bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital@Home: a proof of concept
Authors: Umans V , Van Ramshorst J , De Boer S.P.M , Bos-Schaap A.J.C.M , Walburg S 
Published: November 2020

Abstract

Background
Expenditure in healthcare in the Netherlands is so increasing that currently 1 in 7 employees are working in the health care/cure. Future expansion is under constrain given the 10% of GDP use and shortage of working force.Dutch healthcare consists of a cure section (mostly hospitals) and nursing care@home. Both entities have different national budgets (€25 + €20bln)

Methods
In a proof of concept, we explored a new Hospital@Home (H@H) model combining hospital cure and home-care budgets in a 800 mi2 district with 850,000 inhabitants. The objective comprises 4 proofs: (1)provide hospital care@home, (2) combine financial budgets (3) increasing working forces by combining teams, (4) increased satisfaction of pts and nursing staff.

Results
We proofed a joining budgets of the hospital and home-care group for cardiology. The homecare-budget was sufficient to hire 3 nurse practitioners who are trained by the cardiologists and work with 16 home-care cardiovascular nurses for H@H treatment. The hospital budget provided a virtual EHR cardiology ward and supplied the home care-nurses with a nursing app to assess the patients EHR. Budgets were sufficient to obtain the home-heartfailure monitoring application. The cardiology-group developed the H@H program for endocarditis treatment and heartfailure telemonitoring. Clinically, in the first 6 months, 50% of hospitalized endocarditis pts were treated with iv antibiotics@home with an average 16.5 days per pt shorter admission days without complications. 33% of eligible hospitalized heartfailure pts consented for telemonitoring@home while up-titrated on medication. Video-consulting reduced outpatient visits with 75%. Patient satisfaction was 75/100.

Conclusion
In this proof of concept, the H@H program provided hospital cure at home by merging hospital and home-care nursing staff and ICT budgets. Patient satisfaction score were driven by shorter admissions and less hospital visits. We call for further exploration of efforts to facilitate combined home-care and hospital-cure transmural budgets to confirm this proof of concept.

Funding Acknowledgement
Type of funding source: None
ICHealth: large-scale digital health data on evidence-based cardiovascular medications, hospitalizations and epidemiological characteristics of heart failure patients in Brazil
Authors: Santo K , Marton P , Lapa M , Pereira P , Amaro E , Berwanger O 
Published: November 2020

Abstract

Introduction
Heart failure (HF) is one of the main causes of morbimortality in Brazil. However, little is known about the characteristics of the Brazilian HF population assisted at the community level, including the use of HF medications and frequency of hospitalizations. ePHealth is an app-based large-scale digital data collection platform that currently has health data on more than 1.5 million people.

Purpose
To assess the use of evidence-based HF medications, hospitalizations and epidemiological characteristics of HF patients in Brazil.

Methods
This is an observational retrospective study of the digital health data collected using the ePHealth platform on individuals, who self-reported a diagnosis of HF. Data collected included sociodemographics, clinical data, risk factors, comorbidities, medications and hospitalizations.

Results
Data collected at more than 40,000 home visits on 5907 individuals with HF were analysed. Majority of them were female, aged 55 to 75 years and brown (Figure 1). About 36% were married, 20% were illiterate, 65% were retired and 66% earned ≤2 minimum wages. Mean BMI was 26.7 kg/m2 (SD 5.9), risk factors and comorbidities were frequent (Figure 1). The use of HF medications was very low (Table 1). There were 575 hospitalizations (9.7%), due to the main following reasons: probable or definite heart failure decompensation (89, 15.5%), heart attack (60, 10.4%), cardiovascular procedures (54, 9.4%) and stroke (42, 7.3%).

Conclusion
This data suggests that community-level use of evidence-based cardiovascular medications in a population of individuals with HF in Brazil is very low and that hospitalizations are frequent. This study also provides a better understanding of the characteristics of a population of HF individuals, using large-scale real-world data collected on a community-level via an entirely digital platform. ePHealth is a disruptive platform able to provide data on the burden of HF and other cardiovascular diseases, informing decisions on implementation of prevention and management programmes.
Figure 1. HF population characteristics

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): ePHealth
Burnout in residency: are cardiology residents more affected?
Authors: Sigal A.R , Alves De Lima A.E , Cousirat Liendro M 
Published: November 2020

Abstract

Introduction
Burnout syndrome is a state of mental and physical wear caused by stressful working conditions, characterized by depersonalization, tiredness and lack of personal fulfillment. Its consequences are severe, ranging from sleep disorders to higher suicide risk. Residents in training are more prone to suffering this syndrome, especially in Argentina where over 30% of cardiology residents work over 80 hours and sleep less than 35 hours a week. There is a lack of robust data in Argentina regarding the incidence of this syndrome in residents and whether cardiology residents are more prone to suffering it compared to other clinical specialties.

Methods
We conducted a national, multicentric, voluntary, self-administered survey to determine burnout levels in residents across multiple specialties. Burnout syndrome was defined using the Maslach inventory tool as having all three of the following: high scores in tiredness (&gt;26) and depersonalization (&gt;9), and low score in personal fulfillment (&gt;34). Discreet variables were analyzed by median and interquartile range, while proportions were used for nominal variables. We used Chi-squared test to compare categorical variables.

Results
312 residents from 15 Argentinian provinces completed the survey, of which 148 (47.4%) represented cardiology residents, 112 (35.9%) other clinical specialties, and 52 (16.7%) surgical specialties. 63.1% were female. 16% were first year residents, 25% second year, 23% third year and 25% fourth year, with 8% chief of residents. 41% were from the public setting. 24% of all residents screened had a positive test for burnout syndrome. Cardiology residents had a higher burnout incidence (27.7%) than residents of other specialties (17%) (OR 1.87; 95% IC 1.02–3.45; p=0.04). A numerical (but not statistically significant) trend for higher lack of personal realization was found (OR 1.67; 95% CI 0.97–2.88; p=0.06).

Conclusion
In this trial, a higher incidence of burnout syndrome was found in Argentine cardiology residents than in other clinical specialties. This may be explained by an almost significant increase in lack of personal realization. Trials with an increased sample size need to be carried out to reinforce this hypothesis and determine causation, in order to support and influence policymakers to create a less stresful work environment in order to prevent burnout syndrome.

Funding Acknowledgement
Type of funding source: None
Independent predictors of repeat emergency room presentations in patients with noncardiac chest pain: insights from a cohort of 1066 consecutive patients with 4770 repeat presentations
Authors: Yang Y.H , Grainger R , Gornall M , Obeidat M , Campbell M , Batouskaya K , Khand A 
Published: November 2020

Abstract

Introduction
Repeat attendances with noncardiac chest pain (NCCP) to emergency room (ER) are frequent..Our aim was to analyse predictors of repeat presentations to ER in patients with NCCP.

Methods
We prospectively enrolled 1066 consecutive presentations with NCCP to a major urban hospital ER. Index of multiple deprivation (IMR) was computed. Charlson comorbidity (CCM) index was determined. Repeat presentation to ER to any national hospital was determined by a national linked database (pop. 53.5m).

Results
Median age was 43 (IQR 28, 59), 50.8% were male. 63% were current or previous smokers. 1 year incidence of adjudicated MI, coronary revascularisation and all-cause death was 0.6%, 2% and 5.3% respectively. There was a total of 4770 repeat ER presentations. After taking account of death independent predictors for repeat presentation were current smoking (OR 1.844, p=0.001) and CCM score ≥1 (OR 1.58, p=0.014) (table).

Conclusions
Smoking and patients with multiple comorbidities represent health policy targets for lessening hospital burden of NCCP.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Liverpool University Hospital NHS Trust; North-West Educational Cardiac Group
Cardiovascular disease recurrence and long-term mortality in a tri-ethnic British cohort: a retrospective study
Authors: Vyas M , Chaturvedi N , Hughes A , Marmot M , Tillin T 
Published: November 2020

Abstract

Background
People of South Asian and of African Caribbean descent have elevated risks of some cardiovascular diseases compared to Europeans. How ethnicity relates to recurrent risk, and explanations for between ethnic group differences in recurrence are unclear. We characterized long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a tri-ethnic British cohort.

Methods
We linked hospital and mortality records of a population-based cohort of South Asian, African Caribbean and European men and women aged 40–69 years with no prior history of cardiovascular disease. We identified index and recurrent cardiovascular events (stroke, transient ischaemic attack, myocardial infarction, or ischaemic heart disease), and mortality from 1988 to 2017. Using multivariable proportional hazards models, we separately calculated the adjusted hazard ratios (HR) of MACE and death following index event. We adjusted for demographics, vascular and lifestyle risk factors. We used interaction terms to evaluate if diabetes or decade of index event modified the association between ethnicity and outcomes.

Results
We included 801 participants with first non-fatal cardiovascular events, 647 coronary and 127 cerebrovascular, of whom 335 (41.8%) were European, 396 (49.5%) South Asian, and 70 (8.7%) African Caribbean. During a mean follow-up of 5.3 years, 537 patients developed MACE and 338 died. Crude incidence rate of MACE was higher in South Asians (135.9 per 1000-person-years) compared to Europeans (117.1) and African Caribbeans (123.6). Higher risk of MACE in South Asian compared to Europeans was eliminated in the adjusted models (HR 0.97, 95% confidence interval 0.77–1.21), whereas their mortality advantage was eliminated when the younger age at index event was accounted for (HR 0.95, 0.72–1.26). African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 0.74–1.47; and HR death 1.07, 0.70–1.64). There was no modification by diabetes for outcomes, whereas survival following index event improved more in South Asian, than African Caribbean, compared to European over three decades (Pinteraction = 0.04).

Conclusions
Baseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): UK Medical Research Council, Wellcome Trust
Study design, result reporting and publication of late-stage cardiovascular trials
Authors: Kapelios C , Naci H , Vardas P , Mossialos E 
Published: November 2020

Abstract

Introduction
Preregistration of study protocols in publicly accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on the characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited.

Methods
The purpose of this study was to perform a comprehensive analysis of the characteristics of late-stage, cardiovascular disease (CVD) trials registered in Clinicaltrials.gov. We searched for interventional, late-phase (annotated as phase III) CVD studies in adults first posted after 1/1/2013 and completed up to 31/12/2018. Data on study design, result reporting, result spinning and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined.

Results
The search yielded 352 studies. One hundred were excluded from further analysis because they were misclassified as CVD studies, while 2 were excluded as duplicate entries. In total, 250 CVD trials were included in the analysis. The most commonly studied fields were hypertension, coronary artery disease and heart failure. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. 179 trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P&lt;0.001 and 55.0% vs. 26.3%, P=0.033, respectively). Sixty three studies (25.2%) had results posted on clinicaltrials.gov, and 116 (46.4%) had results published in the scientific literature. No clear indication of result spinning was found in 96 (85%) of published studies. In multivariate analysis, industry sponsorship was statistically significantly associated with results posting (OR: 3.56; 95% CI:1.67–7.60, P=0.001) and publication (OR: 0.41; 95% CI:0.23–0.75, P=0.004). Results spinning was associated with confirmation of the primary hypothesis (OR: 0.23; 95% CI: 0.07–0.75, P=0.015) and results posting (OR: 0.08; 95% CI: 0.01–0.65, P=0.018).

Conclusions
Among late-stage cardiovascular trials only 1/4 had their results posted on clinicaltrials.gov and less than half had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Having industry as a sponsor was independently associated with increased likelihood of results posting, but decreased likelihood of results publication. Results reporting was significantly associated with lower risk of results spinning.

Funding Acknowledgement
Type of funding source: None
Antibodies against the c-terminus of apoA-1 as predictors of death in the general population but not as therapeutic targets actionable through cognate peptides immunomodulation
Authors: Vuilleumier N , Antiochos P , Marques Vidal P , Virzi J , Pagano S , Satta N , Hartley O , Brandt K , Burger F , Montecucco F , Kutalik Z , Waeber G , Mach F , Vollenweider P 
Published: November 2020

Abstract

Aims
Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgGs) have emerged as an independent biomarker for cardiovascular disease and mortality in humans, promote death in ApoE−/− mice, and seem to be preferentially oriented against the c-terminal part of apoA-1 (cterA1). Corresponding specific mimetic peptides were shown to reverse anti-apoA-1 IgG pro-inflammatory effects in vitro. We evaluated the association of IgG against c-terminus apoA-1 (anti-cterA1 IgGs) with all-cause mortality in the community and tested the ability of two cterA1 mimetic peptides to reverse the anti-apoA-1 IgG-induced inflammation in vitro and mortality in ApoE−/− mice.

Methods
Anti-cterA1 IgGs were measured on serum samples of 5220 consecutive participants included in the CoLaus study with median follow-up duration of 5.6 years. The primary study outcome was all-cause mortality. Two chemically engineered optimized cterA1 mimetic peptides were tested i) on HEK cells to modulate interleukin-8 (IL-8) and tumor necrosis-alpha (TNF-α) production, and ii) in apoE−/− mice exposed to 16 weeks of anti-apoA-1 IgG passive immunisation.

Results
Anti-cterA1 IgG independently predicted all-cause mortality, each standard deviation of anti-cterA1 IgG being associated with a 18% increase in mortality risk (Hazard Ratio:1.18, 95%confidence intervals:1.04–1.33; p=0.009). Both cterA1 mimetic peptides reduced the anti-apoA-1 IgG-induced inflammation in a dose-dependent manner in vitro, but did not rescue the anti-apoA-1 IgG-associated mortality in mice.

Conclusions
Anti-cterA1 IgG independently predict all-cause mortality in the general population. By failing to reverse the anti-apoA-1 IgG-induced mortality in mice, our data do not support the hypothesis that these autoantibodies could be actionable through cognate peptides immunomodulation.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by a grant from the Leenaards Foundation (grant number 3698 to N.V.) by the Swiss National Science Foundation (grant number 310030-163335 to N.V.) and by the De Reuter Foundation (grant number 315112 to N.V.).
Role of phosphodiesterases in the development of takotsubo syndrome
Authors: Huebscher D , Borchert T , Hasenfuss G , Nikolaev V.O , Streckfuss-Boemeke K 
Published: November 2020

Abstract

Background/Purpose
Takotsubo syndrome (TTS) is characterized by acute transient left ventricular dysfunction in the absence of obstructive coronary lesions. We identified a higher sensitivity to catecholamine-induced stress toxicity as mechanism associated with the TTS phenotype in our former study, but the pathogenesis of TTS is still not completely understood. In this study our aim was to prove the hypothesis of an altered phosphodiesterase (PDE)-dependent 3',5'-cyclic adenosine monophosphate (cAMP)-signaling in TTS in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

Methods and results
We generated functional TTS-iPSC-CMs and treated them with catecholamines to mimic a TTS-phenotype. To directly address the hypothesis that local cAMP dynamics might be altered in TTS, we used Förster resonance energy transfer (FRET) based cAMP sensors, which are specifically located in the cytosol or at the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA) micro domain. We demonstrated that β-adrenergic receptor (β-AR) stimulations resulted in stronger cytosolic FRET responses in TTS-CMs compared to controls. In contrast, no differences of cAMP level were observed in the SERCA-PLN micro domain between TTS- and control-iPSC-CMs. To analyze the interplay of β-AR signaling and specific PDE contribution to the cAMP signaling in TTS, specific PDE-inhibitors were used. We were able to show in the cytosol that after β-AR stimulation, the strong effects of the PDE4 family of control cells were significantly decreased in diseased TTS CMs, which is in line with previously described reduced PDE4 activity in failing mouse hearts. In contrast, the contribution of PDE3 to cytoplasmic cAMP degradation was increased in TTS (Figure 1 A). This is in line with increased PDE3A and down-regulated PDE4D protein expression in TTS-iPSC-CMs compared to control cells. Analysis of PDE-dependent cAMP level in the SERCA micro domain show also a significantly reduced PDE4 activity. But the dynamic cytosolic PDE contribution of PDE2 and PDE3 after catecholamine treatment in TTS is lost in SERCA micro domain (Figure1B).

Conclusion
Our data showed for the first time alterations of local cAMP signaling in healthy and diseased TTS-iPSC-CMs. We demonstrated an isozym shift from PDE4 in control to PDE3 and PDE2 in TTS and identified PDE4 as an important player in the β-adrenergic cAMP signaling in TTS. Therefore, PDE4 activators may be a possible new therapeutic target option in the treatment of TTS.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): DZHK
Preclinical proof-of-concept study: antisense-mediated knockdown of CALM as a therapeutic strategy for calmodulinopathy
Authors: Yamamoto Y , Makiyama T , Wuriyanghai Y , Kohjitani H , Gao J , Kashiwa A , Hai H , Aizawa T , Imamura T , Ishikawa T , Yoshida Y , Ohno S , Horie M , Makita N , Kimura T 
Published: November 2020

Abstract

Background
Calmodulin (CaM) is a ubiquitous Ca2+ sensor molecule encoded by three distinct calmodulin genes, CALM1–3, and has an important role for cardiac ion channel function. Recently, heterozygous missense mutations in CALM genes were reported to cause a new category of life-threatening genetic arrhythmias such as long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), which is called as “calmodulinopathy”. The patients with calmodulinopathy show poor prognosis and there is no effective treatment for them.

Purpose
Considering the dominant-negative effect of mutant calmodulin proteins produced by heterozygous missense mutations in CALMs, we aimed to prove the concept of antisense-based therapy to treat calmodulinopathy using human iPS cell-derived cardiomyocyte (hiPSC-CM) model.

Methods
We designed multiple locked nucleic acid (LNA) gapmer-antisense oligonucleotides (ASOs) targeting CALM2 and analyzed the silencing efficiency and toxicity in cultured cells to select the most potent ASO. Using CMs differentiated from hiPSCs which were generated form a 12-year-old boy with LQTS carrying a heterozygous CALM2-N98S mutation, CALM2 expression and action potentials (APs) were analyzed to evaluate the efficacy of ASOs.

Results
We identified several ASOs which reduced CALM2 expression without affecting cell viability in human cultured cells (HepG2) (ASO 50 nM, n=2; Figure 1A). Considering further experiments in vivo mouse model, we investigated the CALM2 silencing activity in mouse cultured cells (3T3-L1) without transfection (free-uptake) (ASO 1 μM, n=2; †ASOs have homologous sequence between human and mouse; Figure B). After free-uptake CALM2 silencing analysis in 3T3-L1 cells, we identified that ASO #2 has the most potent CALM2 silencing activity and low cytotoxicity (Figure 1B). ASO #2 effectively reduced CALM2 expression even in hiPSC-CMs (ASO(−): n=3, lipofection: n=4, free-uptake: n=3; P&lt;0.05; Figure 1C). In action potential recordings, we demonstrated that ASO #2 ameliorated prolonged AP durations (APD90) in N98S-hiPSC-CMs at 0.5 Hz pacing (ASO(−): 666±123 ms (n=7), lipofection: 329±21 ms (n=8), free-uptake: 388±34 ms (n=12); P&lt;0.05; Figure 1D).

Conclusion
Our results using patient-derived hiPSC-CM model suggest that ASO-based therapy might be a promising strategy for the treatment of calmodulinopathy.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Nissan Chemical Corporation