Towards individualised treatment of out-of-hospital cardiac arrest patients: an update on technical innovations in the prehospital chain of survival.

Out-of-hospital cardiac arrest (OHCA) is a major healthcare problem, with approximately 200 weekly cases in the Netherlands. Its critical, time-dependent nature makes it a unique medical situation, of which outcomes strongly rely on infrastructural factors and on-scene care by emergency medical services (EMS). Survival to hospital discharge is poor, although it has substantially improved, to roughly 25% over the last years. Recognised key factors, such as bystander resuscitation and automated external defibrillator use at the scene, have been markedly optimised with the introduction of technological innovations. In an era with ubiquitous smartphone use, the Dutch digital text message alert platform HartslagNu ( www.hartslagnu.nl ) increasingly contributes to timely care for OHCA victims. Guidelines emphasise the role of cardiac arrest recognition and early high-quality bystander resuscitation, which calls for education and improved registration at HartslagNu. As for EMS care, new technological developments with future potential are the selective use of mechanical chest compression devices and extracorporeal life support. As a future innovation, 'smart' defibrillators are under investigation, guiding resuscitative interventions based on ventricular fibrillation waveform characteristics. Taken together, optimisation of available prehospital technologies is crucial to further improve OHCA outcomes, with particular focus on more available trained volunteers in the first phase and additional research on advanced EMS care in the second phase.

Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial.

BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender. CONCLUSIONS: The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.

Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae.

Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal gene transfer through plasmids plays a major role. The identification of plasmid characteristics and their association with different bacterial hosts provides crucial knowledge that is essential to understand the contribution of plasmids to the transmission of AMR determinants. Molecular identification of plasmid and strain genotypes elicits a distinction between spread of AMR genes by plasmids and dissemination of these genes by spread of bacterial clones. For this reason several methods are used to type the plasmids, e.g. PCR-based replicon typing (PBRT) or relaxase typing. Currently, there are 28 known plasmid types in Enterobacteriaceae distinguished by PBRT. Frequently reported plasmids [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN and IncH] are the ones that bear the greatest variety of resistance genes. The purpose of this review is to provide an overview of all known AMR-related plasmid families in Enterobacteriaceae, the resistance genes they carry and their geographical distribution.

Methotrexate and azathioprine for severe atopic dermatitis: a 5-year follow-up study of a randomized controlled trial.

BACKGROUND: Systemic treatment is indicated for moderate-to-severe atopic dermatitis (AD) refractory to topical treatment. Long-term evidence, up to 5 years, of off-label prescribed methotrexate (MTX) and azathioprine (AZA) is lacking. OBJECTIVES: To investigate long-term effectiveness, safety and drug survival of MTX and AZA. METHODS: In an open-label follow-up phase of a clinical trial, patients were seen every 3 months for 5 years. MTX and AZA doses could be increased or decreased concurrent with daily clinical practice. Primary effectiveness outcomes were mean absolute and relative reduction in SCORing Atopic Dermatitis (SCORAD) index and Investigator's Global Assessment (IGA) after 5 years compared with baseline. To assess safety, the type, frequency, severity and relatedness to treatment of adverse events were investigated. Drug survival was analysed by Kaplan-Meier curves. RESULTS: Thirty-five of 43 originally included patients participated, of whom 27 completed the follow-up. At year 5, the mean relative reduction in SCORAD index was similar in the MTX and AZA groups: 53% and 54% using descriptive analysis. Twelve serious adverse events occurred in 5 years; for three there was a possible causal relationship. Drug survival demonstrated a longer survival for MTX, but survival in both groups was low after 5 years (MTXn = 5, AZAn = 1). CONCLUSIONS: Based on this relatively small pragmatic study, MTX and AZA seem to be effective and safe as maintenance treatments in moderate-to-severe AD up to 5 years. Few patients in both groups survive on their originally allocated drug although some discontinued because of controlled AD.

Periprocedural anticoagulation in atrial fibrillation: Update on electrical cardioversion and ablation.

In this manuscript, we discuss the most important changes in the field of anticoagulant treatment in patients with atrial fibrillation in the setting of electrical cardioversion or catheter ablation. Moreover, we provide practical guidance as well as information on daily practice.

Changes in automated external defibrillator use and survival after out-of-hospital cardiac arrest in the Nijmegen area.

PURPOSE: Out-of-hospital cardiac arrests (OHCAs) are a major healthcare problem. Over the years, several initiatives have contributed to more lay volunteers providing cardiopulmonary resuscitation (CPR) and increased use of automated external defibrillators (AEDs) in the Netherlands. As part of a quality and outcomes program, we registered bystander CPR, AED use and outcome in the Nijmegen area. METHODS: Prospective resuscitation registry with a study cohort of non-traumatic OHCA cases from 2013-2016 and historical controls from 2008-2011. In line with previous reports, we studied patients transported to the hospital (Radboudumc, Nijmegen, the Netherlands) and excluded arrests witnessed by the emergency medical service (EMS). Primary outcomes were return of spontaneous circulation (ROSC) and survival to discharge. RESULTS: In the study cohort (n = 349) the AED was attached more often than in the historical cohort (n = 180): 46% vs. 23% and the proportion of bystander CPR was higher: 78% vs. 63% (both p < 0.001). A higher proportion of patients received an AED shock (39% vs. 15%, p < 0.001) and the number of required shocks by the EMS was lower (2 vs. 4, p = 0.004). Survival to discharge was higher (47% vs. 33%, p = 0.002) without differences in ROSC. The survival benefit was restricted to patients with a shockable initial rhythm. In both cohorts, bystander CPR and AED use were independently associated with survival. CONCLUSION: In patients admitted after OHCA, survival to discharge has markedly improved to 40-50%, comparable with other Dutch registries. As increased bystander CPR and the doubled use of AEDs seem to have contributed, all civilian-based resuscitation initiatives should be encouraged.

Real-life use of Rivaroxaban in the Netherlands: data from the Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation (XANTUS) registry.

BACKGROUND: The Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation (XANTUS) registry investigated the safety and efficacy of the factor Xa inhibitor rivaroxaban. We studied the Dutch XANTUS cohort to a ssess drug safety and prescription patterns in the Netherlands. METHODS: The XANTUS registry was designed as a European prospective, observational study among patients with non-valvular atrial fibrillation. Major bleeding and all-cause mortality were assessed every three months during a 1-year follow-up period. In this Dutch sub-cohort we were also specifically interested in dosing regimens and the incidence and reasons for temporary or permanent discontinuation. RESULTS: Patients (n = 899) had a mean age of 69 (SD ± 9) years and 64.8% were male. The median CHA2DS2-VASc score was 2 (IQR 2-4) and the median HAS-BLED score was 2 (IQR 1-2). Major bleeding occurred in 19 patients (2.4 per 100 patient-years) and 8 patients (1.0 per 100 patient-years) died during the 1­year follow-up period. According to renal function, label-discordant dosing was observed in 48 (8.3%) patients. Finally, 124 patients (13.8%) reported a temporary interruption of rivaroxaban treatment and 11.8% switched to another oral anticoagulant therapy after permanent discontinuation of rivaroxaban. CONCLUSION: In the Dutch subset of the XANTUS registry, we observed low rates of major bleeding and label-discordant dosing and high persistence rates during one year of follow-up in patients receiving rivaroxaban in routine clinical practice. However, documenting the motivation of novel oral anticoagulant (NOAC) type and dose is essential to study label-discordant prescription, a potential safety paradox and identify patient characteristics to optimise NOAC use and adherence.

Bacterial meningitis in solid organ transplant recipients: a population-based prospective study.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of infections of the central nervous system. However, the incidence and clinical course of bacterial meningitis in SOT recipients are unclear. We studied occurrence, disease course, and prognosis of bacterial meningitis in SOT recipients in the Netherlands. METHODS: All patients with a medical history of solid organ transplantation were selected from our nationwide prospective cohort study on community-acquired bacterial meningitis in patients >16 years old, performed from March 1, 2006 to October 31, 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected prospectively. For transplant recipients, additional information was collected retrospectively. RESULTS: We identified 6 SOT recipients, all receiving renal transplants. The annual incidence of bacterial meningitis was 7-fold higher (95% confidence interval [CI] 2.94-17.02, P < 0.001) for renal transplant recipients as compared with the general population (9.56 [95% CI 3.98-22.96] vs. 1.35 [95% CI 1.28-1.43] per 100,000 patients per year). One of the 6 patients (17%) presented with the classic presentation of bacterial meningitis (fever, neck stiffness, and change in mental status). Seizures were common, occurring in 33% of patients. Streptococcus pneumoniae and Listeria monocytogenes were identified in 2 patients each, and Escherichia coli and Pseudomonas aeruginosa were both identified once. Four of 6 patients (67%) had an unfavorable functional outcome. CONCLUSION: Bacterial meningitis is a rare but devastating complication of solid organ transplantation. SOT recipients are at high risk for developing meningitis, and recognition of this condition may be difficult, owing to atypical clinical manifestation.

Chest compression duration influences outcome between integrated load-distributing band and manual CPR during cardiac arrest.

BACKGROUND: The Circulation Improving Resuscitation Care (CIRC) Trial found equivalent survival in adult out-of-hospital cardiac arrest (OHCA) patients who received integrated load-distributing band CPR (iA-CPR) compared to manual CPR (M-CPR). We hypothesized that as chest compression duration increased, iA-CPR provided a survival benefit when compared to M-CPR. METHODS: A pre-planned secondary analysis of OHCA of presumed cardiac etiology from the randomized CIRC trial. Chest compressions duration was defined as the total number of minutes spent on compressions during resuscitation and identified from transthoracic impedance and accelerometer data recorded by the EMS defibrillator. Logistic regression was used to model the interaction between treatment and duration of chest compressions and was covariate-adjusted for trial site, patient age, witnessed arrest, and initial shockable rhythm. Primary outcome was survival to hospital discharge. RESULTS: We enrolled 4231 subjects and of those, 2012 iA-CPR and 2002 M-CPR had complete outcome and duration of chest compressions data. While covariate-adjusted odds ratio for survival to hospital discharge was 1.86 in favor of iA-CPR (95% CI 1.16-3.0), there was an interaction between duration and study arm. When this was factored into the multivariate equation, the odds ratio for survival to hospital discharge showed a significant benefit for iA-CPR vs. M-CPR for chest compression duration greater than 16.5 min. CONCLUSION: After adjusting for compression duration and duration-treatment interaction, iA-CPR showed a significant benefit for survival to hospital discharge vs. M-CPR in patients with OHCA if chest compression duration was longer than 16.5 min.

Impact of the papillary muscles on cardiac magnetic resonance image analysis of important left ventricular parameters in hypertrophic cardiomyopathy.

PURPOSE: The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown. METHODS: We performed Cine-CMR in (1) clinical HCM patients (n = 55) and (2) subclinical HCM mutation carriers without hypertrophy (n = 14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles. RESULTS: Papillary muscle mass in group 1 was 6.6 ± 2.5 g/m(2) and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5 ± 1.8 % and in LV mass of 8.7 ± 2.6 %. For group 2 these figures were 4.0 ± 0.9 g/m(2), 3.8 ± 1.0 % and 9.5 ± 1.8 %, respectively. With a coefficient of variation of 4 %, this 9 % difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms. CONCLUSIONS: In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.

Photo(chemo)therapy in the management of atopic dermatitis: an updated systematic review with implications for practice and research.

BACKGROUND: Photo(chemo)therapy is a common treatment modality in patients with atopic dermatitis (AD), but evidence on its effectiveness has not been recently systematically reviewed. OBJECTIVES: To evaluate the effect of treatment with photo(chemo)therapy in patients with AD and to make treatment recommendations on basis of the evidence. METHODS: We performed an electronic literature search in MEDLINE (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), Global Resource of EczemA Trials (GREAT) and prospective trial registers, complemented with a search of PubMed to find recent studies not yet available in OVID MEDLINE. All randomized controlled trials (RCTs) on phototherapy for the treatment of AD were considered for data extraction. RESULTS: Nineteen studies were included (905 participants). The identified RCTs were generally clinically and qualitatively heterogeneous. Therefore a formal meta-analysis was not feasible. Conclusions must be drawn carefully because of small sample sizes, varying study quality and sometimes the absence of direct comparisons, but on the basis of the included evidence, ultraviolet (UV) A1 and narrowband (NB)-UVB appeared the most effective treatment modalities for the reduction of clinical signs and symptoms. No difference between high-dose UVA1 and medium-dose UVA1 was seen. UVAB was shown to be more effective than UVA and broadband-UVB for the improvement of clinical symptoms, but not compared with UVA1. Other effective treatment options include full-spectrum light, psoralen plus UVA and balneophototherapy. No serious side-effects were reported. CONCLUSIONS: Phototherapy can be a valid therapeutic option for patients with AD. Based on the results of this review, preference is given to UVA1 and NB-UVB. Further well-designed, adequately powered RCTs are required.

Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin.

BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy volunteers, but at lower cardiovascular doses no beneficial effects were observed. AIM: To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Questions about demographics, gastrointestinal symptoms in general and specific symptoms, comorbidity, and medication use including bioequivalent doses of ECC (100 mg) and plain aspirin (80 mg) were stated. We investigated the prevalence of self-reported gastrointestinal symptoms on ECC compared with plain aspirin using univariate and multivariate logistic regression analyses. RESULTS: A total of 16,715 questionnaires (32 %) were returned and eligible for analysis. Of these, 911 (5 %) respondents reported the use of plain aspirin, 633 (4 %) ECC and 15,171 reported using neither form of aspirin (91 %). The prevalence of self-reported gastrointestinal symptoms in general was higher in respondents using ECC (27.5 %) compared with plain aspirin (26.3 %), but did not differ significantly with either univariate (OR 1.06, 95 %CI 0.84-1.33), or multivariate analysis (aOR 1.08, 95 %CI 0.83-1.41). Also, none of the specific types of symptoms differed between the two aspirin formulations. CONCLUSIONS: In this large cohort representative of the general Dutch population, low-dose ECC is not associated with a reduction in self-reported gastrointestinal symptoms compared with plain aspirin.

Diagnostic accuracy of clinical and laboratory characteristics in suspected non-surgical nosocomial central nervous system infections.

BACKGROUND: The diagnosis of meningitis in non-surgical hospitalized patients is often difficult and diagnostic accuracy of clinical, laboratory, and radiological characteristics is unknown. AIM: To assess diagnostic accuracy for individual clinical characteristics of patients suspected of non-surgical nosocomial central nervous system (CNS) infections. METHODS: In a prospective multi-centre cohort study in the Netherlands with adults suspected of CNS infections, consecutive patients who underwent a lumbar puncture for the suspicion of a non-surgical nosocomial CNS infection were included. All episodes were categorized into five final clinical diagnosis categories, as reference standard: CNS infection, CNS inflammatory disease, systemic infection, other neurological disease, or non-systemic, non-neurological disease. FINDINGS: Between 2012 and 2022, 114 out of 1275 (9%) patients included in the cohort had suspected non-surgical nosocomial CNS infection: 16 (14%) had a confirmed diagnosis, including four (25%) with bacterial meningitis, nine (56%) with viral CNS infections, two (13%) fungal meningitis, and one (6%) parasitic meningitis. Diagnostic accuracy of individual clinical characteristics was generally low. Elevated CSF leucocyte count had the highest sensitivity (81%; 95% confidence interval (CI): 54-96) and negative predictive value (NPV) (96%; 95% CI: 90-99). When combining the presence of abnormalities in neurological or CSF examination, sensitivity for diagnosing a CNS infection was 100% (95% CI: 79-100) and NPV 100% (95% CI: 78-100). CSF examination changed clinical management in 47% of patients. CONCLUSION: Diagnostic accuracy for individual clinical characteristics was low, with elevated CSF leucocyte count having the highest sensitivity and NPV.

Dilemmas concerning heart procurement in controlled donation after circulatory death.

With an expanding population at risk for heart failure and the resulting increase in patients admitted to the waiting list for heart transplantation, the demand of viable organs exceeds the supply of suitable donor hearts. Use of hearts after circulatory death has reduced this deficit. Two primary techniques for heart procurement in circulatory death donors have been described: direct procurement and perfusion and thoraco-abdominal normothermic regional perfusion. While the former has been accepted as an option for heart procurement in circulatory death donors, the latter technique has raised some ethical questions in relation to the dead donor rule. In this paper we discuss the current dilemmas regarding these heart procurement protocols in circulatory death donors.

The multidrug resistance protein breast cancer resistance protein (BCRP) protects adipose-derived stem cells against ischemic damage.

Adipose tissue-derived stem cells (ASCs) are promising candidates for regenerative therapy, like after myocardial infarction. However, when transplanted into the infarcted heart, ASCs are jeopardized by the ischemic environment. Interestingly, it has been shown that multidrug resistance (MDR) proteins like the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) have a protective effect in haematopoietic stem cells. In ASC, however, only expression of BCRP was shown until now. In this study, we therefore analysed the expression and functional activity of BCRP and P-gp and their putative function in ischemia in ASC. BCRP and P-gp protein expression was studied over time (passages 2-6) using western blot analysis and immunohistochemical staining. MDR activity was analysed using protein-specific substrate extrusion assays. Ischemia was induced using metabolic inhibition. All analyses demonstrated protein expression and activity of BCRP in ASCs. In contrast, only minor expression of P-gp was found, without functional activity. BCRP expression was most prominent in early passage ASCs (p2) and decreased during culture. Finally, ischemia induced expression of BCRP. In addition, when BCRP was blocked, a significant increase in dead ASCs was found already after 1 h of ischemia. In conclusion, ASCs expressed BCRP, especially in early passages. In addition, we now show for the first time that BCRP protects ASCs against ischemia-induced cell death. These data therefore indicate that for transplantation of ASCs in an ischemic environment, like myocardial infarction, the optimal stem cell protective effect of BCRP theoretically will be achieved with early culture passages ASCs.

[Bacterial meningitis]. / Bacteriële meningitis.

Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone.

Variability in the diagnostic and management practices of post-hemorrhagic ventricular dilatation in very preterm infants across Canadian centers and comparison with European practices.

OBJECTIVES: To investigate the variability in diagnostic and therapeutic approaches to posthemorrhagic ventricular dilatation (PHVD) among Canadian neonatal centers, and secondary exploration of differences in approaches between Canadian and European practices. METHODS: We conducted a survey among Canadian tertiary neonatal centers on their local practices for managing very preterm infants with PHVD. The survey covered questions on the diagnostic criteria, timing and type of interventions and resources utilization (transfer to neurosurgical sites and neurodevelopmental follow-up). In a secondary exploration, Canadian responses were compared with responses to the same survey from European centers. RESULTS: 23/30 Canadian centers (77%) completed the survey. There was no consensus among Canadian centers on the criteria used for diagnosing PHVD or to initiate intervention. The therapeutic interventions also vary, both for temporizing procedures or permanent shunting. Compared to European practices, the Canadian approach relied less on the sole use of ultrasound criteria for diagnosing PHVD (43 vs 94%, p < 0.0001) or timing intervention (26 vs 63%, p = 0.007). Majority of European centers intervened early in the development of PHVD based on ultrasound parameters, whereas Canadian centers intervened based on clinical hydrocephalus, with fewer centers performing serial lumbar punctures prior to neurosurgical procedures (40 vs 81%, p = 0.003). CONCLUSION: Considerable variability exists in diagnosis and management of PHVD in preterm infants among Canadian tertiary centers and between Canadian and European practices. Given the potential implications of the inter-center practice variability on the short- and long-term outcomes of preterm infants with PHVD, efforts towards evidence-based Canada-wide practice standardization are underway.

Pharmaco-invasive therapy: Early implementation of statins and proprotein convertase subtilisin/kexin type 9 inhibitors after acute coronary syndrome.

Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

The impact of alcohol use on the quality of cardiopulmonary resuscitation among festival attendees: A prespecified analysis of a randomised trial.

BACKGROUND: Cardiac arrests often occur in public places, but despite the undisputed impact of bystander CPR, it is debated whether one should act as a rescuer after alcohol consumption due to the perceived adverse effects. We provide the first objective data on the impact of alcohol levels on CPR-skills. METHODS: Pre-specified analysis of a randomised study at the Lowlands music festival (August 2019, the Netherlands) on virtual reality vs face-to-face CPR-training. Participants with an alcohol level ≥ 0.5‰ (WHO-endorsed cut-off for traffic participation) were eligible provided they successfully completed a tandem gait test. We studied alcohol levels (AL, ‰) in relation to CPR-quality (compression depth and rate) and CPR-scenario performance. RESULTS: Median age of the 352 participants was 26 (22-31) years, 56% were female, with n = 214 in Group 1 (AL = 0‰), n = 85 in Group 2 (AL = 0-0.5‰) and n = 53 in Group 3 (AL ≥ 0.5‰). There were no significant differences in CPR-quality (depth: 57 [49-59] vs 57 [51-60] vs 55 mm [47-59], p = 0.16; rate: 115 [104-121] vs 114 [106-122] vs 111 min-1 [95-120], p = 0.19). There were no significant correlations between alcohol level and compression depth (Spearman's rho -0.113, p = 0.19) or rate (Spearman's rho -0.073, p = 0.39). CPR-scenario performance scores (maximum 13) were not different between groups (12 (9-13) vs 12 (9-13) vs 11 (9-13), p = 0.80). CONCLUSION: In this study on festival attendees, we found no association between alcohol levels and CPR-quality or scenario performance shortly after training. TRIAL REGISTRATION: Lowlands Saves Lives is registered on https://www. CLINICALTRIALS: gov (NCT04013633).