Therapeutic hypothermia may increase survival with good neurologic outcome after out-of-hospital cardiac arrest.¹ Experimental data show that therapeutic hypothermia in cardiac arrest reduces ischemic and reperfusion brain injury, with a beneficial effect of early intra-arrest cooling (ie, cooling started during cardiopulmonary resuscitation [CPR]) compared with cooling initiated at a later stage.^2-4 However, the majority of clinical studies have examined the effect of therapeutic hypothermia when cooling was initiated after hospital arrival, most often at the intensive care unit (ICU), several hours after the cardiac arrest.^1,5 Currently, treatment guidelines recommend hospital use of therapeutic hypothermia or temperature control at a temperature of 32°C to 36°C for at least 24 hours, with the strongest indication in patients with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as first rhythm.^6,7

The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors' neurocognitive function and societal participation.

Background: Despite the acknowledged importance of socioeconomic factors as regards cardiovascular-disease onset, and survival, the relationship between individual-level socioeconomic factors and survival after out-of-hospital cardiac arrest (OHCA) is not fully established. Our aim was to investigate whether socioeconomic variables are associated with 30-day survival after OHCA. Methods: We linked data from the Swedish Registry for Cardiopulmonary Resuscitation with individual-level data on socioeconomic factors (i.e. educational level and disposable income) from Statistics Sweden. Confounding and mediating variables included demographic factors, comorbidity and Utstein resuscitation variables. Outcome was 30-day survival. Multiple modified Poisson regression was used for the main analyses. Results: A total of 31,373 OHCAs occurring in 2010-2017 were included. Crude 30-day survival rates by income quintiles were: Q1 (low) 414/6277 (6.6%), Q2=339/6276 (5.4%), Q3=423/6275 (6.7%), Q4=652/6273 (10.4%) and Q5 (high) 928/6272 (14.8%). In adjusted analysis, the chance of survival by income level followed a gradient-like increase, with a risk ratio (RR) of 1.86 (95% CI 1.65-2.09) in the highest-income quintile vs. the lowest. This association remained after adjusting for comorbidity, resuscitation factors and initial rhythm. A higher educational level was associated with improved 30-day survival, the RR associated with post-secondary education ≥ 4 years being 1.51 (95% CI 1.30-1.74). Survival disparities by income and educational level were observed in both men and women. Conclusions: In this nationwide observational study using individual-level socioeconomic data, higher income and higher educational level were associated with better 30-day survival following OHCA, in both sexes.

To determine whether immigrant background and socioeconomic status were associated with increased risk to develop severe Coronavirus disease 2019 (COVID-19) requiring mechanical ventilation at the intensive care unit and to study their effects on 90-day mortality. Nationwide case–control study with personal-level data from the Swedish Intensive Care register linked with socioeconomic data from Statistics Sweden and comorbidity data from the national patient register. For each case of COVID-19 treated with mechanical ventilation at the intensive care unit (outcome), 10 population controls were matched for age, sex and area of residence. Logistic and Cox regression were used to study the association between the exposure (immigrant background, income and educational level) and 90-day mortality. In total, 4 921 cases and 49 210 controls were matched. In the adjusted model, the risk of severe COVID-19 was highest in individuals born in Asia (Odds ratio [OR] = 2.44, 95% confidence interval [CI] = 2.20–2.69), South America (OR = 2.34, 95% CI = 1.82–2.98) and Africa (OR = 2.11, 95% CI = 1.76–2.50). Post-secondary education was associated with a lower risk of severe COVID-19 (OR = 0.75, CI = 0.69–0.82) as was the highest (vs. lowest) income quintile (OR = 0.87, CI = 0.77–0.97). In the fully adjusted Cox-regression analysis birth region of Africa (OR 1.38, CI = 1.03–1.86) and high income (OR 0.75, CI 0.63–0.89) were associated with 90-day mortality. Immigrant background, educational level and income were independently associated with acquiring severe COVID-19 with need for mechanical ventilation.

Purpose To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest. Methods A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1–2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes. Results In total, 300 patients were analyzed and the proportion with CPC 1–2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95–3.85, p = .07. In patients with shockable rhythm, CPC 1–2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06–9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12–4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55–18.3, p = .008. Conclusions In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.