bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk matrix approach: a helpful tool weighing probability and impact when deciding on preventive and diagnostic interventions
Authors: Lemmens Stéphanie M. P. , Lopes van Balen Veronica A. , Röselaers Yvonne C. M. , Scheepers Hubertina C. J. , Spaanderman Marc E. A. 
Published: February 2022

Abstract
Background
Clinical guidelines are developed to lower risks, mostly viewed upon as probability. However, in daily practice, risk is perceived as the combination of probability and the impact of desired and adverse events. This combination of probability and impact can be visualized in a risk matrix. We evaluated the effect of interventions and diagnostic thresholds on modeled risk, by using the risk matrix approach (RMA) in a clinical guideline development process, and investigated which additional factors affected choices.

Methods
To improve care outcomes, we developed new guidelines in which care professionals had to decide upon novel interventions and diagnostic thresholds. A risk matrix showed the probability and impact of an intervention, together with the corresponding risk category. First, professionals’ opinion on required performance characteristics on risk were evaluated by a qualitative online survey. Second, qualitative assessment of possible additional factors affecting final decisions, that followed from group discussion and guideline development were evaluated.

Results
Upfront, professionals opinioned that non-invasive interventions should decrease the general population risk, whereas invasive interventions should decrease the risk in high-risk groups. Nonetheless, when making guidelines, interventions were introduced without reaching the predefined threshold of desired risk reduction. Professionals weighed other aspects besides risk reduction, as financial aspects and practical consequences for daily practice in this guideline-making process.

Conclusion
Professionals are willing to change policies at much lower level of anticipated effectiveness than defined upfront. Although objectively presented data structured group discussions, decisions in guideline development are affected by several other factors than risk reduction alone.
Effectiveness of a multi-faceted intervention to deprescribe proton pump inhibitors in primary care: protocol for a population-based, pragmatic, cluster-randomized controlled trial
Authors: Nguyen-Soenen Jérôme , Rat Cédric , Gaultier Aurélie , Schirr-Bonnans Solène , Tessier Philippe , Fournier Jean-Pascal 
Published: February 2022

Abstract
Background
Inappropriately using proton pump inhibitors (PPI) is associated with severe adverse drug reactions and may have major consequences on healthcare costs. Deprescribing (the process by which a healthcare professional supervises the withdrawal of an inappropriate medication, to manage polypharmacy and improve outcomes) should be considered when an inappropriate PPI prescription is identified. Deprescribing interventions directed solely to prescribers have limited efficacy and are rarely targeted to patients. The aim of this trial is to assess the efficacy of a multi-faceted intervention with patients and general practitioners (GPs) to deprescribe PPI.

Methods
We will conduct a pragmatic, cluster-randomized, population-based, controlled trial in two regions of Western France. GPs with practices with over 100 patients, and their adult patient to whom over 300 defined daily doses (DDD) of PPIs have been dispensed in the year before baseline will be included. A total of 1300 GPs and 33,000 patients will be cluster-randomized by GPs practices. Three arms will be compared: i) a multi-faceted intervention associating a) a patient education brochure about PPI deprescribing sent directly to patients (the brochure was designed using a mixed-methods study), and b) a personalized letter with the Bruyere’s PPI deprescribing algorithm sent to their respective GPs, or ii) a single intervention where only the GPs received the letter and algorithm, or iii) no intervention.
The primary outcome will be PPI deprescribing, defined as the proportion of patients achieving at least a 50% decrease in the amount of PPI dispensed to them (DDD/year) at 12 months compared to baseline. Secondary outcomes will include incremental cost-utility ratio (using EQ-5D-5L scale and National Health Insurance’s database), acid rebound (using the Gastroesophageal Reflux Disease Impact Scale), and the patients’ attitudes towards deprescribing (using the French rPATD).

Discussion
Based on previous trials, we anticipate more than 10% “successful PPI deprescribing” in the multi-faceted intervention compared to the single intervention on GPs and the control arm. The study has been funded through a national grant and will be launched in autumn 2020, for early results by the end of 2022.

Trial registration
Clinicaltrials.gov NCT04255823; first registered on February 5, 2020.
Cost-effectiveness analysis of dapagliflozin for the treatment of type 2 diabetes mellitus in Spain: results of the DECLARE-TIMI 58 study
Authors: Escobar Carlos , Morales Cristóbal , Capel Margarita , Simón Susana , Pérez-Alcántara Ferran , Pomares Elisenda 
Published: February 2022

Abstract
Background
The objective of this study was to carry out a cost-effectiveness analysis of dapagliflozin, as an add-on therapy to standard of care (SoC), for the treatment of type 2 diabetes mellitus (T2DM) in Spain, based on the results of the DECLARE-TIMI 58 trial.

Methods
A discrete event simulation model (Cardiff T2DM) based on the data observed in the DECLARE-TIMI 58 trial was adapted to the Spanish setting to estimate the costs and health outcomes of treatment with dapagliflozin in patients with T2DM who had or were at risk of atherosclerotic cardiovascular disease. Macrovascular events (hospitalization for heart failure, myocardial infarction, stroke, and unstable angina), end-stage renal disease and cardiovascular and non-cardiovascular mortality were modeled according to the survival equations of the DECLARE-TIMI 58 study. Microvascular events (blindness and ulcers) were estimated based on the risk equations of the UK Prospective Diabetes Study. The analysis was conducted from the Spanish National Health System perspective and the time horizon was 30 years. The results were evaluated in terms of cost per quality-adjusted life year (QALY) gained. Only direct health costs were included, and a 3% discount rate was applied to costs and health outcomes. Univariate and probabilistic sensitivity analyses (PSA) were made to assess the robustness of the results.

Results
In the main analysis, dapagliflozin was a dominant therapeutic option compared with placebo, with greater effectiveness (0.08 QALYs) and lower associated total costs per patient (€ -2,921). The univariate sensitivity analysis and the PSA confirmed the robustness of the results. The PSA showed the probability that dapagliflozin was a dominant alternative compared with placebo was 84.2% and that it was cost-effective of 92.1%, under a willingness-to-pay of € 20,000/QALY gained.

Conclusions
The analysis of data from the DECLARE-TIMI 58 trial shows that dapagliflozin would be a cost-effective option in Spain for the treatment of adult patients with T2DM, as an add-on therapy to SoC, compared with placebo.
Challenges, opportunities, and potential roles of the private primary care providers in tuberculosis and diabetes mellitus collaborative care and control: a qualitative study
Authors: Arini Merita , Sugiyo Dianita , Permana Iman 
Published: February 2022

Abstract
Introduction
The comorbidity of tuberculosis and diabetes mellitus (TB-DM) is a looming global co-epidemic problem. Despite the Indonesian Government’s ongoing effort to impose regulation for collaborative TB-DM management, the involvement of private primary care providers (PPCs) has not been considered before the COVID-19 pandemic. This study aimed to capture the PPCs’ existing practices and explore their challenges, opportunities, and potential roles in the collaborative TB-DM services and control.

Methods
A descriptive qualitative research design was used to collect data. Two Focus Group Discussions (FGDs) were conducted with 13 healthcare workers (HCWs) from different private clinics and eight private/solo general practitioners (GPs) from Yogyakarta City, Indonesia. We triangulated these data with data from FGDs of HCWs community health centers (CHCs) and in-depth interviews of three regional health regulators, five hospitals staff members, and a representative of national health insurance. The discussions were audio-recorded, transcribed verbatim, and subjected to thematic analysis.

Results
PPCs have not been initiated into the implementation of the collaborative TB-DM programme. The themes identified in this study were health system-related barriers, knowledge and perception of HCWs, lack of implementation of bi-directional screening, and needs of multisector role. The potential roles identified for PPCs include involvement in health promotion, bi-directional screening, patient referral, and data reporting according to the TB-DM programme indicators. However, more thorough improvement of PPCs’ capacity and logistic supplies are needed to provide comprehensive TB treatment.

Conclusion
Although PPCs’ involvement in implementing collaborative TB-DM services has yet to be considered, their potential role should not be neglected. Therefore, it is essential to increase their involvement by enhancing their capacity and improving the Public-Private Mix. PPCs’ engagement should be initiated and maintained to ensure the sustainability of the programme.
Terminology and descriptions of navigation and related practices for children with neurodisability and their families: a scoping review
Authors: Gardiner Emily , Wong Vivian , Lin Grace , Miller Anton R. 
Published: February 2022

Abstract
Background
Children with neurodisability (ND) represent a significant population with a demonstrated need for coordinated support. Patient navigation has a primary focus on: facilitating access to and connection amongst fragmented systems; as well as the provision of educational and emotional support. Given the distinct needs of children with ND and their families, programs built upon such core concepts could be of great benefit. The diversity of terminology encompassing navigation-related concepts and activities (e.g., care coordination, case management, family support), however, presents challenges to both practice and research. This scoping review examined the terminology and descriptions provided within published articles on navigation-type models for children with ND and their families.

Methods
The scoping review was conducted according to the Joanna Briggs Institute methodology. A preliminary search was completed on PubMed (NCBI), MEDLINE (Ovid) and CINAHL (EBSCO) to identify initial search terms, upon which a full search strategy was developed and executed in MEDLINE (Ovid) and CINAHL (EBSCO). After screening records according to our inclusion and exclusion criteria, a full-text review of relevant articles was conducted and data extracted using a researcher-developed tool. Under close supervision by the research team, study selection was primarily performed by one author.

Results
Of the 2597 papers identified, 33 were included in the final review. From the included papers, a total of 49 terms were extracted, 20 of which were unique. Across the diversity of terminology observed, articles provided detailed and rich descriptions characterized by four central domains, namely: (i) what navigation-related resources, supports and services aim to facilitate and (ii) provide; (iii) descriptions of their intended outcomes; as well as (iv) guiding principles.

Conclusions
This scoping review addresses a gap in our knowledge related to the specification of patient navigation and related supports as applied to the specific context of children with ND and their families. Given the particular needs of this population, we propose an empirically-informed integrative model that synthesizes the findings from this scoping review. We suggest that this framework can be used as a guide to the mindful characterization of how supports aiming to connect children and families to needed service are termed and described within future research and in practice.
Use and exchange of knowledge in the introduction of hospital-based home rehabilitation after a stroke: barriers and facilitators in change management
Authors: Karlsson Margareta , Nordström Birgitta 
Published: February 2022

AbstractBackgroundThe purpose of the study was to contribute to research and practice on how the use and exchange of knowledge can facilitate change in health care, specifically methods supporting managers. The study also aimed to investigate barriers related to governance principles that may affect organizational ability to improve quality of care. To achieve the purpose, the study followed a project of hospital-based home rehabilitation after a stroke at a hospital in Norrbotten County, Sweden.MethodsSeven individual interviews were performed to obtain information from the project members and the managers involved in the project. A group interview with the team and their immediate manager were conducted after the project ended. A thematic analysis was performed to identify and present patterns that formed the results of the study.ResultsThe study shows how knowledge was identified, gathered, used, and disseminated in the project. The analysis pointed out how knowledge played an important role from two perspectives: in evidence-based practice in rehabilitation work and for change management. Knowledge exchange and learning across organizational boundaries increased the pace, efficiency, and effectiveness, but collaboration on knowledge, in the sense of joint activities based on a common purpose, only took place within the rehabilitation work. Furthermore, there were indications that governance principles, such as the distribution of financial responsibility and the requirements for official recommendations, influenced the pace of change.ConclusionsIt was shown that the exchange of knowledge and collaboration can facilitate change in health care, but that communication needs to be planned and prioritised. Readiness for change was the basis for the success of the project and for ensuring commitment among those involved. There is also a need for the management to understand how governance principles may affect the efficiency of change work.
Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti
Authors: Inaba Kazue , Ebihara Kana , Senda Miki , Yoshino Ryunosuke , Sakuma Chisako , Koiwai Kotaro , Takaya Daisuke , Watanabe Chiduru , Watanabe Akira , Kawashima Yusuke , Fukuzawa Kaori , Imamura Riyo , Kojima Hirotatsu , Okabe Takayoshi , Uemura Nozomi , Kasai Shinji , Kanuka Hirotaka , Nishimura Takashi , Watanabe Kodai , Inoue Hideshi , Fujikawa Yuuta , Honma Teruki , Hirokawa Takatsugu , Senda Toshiya , Niwa Ryusuke 
Published: February 2022

AbstractBackgroundMosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated.ResultsHere, we report that several flavonoids, including daidzein, inhibit the activity of glutathioneS-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquitoAedes aegypti. The crystal structure of the Nobo protein ofAe. aegypti(AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4′,6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressedAe. aegyptilarval development more efficiently than daidzein.ConclusionOur study demonstrates the mode of action of flavonoids on theAe. aegyptiNobo protein at the atomic, enzymatic, and organismal levels.
Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study
Authors: Kulbacka-Ortiz Katarzyna , Triest Filip J. J. , Franssen Frits M. E. , Wouters Emiel F. M. , Studnicka Michael , Vollmer William M. , Lamprecht Bernd , Burney Peter G. J. , Amaral Andre F. S. , Vanfleteren Lowie E. G. W. 
Published: February 2022

Abstract
Background
Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities.

Methods
A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires.

Results
Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37–1.86) for CVD, 1.53 (95% CI 1.40–1.66) for hypertension, and 1.98 (95% CI 1.71–2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33–1.79) for CVD, 1.50 (95% CI 1.39–1.63) for hypertension, and 1.86 (95% CI 1.59–2.17) for diabetes.

Conclusion
In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.
The value of ROX index in predicting the outcome of high flow nasal cannula: a systematic review and meta-analysis
Authors: Junhai Zhen , Jing Yan , Beibei Cao , Li Li 
Published: February 2022

Abstract
Background
High flow nasal cannula (HFNC) therapy is widely employed in acute hypoxemic respiratory failure (AHRF) patients. However, the techniques for predicting HFNC outcome remain scarce.

Methods
PubMed, EMBASE, and Cochrane Library were searched until April 20, 2021. We included the studies that evaluated the potential predictive value of ROX (respiratory rate-oxygenation) index for HFNC outcome. This meta-analysis determined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and pooled area under the summary receiver operating characteristic (SROC) curve.

Results
We assessed nine studies with 1933 patients, of which 745 patients experienced HFNC failure. This meta-analysis found that sensitivity, specificity, PLR, NLR, diagnostic score, and DOR of ROX index in predicting HFNC failure were 0.67 (95% CI 0.57–0.76), 0.72 (95% CI 0.65–0.78), 2.4 (95% CI 2.0–2.8), 0.46 (95% CI 0.37–0.58), 1.65(95% CI 1.37–1.93), and 5.0 (95% CI 4.0–7.0), respectively. In addition, SROC was 0.75 (95% CI 0.71–0.79). Besides, our subgroup analyses revealed that ROX index had higher sensitivity and specificity for predicting HFNC failure in COVID-19 patients, use the cut-off value > 5, and the acquisition time of other times after receiving HFNC had a greater sensitivity and specificity when compared to 6 h.

Conclusions
This study demonstrated that ROX index could function as a novel potential marker to identify patients with a higher risk of HFNC failure. However, the prediction efficiency was moderate, and additional research is required to determine the optimal cut-off value and propel acquisition time of ROX index in the future.
PROSPERO registration number: CRD42021240607.
Whole blood fatty acid profile of young subjects and adherence to the Mediterranean diet: an observational cohort study
Authors: Syrén Marie-Louise , Turolo Stefano , de Marco Erika Adalgisa , De Cosmi Valentina , Risé Patrizia , Marangoni Franca , Minoli Dario Guido , Manzoni Gianantonio , Agostoni Carlo 
Published: February 2022

Abstract
Background
Relatively little is known about the physiological whole blood fatty acid composition in young people. Likewise, few studies have addressed the question of correlations between Mediterranean diet (MedDiet) adherence and blood fatty acids in childhood.

Methods
The fatty acid profile in whole blood from subjects, 46 days-19 years old (n = 152), without acute, chronic, or inflammatory diseases was analysed by gas chromatography. Dietary data was extracted from a 24-h recall in a subgroup of subjects (n = 60) into a modified Diet Quality Index for Children (KIDMED) questionnaire to evaluate MedDiet adherence. The cohort was divided into three age groups: < 2, 2- < 10, and 10–19 years. Kruskal-Wallis test and Bonferroni post hoc test were used to check for age group fatty acid differences. For correlations, Spearman’s correlation coefficient and partial Spearman’s correlation coefficient were used.

Results
Linoleic acid, EPA, DHA, palmitic acid, and total saturated fatty acids were stable over age groups. Dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), total polyunsaturated FAs (PUFA), and total omega-6 PUFA increased from age group < 2 years; alpha-linolenic acid, total omega-3 PUFA, oleic acid, and total monounsaturated FAs decreased. Adherence to the MedDiet was at low-medium level in 91.7% of the subjects. In the age group 2- < 10 yrs., the degree of adherence correlated positively with total MUFA and PUFA balance, negatively with total PUFA, total n6-PUFA, AA/DHA, AA/EPA, and n6/n3. Age did not influence the correlations as to PUFA balance and AA/EPA.

Conclusions
Increased FA proportions with age were seen in the n6-series of PUFA. The n3-FA species decreased or were stable. The vast majority of the subjects with dietary data, 92%, obtained a KIDMED score indicative of low-medium adherence to the MedDiet. The score correlated negatively with various n6-species, i.e. the MedDiet suppressed circulating n6-PUFA. Whole blood may be used to investigate FAs and MedDiet adherence correlations which may be applied in the study of health issues in childhood.