bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building integrated, adaptive and responsive healthcare systems – lessons from paramedicine in Ontario, Canada
Authors: Allana Amir , Kuluski Kerry , Tavares Walter , Pinto Andrew D. 
Published: May 2022

Abstract
Background
Being responsive and adaptive to local population needs is a key principle of integrated care, and traditional top-down approaches to health system governance are considered to be ineffective. There is need for more guidance on taking flexible, complexity-aware approaches to governance that foster integration and adaptability in the health system. Over the past two decades, paramedics in Ontario, Canada have been filling gaps in health and social services beyond their traditional mandate of emergency transport. Studying these grassroots, local programs can provide insight into how health systems can be more integrated, adaptive and responsive.

Methods
Semi-structured interviews were conducted with people involved in new, integrated models of paramedic care in Ontario. Audio recordings of interviews were transcribed and coded inductively for participants’ experiences, including drivers, enablers and barriers to implementation. Thematic analysis was done to ascertain key concepts from across the dataset.

Results
Twenty-six participants from across Ontario’s five administrative health regions participated in the study. Participants described a range of programs that included acute, urgent and preventative care driven by local relationship networks of paramedics, hospitals, primary care, social services and home care. Three themes were developed that represent participants’ experiences implementing these programs in the Ontario context. The first theme, adapting and being nimble in tension with system structures, related to distributed versus central control of programs, a desire to be nimble and skepticism towards prohibitive legal and regulatory systems. The second theme, evolving and flexible professional role identity, highlighted the value and challenges of a functionally flexible workforce and interest in new roles amongst the paramedic profession. The third theme, unpredictable influences on program implementation, identified events such as the COVID-19 pandemic and changing government priorities as accelerating, redirecting or inhibiting local program development.

Conclusions
The findings of this study add to the discourse on governing health systems towards being more integrated, adaptive and responsive to population needs. Governance strategies include: supporting networks of local organizational relationships; considering the role of a functionally flexible health workforce; promoting a shared vision and framework for collaboration; and enabling distributed, local control and experimentation.
Referral-based transition to subsequent rehabilitation at home after stroke: one-year outcomes and use of healthcare services
Authors: Lindblom Sebastian , Tistad Malin , Flink Maria , Laska Ann Charlotte , von Koch Lena , Ytterberg Charlotte 
Published: May 2022

AbstractBackgroundThere is a lack of knowledge about patients’ journeys across the stroke care continuum, especially regarding the transition from inpatient to outpatient care and rehabilitation. Therefore, the aim of the present study was to explore and describe patterns of healthcare use over a one-year period, health outcomes at 3 and 12 months for patients following a referral-based transition to subsequent rehabilitation in the home, and the caregiver burden on their significant others. A further aim was to explore factors associated with the use of rehabilitation and healthcare after the referral-based transition to continued rehabilitation in the home for people recovering from a stroke.MethodsData regarding healthcare use during the first 12 months post-stroke was collected from the Region Stockholm computerized register. Data on patient characteristics, disease-related data, and functioning were retrieved drawn from medical records and questionnaires. Descriptive statistics were used to present healthcare use, participants’ characteristics, disease-related data, and patient functioning. Multivariable regression models were created to explore associations between the total number of outpatient contacts, total visits with the neurorehabilitation team, and the independent variables.ResultsThe mean age for the 190 participants was 73 years for men and 78 years for women. Twenty-one participants (11%) had an acute rehospitalization within 30 days after discharge, and 41 participants (21%) were re-hospitalized within 90 days. Twenty-two (12%) of the participants had no visits with the neurorehabilitation team, 73 (39%) participants had 1–3 visits, 57 (30%) had 4–16 visits, and 38 (20%) had ≥17 visits. Female sex and length of hospital stay were associated with a higher number of visits with the neurorehabilitation team. Living alone, higher self-rated recovery, and being able to walk independently were associated with a lower number of visits with the neurorehabilitation team. Female sex, having home help services before the stroke, longer length of hospital stay, and more comorbidities were associated with a higher number of outpatient contacts.ConclusionsThe findings indicate that there is no generic pattern of healthcare use during the first-year post-stroke in patients receiving referral-based transition to continued rehabilitation in the home. The different patterns of healthcare use seemed to mirror the participants’ level of functioning. However, there is a need to further investigate how follow-up and rehabilitation correspond to the needs of patients and their significant others in the short- and long-term perspective.Trial registrationClinicalTrials.gov, registration number:NCT02925871. Date of registration: October 6, 2016.
Increasing person-centeredness in psychosis inpatient care: staff experiences from the Person-Centered Psychosis Care (PCPC) project
Authors: Allerby K. , Goulding A. , Ali L. , Waern M. 
Published: May 2022

Abstract
Background
Interventions to increase person-centeredness in hospital care for persons with psychotic illness are needed. Changing care delivery is however a complex venture, requiring staff to reconsider their mindsets and ways of working. A multidisciplinary educational intervention for hospital staff at four wards was launched to increase person-centeredness in the care of patients with schizophrenia and similar psychoses. This study aims to explore staff experiences of working to increase person-centeredness.

Methods
A heterogenic sample of staff (n = 23) from all participating wards were recruited for six focus group interviews. Semi-structured questions covered staff perceptions of person-centered care and the process of increasing person-centeredness. Transcribed data was analyzed using thematic analysis according to Braun and Clarke.

Results
Staff viewed person-centered care as an approach rather than a method. They described central aspects of person-centered care, such as recognizing the patient as a capable person who can participate in her/his care. Statements further showed how these core features were put into practice. Changes related to the intervention were presented in terms of evolving patient and staff roles, improved contact with patients, more flexible care routines, and a more positive ward climate. Neither psychotic symptoms nor involuntary status were considered barriers for person-centered care, but organizational factors beyond staff control seemed to impact on implementation.

Conclusions
After implementation, participants displayed good understanding of the core concepts of person-centered care in both thinking and action. They attributed several improvements in the care milieu to an increased level of person-centeredness. Psychotic behavior and involuntary treatment did not present major barriers to person-centered care. Findings suggest person-centered care is feasible in the psychosis inpatient setting and could improve quality of care.

Trial registration
The study is part of a larger study evaluating the intervention Person-Centered Psychosis Care (PCPC). It was registered retrospectively at clinicaltrials.gov, identifier NCT03182283.
The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy
Authors: Wang Yiran , Wu Mandi , Li Yichen , Yuen Ho Him , He Ming-Liang 
Published: May 2022

AbstractThe global pandemic of COVID-19 has caused huge causality and unquantifiable loss of social wealth. The innate immune response is the first line of defense against SARS-CoV-2 infection. However, strong inflammatory response associated with dysregulation of innate immunity causes severe acute respiratory syndrome (SARS) and death. In this review, we update the current knowledge on how SARS-CoV-2 modulates the host innate immune response for its evasion from host defense and its corresponding pathogenesis caused by cytokine storm. We emphasize Type I interferon response and the strategies of evading innate immune defense used by SARS-CoV-2. We also extensively discuss the cells and their function involved in the innate immune response and inflammatory response, as well as the promises and challenges of drugs targeting excessive inflammation for antiviral treatment. This review would help us to figure out the current challenge questions of SARS-CoV-2 infection on innate immunity and directions for future studies.
Combining photo-elicitation and discourse analysis to examine adolescents’ sexuality in rural Zambia
Authors: Mulubwa Chama , Hurtig Anna-Karin , Zulu Joseph Mumba , Michelo Charles , Sandøy Ingvild Fossgard , Goicolea Isabel 
Published: May 2022

Abstract
Introduction
This article aimed to analyse constructions of adolescents’ sexualities and sexual health and the consequences of these discourses for adolescents’ exercise of their sexual reproductive health and rights (SRHR) in rural Zambia.

Methods
Interpretative repertoires, which is rooted in discursive psychology was used to analyse data from photo-elicitations interviews and focus group discussions. Our participants included 25 adolescents who participated in a SRHR intervention that aimed to reduce adolescents’ pregnancies and early marriages.

Results
We identified three interpretative repertories: 1) sex is for mature people in which adolescents positioned themselves as ‘immature, and young to engage in sex; 2) gendered respectful behaviours in which what was considered disrespectful (and respectful) behaviour in relation to sexuality were strongly influenced by gender, and more clearly defined for girls than it was for boys. Sexuality was not only about individual choices but about being respectful to parents; and 3) acquiring and using knowledge about sexuality in which adolescents conflicted between having and applying SRHR knowledge.

Conclusion
These repertories offer an important context that shape how adolescents negotiate, adopt and resist SRHR interventions. Future interventions that target adolescents’ SRHR must aim to address the sexual scripts that serve to erect barriers against positive sexual behaviours, including access to SRHR services that promote safer sex.
Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins
Authors: Mesnage Robin , Bowyer Ruth C. E. , El Balkhi Souleiman , Saint-Marcoux Franck , Gardere Arnaud , Ducarmon Quinten Raymond , Geelen Anoecim Robecca , Zwittink Romy Daniëlle , Tsoukalas Dimitris , Sarandi Evangelia , Paramera Efstathia I. , Spector Timothy , Steves Claire J. , Antoniou Michael N. 
Published: May 2022

Abstract
Background
Dietary habits have a profound influence on the metabolic activity of gut microorganisms and their influence on health. Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute to the development of chronic disease by affecting the gut microbiome. We performed the first pesticide biomonitoring survey of the British population, and subsequently used the results to perform the first pesticide association study on gut microbiome composition and function from the TwinsUK registry.

Methods
Dietary exposure of 186 common insecticide, herbicide, or fungicide residues and the faecal microbiome in 65 twin pairs in the UK was investigated. We evaluated if dietary habits, geographic location, or the rural/urban environment, are associated with the excretion of pesticide residues. The composition and metabolic activity of faecal microbiota was evaluated using shotgun metagenomics and metabolomics respectively. We performed a targeted urine metabolomics analysis in order to evaluate whether pesticide urinary excretion was also associated with physiological changes.

Results
Pyrethroid and/or organophosphorus insecticide residues were found in all urine samples, while the herbicide glyphosate was found in 53% of individuals. Food frequency questionnaires showed that residues from organophosphates were higher with increased consumption of fruit and vegetables. A total of 34 associations between pesticide residue concentrations and faecal metabolite concentrations were detected. Glyphosate excretion was positively associated with an overall increased bacterial species richness, as well as to fatty acid metabolites and phosphate levels. The insecticide metabolite Br2CA, reflecting deltamethrin exposure, was positively associated with the phytoestrogens enterodiol and enterolactone, and negatively associated with some N-methyl amino acids. Urine metabolomics performed on a subset of samples did not reveal associations with the excretion of pesticide residues.

Conclusions
The consumption of conventionally grown fruit and vegetables leads to higher ingestion of pesticides with unknown long-term health consequences. Our results highlight the need for future dietary intervention studies to understand effects of pesticide exposure on the gut microbiome and possible health consequences.
What are the short-term annual cost savings associated with kidney transplantation?
Authors: Koto Prosper , Tennankore Karthik , Vinson Amanda , Krmpotic Kristina , Weiss Matthew J. , Theriault Chris , Beed Stephen 
Published: May 2022

Abstract
Background
Kidney transplantation (KT) is often reported in the literature as associated with cost savings. However, existing studies differ in their choice of comparator, follow-up period, and the study perspective. Also, there may be unobservable heterogeneity in health care costs in the patient population which may divide the population into groups with differences in cost distributions. This study estimates the cost savings associated with KT from a payer perspective and identifies and characterizes both high and low patient cost groups.

Method
The current study was a population-based retrospective before-and-after study. The timespan involved at most three years before and after KT. The sample included end-stage kidney disease patients in Nova Scotia, a province in Canada, who had a single KT between January 1, 2011, and December 31, 2018. Each patient served as their control. The primary outcome measure was total annual health care costs. We estimated cost savings using unadjusted and adjusted models, stratifying the analyses by donor type. We quantified the uncertainty around the estimates using non-parametric and parametric bootstrapping. We also used finite mixture models to identify data-driven cost groups based on patients’ pre-transplantation annual inpatient costs.

Results
The mean annual cost savings per patient associated with KT was $19,589 (95% CI: $14,013, $23,397). KT was associated with a 24–29% decrease in mean annual health care costs per patient compared with the annual costs before KT. We identified and characterized patients in three cost groups made of 2.9% in low-cost (LC), 51.8% in medium-cost (MC) and 45.3% in high-cost (HC). Cost group membership did not change after KT. Comparing costs in each group before and after KT, we found that KT was associated with 17% mean annual cost reductions for the LC group, 24% for the MC group and 26% for the HC group. The HC group included patients more likely to have a higher comorbidity burden (Charlson comorbidity index ≥ 3).

Conclusions
KT was associated with reductions in annual health care costs in the short term, even after accounting for costs incurred during KT.
Disability burden due to musculoskeletal conditions and low back pain in Australia: findings from GBD 2019
Authors: de Luca Katie , Briggs Andrew M. , French Simon D. , Ferreira Manuela L. , Cross Marita , Blyth Fiona , March Lyn 
Published: May 2022

Abstract
Background
To report the national prevalence, years lived with disability (YLDs) and attributable risk factors for all musculoskeletal conditions and separately for low back pain (LBP), as well as compare the disability burden related to musculoskeletal with other health conditions in Australia in 2019.

Methods
Global Burden of Disease (GBD) 2019 study meta-data on all musculoskeletal conditions and LBP specifically were accessed and aggregated. Counts and age-standardised rates, for both sexes and across all ages, for prevalence, YLDs and attributable risk factors are reported.

Results
In 2019, musculoskeletal conditions were estimated to be the leading cause of YLDs in Australia (20.1%). There were 7,219,894.5 (95% UI: 6,847,113–7,616,567) prevalent cases of musculoskeletal conditions and 685,363 (95% UI: 487,722–921,471) YLDs due to musculoskeletal conditions. There were 2,676,192 (95% UI: 2,339,327–3,061,066) prevalent cases of LBP and 298,624 (95% UI: 209,364–402,395) YLDs due to LBP. LBP was attributed to 44% of YLDs due to musculoskeletal conditions. In 2019, 22.3% and 39.8% of YLDs due to musculoskeletal conditions and LBP, respectively, were attributed to modifiable GBD risk factors.

Conclusions
The ongoing high burden due to musculoskeletal conditions impacts Australians across the life course, and in particular females and older Australians. Strategies for integrative and organisational interventions in the Australian healthcare system should support high-value care and address key modifiable risk factors for disability such as smoking, occupational ergonomic factors and obesity.
Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases
Authors: Ho Wing-Hong Jonathan , Law Andrew M. K. , Masle-Farquhar Etienne , Castillo Lesley E. , Mawson Amanda , O’Bryan Moira K. , Goodnow Christopher C. , Gallego-Ortega David , Oakes Samantha R. , Ormandy Christopher J. 
Published: May 2022

AbstractBackgroundThe interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. UsingN-ethyl-N-nitrosourea mutagenesis, we found a mouse with an activating mutation in oligoadenylate synthetase 2 (Oas2), a sensor of viral double stranded RNA, that resulted in an interferon response and prevented lactation in otherwise healthy mice.MethodsTo determine if sole activation ofOas2could alter the course of mammary cancer, we combined theOas2mutation with theMMTV-PyMToncogene model of breast cancer and examined disease progression and the effects of checkpoint immunotherapy using Kaplan–Meier survival analysis with immunohistochemistry and flow cytometry.ResultsOas2mutation prevented pregnancy from increasing metastases to lung. Checkpoint immunotherapy with antibodies against programmed death-ligand 1 was more effective when theOas2mutation was present.ConclusionsThese data establish OAS2 as a therapeutic target for agents designed to reduce metastases and increase the effectiveness of checkpoint immunotherapy.
Hereditary angioedema due to C1 inhibitor deficiency: real-world experience from the Icatibant Outcome Survey in Spain
Authors: Guilarte Mar , Sala-Cunill Anna , Baeza María Luisa , Cabañas Rosario , Hernández María Dolores , Ibañez Ethel , de Larramendi Carlos Hernando , Lleonart Ramon , Lobera Teófilo , Marqués Luis , de San Pedro Blanca Sáenz , Botha Jaco , Andresen Irmgard , Caballero Teresa ,   for the IOS Study Group
Published: May 2022

Abstract
Background
The Icatibant Outcome Survey (IOS) is an international registry monitoring the use of icatibant, a bradykinin B2 receptor antagonist indicated for the acute treatment of hereditary angioedema (HAE) attacks. Our goal was to assess disease characteristics and icatibant treatment outcomes in patients with HAE due to C1 inhibitor deficiency (HAE type 1 or 2 (HAE-1/2)) from Spain relative to other countries participating in IOS.

Methods
Descriptive retrospective analyses of data are reported from 10 centers in Spain vs 51 centers in 12 other participating countries (July 2009 to January 2019).

Results
No meaningful differences were identified between patients in Spain (n = 119) and patients across other countries (n = 907) regarding median age at symptom onset (15.0 vs 12.0 years) or diagnosis (22.3 vs 20.5 years). Overall HAE attack rates (total attacks/total years of follow-up) were 2.66 in Spain and 1.46 across other countries. Patients in Spain reported fewer severe/very severe HAE attacks before treatment (41.0% vs 45.9%; P < 0.0001) and, for icatibant-treated attacks, longer median time to treatment (2.9 vs 1.0 h), time to attack resolution (18.0 vs 5.5 h), and total attack duration (24.6 vs 8.0 h). Use of androgens for long-term prophylaxis was higher in Spain (51.2% vs 26.7%).

Conclusion
Patients with HAE-1/2 in Spain reported fewer severe/very severe attacks, administered icatibant later, and had longer-lasting attacks than did patients across other countries in IOS. These differences may indicate varying disease management practices (e.g., delayed icatibant treatment) and reporting. Efforts to raise awareness on the benefits of early on-demand treatment may be warranted.
Trial registration: NCT01034969.
Cell membrane fluidity and ROS resistance define DMSO tolerance of cryopreserved synovial MSCs and HUVECs
Authors: Mizuno Mitsuru , Matsuzaki Takahisa , Ozeki Nobutake , Katano Hisako , Koga Hideyuki , Takebe Takanori , Yoshikawa Hiroshi Y. , Sekiya Ichiro 
Published: May 2022

Abstract
Objectives
Synovial mesenchymal stem cells (MSCs) have high freeze–thaw tolerance, whereas human umbilical vein endothelial cells (HUVECs) have low freezing tolerance. The differences in cell type-specific freeze–thaw tolerance and the mechanisms involved are unclear. This study thus aimed to identify the biological and physical factors involved in the differences in freeze–thaw tolerance between MSCs and HUVECs.

Materials and methods
For biological analysis, MSC and HUVEC viability after freeze-thawing and alteration of gene expression in response to dimethyl sulfoxide (DMSO, a cryoprotectant) were quantitatively evaluated. For physical analysis, the cell membrane fluidity of MSCs and HUVECs before and after DMSO addition was assessed using a histogram for generalized polarization frequency.

Results
HUVECs showed lower live cell rates and higher gene expression alteration related to extracellular vesicles in response to DMSO than MSCs. Fluidity measurements revealed that the HUVEC membrane was highly fluidic and sensitive to DMSO compared to that of MSCs. Addition of CAY10566, an inhibitor of stearoyl-coA desaturase (SCD1) that produces highly fluidic desaturated fatty acids, decreased the fluidity of HUVECs and increased their tolerance to DMSO. The combination of CAY10566 and antioxidant glutathione (GSH) treatment improved HUVEC viability from 57 to 69%. Membrane fluidity alteration may thus contribute to pore-induced DMSO influx into the cytoplasm and reactive oxygen species production, leading to greater cytotoxicity in HUVECs, which have low antioxidant capacity.

Conclusions
Differences in freeze–thaw tolerance originate from differences in the cell membranes with respect to fluidity and antioxidant capacity. These findings provide a basis for analyzing cell biology and membrane-physics to establish appropriate long-term preservation methods aimed at promoting transplantation therapies.