or control group (n = 25). An adapted implementation intervention consisting of seven strategies was developed to support schools to implement PA4E1 over 24-months. The primary outcome was the proportion of schools implementing at least four of the 7 PA practices, assessed via computer assisted telephone interviews (CATI) with Head Physical Education Teachers. Secondary outcomes included the mean number of PA practices implemented, fidelity and reach, cost and cost-effectiveness. Logistic regression models assessed program effects.

Results
At baseline, no schools implemented four of the 7 PA practices. At 24-months, significantly more schools in the program group (16/23, 69.6%) implemented at least four of the 7 PA practices than the control group (0/25, 0%) (p < 0.001). At 24-months, program schools were implementing an average of 3.6 more practices than control schools (4.1 (1.7) vs. 0.5 (0.8), respectively) (P < 0.001). Fidelity and reach of the implementation intervention were high (> 75%). The total cost of the program was $415,112 AUD (2018) ($17,296 per school; $117.30 per student).

Conclusions
The adapted implementation intervention provides policy makers and researchers with an effective and potentially cost-effective model for scaling-up the delivery of PA4E1 in secondary schools. Further assessment of sustainability is warranted.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12617000681358 prospectively registered 12th May 2017.
Ex vivo expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells through different receptor-ligand interactions
Authors: Jung Daun , Baek Young Seok , Lee In Jee , Kim Ki Yeon , Jang Heejoo , Hwang Sohyun , Jung Jieun , Moon Yong-wha , Park Kyung-Soon , Choi Yong-Soo , An Hee Jung 
Published: October 2021

AbstractBackgroundRecently, allogeneic natural killer (NK) cells have gained considerable attention as promising immunotherapeutic tools due to their unique biological functions and characteristics. Although many NK expansion strategies have been reported previously, a deeper understanding of cryopreserved allogeneic NK cells is needed for specific therapeutic approaches.MethodsWe isolated CD3−CD56+primary natural killer (pNK) cells from healthy donors and expanded them ex vivo using a GMP-compliant method without any feeder to generate large volumes of therapeutic pNK cells and cryopreserved stocks. After validation for high purity and activating phenotypes, we performed RNA sequencing of the expanded and cryopreserved pNK cells. The pNK cells were used against various cancer cell lines in 7-AAD/CFSE cytotoxicity assay. For in vivo efficacy study, NSG mice bearing subcutaneous cisplatin-resistant A2780cis xenografts were treated with our pNK cells or cisplatin. Antitumor efficacy was assessed by measuring tumor volume and weight.ResultsCompared to the pNK cells before expansion, pNK cells after expansion showed 2855 upregulated genes, including genes related to NK cell activation, cytotoxicity, chemokines, anti-apoptosis, and proliferation. Additionally, the pNK cells showed potent cytolytic activity against various cancer cell lines. Interestingly, our activated pNK cells showed a marked increase in NKp44 (1064-fold), CD40L (12,018-fold), and CCR5 (49-fold), and did not express the programmed cell death protein 1(PD-1). We also demonstrated the in vitro and in vivo efficacies of pNK cells against cisplatin-resistant A2780cis ovarian cancer cells having a high programmed death-ligand 1(PD-L1) and low HLA-C expression.ConclusionsTaken together, our study provides the first comprehensive genome wide analysis of ex vivo-expanded cryopreserved pNK cells. It also indicates the potential use of expanded and cryopreserved pNK cells as a highly promising immunotherapy for anti-cancer drug resistant patients.
The clinical and cost-effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: study protocol of a multicenter pragmatic randomized controlled trial
Authors: Solis Ericka C. , Carlier Ingrid V. E. , van der Wee Nic J. A. , van Hemert Albert M. 
Published: October 2021

Abstract
Background
After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the “Patient and Partner Education Program for All Chronic Illnesses” (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers.

Methods
Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months.

Discussion
This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers.

Trial registration
Netherlands Trial Register Identifier NTR5973. Registered on 20 July 2016.
Adapting the design of a Web-based decision support clinical trial during the COVID-19 pandemic
Authors: Meline Jessica , Prigge Jason M. , Dye Debbie , Rieder Julie , Asan Onur , Chhatre Sumedha , Fraenkel Liana , Kravetz Jeffrey D. , Rodriguez Keri L. , Whittle Jeff , Kaminstein Dana , Schapira Marilyn M. 
Published: October 2021

Abstract
Background
The public health crises that emerged in the COVID-19 pandemic significantly impacted the provision of medical care and placed sudden restrictions on ongoing clinical research. Patient-facing clinical research confronted unique challenges in which recruitment and study protocols were halted and then adapted to meet safety procedures during the pandemic. Our study protocol included the use of a Lung Cancer Screening Decision Tool (LCSDecTool) in the context of a primary care visit and was considerably impacted by the pandemic.
We describe our experience adapting a multi-site clinical trial of the LCSDecTool within the Department of Veterans Affairs Health Care System. We conducted a randomized controlled trial (RCT) comparing the LCSDecTool to a control intervention. Outcomes included lung cancer screening (LCS) knowledge, shared decision-making, and uptake and adherence to LCS protocol. We identified three strategies that led to the successful adaptation of the study design during the pandemic: (1) multi-level coordination and communication across the organization and study sites, (2) flexibility and adaptability in research during a time of uncertainty and changes in regulation, and (3) leveraging technology to deliver the intervention and conduct study visits, which raised issues concerning equity and internal and external validity.

Conclusion
Our experience highlights strategies successfully employed to adapt an intervention and behavioral research study protocol during the COVID-19 pandemic. This experience will inform clinical research moving forward both during and subsequent to the constraints placed on research and clinical care during the COVID-19 pandemic.