bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcomes of adding alpha-glucosidase inhibitors in insulin-treated patients with type 2 diabetes
Authors: Yen Fu-Shun , Wei James Cheng-Chung , Lin Mei-Chen , Hsu Chih-Cheng , Hwu Chii-Min 
Published: February 2021

Abstract
Background
In insulin-treated patients with type 2 diabetes mellitus (T2DM), glycemic control is usually suboptimal.

Methods
This study compared the risks of mortality and cardiovascular events in insulin-treated patients adding or not adding alpha-glucosidase inhibitors (AGIs).

Results
This cohort study included data from the Taiwan National Health Insurance Research Database. In total, 17,417 patients newly diagnosed as having T2DM and undergoing insulin therapy during 2000–2012 were enrolled. Overall incidence rates of all-cause mortality, hospitalized coronary artery disease (CAD), stroke, and heart failure were compared between 4165 AGI users and 4165 matched nonusers. The incidence rates of all-cause mortality were 17.10 and 19.61 per 1000 person-years in AGI nonusers and users, respectively. Compared with nonusers, AGI users had a higher mortality risk [adjusted hazard ratio (aHR) = 1.21, 95% confidence interval (CI) = 1.05–1.40; p = 0.01]. Regarding AGI use, aHRs (95% CI) for cardiovascular death, non-cardiovascular death, hospitalized CAD, stroke, and heart failure were 1.20 (0.83–1.74), 1.27 (1.07–1.50), 1.12 (0.95–1.31), 0.98 (0.85–1.14), and 1.03 (0.87–1.22) respectively.

Conclusion
AGI use was associated with higher risks of all-cause mortality and non-cardiovascular death in insulin-treated patients with T2DM. Therefore, adding AGIs in insulin-treated patients may not be appropriate.
Participant-reported effect of an Indigenous health continuing professional development initiative for specialists
Authors: Barnabe Cheryl , Kherani Raheem B. , Appleton Tom , Umaefulam Valerie , Henderson Rita , Crowshoe Lynden 
Published: February 2021

Abstract
Background
Health outcomes of Indigenous patients are impacted by culturally unsafe specialty care environments. The ‘Educating for Equity (E4E)’ program is a continuing professional development (CPD) intervention which incorporates skill-based teaching to improve Indigenous patient experiences and outcomes in healthcare interactions.

Methods
The E4E program was delivered to rheumatologists in two phases, each delivered as experiential learning workshops where participants engaged with and applied course content within an interactive format focusing on real-time feedback. The phase 1 workshop focused on skill development of E4E Framework concepts and principles. Phase 2 concentrated on building capacity for teaching of E4E content. Evaluation of the program’s effectiveness was through longitudinal responses to the Social Cultural Confidence in Care Survey (SCCCS), self-reported strategies employed to address social issues and improve therapeutic relationships, engagement with teaching others, and satisfaction with the program.

Results
Two cohorts of participants have participated in the program (n = 24 Phase 1, n = 10 Phase 2). For participants completing both phases of training, statistically significant improvements were observed in exploring social factors with patients, gaining knowledge and skills related to cultural aspects of care, improved communication and relationship building, and reflections on held stereotypes. Strategies to address social issues and build therapeutic relationships remained consistent throughout participation, while the training enhanced exploration and confidence to ask about cultural and traditional practices, and stronger communication strategies for exploring beliefs, expectations, social barriers, and residential school impacts on health. Participants reported feeling prepared to teach Indigenous health concepts to others and subsequently lead teaching with residents, fellows, and allied health professionals. Satisfaction with the delivery and content of the workshops was high, and participants valued interactions with peers in learning.

Conclusions
This CPD intervention had a beneficial impact on self-reported confidence and enhanced practice strategies to engage with Indigenous patients.
User-centered and theory-based design of a professional training program on shared decision-making with older adults living with neurocognitive disorders: a mixed-methods study
Authors: Lawani Moulikatou Adouni , Turgeon Yves , Côté Luc , Légaré France , Witteman Holly O. , Morin Michèle , Kroger Edeltraut , Voyer Philippe , Rodriguez Charo , Giguere Anik 
Published: February 2021

Abstract
Background
We know little about the best approaches to design training for healthcare professionals. We thus studied how user-centered and theory-based design contribute to the development of a distance learning program for professionals, to increase their shared decision-making (SDM) with older adults living with neurocognitive disorders and their caregivers.

Methods
In this mixed-methods study, healthcare professionals who worked in family medicine clinics and homecare services evaluated a training program in a user-centered approach with several iterative phases of quantitative and qualitative evaluation, each followed by modifications. The program comprised an e-learning activity and five evidence summaries. A subsample assessed the e-learning activity during semi-structured think-aloud sessions. A second subsample assessed the evidence summaries they received by email. All participants completed a theory-based questionnaire to assess their intention to adopt SDM. Descriptive statistical analyses and qualitative thematic analyses were integrated at each round to prioritize training improvements with regard to the determinants most likely to influence participants’ intention.

Results
Of 106 participants, 98 completed their evaluations of either the e-learning activity or evidence summary (93%). The professions most represented were physicians (60%) and nurses (15%). Professionals valued the e-learning component to gain knowledge on the theory and practice of SDM, and the evidence summaries to apply the knowledge gained through the e-learning activity to diverse clinical contexts. The iterative design process allowed addressing most weaknesses reported. Participants’ intentions to adopt SDM and to use the summaries were high at baseline and remained positive as the rounds progressed. Attitude and social influence significantly influenced participants' intention to use the evidence summaries (P < 0.0001). Despite strong intention and the tailoring of tools to users, certain factors external to the training program can still influence the effective use of these tools and the adoption of SDM in practice.

Conclusions
A theory-based and user-centered design approach for continuing professional development interventions on SDM with older adults living with neurocognitive disorders and their caregivers appeared useful to identify the most important determinants of learners’ intentions to use SDM in their practice, and validate our initial interpretations of learners’ assessments during the subsequent evaluation round.
Differences in ambulatory care fragmentation by race
Authors: Kern Lisa M. , Rajan Mangala , Colantonio Lisandro D. , Reshetnyak Evgeniya , Ringel Joanna Bryan , Muntner Paul M. , Casalino Lawrence P. , Pinheiro Laura C. , Safford Monika M. 
Published: February 2021

Abstract
Background
More fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with more subsequent healthcare utilization (such as more tests, procedures, emergency department visits, and hospitalizations) than less fragmented ambulatory care. It is not known if race and socioeconomic status are associated with fragmented ambulatory care.

Methods
We conducted a longitudinal analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, using the REGARDS baseline visit plus the first year of follow-up. We included participants ≥65 years old, who had linked fee-for-service Medicare claims, and ≥ 4 ambulatory visits in the first year of follow-up. We used Tobit regression to determine the associations between race, annual household income, and educational attainment at baseline and fragmentation score in the subsequent year (as measured with the reversed Bice-Boxerman Index). Covariates included other demographic characteristics, medical conditions, medication use, health behaviors, and psychosocial variables. Additional analyses categorized visits by the type of provider (primary care vs. specialist).

Results
The study participants (N = 6799) had an average age of 73.0 years, 53% were female, and 30% were black. Nearly half had low annual household income (<$35,000) and 41% had a high school education or less. Overall, participants had a median of 10 ambulatory visits to 4 providers in the 12 months following their baseline study visit. Participants in the highest quintile of fragmentation scores had a median of 11 visits to 7 providers. Black race was associated with an absolute adjusted 3% lower fragmentation score compared to white race (95% confidence interval (2% lower to 4% lower; p < 0.001). This difference was explained by blacks seeing fewer specialists than whites. Income and education were not independent predictors of fragmentation scores.

Conclusions
Among Medicare beneficiaries, blacks had less fragmented ambulatory care than whites, due to lower utilization of specialty care. Future research is needed to determine the effect of fragmented care on health outcomes for blacks and whites.
The effectiveness of different patient referral systems to shorten waiting times for elective surgeries: systematic review
Authors: Rathnayake Dimuthu , Clarke Mike 
Published: February 2021

Abstract
Background
Long waiting times for elective surgery are common to many publicly funded health systems. Inefficiencies in referral systems in high-income countries are more pronounced than lower and middle-income countries. Primary care practitioners play a major role in determining which patients are referred to surgeon and might represent an opportunity to improve this situation. With conventional methods of referrals, surgery clinics are often overcrowded with non-surgical referrals and surgical patients experience longer waiting times as a consequence. Improving the quality of referral communications should lead to more timely access and better cost-effectiveness for elective surgical care. This review summarises the research evidence for effective interventions within the scope of primary-care referral methods in the surgical care pathway that might shorten waiting time for elective surgeries.

Methods
We searched PubMed, EMBASE, SCOPUS, Web of Science and Cochrane Library databases in December-2019 to January-2020, for articles published after 2013. Eligibility criteria included major elective surgery lists of adult patients, excluding cancer related surgeries. Both randomised and non-randomised controlled studies were eligible. The quality of evidence was assessed using ROBINS-I, AMSTAR 2 and CASP, as appropriate to the study method used. The review presentation was limited to a narrative synthesis because of heterogeneity. The PROSPERO registration number is CRD42019158455.

Results
The electronic search yielded 7543 records. Finally, nine articles were considered as eligible after deduplication and full article screening. The eligible research varied widely in design, scope, reported outcomes and overall quality, with one randomised trial, two quasi-experimental studies, two longitudinal follow up studies, three systematic reviews and one observational study. All the six original articles were based on referral methods in high-income countries. The included research showed that patient triage and prioritisation at the referral stage improved timely access and increased the number of consultations of surgical patients in clinics.

Conclusions
The available studies included a variety of interventions and were of medium to high quality researches. Managing patient referrals with proper triaging and prioritisation using structured referral formats is likely to be effective in health systems to shorten the waiting times for elective surgeries, specifically in high-income countries.
C2HEST score predicts clinical outcomes in heart failure with preserved ejection fraction: a secondary analysis of the TOPCAT trial
Authors: Liang Weihao , Wu Yuzhong , Xue Ruicong , Wu Zexuan , Wu Dexi , He Jiangui , Dong Yugang , Lip Gregory Y. H. , Zhu Wengen , Liu Chen 
Published: February 2021

Abstract
Background
The C2HEST score has been validated for predicting AF in the general population or post-stroke patients. We aimed to assess whether this risk score could predict incident AF and other clinical outcomes in heart failure with preserved ejection fraction (HFpEF) patients.

Methods
A total of 2202 HFpEF patients without baseline AF in the TOPCAT trial were stratified by baseline C2HEST score. Cox proportional hazard model and competing risk regression model was used to explore the relationship between C2HEST score and outcomes, including incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The discriminative ability of the C2HEST score for various outcomes was assessed by calculating the area under the curve (AUC).

Results
The incidence rates of incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization were 1.79, 0.70, 3.81, 2.42, 15.50, and 3.32 per 100 person-years, respectively. When the C2HEST score was analyzed as a continuous variable, increased C2HEST score was associated with increased risk of incident AF (HR 1.50, 95% CI 1.29–1.75), as well as increased risks of all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The AUC for the C2HEST score in predicting incident AF (0.694, 95% CI 0.640–0.748) was higher than all-cause death, cardiovascular death, any hospitalization, or HF hospitalization.

Conclusions
The C2HEST score could predict the risk of incident AF as well as death and hospitalization with moderately good predictive abilities in patients with HFpEF. Its simplicity may allow the possibility of quick risk assessments in busy clinical settings.
Neurophysiological validation of simultaneous intrinsic and reflexive joint impedance estimates
Authors: van ’t Veld Ronald C. , Schouten Alfred C. , van der Kooij Herman , van Asseldonk Edwin H. F. 
Published: February 2021

Abstract
Background
People with brain or neural injuries, such as cerebral palsy or spinal cord injury, commonly have joint hyper-resistance. Diagnosis and treatment of joint hyper-resistance is challenging due to a mix of tonic and phasic contributions. The parallel-cascade (PC) system identification technique offers a potential solution to disentangle the intrinsic (tonic) and reflexive (phasic) contributions to joint impedance, i.e. resistance. However, a simultaneous neurophysiological validation of both intrinsic and reflexive joint impedances is lacking. This simultaneous validation is important given the mix of tonic and phasic contributions to joint hyper-resistance. Therefore, the main goal of this paper is to perform a group-level neurophysiological validation of the PC system identification technique using electromyography (EMG) measurements.

Methods
Ten healthy people participated in the study. Perturbations were applied to the ankle joint to elicit reflexes and allow for system identification. Participants completed 20 hold periods of 60 seconds, assumed to have constant joint impedance, with varying magnitudes of intrinsic and reflexive joint impedances across periods. Each hold period provided a paired data point between the PC-based estimates and neurophysiological measures, i.e. between intrinsic stiffness and background EMG, and between reflexive gain and reflex EMG.

Results
The intrinsic paired data points, with all subjects combined, were strongly correlated, with a range of $$r = [0.87\ 0.91]$$

r
=
[
0.87

0.91
]

in both ankle plantarflexors and dorsiflexors. The reflexive paired data points were moderately correlated, with $$r = [0.64\ 0.69]$$

r
=
[
0.64

0.69
]

in the ankle plantarflexors only.

Conclusion
An agreement with the neurophysiological basis on which PC algorithms are built is necessary to support its clinical application in people with joint hyper-resistance. Our results show this agreement for the PC system identification technique on group-level. Consequently, these results show the validity of the use of the technique for the integrated assessment and training of people with joint hyper-resistance in clinical practice.
The combined effect of food additive titanium dioxide and lipopolysaccharide on mouse intestinal barrier function after chronic exposure of titanium dioxide-contained feedstuffs
Authors: Zhang Yongliang , Duan Shumin , Liu Ying , Wang Yun 
Published: February 2021

Abstract
Objective
Up to 44% of particulates of food-grade titanium dioxide (TiO2) are in nanoscale, while the effect and combined effect of which with other substances on intestinal barrier haven’t been fully understood yet. This study is aimed to study the effect of two kinds of TiO2 nanoparticles (TiO2 NPs and TiO2 MPs) on intestinal barrier functions, to reveal the combined effect of TiO2 NPs and Lipopolysaccharide (LPS) on intestinal barrier.

Methods
Male ICR mice were randomly divided into 18 groups (3 feed types * 3 exposure length * 2 LPS dosage) and were fed with normal or TiO2-mixed feed (containing 1% (mass fraction, w/w) TiO2 NPs or TiO2 MPs) for 1, 3, 6 months, followed by a single oral administration of 0 or 10 mg/(kg body weight) LPS. Four hours later, the transportation of TiO2, the intestinal barrier functions and the inflammatory response were evaluated.

Results
Both TiO2 notably increased the intestinal villi height / crypt depth ratios after 1 and 3 months of exposure, and increased the expression of ileal tight junction proteins (ZO-1 and occludin) after 1 month of exposure. After 6 months of exposure, TiO2 NPs led to reduced feed consumption, TiO2 MPs caused spare microvilli in small intestine and elevated Ti content in the blood cells. The intestinal permeability didn’t change in both TiO2 exposed groups. After LPS administration, we observed altered intestinal villi height / crypt depth ratios, lowered intestinal permeability (DAO) and upregulated expression of ileal ZO-1 in both (TiO2 +LPS) exposed groups. There are no significant changes of ileal or serum cytokines except for a higher serum TNF-α level in LPS treated group. The antagonistic effect was found between TiO2 NPs and LPS, but there are complicated interactions between TiO2 MPs and LPS.

Conclusion
Long-term intake of food additive TiO2 could alter the intestinal epithelial structure without influencing intestinal barrier function. Co-exposure of TiO2 and LPS would enhance intestinal barrier function without causing notable inflammatory responses, and there is antagonistic effect between TiO2 NPs and LPS. All the minor effects observed might associate with the gentle exposure method where TiO2 being ingested with feed.
Adjuvant radiotherapy versus observation following gross total resection for atypical meningioma: a systematic review and meta-analysis
Authors: Chun Se-Woong , Kim Kyung Min , Kim Min-Sung , Kang Ho , Dho Yun-Sik , Seo Youngbeom , Kim Jin Wook , Kim Yong Hwy , Park Chul-Kee 
Published: February 2021

AbstractBackgroundThe impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR.MethodsPubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel–Haenszel method and the inverse variance-weighted method, appropriately.ResultsData from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36–0.68;p < 0.0001). Pooled HRs of PFS at 1-year, 3-year, 5-year, and > 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity.ConclusionsFor AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.
Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells
Authors: Chen Wenjing , Ma Chunli , Li Guanghao , Jia Zhipeng , Yang Xuelian , Pan Xinghui , Ma Dexing 
Published: February 2021

AbstractAvian coccidiosis caused by Eimeria leads to huge economic losses on the global poultry industry. In this study, microneme adhesive repeat regions (MARR) bc1 of E. tenella microneme protein 3 (EtMIC3-bc1) was used as ligand, and peptides binding to EtMIC3 were screened from a phage display peptide library. The positive phage clones were checked by enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was applied to further verify the binding capability between the positive phages and recombinant EtMIC3-bc1 protein or sporozoites protein. The inhibitory effects of target peptides on sporozoites invasion of MDBK cells were measured in vitro. Chickens were orally administrated with target positive phages and the protective effects against homologous challenge were evaluated. The model of three-dimensional (3D) structure for EtMIC3-bc1 was conducted, and molecular docking between target peptides and EtMIC3-bc1 model was analyzed. The results demonstrated that three selected positive phages specifically bind to EtMIC3-bc1 protein. The three peptides A, D and W effectively inhibited invasion of MDBK cells by sporozoites, showing inhibited ratio of 71.8%, 54.6% and 20.8%, respectively. Chickens in the group orally inoculated with phages A displayed more protective efficacies against homologous challenge than other groups. Molecular docking showed that amino acids in three peptides, especially in peptide A, insert into the hydrophobic groove of EtMIC3-bc1 protein, and bind to EtMIC3-bc1 through intermolecular hydrogen bonds. Taken together, the results suggest EtMIC3-binding peptides inhibit sporozoites entry into host cells. This study provides new idea for exploring novel strategies against coccidiosis.