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.

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.

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.

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.

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.

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.

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.

[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.

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.

Surgically facilitated experimental movement of teeth: systematic review.

Several surgical techniques based on corticotomy and dental distraction have been developed to improve the movement of teeth and reduce the duration of orthodontic treatment. In this systematic review we have critically assessed published studies on the experimental movement of teeth to find out whether operations such as corticotomy and dental distraction osteogenesis increase the rate of movement, and to find out which biological mechanisms are engaged during surgically facilitated orthodontics, and which complications may be seen. We searched PubMed and Embase for publications until January 2014 and screened the titles and abstracts. Articles that met the inclusion criteria were retrieved in full and assessed independently by 2 of the authors. A total of 22 studies were included, and corticotomy and distraction techniques were the main surgical methods. Generally, all studies reported that movement of teeth was faster after operation than with conventional orthodontics. The peak velocity was always at an early postoperative stage regardless of the surgical technique used. Immunohistological data showed simultaneous regional increases in catabolic and anabolic activity. Histomorphometric data showed more direct resorption of bone and less hyalinisation after operation, and a reduced bone volume density around the surgical site. When present, complications such as root resorption or periodontal problems were minimal. Current experimental animal studies show that procedures such as corticotomy and dental distraction can accelerate the movement of teeth without severe complications because of the regional increase in catabolic and anabolic remodelling.

Evaluation of the relationship between cetuximab therapy and corrected QT interval changes in patients with advanced malignancies from solid tumors.

PURPOSE: Greater scrutiny is being placed on developing a full understanding of potential cardiotoxicity of therapeutic agents, especially on the potential to prolong the QTc interval which can lead to arrhythmias such as torsade de pointes and sudden death. This trial was designed to specifically evaluate the effect, if any, of cetuximab on the QTc interval in patients with advanced solid tumors. METHODS: Cetuximab was administered as an initial dose of 400 mg/m(2) on day 1 (week 1) followed by a maintenance dose of 250 mg/m(2) weekly thereafter. ECG monitoring was performed at screening, baseline (week 1 preceding dosing), and during week 1 to 5 of treatment. Cetuximab concentration-to-QTc relationship was evaluated based on cetuximab serum samples obtained at the time of each ECG measurement to allow for accurate correlation between any observed QT/QTc changes and cetuximab serum concentration. RESULTS: At the recommended dose (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), cetuximab had no clinically meaningful effect on QTc interval, PR or QRS intervals, or heart rate and there was no apparent concentration-dependent effect of cetuximab on any of these electrocardiogram parameters. Safety observations in patients treated with cetuximab in this study were consistent with the agent's known safety profile. CONCLUSION: These results suggest that cetuximab can be safely administered as a single agent without risk of effect on QTc interval.

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.

Severity score for predicting pneumonia in inhalation injury patients.

Inhalation injuries contribute significantly to morbidity and mortality in both children and adults with burns. Pneumonia is a major compromising factor in these patients. The purpose of this article was to evaluate the characteristics, impact factors, incidence, morbidity, and mortality of pneumonia in inhalation injuries. Furthermore, a severity score has been formulated to help predict the probability of developing pneumonia following inhalation injuries. A retrospective study was performed of 214 patients, treated for inhalation injuries from 1999 to 2009 at the Burn Center in Chang Gung Memorial Hospital, Linkou, Taiwan. Patients' characteristics, length of hospitalization, total burn surface area, initial PaO2:FiO2 ratio, number of intubated days, bronchoscope grade, initial carboxyhemoglobin level (COHb) and mortality rate were recorded. A Student's t-test was used for comparison of inhalation injury patients with and without pneumonia and was also used for comparing a TBSA of >20% to those with a TBSA of ≤20% in patients with inhalation injury and pneumonia. Logistic regression analyses were utilized to create a severity score related to pneumonia. 129 patients with inhalation injury were included in the analysis. Overall, 38% (49/129) patients developed pneumonia. Pneumonia associated with inhalation injury occurred more often in patients with a TBSA>20% (P<0.05). The intubation days, bronchoscope grade and COHb level of pneumonia patients were significantly longer (P<0.05). Initial PaO2:FiO2 ratio (PaO2/FiO2) was significantly lower in patients with pneumonia (P<0.05). Mortality following pneumonia was increased sevenfold (P<0.05). Hospitalization days and intubation days were significantly longer in TBSA>20%. Logistic regression analysis was performed to find out the impact factors of pneumonia in inhalation injury patients and to set a severity score. Patients age >60 years, TBSA >20%, bronchoscope grade is 3 or 4, initial PaO2/FiO2≦300 and initial COHb level>10% showed a significant difference (P<0.05). The total severity scale was set at 5 points. Each impact factor was given one point and when the score ≥2 it means patients have high risk of development of pneumonia. This study had identified the significant risk factors for potential development of pneumonia in a group of inhalation injury patients. The impact of these risk factors should be validated in further prospective trials to improve outcome or at least reduce the incidence of the surrogate diagnosis of pneumonia.

Free jejunal diversionary conduit flaps following radiation damage to the pharynx: a technique for regaining oral feeding while preserving vocal function.

UNLABELLED: Radiotherapy is an accepted primary treatment modality for head and neck malignancies. However, in severe cases, the chronic radiation damage has resulted in dysphagia, aspiration and choking. Failure in conservative therapeutic strategies for this swallowing dysfunction will result in either preservation of voice with loss of oral feeding, or vice versa. We introduce our surgical technique based on the free jejunal diversionary conduit flaps, which helps patients to resume oral feeding and preserves vocal function, while reducing the risk of aspiration. METHOD: Six patients suffering from swallowing dysfunction following radiotherapy were enrolled. All were dependent on tube feeding. A subcutaneously transferred free jejunal flap connected the left buccogingival sulcus to the cervical oesophagus, which permanently separates the airway from the native aerodigestive tract by creating a new inlet for food passage. Simultaneously created pharyngostomy drains accumulation of saliva and food residue in the epiglottic vallecula and the pyriform sinus. For the cases with tight fibrotic neck skin, we divided this technique into two stages. RESULTS: All cases could take at least semi-solid food orally, with some minor complications in the initial four cases. Five cases were independent of tube feeding. Two recent cases with modifications did not experience any complication and could start oral intake much earlier (7 days after surgery) than previous cases (118 days on average). CONCLUSION: The free jejunal diversionary conduit flaps offer post-radiotherapy patients with swallowing dysfunction the option to resume oral feeding while preserving their voice and reducing the risk of aspiration.

Economic evaluation of ezetimibe combined with simvastatin for the treatment of primary hypercholesterolaemia.

OBJECTIVE: This study aims to assess the cost-effectiveness of ezetimibe plus simvastatin (E/S) versus atorvastatin or simvastatin monotherapy as second-line treatment of primary hypercholesterolaemia from the Dutch healthcare perspective. METHODS: The evaluation used a Markov model and patient data from the Dutch EASEGO study in which patients failing to reach goal low-density lipoprotein cholesterol levels on atorvastatin 10 mg or simvastatin 20 mg had their dose doubled or switched to ezetimibe 10 mg plus generic simvastatin 20 mg (E10/S20). The second scenario, based on Dutch guidelines, switched patients from simvastatin 40 mg to atorvastatin 40 mg, or ezetimibe 10 mg was added to simvastatin 40 mg (E10/S40). The key effectiveness input measure was change in total cholesterol/high-density lipoprotein ratio obtained from the EASEGO study. In conformity with published studies linking reduced lipid levels to reduced risk of cardiovascular events, the present model assumed that a lipid decrease with ezetimibe may be a signal for reduced risk of cardiovascular events. Model parameters were derived from published literature. Sensitivity analyses were performed for the key parameters. RESULTS: In the EASEGO scenario, incremental cost-effectiveness ratio for E10/S20 was 3497/quality-adjusted life-years (QALY) vs atorvastatin 20 mg and 26,417/QALY vs simvastatin 40 mg. In the Dutch guidelines scenario, E10/S40 was dominant (more effective and cost-saving) vs atorvastatin 40 mg. Varying model inputs had limited impact on the cost-effectiveness of E/S. CONCLUSIONS: The analysis showed the cost-effectiveness of E/S versus atorvastatin 20 mg or simvastatin 40 mg (EASEGO scenario) at a threshold of 30,000/QALY and vs atorvastatin 40 mg was dominant (Dutch guidelines). Thus, E/S seems a valuable cost-effective second-line treatment option for patients not attaining lipid treatment goals.