The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

Knowledge and awareness of COVID-19 among Indonesian migrant workers in the Greater China Region.

OBJECTIVES: Migrant workers are one of the most vulnerable population groups during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated knowledge and awareness of COVID-19 among Indonesian migrant workers (IMWs) in Macao (SAR), Hong Kong (SAR), and Taiwan. STUDY DESIGN: This was a cross-sectional study. METHODS: Data were collected through an online survey in February and March 2020 to gain information on (1) participants' sociodemographic characteristics, (2) experience and awareness regarding COVID-19 information, and (3) knowledge and understanding of COVID-19. A series of Chi-squared, t-test, and logistic regression analyses were conducted. RESULTS: The survey was completed by 491 participants (92.1% female). Knowledge of COVID-19 was obtained from multiple sources, including a large proportion from online social media. However, participants who obtained information from their employer, local social networks, and migrant organisations answered a greater number of questions correctly. One-third of participants reported receiving hoax, fake news, and incorrect information and obtained information from unverified sources. Participants were most interested in information about how to cure COVID-19, and 57.8% knew that no specific drug or vaccine was currently available. Almost all participants correctly identified fever and wearing a facemask as the main COVID-19 symptom and prevention strategy, respectively. Participants with senior high school or higher education and who worked as domestic or care workers had a greater knowledge of COVID-19 than their counterparts. CONCLUSIONS: Public health communication strategies using multiple channels, including employers and community organisations, would help to minimise COVID-19 knowledge gaps. In addition, it is recommended that digital literacy content is added to public health campaigns.

Indications for an early invasive strategy in NSTE-ACS patients.

An early invasive strategy in patients who have acute coronary syndrome without ST-elevation (NSTE-ACS) can improve clinical outcome in high-risk subgroups. According to the current guidelines of the European Society of Cardiology (ESC), the majority of NSTE-ACS patients are classified as "high-risk". We propose to prioritise patients with a global registry of acute coronary events (GRACE) risk score >140 over patients with isolated troponin rise or electrocardiographic changes and a GRACE risk score <140. We also acknowledge that same-day transfer for all patients at a high risk is not necessary in the Netherlands since the majority of Dutch cardiology departments are equipped with a catheterisation laboratory where diagnostic coronary angiography is routinely performed in NSTE-ACS patients. Therefore, same-day transfer should be restricted to true high-risk patients (in addition to those NSTE-ACS patients with very high-risk (VHR) criteria) in centres without coronary angiography capabilities.

Treatment patterns of non-ST-elevation acute coronary syndrome patients presenting at non-PCI centres in the Netherlands and possible logistical consequences of adopting same-day transfer to PCI centres: a registry-based evaluation.

BACKGROUND: European Society of Cardiology (ESC) guidelines recommend same-day transfer to a percutaneous coronary intervention (PCI) centre for angiography in high-risk (ESC-HR) patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We describe the treatment patterns of NSTE-ACS patients presenting at non-PCI centres and evaluate the logistical consequences of adopting same-day transfer. METHODS: From August 2016 until January 2017, all consecutive NSTE-ACS patients presenting at 23 non-PCI centres in the Netherlands were recorded. We built an online case report form in collaboration with the National Cardiovascular Database Registry to collect information on risk stratification by the attending physician, timing and location of angiography, and treatment. RESULTS: We included 871 patients (mean age 69.1 ± 12.8). 55.8% were considered ESC-HR. Overall, angiography at non-PCI centres was 55.1% and revascularisation was 54.1%. Among ESC-HR patients, angiography at non-PCI centres was 51.4% and revascularisation was 54.9%. Angiography <24 h was 55.6% in patients with angiography at a non-PCI centre and 74.3% in patients with angiography at a PCI-centre. Assuming patients would receive similar treatment, adoption of same-day transfer would increase transfers of ESC-HR patients who undergo PCI (44.3%), but also increases transfers of medically treated patients (36.2%) and patients awaiting coronary bypass artery grafting (9.1%). CONCLUSIONS: In this registry of NSTE-ACS patients at non-PCI centres, the majority of ESC-HR patients underwent angiography at a non-PCI centre. Same-day transfer occurred in one-quarter of the ESC-HR patients, despite guideline recommendation. Nonselective adoption of same-day transfer to a PCI centre would increase transfers of ESC-HR patients who undergo PCI, however, equally increases transfers of patients who are medically treated.

2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: comments from the Dutch ACS working group.

On behalf of the Dutch ACS working group, we discuss the most important changes in recommendations in the 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation relevant for both the general and interventional cardiologist.

Single mode 4.3 kW output power from a diode-pumped Yb-doped fiber amplifier.

We investigate the average power scaling of two diode-pumped Yb-doped fiber amplifiers emitting a diffraction-limited beam. The first fiber under investigation with a core diameter of 30 µm was able to amplify a 10 W narrow linewidth seed laser up to 2.8 kW average output power before the onset of transverse mode instabilities (TMI). A further power scaling was achieved using a second fiber with a smaller core size (23µm), which allowed for a narrow linewidth output power of 3.5 kW limited by stimulated Brillouin scattering (SBS). We mitigated SBS using a spectral broadening mechanism, which allowed us to further increase the output power to 4.3 kW only limited by the available pump power. Up to this power level, a high slope efficiency of 90% with diffraction-limited beam quality and without any sign of TMI or stimulated Raman scattering for a spectral dynamic range of higher than -80 dB was obtained.

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: comments from the Dutch ACS working group.

On behalf of the Dutch ACS working group, we discuss multiple recommendations which have been implemented in the 2015 ESC guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation.

Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention or after acute coronary syndrome : Practical lessons from a review.

To prevent recurrent ischaemic events, dual antiplatelet therapy (DAPT) is the standard of care after percutaneous coronary intervention and in the treatment of acute coronary syndrome. Recent evidence supports an adjusted DAPT duration in selected patients.The current paper aims to encourage cardiologists to actively search for patients benefiting from either shorter or prolonged duration DAPT and proposes an algorithm to identify patients who are likely to benefit from such an alternative strategy.Individualised DAPT duration should be considered in high-risk anatomic and/or clinical subgroups or in patients at increased haemorrhagic risk with low ischaemic risk. Both thrombotic and haemorrhagic risk should be assessed in all patients. In patients undergoing percutaneous coronary intervention, the interventional cardiologist could advise on the minimal duration of DAPT. However, in contrast to the minimum duration of DAPT for stent thrombosis prevention, longer duration DAPT is aimed at prevention of spontaneous myocardial infarction, and not at stent thrombosis, and thus the key to success is to treat the patient's overall thrombotic risk.The advice on the duration of DAPT must be documented in the patient's records and communicated with the treating physician and general practitioner. DAPT duration should be reassessed at least on a yearly basis.

Label-free glycoprofiling with multiplex surface plasmon resonance: a tool to quantify sialylation of erythropoietin.

Protein glycosylation is among the most common and well-defined post-translational modifications due to its vital role in protein function. Monitoring variation in glycosylation is necessary for producing more effective therapeutic proteins. Glycans attached to glycoproteins interact highly specific with lectins, natural carbohydrate-binding proteins, which property is used in the current label-free methodology. We have established a lectin microarray for label-free detection of lectin-carbohydrate interactions allowing us to study protein glycosylation directly on unmodified glycoproteins. The method enables simultaneous measurement of up to 96 lectin-carbohydrate interactions on a multiplex surface plasmon resonance imaging platform within 20 min. Specificity determination of lectins succeeded by analysis of neoglycoproteins and enzymatically remodeled glycoproteins to verify carbohydrate binding. We demonstrated the possibilities for glycosylation fingerprinting by comparing different Erythropoietin sources without the need for any sample pretreatment and we were able to accurately quantify relative sialylation levels of Erythropoietin.

[Accelerated orthodontic treatment]. / De versnelde orthodontische behandeling.

An orthodontic treatment usually involves a long process which often represents an obstacle for patients. To overcome this problem, surgical techniques have been developed to support and accelerate the orthodontic treatment. Two systematic reviews of the literature on clinical research and animal experiments were carried out in order to draw reliable conclusions about the effectiveness of the various surgical techniques. A total of 18 clinical studies and 22 animal experimental studies were analysed. In both reviews of the literature, a study was made of whether the surgical techniques resulted in an accelerated rate of tooth movement and which complications may be observed. In addition, which biological mechanisms take place during surgically facilitated orthodontics was investigated. Both reviews reported accelerated tooth movement with minimal complications after surgical procedures in comparison to conventional orthodontics. An increase in catabolic and anabolic activities was observed. It has to be concluded that based on the quality of the current literature there is still insufficient information for general conclusions and that more standardised prospective research is necessary for a reliable conclusion about the optimal method of treatment.

The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment.

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8440/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full.

High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes. METHODS: In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure. RESULTS: Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction. CONCLUSIONS/INTERPRETATION: This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to 'unmasking' these patients.

In Silico Methods for Environmental Risk Assessment: Principles, Tiered Approaches, Applications, and Future Perspectives.

This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability. In silico models are then introduced and include quantitative structure-activity relationship (QSAR) models, which support filling data gaps when no chemical property or ecotoxicological data are available. In addition, biologically-based models can be applied in more data rich situations and these include generic or species-specific models such as toxicokinetic-toxicodynamic models, dynamic energy budget models, physiologically based models, and models for ecosystem hazard assessment i.e. species sensitivity distributions and ultimately for landscape assessment i.e. landscape-based modeling approaches. Throughout this chapter, particular attention is given to provide practical examples supporting the application of such in silico models in real-world settings. Future perspectives are discussed to address environmental risk assessment in a more holistic manner particularly for relevant complex questions, such as the risk assessment of multiple stressors and the development of harmonized approaches to ultimately quantify the relative contribution and impact of single chemicals, multiple chemicals and multiple stressors on living organisms.

EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

Experimental approach to optimize phytate phosphorus utilization by broiler chickens by addition of supplements.

Supplementation of 1alpha-hydroxycholecal-ciferol (1alpha-OHD(3)), phytase, and Ca levels has been shown to influence phytate P utilization. Two experiments were conducted with 1- to 16-d broilers to investigate the interactions between the effects of 1alpha-OHD(3), phytase, and Ca on phytate P utilization. In experiment 1, the birds were randomly allocated to 13 treatments with 6 levels of 1alpha-OHD(3) from 0 to 11microg/kg, with and without 500 U/kg of phytase supplemented to P-deficient diet. A positive control diet, adequate in Ca and P, was included. In experiment 2, a 3-dimensional rotatable design with 5 levels each of 1alpha-OHD(3), phytase, and Ca was implemented. Supplementation of 1alpha-OHD(3) and phytase increased phytate P utilization, as indicated by an increase in bone ash, phytate P disappearance, and BW. In experiment 1, no interaction between the 1alpha-OHD(3) and phytase effects was determined for any criteria, except for the incidence of P rickets. However, the second experiment showed that there were interactions between the 3 factors (1alpha-OHD(3), phytase, and Ca). The probabilities that observed variation in the 3-way interaction for measured criteria that were due to chance are: BW gain = 0.1364, G:F = 0.11, bone ash percentage = 0.0278, milligrams of bone ash/tibia = 0.0909, Ca rickets = 0.9394, P rickets = 0.4892, tibial dyschondroplasia = 0.5927, and phytate P disappearance = 0.1126. The equations obtained from the regression models were used to generate contour-surface plots. The percentage of bone ash data indicated that low Ca, high phytase, and high 1alpha-OHD(3) levels were needed to optimize phytate P utilization. The results of this study show that this experimental design may be utilized to identify the best levels of nutrients to add to a diet where complex 3-way interactions exist affecting several criteria. The equations may be used to optimize performance based on desired levels of performance and the costs of the inputs.

The effect of several organic acids on phytate phosphorus hydrolysis in broiler chicks.

Supplementation of some organic acids to a P-deficient diet has been shown to improve phytate P utilization. Two experiments were conducted from 0 to 16 d in battery brooders to determine the effect of various organic acids supplementation on phytate P utilization. In both experiments, birds were fed P-deficient corn and soybean meal-based diets. In experiment 1, citric acid, malic acid, fumaric acid, and EDTA were supplemented. Experiment 2 had a 2 x 2 factorial design with 2 sources of Met, 2-hydroxy-4-(methylthio) butanoic acid (HMB) and dl-Met, with or without 500 U/kg of phytase. In experiment 1, the addition of citric, malic, and fumaric acids increased percentage of bone ash, but only the effect of citric acid was significant. The addition of citric and malic acids also significantly increased the retention of P and phytate P (P<0.05). In experiment 2, the addition of phytase to the diet significantly increased 16-d BW gain, feed intake, percentage of bone ash, milligrams of bone ash, phytate P disappearance, and decreased the incidence of P-deficiency rickets. Methionine source did not affect 16-d BW gain, feed intake, feed efficiency, milligrams of bone ash, or P rickets incidence. However, the birds fed HMB had a higher percentage of bone ash and phytate P disappearance compared with the groups fed dl-Met only when phytase was added to the diets. The additions of citric acid and HMB improved phytate P utilization. However, the reason why some organic acids are effective whereas others are not is not apparent.

Risk factors for redetachment and worse visual outcome after silicone oil removal in eyes with complicated retinal detachment.

PURPOSE: The goal of this study was to identify risk factors for redetachment and/or a worse visual outcome after silicone oil removal (SOR) for complicated retinal detachment. METHODS: The authors retrospectively analyzed 287 consecutive eyes with SOR between January 1999 and December 2003. RESULTS: Anatomic success after SOR was achieved in 81% of the eyes. The overall anatomic success at the end of follow-up was 94%. Postoperative ocular hypertension was found in 8% of the eyes, hypotony in 6% of the eyes, and keratopathy in 29% of the eyes. After SOR 43% of the eyes had an improvement in visual acuity of at least two Snellen lines. After multivariate analysis, male sex, the presence of preoperative rubeosis, and proliferative diabetic retinopathy (PDR) were found to be risk factors for recurrent retinal detachment. Male sex, preoperative visual acuity of <0.1 Snellen lines, PDR, the performance of three more operations, any size of retinectomy, and hypotony were found to be associated with a poor visual outcome of Snellen visual acuity <0.1. CONCLUSIONS: Retinal detachment after SOR in the current unselected series of eyes occurred in approximately 20%, which is comparable to the Silicone Oil Study reports, published approximately 20 years ago. However, preoperative selection was then made, and less than 50% of the silicone oil-filled eyes had SOR. The higher overall anatomic success in the current study may be due to improved vitreoretinal surgical techniques.

[Myocardial ischaemia as a result of treatment with capecitabine]. / Myocardischemie als gevolg van behandeling met capecitabine.

A 53-year-old man and a 76-year-old woman were treated with the cytotoxic drug capecitabine as palliative treatment and adjuvant treatment, respectively, because of colorectal carcinoma. Both developed myocardial ischaemia within a few days. In the man, the capecitabine dosage was reduced and metoprolol was prescribed, while in the woman the capecitabine was stopped. According to the literature, the risk of myocardial ischaemia during treatment with capecitabine is approximately 0.4%, irrespective of the patient's medical history. Except in clinical trials, a history of coronary disease is not considered a contraindication for capecitabine treatment. In case stable angina pectoris develops during treatment, continuation of treatment with a reduced dosage of capecitabine can be considered. A switch to treatment with an alternative fluoropyrimidine, such as fluorouracil or raltitrexed, also appears to be safe. However, raltitrexed is no longer available in The Netherlands.

Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice.

Further information on the structure-activity relationships among the synthetic and naturally occurring alkenylbenzene derivatives was obtained by examining their hepatocarcinogenicities for mice following administration of one or a few doses prior to weaning. Under these conditions preweanling male C3H/HeJ mice were more susceptible than male C57BL/6J mice or females of either strain to liver tumor induction by 1'-hydroxyestragole (1'-hydroxy-1-allyl-4-methoxybenzene) and 1'-hydroxysafrole (1'-hydroxy-1-allyl-3,4-methylenedioxybenzene). Male C57BL/6J X C3H/HeJ F1 mice given a single dose of 1'-hydroxyestragole at 12 days of age developed approximately twice as many hepatomas per liver as did those given the same dose per g of body weight at 1 day of age. The acetylenic compounds 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole were the most potent derivatives studied; they were 5- and 10-fold more potent (based on the average numbers of hepatomas per liver) than the corresponding allylic benzene derivatives. 1'-Acetoxyestragole and 1'-acetoxysafrole had activities similar to those of their respective 1'-hydroxy derivatives; estragole derivatives were consistently 2- to 3-fold more potent than the related safrole derivatives. 1'-Hydroxyelemicin (1'-hydroxy-1-allyl-3,4,5-trimethoxybenzene), its acetic acid ester 1'-oxoestragole, and 3'-bromo-trans-anethole (3'-bromo-1-trans-propenyl-4-methoxybenzene) each had very weak, but statistically significant, hepatocarcinogenic activity. The propenylic derivatives cis-anethole, trans-isosafrole, 1:1 cis,trans-isosafrole, 3'-hydroxy-trans-anethole, piperine, and trans-cinnamaldehyde showed no hepatocarcinogenic activity at the levels examined. In contrast, the propenylic derivatives cis- and trans-asarone (1-propenyl-2,4,5-trimethoxybenzene) were each active; the hepatocarcinogenicities of the asarones were not inhibited by prior administration of pentachlorophenol, a sulfotransferase inhibitor that abolished the hepatocarcinogenicity of estragole under the same conditions. Furthermore, precocene II (6,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran), a cyclic propenylic plant metabolite and asarone analogue, showed strong hepatocarcinogenic activity similar to that of 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole; precocene I (the 7-methoxy analogue of precocene II) was less active than precocene II but more active than cis-asarone.