bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism
Authors: Haghikia Arash , Zimmermann Friederike , Schumann Paul , Jasina Andrzej , Roessler Johann , Schmidt David , Heinze Philipp , Kaisler Johannes , Nageswaran Vanasa , Aigner Annette , Ceglarek Uta , Cineus Roodline , Hegazy Ahmed N , van der Vorst Emiel P C , Döring Yvonne , Strauch Christopher M , Nemet Ina , Tremaroli Valentina , Dwibedi Chinmay , Kränkel Nicolle , Leistner David M , Heimesaat Markus M , Bereswill Stefan , Rauch Geraldine , Seeland Ute , Soehnlein Oliver , Müller Dominik N , Gold Ralf , Bäckhed Fredrik , Hazen Stanley L , Haghikia Aiden , Landmesser Ulf 
Published: September 2021

Abstract

Aims
Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.

Methods and results
Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E−/− (Apoe −/−) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe −/− mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [−15.9 mg/dL (−8.1%) vs. −1.6 mg/dL (−0.5%), P = 0.016], total [−19.6 mg/dL (−7.3%) vs. −5.3 mg/dL (−1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: −18.9 mg/dL (−9.1%) vs. −0.6 mg/dL (−0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels.

Conclusion
Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.
Atrial septal defect in adulthood: a new paradigm for congenital heart disease
Authors: Brida Margarita , Chessa Massimo , Celermajer David , Li Wei , Geva Tal , Khairy Paul , Griselli Massimo , Baumgartner Helmut , Gatzoulis Michael A 
Published: September 2021

AbstractAtrial septal defects (ASDs) represent the most common congenital heart defect diagnosed in adulthood. Although considered a simple defect, challenges in optimal diagnostic and treatment options still exist due to great heterogeneity in terms of anatomy and time-related complications primarily arrhythmias, thromboembolism, right heart failure and, in a subset of patients, pulmonary arterial hypertension (PAH). Atrial septal defects call for tertiary expertise where all options may be considered, namely catheter vs. surgical closure, consideration of pre-closure ablation for patients with atrial tachycardia and suitability for closure or/and targeted therapy for patients with PAH. This review serves to update the clinician on the latest evidence, the nuances of optimal diagnostics, treatment options, and long-term follow-up care for patients with an ASD.
TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery
Authors: Dreyfus Julien , Audureau Etienne , Bohbot Yohann , Coisne Augustin , Lavie-Badie Yoan , Bouchery Maxime , Flagiello Michele , Bazire Baptiste , Eggenspieler Florian , Viau Florence , Riant Elisabeth , Mbaki Yannick , Eyharts Damien , Senage Thomas , Modine Thomas , Nicol Martin , Doguet Fabien , Nguyen Virginia , Le Tourneau Thierry , Tribouilloy Christophe , Donal Erwan , Tomasi Jacques , Habib Gilbert , Selton-Suty Christine , Raffoul Richard , Iung Bernard , Obadia Jean-François , Messika-Zeitoun David 
Published: September 2021

Abstract

Aims
Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR).

Methods and results
All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III–IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate &lt;30 mL/min, elevated bilirubin, left ventricular ejection fraction &lt;60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63).

Conclusion
We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).
Virtual visits in cardiovascular disease: a rapid review of the evidence
Authors: Piskulic Danijela , McDermott Susanna , Seal Lauren , Vallaire Shelley , Norris Colleen M. 
Published: September 2021

AbstractGiven the high prevalence of cardiovascular disease (CVD) in Canada and globally, as well as the staggering cost to human life and health systems, there is an urgent need to understand the successful applications of telemedicine in cardiovascular medicine. While telemedicine in cardiology is well documented, reports on virtual care in the form of synchronous, real-time communication between healthcare providers and patients are limited. As a result of the immediate suspension of ambulatory services for cardiology in Alberta, Canada, due to the Coronavirus Disease 2019 pandemic, we undertook a rapid review on the impact of non-virtual visits in cardiovascular ambulatory settings on patients’ healthcare utilization and mortality. Evidence from 12 randomized control trials and 7 systematic reviews was included in the rapid review, with the majority of papers (n = 15) focusing on telemedicine in heart failure. Based on our appraisal of evidence from the last 5 years, virtual visits are non-inferior, or more effective, in reducing hospitalizations and visits to emergency departments in patients with CVD compared to traditional standard in-clinic/ambulatory care. The evidence for a superior effect of virtual visits in reducing mortality was not supported in this review. While telemedicine is an appropriate tool for CVD follow-up care, more research into the efficacy of different components of telemedicine and virtual visits is required.
Predictors of cognitive dysfunction after cardiac surgery: a systematic review
Authors: Bowden Tracey , Hurt Catherine S , Sanders Julie , Aitken Leanne M 
Published: September 2021

Abstract

Aims
Postoperative cognitive dysfunction (POCD) is often experienced by cardiac surgery patients; however, it is not known if some groups of patients experience this more frequently or severely than others.
The aim of this systematic review was to identify preoperative and postoperative predictors of cognitive dysfunction in adults following cardiac surgery.

Methods and results
Eight bibliographic databases were searched (January 2005 to March 2021) in relation to cardiac surgery and cognition. Studies including adult patients who had undergone open cardiac surgery and using a validated measurement of cognitive function were included. Full-text review for inclusion, quality assessment, and data extraction were undertaken independently by two authors.
A total of 2870 papers were identified, of which 36 papers met the inclusion criteria and were included in the review. The majority were prospective observational studies [n = 28 (75.7%)]. In total, 61 independent predictors (45 preoperative and 16 postoperative) were identified as significant in at least one study; advancing age and education level appear important. Age has emerged as the most common predictor of cognitive outcome.

Conclusion
Although a number of predictors of POCD have been identified, they have inconsistently been reported as significantly affecting cognitive outcome. Consistent with previous research, our findings indicate that older patients and those with lower educational levels should be prioritized when developing and trialling interventions to improve cognitive function. These findings are less than surprising if we consider the methodological shortcomings of included studies. It is evident that further high-quality research exploring predictors of POCD is required.

Registration
This review was registered on Prospero, CRD42020167037
Preclinical short QT syndrome models: studying the phenotype and drug-screening
Authors: Fan Xuehui , Yang Guoqiang , Kowitz Jacqueline , Duru Firat , Saguner Ardan M , Akin Ibrahim , Zhou Xiaobo , El-Battrawy Ibrahim 
Published: September 2021

Abstract
Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5–10% of SCDs, mainly in the young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype–phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype–phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome.
Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk)
Authors: Mazzanti Andrea , Trancuccio Alessandro , Kukavica Deni , Pagan Eleonora , Wang Meng , Mohsin Muhammad , Peterson Derick , Bagnardi Vincenzo , Zareba Wojciech , Priori Silvia G 
Published: September 2021

Abstract

Aims
Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model.

Methods and results
The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61–0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70–0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3–13.6).

Conclusion
The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants.
Environment—lockdown, air pollution and related diseases: could we learn something and make it last?
Authors: Jevtic Marija , Matkovic Vlatka , van den Hazel Peter , Bouland Catherine 
Published: September 2021

Abstract
Although the pandemic has caused substantial losses in economic prosperity and human lives, it has also some positive impacts on the environment. Restricted mobility, complete closure, less traffic and industry have led to improved air quality especially in urban settings. Not only is air pollution an important determinant of chronic diseases, such as heart and lung disorders, but it has also been shown that poor air quality increases the risk of COVID-19.
In this article, we review some of the findings on changes in air quality during the pandemic, and its potential effects on health. We need to continue to monitor the effects of change in air quality, due to COVID-19 lockdown or other factors, but also keep all our efforts to improve air quality even faster and more persistent, bringing the pollution levels below what WHO recommends are safe to live with.
Integrating case-finding and initial management for osteoarthritis, anxiety, and depression into primary care long-term condition reviews: results from the ENHANCE pilot trial
Authors: Healey Emma L , Mallen Christian D , Chew-Graham Carolyn A , Nicholls Elaine , Lewis Martyn , Lawton Sarah A , Finney Andrew G , Tan Valerie , Cooper Vince , Dziedzic Krysia S , Liddle Jennifer , Wathall Simon , Jinks Clare 
Published: September 2021

Abstract

Background
Multimorbidity is increasingly the norm; however, primary care remains focused on single diseases. Osteoarthritis, anxiety, and depression are frequently comorbid with other long-term conditions (LTCs), but rarely prioritized by clinicians.

Objectives
To test the feasibility of a randomized controlled trial (RCT) of an intervention integrating case-finding and management for osteoarthritis, anxiety, and depression within LTC reviews.

Methods
A pilot stepped-wedge RCT across 4 general practices recruited patients aged ≥45 years attending routine LTC reviews. General practice nurses provided usual LTC reviews (control period), then, following training, delivered the ENHANCE LTC review (intervention period). Questionnaires, an ENHANCE EMIS-embedded template and consultation audio-recordings, were used in the evaluation.

Results
General practice recruitment and training attendance reached prespecified success criteria. Three hundred and eighteen of 466 (68%) of patients invited responded; however, more patients were recruited during the control period (206 control, 112 intervention). Eighty-two percent and 78% returned their 6-week and 6-month questionnaires, respectively. Integration of the ENHANCE LTC review into routine LTC reviews varied. Case-finding questions were generally used as intended for joint pain, but to a lesser extent for anxiety and depression. Initial management through referrals and signposting were lacking, and advice was more frequently provided for joint pain. The stepped-wedge design meant timing of the training was challenging and yielded differential recruitment.

Conclusion
This pilot trial suggests that it is feasible to deliver a fully powered trial in primary care. Areas to optimize include improving the training and reconsidering the stepped-wedge design and the approach to recruitment by targeting those with greatest need.

Trial registration
ISRCTN registry (ISRCTN: 12154418). Date registered: 6 August 15. Date first participant was enrolled: 13 July 2015. https://www.isrctn.com/ISRCTN12154418?q=depression%20schizophrenia&filters=conditionCategory:Not%20Applicable&sort=&offset=5&totalResults=9&page=1&pageSize=20&searchType=basic-search.
General practitioners’ views of pharmacist services in general practice: a qualitative evidence synthesis
Authors: Hurley Eoin , Gleeson Laura L , Byrne Stephen , Walsh Elaine , Foley Tony , Dalton Kieran 
Published: September 2021

AbstractBackgroundPharmacist services in general practice are expanding worldwide, with evidence to show pharmacists’ presence in general practice has financial, workload, and clinical benefits. Yet, little is known globally about general practitioners’ (GPs’) views on their presence in general practice.ObjectiveTo synthesize the qualitative research evidence on GPs’ views of pharmacist services in general practice.MethodsQualitative evidence synthesis; 8 electronic databases were searched from inception to April 2021 for qualitative studies that reported the views of GPs regarding pharmacist services in general practice. Data from included studies were analyzed using thematic synthesis. The Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach was used to assess the confidence in individual review findings.ResultsNineteen studies were included, which captured the views of 159 GPs from 8 different countries. Four analytical themes describing the factors that should be considered in the development or optimization of pharmacist services in general practice, based on the views of GPs, were developed from the coded data and descriptive themes: (i) optimal environment for a pharmacist, (ii) the ideal pharmacist characteristics, (iii) complex stakeholder relationships, and (iv) benefits of an effective pharmacist.ConclusionBased on the synthesis of GPs’ views, we have created a conceptual model of factors that should be considered by policymakers, GPs, pharmacists, and other relevant stakeholders when developing or optimizing pharmacist services in general practice going forward.
The use and safety of corticosteroid injections for shoulder pain in general practice: a retrospective cohort study
Authors: van Doorn Pieter F , Schiphof Dieuwke , Rozendaal Rianne M , Ottenheijm Ramon P G , van der Lei Johan , Bindels Patrick J E , de Schepper Evelien I T 
Published: September 2021

Abstract

Background
Guidelines for shoulder pain in general practice recommend treatment with corticosteroid injections (CSI) if initial pain management fails. However, little is known about the actual use and safety of CSIs in treatment by general practitioners (GP).

Objective
The objective of this study was to gain insight into the use and safety of CSIs for patients with a new episode of shoulder pain in general practice.

Methods
A retrospective cohort study was conducted using a healthcare database containing the electronic medical records of approximately 200,000 patients in general practice. A search algorithm was constructed to identify patients with a new episode of shoulder pain between January 2012 and December 2017. Data on the use of CSIs in 2 random samples (n = 1,000) were manually validated for a 12-month period after the diagnosis.

Results
In total, 26% of the patients with a new episode of shoulder pain received a CSI. The patient’s age (OR 1.03, 95% CI 1.02–1.04) and a history of shoulder pain (OR 1.52, 95% CI 1.13–2.12) were significantly associated with the administration of a CSI. Half of the patients received the CSI in the first consultation. The patient’s age was positively associated with the likelihood of receiving the CSI in the first consultation (OR 1.01, 95% CI 1.00–1.02). No serious adverse reactions were recorded by the GP.

Conclusion
In contrast to the guidelines, CSIs were frequently administered in the first consultation. Older patients and patients with a history of shoulder pain were more likely to receive a CSI for shoulder pain.
Women family physicians’ working conditions and career satisfaction: a multinational study
Authors: Usta Jinan , Candib Lucy M , Oyola Sonia , Abdul Razzak Farah , Antoun Jumana 
Published: September 2021

Abstract

Background
As the proportion of women in family medicine increases, their well-being and job satisfaction become concerns.

Objectives
This study aimed to uncover the working conditions and career satisfaction of women family physicians across multiple countries.

Methods
A cross-sectional survey of the WONCA Working Party on Women and Family Medicine listserv members to assess working conditions and career satisfaction, with snowballing recruitment. Aspects of physician job satisfaction were measured using the validated Physician Work-Life Survey and calculated as the sum of the scores of each positive item divided by the total number of questions and multiplied by 10. The association between satisfaction and the continent and the country income level was performed using a one-way ANOVA test (P &lt; 0.05).

Results
A total of 315 participants across 49 countries responded to the survey with 205 complete responses. Women family physicians reported high overall career satisfaction (8.2 ± 2.3) but were less satisfied with some aspects of their career such as pay (5.3 ± 3.4), personal time (3.5 ± 2.6), and administrative tasks (3.2 ± 3.7). Despite the widespread experience of sexism at work, satisfaction with personal career aspects was universal at the continent and income level, while satisfaction with other career aspects relevant to relationships in work environment and resources varied.

Conclusion
Women family physicians around the world are overall satisfied with their careers. However, variation in certain working conditions among countries leaves room for improvement, drawing attention to the need for national review of working environments and pay scales.