bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation is recognized as a fundamental early phase of integrated knowledge translation (IKT): qualitative interviews with researchers and research users in IKT partnerships
Authors: Zych Maria Maddalena , Berta Whitney B. , Gagliardi Anna R. 
Published: October 2019

Abstract

Background
Health care researcher-research user partnerships, referred to as integrated knowledge translation (IKT), have been adopted on an international basis, and are an effective means of co-generating and implementing evidence into policy and practice. Prior research suggests that an initiation period is essential for establishing functional partnerships. To characterize IKT initiation and describe determinants of IKT initiation success, this study explored IKT initiation processes, enablers, and barriers among researchers and research users involved in IKT partnerships.

Methods
A descriptive qualitative approach was used compliant with COREQ standards. Canadian researchers and research users in research collaborations were identified on publicly-available directories and web sites, and referred by those interviewed. They were asked to describe how partnerships were initiated, influencing factors, the length of initiation, and interventions needed to support initiation. Sampling was concurrent with data collection and analysis to achieve thematic saturation. Data were analyzed using constant comparative technique by all members of the research team.

Results
In total, 22 individuals from 6 provinces were interviewed (9 researchers, 11 research users, 2 connectors). They confirmed that IKT initiation is a distinct early phase of partnerships. The period ranged from 6 months to 2 years for 75.0% of participants in pre-existing partnerships, to 6 years for newly-formed partnerships. High-level themes were: Newly identifying and securing partners is an intensive process; Processes and activities take place over a protracted period through multiple interactions; Identifying and engaging committed partners is reliant on funding; and Partnership building is challenged by maintaining continuity and enthusiasm. Participants underscored the need for an IKT partner matching forum, IKT initiation toolkit, and funding for non-research activities required during IKT initiation to establish functional researcher-research user partnerships. Themes were largely similar regardless of participant years of experience with IKT or being involved in a new versus pre-existing partnership.

Conclusions
IKT initiation is a recognized and important early phase of IKT that establishes functional partnerships, and once established, ongoing partnership for subsequent projects is likely. Further research is needed to develop and evaluate approaches recommended by participants for stimulating IKT initiation.
A multistage mixed methods study protocol to evaluate the implementation and impact of a reconfiguration of acute medicine in Ireland’s hospitals
Authors: Hurley E. , McHugh S. , Browne J. , Vaughan L. , Normand C. 
Published: October 2019

AbstractBackgroundTo address deficits in the delivery of acute services in Ireland, the National Acute Medicine Programme (NAMP) was established in 2010 to optimise the management of acutely ill medical patients in the hospital setting, and to ensure their supported discharge to primary and community-based care. NAMP aims to reduce inappropriate hospital admissions, reduce length of hospital stay and ensure patients receive timely treatment in the most appropriate setting. It does so primarily via the development of Acute Medical Assessment Units (AMAUs) for the rapid assessment and management of medical patients presenting to hospitals, as well as streamlining the care of those admitted for further care. This study will examine the impact of this programme on patient care and identify the factors influencing its implementation and operation.MethodsWe will use a multistage mixed methods evaluation with an explanatory sequential design. Firstly, we will develop a logic model to describe the programme’s outcomes, its components and the mechanisms of change by which it expects to achieve these outcomes. Then we will assess implementation by measuring utilisation of the Units and comparing the organisational functions implemented to that recommended by the NAMP model of care. Using comparative case study research, we will identify the factors which have influenced the programme’s implementation and its operation using the Consolidated Framework for Implementation Research to guide data collection and analysis. This will be followed by an estimation of the impact of the programme on reducing overnight emergency admissions for potentially avoidable medical conditions, and reducing length of hospital stay of acute medical patients. Lastly, data from each stage will be integrated to examine how the programme’s outcomes can be explained by the level of implementation.DiscussionThis formative evaluation will enable us to examine whether the NAMP is improving patient care and importantly draw conclusions on how it is doing so. It will identify the factors that contribute to how well the programme is being implemented in the real-world. Lessons learnt will be instrumental in sustaining this programme as well as planning, implementing, and assessing other transformative programmes, especially in the acute care setting.
Key challenges for delivering clinical impact with artificial intelligence
Authors: Kelly Christopher J. , Karthikesalingam Alan , Suleyman Mustafa , Corrado Greg , King Dominic 
Published: October 2019

Abstract

Background
Artificial intelligence (AI) research in healthcare is accelerating rapidly, with potential applications being demonstrated across various domains of medicine. However, there are currently limited examples of such techniques being successfully deployed into clinical practice. This article explores the main challenges and limitations of AI in healthcare, and considers the steps required to translate these potentially transformative technologies from research to clinical practice.

Main body
Key challenges for the translation of AI systems in healthcare include those intrinsic to the science of machine learning, logistical difficulties in implementation, and consideration of the barriers to adoption as well as of the necessary sociocultural or pathway changes. Robust peer-reviewed clinical evaluation as part of randomised controlled trials should be viewed as the gold standard for evidence generation, but conducting these in practice may not always be appropriate or feasible. Performance metrics should aim to capture real clinical applicability and be understandable to intended users. Regulation that balances the pace of innovation with the potential for harm, alongside thoughtful post-market surveillance, is required to ensure that patients are not exposed to dangerous interventions nor deprived of access to beneficial innovations. Mechanisms to enable direct comparisons of AI systems must be developed, including the use of independent, local and representative test sets. Developers of AI algorithms must be vigilant to potential dangers, including dataset shift, accidental fitting of confounders, unintended discriminatory bias, the challenges of generalisation to new populations, and the unintended negative consequences of new algorithms on health outcomes.

Conclusion
The safe and timely translation of AI research into clinically validated and appropriately regulated systems that can benefit everyone is challenging. Robust clinical evaluation, using metrics that are intuitive to clinicians and ideally go beyond measures of technical accuracy to include quality of care and patient outcomes, is essential. Further work is required (1) to identify themes of algorithmic bias and unfairness while developing mitigations to address these, (2) to reduce brittleness and improve generalisability, and (3) to develop methods for improved interpretability of machine learning predictions. If these goals can be achieved, the benefits for patients are likely to be transformational.
Immune inhibitory function of bovine CTLA-4 and the effects of its blockade in IFN-γ production
Authors: Watari Kei , Konnai Satoru , Maekawa Naoya , Okagawa Tomohiro , Suzuki Yasuhiko , Murata Shiro , Ohashi Kazuhiko 
Published: October 2019

AbstractBackgroundCytotoxic T-lymphocyte antigen 4 (CTLA-4) is known as an immune inhibitory receptor that is expressed on activated effector T cells and regulatory T cells. When CTLA-4 binds to CD80 or CD86, immunoinhibitory signals are transmitted to retain a homeostasis of the immune response. Recent studies have reported that CTLA-4 is upregulated in chronic infections and malignant neoplasms, contributing to host immune dysfunction. On the other hand, the blockade of CTLA-4 and CD80 or CD86 binding by antibody restores the immune response against these diseases. In a previous report, we indicated that the expression of CTLA-4 was closely associated with disease progression in cattle infected with the bovine leukemia virus (BLV). In this study, we established an anti-bovine CTLA-4 antibody to confirm its immune enhancing effect.ResultsBovine CTLA-4-Ig binds to bovine CD80 and CD86 expressing cells. Additionally, CD80 and CD86 bind to CTLA-4 expressing cells in an expression-dependent manner. Bovine CTLA-4-Ig significantly inhibited interferon-gamma (IFN-γ) production from bovine peripheral blood mononuclear cells (PBMCs) activated by Staphylococcus enterotoxin B (SEB). An established specific monoclonal antibody (mAb) for bovine CTLA-4 specifically recognized only with bovine CTLA-4, not CD28, and the antibody blocked the binding of CTLA-4-Ig to both CD80 and CD86 in a dose-dependent manner. The bovine CTLA-4 mAb significantly restored the inhibited IFN-γ production from the CTLA-4-Ig treated PBMCs. In addition, the CTLA-4 mAb significantly enhanced IFN-γ production from CTLA-4 expressing PBMCs activated by SEB. Finally, we examined whether a CTLA-4 blockade by CTLA-4 mAb could restore the immune reaction during chronic infection; the blockade assay was performed using PBMCs from BLV-infected cattle. The CTLA-4 blockade enhanced IFN-γ production from the PBMCs in response to BLV-antigens.ConclusionsCollectively, these results suggest that anti-bovine CTLA-4 antibody can reactivate lymphocyte functions and could be applied for a new therapy against refractory chronic diseases. Further investigation is required for future clinical applications.
Pigmentary keratitis in pugs in the United Kingdom: prevalence and associated features
Authors: Maini S. , Everson R. , Dawson C. , Chang Y. M. , Hartley C. , Sanchez R. F. 
Published: October 2019

AbstractBackgroundPigmentary keratitis (PK) is commonly recognised in Pugs, but its aetiology is not completely understood. The aim of this study was to determine the prevalence and associated features of PK in Pugs in the United Kingdom (UK).ResultsA total of 210 Pugs (420 eyes) were recruited from 12 UK dog shows and social events. The median age of Pugs recruited was 2.50 years (range 0.25–16.25 years). Pigmentary keratitis was detected in 369/420 (87.8%) eyes and in at least one eye 193/210 (91.9%) Pugs, of which 17/193 (8.8%) were affected unilaterally and 176/193 (91.2%) bilaterally. Pigmentary keratitis was typically mild to moderate (46.3 and 49.9% of eyes, respectively). Detection of PK was significantly associated with increased age (P = 0.002) and the presence of medial entropion of the lower eyelid (MELE) (P = 0.001). Severity of PK was significantly associated with the grade of MELE (P < 0.001). There was also a correlation between the presence of limbal pigment and PK (P = 0.036) that warrants further study.ConclusionsThis study estimated a high disease prevalence of PK in UK Pugs, and demonstrated significant associations with age and the presence of MELE. These associations, which have not been previously reported, offer an insight into the underlying pathophysiology of this condition in Pugs. The results encourage further population research, such as prospective longitudinal studies. These findings also support the development of clinical and breeding strategies based on the reduction of MELE and, possibly, limbal pigment.
Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)
Authors: Donohue James F. , Kerwin Edward , Sethi Sanjay , Haumann Brett , Pendyala Srikanth , Dean Lorna , Barnes Chris N. , Moran Edmund J. , Crater Glenn 
Published: October 2019

Abstract

Background
Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial.

Methods
In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium.

Results
Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms.

Conclusions
Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD.

Trial registration
NCT02518139; Registered 5 August 2015.
BMI is associated with FEV1 decline in chronic obstructive pulmonary disease: a meta-analysis of clinical trials
Authors: Sun Yilan , Milne Stephen , Jaw Jen Erh , Yang Chen Xi , Xu Feng , Li Xuan , Obeidat Ma’en , Sin Don D. 
Published: October 2019

Abstract

Background
There is considerable heterogeneity in the rate of lung function decline in chronic obstructive pulmonary disease (COPD), the determinants of which are largely unknown. Observational studies in COPD indicate that low body mass index (BMI) is associated with worse outcomes, and overweight/obesity has a protective effect – the so-called “obesity paradox”. We aimed to determine the relationship between BMI and the rate of FEV1 decline in data from published clinical trials in COPD.

Methods
We performed a systematic review of the literature, and identified 5 randomized controlled trials reporting the association between BMI and FEV1 decline. Four of these were included in the meta-analyses. We analyzed BMI in 4 categories: BMI-I (< 18.5 or <  20 kg/m2), BMI-II (18.5 or 20 to < 25 kg/m2), BMI-III (25 to < 29 or < 30 kg/m2) and BMI-IV (≥29 or ≥ 30 kg/m2). We then performed a meta-regression of all the estimates against the BMI category.

Results
The estimated rate of FEV1 decline decreased with increasing BMI. Meta-regression of the estimates showed that BMI was significantly associated with the rate of FEV1 decline (linear trend p = 1.21 × 10− 5).

Conclusions
These novel findings support the obesity paradox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention.
Mesenchymal stromal cell conditioned media for lung disease: a systematic review and meta-analysis of preclinical studies
Authors: Emukah Chimobi , Dittmar Evan , Naqvi Rija , Martinez John , Corral Alexis , Moreira Axel , Moreira Alvaro 
Published: October 2019

Abstract

Background
Inflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM) can attenuate inflammation. Our aim was threefold: (1) summarize the existing animal literature evaluating CdM as a therapeutic agent for pediatric/adult lung disease, (2) quantify the effects of CdM on inflammation, and (3) compare inflammatory effects of CdM to MSCs.

Methods
Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed in five databases. Meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD).

Results
A total of 10 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, and acute respiratory distress syndrome. CdM decreased inflammatory cells (1.02 SMD, 95% CI 0.86, 1.18) and cytokines (0.71 SMD, 95% CI 0.59, 0.84). The strongest effect for inflammatory cells was in bronchopulmonary dysplasia (3.74 SMD, 95% CI 3.13, 4.36) while pulmonary hypertension had the greatest reduction in inflammatory cytokine expression (1.44 SMD, 95% CI 1.18, 1.71). Overall, CdM and MSCs had similar anti-inflammatory effects.

Conclusions
In this meta-analysis of animal models recapitulating lung disease, CdM improved inflammation and had an effect size comparable to MSCs. While these findings are encouraging, the risk of bias and heterogeneity limited the strength of our findings.
What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study)
Authors: Jaffuel Dany , Philippe Carole , Rabec Claudio , Mallet Jean-Pierre , Georges Marjolaine , Redolfi Stefania , Palot Alain , Suehs Carey M. , Nogue Erika , Molinari Nicolas , Bourdin Arnaud 
Published: October 2019

Abstract

Backgrounds
As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions.

Methods
The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal.

Results
177/214 patients were analysed (87.57% male) with a median (IQ25–75) age of 71 (65–77) years, an ASV-treatment duration of 2.88 (1.76–4.96) years, an ASV-usage of 6.52 (5.13–7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6–13.5) to 6 (3–9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38–62)/h to a residual device index of 1.9 (0.7–3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05).

Conclusions
In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management.

Trial registration
The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986) on 1 April 2015.
Developmental potential of surplus morulas with delayed and/or incomplete compaction after freezing-thawing procedures
Authors: Tsai Ni-Chin , Su Yu-Ting , Lin Yu-Ju , Chiang Hsin-Ju , Huang Fu-Jen , Kung Fu-Tsai , Lan Kuo-Chung 
Published: October 2019

Abstract

Background
Morulas with delayed growth sometimes coexist with blastocysts. There is still limited evidence regarding the optimal disposal of surplus morulas. With the advancement of vitrification, the freezing-thawing technique has been widely applied to zygotes with 2 pronuclei, as well as embryos at the cleavage and blastocyst stages. The freezing of morulas, however, has rarely been discussed. The purpose of this study was to investigate whether these poor-quality and slow-growing morulas are worthy of cryopreservation.

Methods
This is a retrospective, observational, proof-of-concept study. A total of 1033 day 5/6 surplus morulas were cryopreserved from January 2015 to December 2018. The study included 167 women undergoing 180 frozen embryo transfer cycles. After the morulas underwent freezing-thawing procedures, their development was monitored for an additional day. The primary outcome was the blastocyst formation rate. Secondary outcomes were clinical pregnancy rate, live birth rate and abortion rate.

Results
A total of 347 surplus morulas were thawed. All studied morulas showed delayed compaction (day 5, n = 329; day 6, n = 18) and were graded as having low (M1, n = 54), medium (M2, n = 138) or high (M3, n = 155) fragmentation. The post-thaw survival rate was 79.3%. After 1 day in extended culture, the blastocyst formation rate was 66.6%, and the top-quality blastocyst formation rate was 23.6%. The day 5 morulas graded as M1, M2, and M3 had blastocyst formation rates of 88.9, 74.0, and 52.8% (p < 0.001), respectively, and the top-quality blastocyst formation rates were 64.8, 25.2, and 9.0% (p < 0.001), respectively. The clinical pregnancy rate was 33.6%.

Conclusions
The post-thaw blastocyst formation rate was satisfactory, with approximately one-half of heavily fragmented morulas (M3) developing into blastocysts. Most of the poor-quality morulas were worth to freeze, with the reasonable goal of obtaining pregnancy and live birth. This alternative strategy may be a feasible approach for coping with poor-quality surplus morulas in non-PGS (preimplantation genetic screening) cycles.