Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function.

BACKGROUND: Exposure to wood smoke is associated with respiratory symptoms, whereas knowledge on systemic effects is limited. We investigated effects on systemic inflammation, oxidative stress and microvascular function (MVF) after controlled wood smoke exposure. METHODS: In a randomised, double-blinded, cross-over study 20 non-smoking atopic subjects were exposed at rest to 14, 220, or 354 µg/m3 of particles from a well-burning modern wood stove for 3 h in a climate controlled chamber with 2 week intervals. We investigated the level of oxidatively damaged DNA, inflammatory markers and adhesion molecules before and 0, 6 and 20 h after exposure. Six h after exposure we measured MVF non-invasively by digital peripheral artery tonometry following arm ischemia. RESULTS: The MVF score was unaltered after inhalation of clean air (1.58 ± 0.07; mean ± SEM), low (1.51 ± 0.07) or high (1.61 ± 0.09) concentrations of wood smoke particles in atopic subjects, whereas unexposed non-atopic subjects had higher score (1.91 ± 0.09). The level of oxidatively damaged DNA, mRNA of ITGAL, CCL2, TNF, IL6, IL8, HMOX1, and OGG1 and surface marker molecules ICAM1, ITGAL and L-selectin in peripheral blood mononuclear cells were not affected by inhalation of wood smoke particles. CONCLUSIONS: Exposure to wood smoke had no effect on markers of oxidative stress, DNA damage, cell adhesion, cytokines or MVF in atopic subjects.

Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans.

BACKGROUND: There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 µg/m(3), 400 µg/m(3), and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO), exhaled breath condensate (EBC) and nasal lavage (NAL) samples were collected before, and at various intervals after exposure. RESULTS: No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. CONCLUSION: In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

Quality of bystander cardiopulmonary resuscitation during real-life out-of-hospital cardiac arrest.

BACKGROUND: Cardiopulmonary resuscitation (CPR) can increase survival in out-of-hospital cardiac arrest (OHCA). However, little is known about bystander CPR quality in real-life OHCA. AIM: To describe bystander CPR quality based on automated external defibrillator (AED) CPR process data during OHCA and compare it with the European Resuscitation Council 2010 and 2015 Guidelines. METHODS: We included OHCA cases from the Capital Region, Denmark, (2012-2016) where a Zoll AED was used before ambulance arrival. For cases with at least one minute of continuous data, the initial 10min of CPR data were analysed for compression rate, depth, fraction and compressions delivered for each minute of CPR. Data are presented as median [25th;75th percentile]. RESULTS: We included 136 cases. Bystander median compression rate was 101min-1 [94;113], compression depth was 4.8cm [3.9;5.8] and compressions per minute were 62 [48;73]. Of all cases, the median compression rate was 100-120min-1 in 42%, compression depth was 5-6cm in 26%, compression fraction≥60% in 51% and compressions delivered per minute exceeded 60 in 54%. In a minute-to-minute analysis, we found no evidence of deterioration in CPR quality over time. The median peri-shock pause was 27s [23;31] and the pre-shock pause was 19s [17;22]. CONCLUSIONS: The median CPR performed by bystanders using AEDs with audio-feedback in OHCA was within guideline recommendations without deterioration over time. Compression depth had poorer quality compared with other parameters. To improve bystander CPR quality, focus should be on proper compression depth and minimizing pauses.

A novel protocol for dispatcher assisted CPR improves CPR quality and motivation among rescuers-A randomized controlled simulation study.

BACKGROUND: Emergency dispatchers use protocols to instruct bystanders in cardiopulmonary resuscitation (CPR). Studies changing one element in the dispatcher's protocol report improved CPR quality. Whether several changes interact is unknown and the effect of combining multiple changes previously reported to improve CPR quality into one protocol remains to be investigated. We hypothesize that a novel dispatch protocol, combining multiple beneficial elements improves CPR quality compared with a standard protocol. METHODS: A novel dispatch protocol was designed including wording on chest compressions, using a metronome, regular encouragements and a 10-s rest each minute. In a simulated cardiac arrest scenario, laypersons were randomized to perform single-rescuer CPR guided with the novel or the standard protocol. PRIMARY OUTCOME: a composite endpoint of time to first compression, hand position, compression depth and rate and hands-off time (maximum score: 22 points). Afterwards participants answered a questionnaire evaluating the dispatcher assistance. RESULTS: The novel protocol (n=61) improved CPR quality score compared with the standard protocol (n=64) (mean (SD): 18.6 (1.4)) points vs. 17.5 (1.7) points, p<0.001. The novel protocol resulted in deeper chest compressions (mean (SD): 58 (12)mm vs. 52 (13)mm, p=0.02) and improved rate of correct hand position (61% vs. 36%, p=0.01) compared with the standard protocol. In both protocols hands-off time was short. The novel protocol improved motivation among rescuers compared with the standard protocol (p=0.002). CONCLUSIONS: Participants guided with a standard dispatch protocol performed high quality CPR. A novel bundle of care protocol improved CPR quality score and motivation among rescuers.

Editor's Choice-Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction - the NONSTEMI trial phase I.

BACKGROUND: The 2015 European Society of Cardiology non-ST-elevation myocardial infarction (NSTEMI) guidelines recommend angiography within 24 h in high-risk patients with NSTEMI. An organized STEMI-like approach with pre-hospital or immediate in-hospital triage for acute coronary angiography (CAG) may be of therapeutic benefit but it remains unknown whether the patients can be properly diagnosed in the pre-hospital setting. We aim to evaluate whether it is feasible to diagnose patients with NSTEMI in the pre-hospital phase or immediately upon admission. METHODS AND RESULTS: We randomized 250 patients to either acute or subacute CAG (i.e. <72 h of admission). Pre-hospital electrocardiogram acquisition and point-of-care troponin-T measurement ensured that 148 (59%) patients were identified already in the ambulance, whereas the remaining 102 (41%) patients were identified immediately after hospital admission. An acute coronary syndrome was verified in 215 (86%) and NSTEMI in 159 (64%) patients. The CAG rate was significantly higher in the acute CAG group (98% vs. 87%, p<0.001). A culprit lesion was identified in 74% and 64% of the patients underwent coronary revascularization: acute CAG group: 53% percutaneous coronary intervention, 5% hybrid, 7% coronary artery bypass grafting; conventional treatment: 48% percutaneous coronary intervention, 2% hybrid, 14% coronary artery bypass grafting, p=0.32. In patients randomized to acute CAG, time from randomization to CAG was 1.1 h; in patients randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization. CONCLUSION: Diagnosing NSTEMI patients in the pre-hospital phase or immediately upon hospital admission is feasible. Acute CAG may impact the mode of revascularization and is associated with earlier revascularization and shorter hospital stay. The clinical benefit of acute CAG in NSTEMI patients remains to be clarified.

Systemic effects of wood smoke in a short-term experimental exposure study of atopic volunteers.

OBJECTIVE: To investigate whether short-term systemic effects of wood smoke occurred in atopic subjects after experimental wood smoke exposures. METHODS: A double-blind climate chamber study was conducted on 20 healthy atopic subjects with exposures to filtered air and wood smoke. Pneumoproteins, coagulation and adhesion factors, and cytokines were measured. Heart rate was monitored with pulse monitors. Data were analyzed with mixed models. RESULTS: Few differences in the outcomes were observed. Plasma tissue factor remained elevated during filtered air exposure (P = 0.002). P-selectin declined independent of exposure (P = 0.0006). Interleukin-6 increased after filtered air (P = 0.03). CONCLUSIONS: The study confirmed previous observations among nonatopics of limited changes after a 3-hour wood smoke exposure.

Positive patients' attitudes to prehospital care.

INTRODUCTION: The aim of the study was to elucidate the patients' perceptions of the whole prehospital "chain-of survival" from the 1-1-2 call was made to arrival at the hospital; we wanted to study especially the impact different urgency levels had on patients' overall impression. MATERIAL AND METHODS: The study was based on 1-1-2 medical emergency calls and forms a part of a larger postal survey among 6,535 patients who requested and received ambulance services. The answers were dichotomized into "problem scores" and "non-problem scores". The patients' overall impression was analysed in logistic regression models. RESULTS: The study was based on 1,419 answers (response rate 58%). Overall, 98% of 1-1-2-patients characterized the prehospital care as "Very good" (82%) or "Good" (16%). Patients' overall perceptions were dependent on age, evaluated urgency, and the information they received about expected response time. Patients' self-evaluated urgency level was lower than that assessed by the prehospital. CONCLUSION: The study shows that patients have a very positive attitude towards prehospital care, including criteria-based medical dispatch of ambulances. The overall impression of patients with urgency level A was significantly better than that of patients with urgency level B. The issues with most potential for improvement are: the assistance provided when calling 1-1-2 (first answered by the police and then the medical personnel), the prehospital personnel explaining what they were doing, the involvement of relatives and better information about expected ambulance response time. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter.

Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50 µg/ml or 100 µg/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1 µg/ml increased VCAM-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially the wood smoke particles caused increased level of DNA strand breaks and oxidised guanines at concentrations with low cytotoxicity. In conclusion, our results indicate that the adherence of monocytes on endothelial cells in wood smoke particle exposed cultures depend on activation of both cell types.